HLTH353 Exam 2

Caffeine Mechanism of Action

Able to block two key receptors for adenosine thus it enhances the release of acetylcholine, norepinephrine, dopamine, GABA and serotonin in the brain and increases circulating catecholamines. Although caffeine has a variety of pharmacodynamic properties, there is a general agreement that exposure is related to its, ability to block two key receptors for adenosine. Adenosine is found throughout the body and decreases neuronal excitability but also inhibits presynaptic neuronal release of a variety, of neurotransmitters, such as acetylcholine, norepinephrine, dopamine, GABA, and serotonin. Thus caffeine's ability to block these receptors enhances the release of these neurotransmitters in, the brain and increases circulating catecholamines. If you do not remember the definition of catecholamines or some of the neurotransmitters I mentioned, go back to the previous lecture, for a quick review.

Hormones of the Adrenal Cortex

Adrenal glands Secretes catecholamines Synthesizes and secretes Corticosteriods Glucocorticoids Mineralcorticoids Adrenal androgens The adrenal glands are small structures anatomically located on top of the two kidneys. They are made up of two independent parts, both of which are involved in the body's response to stress. The adrenal medulla secretes the catecholamines, with epinephrine being prominent. The adrenal cortex synthesizes and secretes two major classes of steroids the corticosteroids, which include glucocorticoids and mineralocorticoids, and adrenal androgens. Cortisol, the major glucocorticoid secreted by the adrenal cortex, exerts its effects primarily on carbohydrate and protein metabolism. Its potent anti-inflammatory effect has led to its use in the symptomatic management of rheumatoid arthritis. The rate in which aldosterone, the major mineralocorticoid secreted by the adrenal cortex, is secreted is inversely related to the dietary intake of salt.

Effects of Opiates Cont.

Although some of the more prominent behavioral, effects of narcotics resemble those effects induced by sedative-hypnotics, there may be a brief stimulant-like effect immediately after administration, particularly when administered intravenously. The most prominent clinically useful effect of opiates is to reduce pain, a complex perception and emotional phenomenon dependent on several neurotransmitter systems located in the spinal cord. Opiates have relatively little influence on the sharp pain initially induced by a noxious stimulant; their major effectiveness is in reducing moderate to severe dull pain that persists for a, noxious stimulus. This is why opiates are typically used in chronic pain conditions and in treatment of postoperative pain but are not by themselves effective during surgery. Other effects of opiates include: hypothermia, decreased blood pressure, flushed warm skin, miosis or pupil constriction, drying secretion, constipation, respiratory depression, decreased sex drive, relaxation, analgesia, and euphoria. When looking at effects of opiate withdrawal, you notice that many of them are opposite those of the standard effects. Withdrawal effects include: hyperthermia, increase in blood pressure, mydriasis or pupil dilation, diarrhea, yawning and panting, sneezing, spontaneous ejaculation or orgasms, restlessness and insomnia, pain and irritability, and depression. In addition to their analgesic properties, opiates, presumably because of activity in the limbic system, also relieve what some call psychological pain- that is, anxieties, feelings of inadequacy, and hostility or aggressive drives- as well as inducing extremely pleasant mood states or euphoria in the majority of users. Intravenous administration, or so-called mainlining, results in what is, subjectively referred to as a "whole-body orgasm" or "rush." Recent imaging studies in human males indicate that the areas of the brain most active during ejaculation include those most active, following heroin injection. However, in general, chronic narcotic use severely reduces the user's sex drive and leads to impotence. Many people who take opiates experience a subjective sense of mental, dullness and often report feeling "fuzzy," "confused," "dreamy," or "spacey." They may also assert that they are forgetful, have difficulties attending to an activity or with problem solving, concentration, and thinking, and make mistakes and get into accidents. For the recreational user, many of these subjective qualities may be viewed as pleasurable, but for the chronic pain patient they can, be distressing and lead to discontinuation of opiate treatment. More dramatic changes in cognitive functioning, such as delirium, have been observed in opiate-treated patients. Administration of opiates, via injection, particularly in patients who have not been exposed to opiates before, likely causes dose-dependent impaired memory, reasoning, and reaction time. However, chronic oral opiate therapy, for patients in pain is rarely associated with significant decreases in cognitive functioning- quite likely because the patients develop tolerance to these effects. In some patients, chronic pain itself, can cause cognitive disturbances; in these patients opiate treatment may actually enhance their cognitive functioning. Actions in the medulla decrease the rate and depth of breathing, suppress the cough, reflex, and induce vomiting and nausea. This last effect generally occurs with the first administration, unless the person is in pain or lying down, but shows relatively rapid tolerance. Narcotics have a number of peripheral actions. Most notably, they induce a marked constriction of the pupil, called "pinpoint pupils," and they slow the movement of the contents of the G.I. tract, resulting in constipation.

Drugs used for Angina Pectoris

Angina pectoris, the principal symptom of ischemic heart disease, is manifested by sudden, severe pressing chest pain that often radiates to the left shoulder and down the left arm.

Amphetamine Street Names

Bennies Black Beauties Hearts Truck Drivers Speed Uppers

Caffeine

Caffeine is the most widely used drug in the world. Your morning cup of coffee, your soda pop at lunch, your afternoon cup of tea, and your chocolate sundae at night all contain this relatively mild stimulant. It is one of several substances referred to as methylxanthines. The typical adult in the US consumes about 200 to 300 mg of caffeine a day, with coffee and tea consumption accounting for the majority of the intake. Based on typical patterns of use throughout, the day and a plasma half-life of about 5 hours, peak caffeine plasma levels typically occur in the early evening. However, owing to variability in absorption, metabolization, and excretion, as well as the fact that numerous metabolites of caffeine are psychoactive, it is difficult to determine the overall time course and impact of caffeine on an individual. The effects of caffeine vary, considerably among individuals in terms of wakefulness, psychomotor coordination, mood alternations, and the autonomic nervous system response. Two cups of coffee, which contains on average about 150 mg, of caffeine, have the mood-elevating and fatigue-relieving properties of threshold doses of some amphetamines. However, larger doses generally do not have more of a mood-elevating effect, and 7 to 10 cups of coffee may cause insomnia, restlessness, mild sensory disturbances, or muscle tenseness, or someone may experience anxiety or panic attacks. Caffeine typically raises blood, pressure slightly in both men and women, but apparently have different mechanisms. Similarly, increases in heart rate can occur with some caffeine doses, but with others it may actually decrease. Persons who consume low to moderate doses of caffeine typically display dose-dependent improvements in arousal, daytime alertness, vigilance, and some aspects of psychomotor performance. It can also increase cognitive functions, such as reaction time, sustained attention, and information processing. Again, with low to moderate doses of caffeine, individuals may experience predominately, positive subjective effects on mood, characterized by increased well-being, energy, and concentration. These beneficial effects are particularly evidenced when the individuals are tested under, conditions of caffeine deprivation or total abstinence in regular caffeine use has been shown to significantly improve auditory vigilance and visual reaction time. Caffeine can produce an increased, capacity for both muscular work and sustained intellectual effort, but it can also disrupt arithmetic skills and task performance when delicate muscular coordination and accurate timing are required. However, in terms of subjective feelings of drunkenness, such as manual dexterity, balance, numerical reasoning, and verbal fluency-the effects of alcohol intoxication are not reduced by caffeine. Thus, an intoxicated driver, after consuming a few cups of coffee, might feel more alert, but he or she will still be impaired in terms of the motor coordination and decision making required, for properly driving a motor vehicle. Caffeine also exhibits some interesting interactions with nicotine. In this case, the evidence suggests that caffeine can enhance the reinforcing, and subjective stimulant qualities of nicotine in humans. On the other hand, cigarette smokers, who generally consume more coffee than nonsmokers, metabolize caffeine at an accelerated rate. Upon smoking cessation, consumption of caffeinated substances can increase caffeine plasma levels on average more than 200 percent-an effect that may persist for as long as 6 months. This in turn could increase the person's "jitteriness" and be a contributing factor in tobacco withdrawal symptoms. These drug interactions, plus the possibility that the consumption of, caffeine-containing beverages can serve as a conditioned stimulus triggering tobacco craving, suggest that the effectiveness of programs to treat nicotine addiction might be improved by, eliminating the use of caffeine prior to the start of treatment.

MDMA or Ecstasy

Brief history Mechanism of action: Potent releaser and/or reuptake inhibitor of monoamines Boosts extracellular levels of serotonin, dopamine, noradrenaline, and acetylcholine Intoxication is neither uniformly predictable nor uniformly controllable. Most users view the ecstasy experience as positive and pleasant negative effects are mostly of physiological origin Primarily a social and experimental drug The latest controversy over monoamine-related hallucinogens is centered on a chemical relative of methamphetamine known as ecstasy. Although commonly referred to as a designer drug, it was synthesized by a legitimate pharmaceutical company over 90 years ago as a potential appetite suppressant-long before the concept of designer drugs came into being. Subjectively, MDMA induces both amphetamine-like and LSD-like effects, although it is relatively free of the hallucinations produced by the LSD-related compounds. Users claim that it leaves them feeling more empathetic, insightful, and aware. Ecstasy has been in the context of large, organized social settings known as raves, which are typically held in large warehouses or dance halls and involve all-night dancing to techno music, computer-generated video, and laser light shows. Partygoers, who may number into the thousands, typically use ecstasy and often drink beverages with amino acids added to them. Ecstasy exerts many of its effects through its actions on serotonergic systems. However, their mechanisms of actions are very different. In contrast to exerting direct actions on the subtypes of 5-HT serotonin receptors, ecstasy is a potent releaser and/or reuptake inhibitor of monoamines, boosting extracellular levels of serotonin, as well as dopamine, noradrenaline, and acetylcholine. Because low doses appear to produce experiences characterized by conscious-altering effects unaccompanied by intense hallucinations, users have often argued that ecstasy, is a unique drug that is distinctively different from mescaline and LSD. As with other hallucinogen drugs, ecstasy intoxication is neither uniformly predictable nor uniformly controllable. Most users view the ecstasy experience as positive and pleasant. The most common subjective positive effects include changes in feelings and emotions; enhanced communication, empathy, and understanding; cognitive insight or mental association changes; euphoria; perceptual distortions or hallucinations; and transcendental or religious experiences. Common negative effects are mostly of physiological origin and include elevation of blood pressure and pulse; muscle tension and jaw clenching; fatigue; insomnia; sweating; blurred vision; loss of motor coordination; and anxiety. The pattern of ecstasy use is also typical of other hallucinogen use, in that it is primarily for social and experiment uses. Adverse reactions depend on the set and setting of the user or occur when higher doses can lead to prolonged physical and psychological reactions, such as anxiety. In one study a substantial percentage of ecstasy users reported experiencing low mood and impaired concentration between ecstasy-taking sessions. The long-term effects most frequently reported included the development of tolerance, impaired ability to concentrate, depression and the feeling of being more open toward other people. A few days after ecstasy exposure, users may report feeling more depressed, abnormal, unsociable, unpleasant, and ill-tempered than control subjects. Long-lasting adverse effects of recreational ecstasy exposure in humans consistent with serotonergic dysfunction have been found with respect to sleep, mood, neuroendocrine function, impulsivity, and other dimensions of personality. One recent study found that while ecstasy use was not associated with mood disorders, heavy ecstasy users exhibited higher levels of depressed mood, which was correlated with, the total number of ecstasy tablets used but was not associated with decreases in serotonin transporter density. Numerous studies with humans have indicated that ecstasy users do more poorly than nonusers in tests of verbal short-term memory, verbal long-term memory, processing speed, and attention.

Growth Hormone

Essential for normal growth and development Thyroid hormones Insulin Growth hormone Estrogens Androgens Growth-stimulating and protein-building properties Excessive secretion Several hormones are essential for normal growth and development, including thyroid hormones, insulin, growth hormone, estrogens, and androgens. Growth hormone has both growth-stimulating and protein-building properties that promote the cellular uptake of amino acids used in the manufacture of proteins. Excessive secretion of growth hormone produces such irregularities in growth as gigantism in children and acromegaly in adults.

Antiarrhythmic Drugs

Cardiac depressants Quinidine Depresses the spontaneous rate of depolarization of myocardial cells Increases the refractory period Procainamide Lidocaine Phenytoin Depresses spontaneous depolarization of ventricular cells. Beta-Adrenergic Blocking Drugs Reduce the responsiveness of the AV node Cardiac Glycosides Calcium Channel Blockers Slow calcium channels The cardiac depressants are general depressants of myocardial electrical activity; they increase the refractory period of heart muscle, thereby abolishing arrhythmias. They also decrease the excitability of the heart muscle, decrease ectopic activity, and decrease myocardial contractibility. Quinidine is closely related to quinine, a drug used for the treatment of malaria. Quinidine depresses the spontaneous rate of depolarization of myocardial cells and increases the refractory period. This general cardiac depressant is useful in treating atrial and ventricle premature contractions and atrial and ventricle tachycardias. It is used primarily to maintain normal sinus rhythm after electrical cardioversion of atrial flutter or atrial fibrillation and to prevent premature ventricular contractions and ventricular tachycardia. It is well absorbed orally, is highly bound to plasma proteins, is largely metabolized in the liver, and is partially excreted by the kidneys. Its half-life is about 6 hours. The drug is usually given orally, since injection can be dangerous. Nausea, vomiting, and diarrhea are common side effects. Other, more serious side effects include ECG changes, hypotension, and allergic responses. Closely resembling quinidine in its actions is procainamide. Its clinical uses in relieving atrial and ventricle arrhythmias are nearly identical to those of quinidine. It is well absorbed orally, is only slightly bound to plasma proteins, is excreted largely unchanged by the kidneys, and has a half-life of about 3 hours. Nausea, vomiting, and diarrhea occur less often than with quinidine, but about 30 percent of patients taking procainamide for prolonged periods of time develop hypersensitivity to the drug. Fevers, blood cell reactions, and other serious problems can result from such hypersensitivity. Thus, the risks of taking the drug must be weighed against the protection it affords against serious cardiac arrhythmias. The widely used local anesthetic lidocaine also is extremely effective intravenously as an antiarrhythmic agent against serious ventricular arrhythmias of sudden onset, especially in patients who have just experienced a myocardial infarction, or a heart attack. Phenytoin is an antiepileptic drug with antiarrhythmic properties. It depresses spontaneous depolarization of ventricle cells. Its half-life is about 18 hours, and it is highly bound to plasma proteins. Numerous side effects are seen with the drug, but usually these are well-tolerated. Therapeutic blood levels are in the range of 10 to 20 micrograms per kilogram. Several drugs classified as beta-adrenergic blocking agents are used as antiarrhythmic agents, in addition to their being used effectively as antihypertensive and antianginal agents. While not frequently used as antiarrythmics, beta blockers such as propranolol reduce the responsiveness of the AV node and the myocardium to endogenous catecholamines; they also decrease heart rate, slow conductions of electrical impulses to the AV node, and decrease contractibility. Because of these actions, propranolol is used primarily to treat atrial tachycardias such as PAT, atrial flutter, and atrial fibrillation. Propranolol's side effects are related to the beta blockade. Because the heart usually compensates for its reduced performance during heart failure to increase sympathetic tone, beta blockade may lead to hypotension and aggravation of the heart failure. The cardiac glycosides including digoxin are an important class of antiarrhythmic drugs, especially in the treatment of atrial flutter and atrial fibrillation, because they can decrease the ventricular rate without affecting the flutter or fibrillation. Sinus tachycardia and PAT associated with congestive heart failure also may respond to this therapy. The ability to shorten the ventricular refractory period, and thus increase cellular excitability, increases the susceptibility to ventricular arrhythmias, especially as blood levels rise above the therapeutic range. The calcium channel blockers are used increasingly as antiarrhythmic agents. The inward movement of calcium ions through calcium channels is involved in the genesis of the depolarization of cardiac cells and therefore in the generation of cardiac electrical impulses. Inward calcium movement is also involved in the contraction of cardiac muscle fibers and in energy storage and utilization. Drug-induced blockade of calcium channels, therefore, would be expected to reduce both the generation of cardiac impulses and the contractibility of cardiac muscle. Such drugs depress cardiac excitability and contractility, and, as such, they are useful as antiarrhythmic agents. Calcium channel blockers also provide dilatation of blood vessels, making them clinically useful as antianginal drugs.

Narcotics Clinical Use

Chronic Pain Acute cancer-related Terminal disease Typical approach to using medicinal opiates Use the lowest effective dose Determine he frequency, intensity, and timing Use a rapid-acting opiate Routes of administration Oral Intravenous Transdermal patch The use of narcotics in medicine to control chronic pain is a particularly, contentious issue due to the conflict between physicians' desire to ease the pain and their concern over causing addiction. Thus for several decades many chronic pain patients have suffered needlessly, even those with intractable pain at the end of life. More recently, however, most physicians acknowledge the opioid therapy to be an invaluable and acceptable treatment for acute cancer-related pain, and pain caused by a terminal disease. The traditional approach in the treatment of chronic pain patients has been to administer morphine or other opiates at fixed intervals, with the expectation, that the analgesia will last for four to six hours. The general approach now takes into account that pain in these patients is typically not constant across days but ebbs and flows with occasional, breakthrough in pain, that if not controlled fairly quickly may be difficult to manage without administering very high doses of an opiate, which then increase the likelihood of the side effects, such as mental clouding and nausea. Fortunately, there are a wide variety of choices of opiates that come in immediate, controlled, or rapid-release formulations. Thus the general approach is to now use the lowest effective dose of a controlled-release formulation that satisfies the patients' baseline pain management needs; determine the frequency, intensity, and timing of their breakthrough pain; and use a rapid-acting opiate to cover breakthrough pain. Better methods of administering opiates have also been developed to improve their efficacy, reduce their side effects, and lower the cost of treatment. For example, transdermally administered opioid analgesics and patient-controlled opiates, in which the patient is allowed to self-administer opiates, either orally or by pushing a button on an electronically controlled pump that delivers small doses of morphine through an I.V. tube. The highly potent opiate fentanyl has been formulated for, transdermal delivery via a subcutaneous patch that provides extended pain relief. It has also been formulated into a flavored lozenge on a handle for oral transmucosal administration, which allows it to be rapidly absorbed and provide better pain control for cancer patients. The handle allows the lozenge to be removed from the mouth if excessive opioid effects appear during administration. Recently, a patient-controlled system has been developed for the rapid transdermal delivery of fentanyl, which eliminates the need for venous access and complicated programming of pumps. It has been found to provide postsurgical pain relief equivalent to that of standard I.V. morphine regimen delivered by a pump. Contrary to popular belief, patients taking opiates solely to, control pain generally do not become addicted, that is, develop an uncontrollable compulsion to use opiates. A more enlightened approach that has come into use involves the patient-controlled approach, that I just described. Numerous studies have shown that patients generally maintain their doses at a reasonable level, often using lower amounts of morphine than when it is administered in the traditionalfashion, experience more pain relief, and decrease their dosage when pain diminishes. Rarely do such patients develop rapid and marked tolerance to, and dependence on, the narcotic; those that do usually are patients who have a history of psychological disturbance or substance abuse.

Fetal Alcohol Syndrome (FAS)

Completely preventable, Commonly characterized by: Mild to moderate mental retardation Small head circumference Absence of the groove between the nose and upper lip Inordinate profusion of hair on the face at birth Folds on eyelids Underdeveloped jaw area Cleft palate Joint anomalies Cardiac irregularities. Symptoms directly related to the amount of alcohol consumed by the mother during pregnancy Prevention Eliminating alcohol consumption during pregnancy To continue this conversation about alcohol, let's look at FAS, or fetal alcohol syndrome. Fetal alcohol syndrome is completely preventable, because it is caused by prenatal exposure to alcohol. First described in 1968, FAS is commonly characterized by mild to moderate mental retardation, small head circumference, absence of the groove between the nose and upper lip, inordinate profusion of hair on the face at birth, folds on eyelids, underdeveloped jaw area, cleft palate, joint abnormalities, and cardiac irregularities. FAS children show smaller head circumference, smaller brain size, and proportionally smaller basal ganglia, diencephalon, and corpus callosum areas than do normal children. Behavioral characteristics are reported in more than 50% of the cases. Compared with normal children, FAS children generally have poor attention spans; exhibit a lack of guilt after misbehaving; are impulsive, poorly coordinated, hyperactive, and irritable; and exhibit strange behavior and speech problems. Many of their behavioral symptoms are very similar to those of the children with ADHD. It is generally accepted that alcohol-related birth effects exist along a continuum, with complete FAS at one end of the spectrum and incomplete features of FAS, termed fetal alcohol effects. The incidence of FAS and the severity of the symptoms are directly related to the amount of alcohol consumed by the mother during the first trimester. Numerous mechanisms have been proposed for the production of FAS. Some studies have pointed to ethanol's ability to disrupt the synthesis of retinoic acid, a metabolite of vitamin A, as a mechanism for inducing FAS, since an optimal level of retinoic acid is needed for normal development of the limbs and CNS. Others have suggested that the teratogenic effects of alcohol are due to altered umbilical-placental blood flow or to the formation of free radicals that have cytotoxic effects. Another possibility stems from some of the pharmacodynamics properties of ethanol, i.e., that ethanol reduces NMDA receptor activity and enhances GABAA receptor activity. Several lines of animal research suggest that when neuronal activity is abnormally suppressed during the developmental period of synaptogenesis, the timing and the sequence of synaptic connections are disrupted. This causes nerve cells to receive an internal signal to commit suicide, a form of programmed cell death that is known as apoptosis. Thus, there is the likelihood that by suppressing neuronal activity, alcohol causes millions of nerve cells in the developing brain to commit suicide. The window of vulnerability for this abnormal apoptosis in humans would include the entire third trimester of pregnancy, because expression of NMDA receptors peaks during this period. Clearly, prevention of FAS/FAE requires decreasing or eliminating alcohol consumption during pregnancy. Teenagers, who are often uninformed about FAS/FAE, need to be better informed about the potential consequences of drinking during pregnancy. Surprisingly, some health care providers still do not appear to be well informed about the danger of consuming alcohol during pregnancy, while others are not equipped to provide the necessary counseling and referral for pregnant women who use alcohol. Warning labels on alcoholic beverages may be helpful in reducing consumption of alcohol by pregnant women, but research so far has indicated that such labels may only have modest effects on personal risk perceptions and drinking behaviors of such individuals.

The "Overdose" Phenomenon

Death induced by narcotic overdose Dose over 30 mg Varying levels of purity Blood levels of narcotics Sharing heroin supply Location of syringe Adulterants Are death associated with high level of narcotics? Perhaps one of the more notable properties of narcotics in the eyes of the general public is their lethality. Reports occur periodically in the mass media describing what appears to be a death induced by an overdose of a narcotic. However, there is little scientific evidence that the vast majority of these deaths are actually due to narcotic overdose. First of all, although respiratory depression and death do occur at high doses of narcotics, such doses are much higher than those that addicts are likely to use. We don't know what the minimum lethal dose of pure heroin is in humans, but in normal, pain-free adults there is no serious toxicity with less than 30 mg of morphine administered via injection. To the vast majority of addicts, that is a lot of heroin to be administered at one time. However, because of the tremendous variation in actual concentration of heroin in illicit samples, it is possible for one to over-administer if one were "unlucky" enough to administer a particularly pure amount—or to administer what one thinks is heroin but is instead some much more potent opiate like fentanyl. Furthermore, addicts generally have developed tolerance to narcotics. Second, there is little evidence from autopsies of addicts who supposedly have died from narcotics that an excessive amount of narcotic was in the body. Nor is there clear evidence that the concentration of heroin found in the syringe or supplies used by the person was particularly high. Third, addicts often share a supply of heroin, but only one may die from the injection. Finally, in some cases, death is so rapid that the needle is still in the arm of the deceased whereas sufficient respiratory depression to cause death with narcotics generally occurs after several minutes or hours. If the majority of deaths associated with illicit narcotics are not due to excessive amounts of narcotics, then to what can these deaths be attributed to. One possibility is that they are due to an interaction between an opiate and another drug. The fact is, it is a rare narcotic user who uses only narcotics. Alcohol use is quite abundant. Mixing a narcotic with cocaine or with a drug that has sedative-hypnotic properties is also common. Such drug mixtures can have synergistic effects or interact in ways still not understood. The deaths of Janis Joplin, Jimi Hendrix, and Elvis Presley probably occurred in this fashion. The adulterants mixed with illicit narcotics may also be a factor. There is an interesting direct correlation between death rates associated with heroin use and the percentage of quinine mixed with heroin. Adding quinine to heroin was first done in the 1930s as a way of preventing malaria, but it was soon discovered to be an effective way of disguising the actual purity of heroin because of its taste and because it acted synergistically with heroin. Since the 1930s, as adding quinine to heroin became more common, the death rates associated with heroin use increased dramatically. It is also possible that many narcotic-related deaths are due to anaphylactic shock—an immediate, transient kind of extreme allergic reaction characterized by contraction of smooth muscle and dilation of capillaries resulting from the release of histamine and other pharmacological active substances. Such a reaction could result in rapid pulmonary edema and asphyxiation which are not uncommon among narcotic-related deaths. In cases of pure opiate overdoses, which would be evidenced by the triad of coma, pinpoint pupils, and depressed respiration, an injection of naloxone rapidly reverses these symptoms—although too high a dose of naloxone can precipitate severe withdrawal and induce cardiac arrhythmias and pulmonary edema. Based on evidence that patients with severe pain may tolerate larger doses of morphine, it is likely that exposure to a painful stimulus may have a stimulatory effect and temporarily reverse the respiratory depression induced by opiate overdose.

Alcoholism

Definitions of this disorder vary. Characterized by: Continuous or periodic impaired control over drinking Preoccupation with alcohol, Use of alcohol despite numerous adverse consequences, Distortions in thinking, most notably denial. Is it a compulsive drug-use disorder? Some experts describe alcoholism In terms of the amount of alcohol consumed Others feel the consequences of alcohol and the attendant behaviors associated with it Whatever the amount ingested, should be emphasized. Is alcohol acts like an "on-off" switch? There has been a considerable amount of discussion as to exactly what constitutes alcohol dependence, or alcoholism, and definitions of this disorder vary. Alcoholism is considered by continuous or periodic impaired control over drinking, preoccupation with alcohol, use of alcohol despite numerous adverse consequences, and distortions in thinking. For example, there may be one of more unsuccessful efforts to cut down or control alcohol use, or the person may continue to use alcohol despite knowledge of having persistent or recurrent social, psychological, or physical problems that are caused by their alcohol use. Alcoholics may have numerous driving accidents under the influence of alcohol, physically abuse their spouse or children, spend a great deal of money on alcohol, miss work because of drinking or recovering from its effects, or experience ulcers or high blood pressure. Alcoholics may also display a marked tolerance to alcohol and a characteristic withdrawal syndrome when alcohol use ceases. It should be emphasized that physical dependence is not necessarily an order for a person to be deemed an alcoholic; many individuals who are not physically dependent on alcohol are still considered alcoholic if the other characteristics are evidenced. However, if a person is physically dependent on alcohol, then he or she is definitely an alcoholic. The prevailing view is that even after such persons stop drinking for some length of time, they are still considered an alcoholic because, should they return to drinking alcohol, the likelihood of the noted characteristics being evidenced is quite high. Some authorities prefer to view alcoholism as a compulsive drug-use disorder, arguing that until chronic exposure to alcohol induces physiological damage, there is nothing distinctive about alcoholics except for their inability to regulate their use of alcohol in spite of experiencing adverse consequences. In 1988 the U.S. Supreme Court ruled that the government may continue viewing alcoholism as "willful misconduct" rather than an uncontrollable disease when awarding veterans' education benefits. However, the disease designation—adopted by the American Medical Association in 1957—is commonly accepted, if only to counteract the disorder's social stigma and to establish that it is treatable and attestable. Some experts describe alcoholism in terms of the amount of alcohol consumed, whereas others feel the consequences of alcohol and the attendant behaviors associated with it, whatever the amount ingested, should be emphasized. Around one out of 10 drinkers could be considered an alcoholic. However, alcoholism rates are highly dependent on age, with these rates reaching a peak at age 21 and generally declining successively for older age groups. Loss of control over one's consumption of alcohol is one factor that is highly debated. Some experts in the area of alcoholism view alcoholics as being qualitatively different from nonalcoholics in this dimension, as if alcohol acts like an "on-off" switch. Others view loss of control along a continuum of degrees of control. This is not a subtle distinction, as it has important bearing on the type of treatment prescribed for alcoholism. For those who believe that alcohol acts like an "on" switch, the primary treatment goal is complete abstinence from alcohol. For those who believe that there is a continuum of control, drinking in moderation is not only feasible but is perhaps a more appropriate goal in many individuals with an alcohol problem. The reasoning here is that some individuals will avoid all treatment modalities, such as Alcoholics Anonymous, Alanone, and Alateen that emphasize complete abstinence, because they cannot see themselves going through life without ever taking another drink.

Drugs and the Gastrointestinal Tract

Drugs used therapeutically for disorders of the gastrointestinal, or GI tract, may be classified according to their primary use. These include the prevention of gastric reflux or reflux esophagitis, treatment of a peptic ulcer, relief of constipation, and relief from diarrhea.

Psychological Effects Cont.

Dysphoric reaction Appetite Sexual Experiences Depression Anxiety Schizophrenia Paranoia Flashbacks While many people find the marijuana experience pleasurable, others do not. Those who do experience pleasurable effects may find them to wax and wane during the period of intoxication, and in some cases they may develop a psychotic reaction or an uncomfortable and unpleasant mood. This generally occurs if the person ingests an amount that is considerably higher than he or she is used to. Such cases are more common with oral administration because the absorption of THC from the G.I. tract is considerably slower than absorption through smoking, and because the person has difficulty in regulating the amount of marijuana ingested. Other effects of marijuana that may be viewed positively by the user are its effects on appetite and sexual experiences, though these appear to be heavily dependent on cultural expectations. For example, North Americans commonly report and, in some cases, exhibit increases in appetite and weight gain. They also report that they experience enhanced sexual stimulation under the influence of marijuana. In other countries, cannabis is used as a sexual depressant or to suppress feelings of hunger. While acute use of marijuana in low doses may enhance the sexual experience, high doses or prolonged use may lead to depression of sexual desire and even impotence. The acute panic anxiety reaction, noted earlier, particular when unexpectedly strong marijuana is used, is the most common adverse psychological effect induced by cannabis use. As is commonly found with other drugs of abuse, the extensive use of cannabis has been found to be associated with an increased incidence of psychological disturbances and psychiatric symptoms. For example, several studies have found significant associations between the use of cannabis and symptoms of depression and anxiety. There are also data to suggest that the development or recurrence of acute psychosis in the context of marijuana use may be associated with a genetic predisposition to schizophrenia. However, in many cases, individuals diagnosed with cannabis-induced psychosis may actually be individuals with paranoia schizophrenia who have used marijuana. Interestingly, out of the hundreds of studies investigating the effects of acute exposure to marijuana or THC in thousands of human subjects, not one has reported a single case of long-lasting psychotic reaction in the subjects. In summary, in assessing residual neuropsychological effects of marijuana use, one must first differentiate among those effects that are direct effects of the drug or those that are symptomsof actual psychiatric disorders that are caused or exacerbated by marijuana from those that are simply attributes of heavy marijuana users. Then one must determine whether the drug residue effects are short-lived, due to the persistence of cannabinoids in the body, or are long lasting, due to toxic effects on the CNS that persist even after all cannabinoids have been eliminated from the body following prolonged abstinence. The data support a residual drug effect or a toxic effect on the CNS that persists even after cannabinoids have left the body is weak. Furthermore, these impairments are so subtle that it remains unclear how important they are for everyday functioning and whether they are reversed after an extended period of abstinence. It is clear that the long-term heavy use of cannabinoids does not produce the severe or grossly debilitating impairment of memory, attention, and cognitive function that is found with chronic alcohol use. Rarely, the flashback phenomenon may also occur with cannabis use. However, there does not appear to be a correlation between the amount of cannabis consumed and the occurrence of a flashback. On the other hand, the probability of the occurrence of a flashback in cannabis users seems to increase with the amount of LSD-like hallucinogens the person has used. Therefore, some individuals' cannabis use may simply be coincidental with their experiencing flashbacks, or it may be a precipitating factor in inducing LSD flashbacks. Although a flashback may range from a mild to a quite vivid recreation of a drug-induced experience, most clinicians feel that it requires little or no treatment.

Naloxone

Fast acting Short duration Poorly absorbed

Nicotine Use

Every year thousands of young people take up smoking tobacco Thousands of people who have smoked for years try to stop "Pack-a-day" smokers currently pay around $2,000 a year for their habit Why do people begin and then continue the smoking behavior? Every year thousands of young people take up smoking tobacco. Over time their use changes from sporadic to occasional to use that is continuous during the day. On the other hand, thousands of people who have smoked for years try to stop; in most cases these attempts fail because the process is so aversive. In fact, several years ago the Surgeon General of the United States, issued a report that stated that the pharmacologic and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine. Most smokers and nonsmokers recognize that there are costs for smoking. Although cheap in comparison to most other drug habits, smoking is not inexpensive. "Pack-a-day" smokers currently, spend around $2,000 a year for their habit. However, this expense is a drop in the bucket compared to the potential health costs of lung cancer, emphysema, cardiovascular dysfunction, and other diseases associated with cigarette use. The problems are compounded by the fact that cigarette smoking is prominent among most abusers of other drugs; for example, more than 90 percent, of alcoholics are smokers. This smoking behavior exacerbates their health risks and complicates their treatment. Questions about what makes people start smoking in the first place and what makes, stopping smoking so difficult for the majority of heavy smokers have been addressed by researches for years. So far, only pieces of the puzzle exist. A large majority of adult smokers in the U.S., report that they began smoking when they were adolescents. A wide variety of studies have indicated that there are numerous predictors of adolescent tobacco use. These indicators include being, a male and being white, holding positive attitudes toward smoking, having concerns over body weight, having parents who smoke or have permissive attitudes toward smoking, perceiving that, smoking has positive effects, having low expectations for school achievement, having easy access to tobacco, and having a number of friends that smoke. Adolescents who take up smoking tend, to exhibit lower self-esteem, perceive themselves as having less internal control over their lives, and have higher levels of trait anxiety than those who do not smoke. About 1/3 to ½ of those, who experiment with cigarettes become regular users. Although there has been a reduction in the prevalence of smoking among many segments of the U.S population-particularly among adults, and black adolescents-and a decline in the per capita consumption, there has been minimal progress in reducing smoking by adolescents. Despite a multitude of studies on tobacco use, it is still not clear what is so reinforcing about the practice. For the majority of individuals, the initial smoking experiences are more likely to be unpleasant than pleasant. Apparently, the psychosocial rewards, such as peer acceptance and role-model identification, are sufficiently strong to maintain smoking behavior until the individual learns to monitor the amount of smoke, and the unpleasant side effects subside. Nicotine has been long presumed to be the most important, but not the only, reinforcing factor behind smoking tobacco. If it were the only factor, then chewing nicotine gum would induce effects similar to smoking tobacco, which it does not, and the treatment for smoking using nicotine gum would be much more effective than it is. In fact, most tobacco smokers cannot describe any attractive effect except what they might describe as the "taste" of tobacco smoke in their mouth, lungs, and nasal passages. One important factor in maintaining the use of tobacco is the ability to reduce negative emotional states, such as sadness, boredom, and anxiety, which may occur as a function of endogenous characteristics, of the individual, environmental stressors, and of course, nicotine withdrawal. Finally, smoking may be reinforcing because it gives one something to do with one's hands, it may affect one's public image, or it may be associated with other social reinforcers, such as the acceptance by one's peers.

Drugs used for Heart Failure

Heart failure refers to the heart's inability to pump sufficient quantities of blood to meet the demands of the body tissues.

Antidotes

Heavy Metals - Demercaprol, edetate calcium, defroamine, and penicillamine Narcotics - Naloxone Acetaminophen - Acetylcysteine Scopolamine and Atropine - Physostigmine Cyanide - Amyl nitrite Others Carbon Monoxide - Oxygen and hyperbaric chamber Few specific drug or poison antidotes exist in medicine, but here are a few in this brief discussion. Heavy metal poisoning is a serious industrial toxicological problem. Terminating exposure is essential. In addition, certain drugs will inactivate absorbed metal ions. Agents utilized include Dimercaprol for mercury, gold, and arsenic poisoning. Edetate calcium disodium for lead poisoning. Deferoxamine for iron poisoning. Penicillamine, an inactive degradation product of penicillin, for copper poisoning and poisoning by several other metals. These four agents chemically react with the metal ion and form water-soluble chelates that tend not to dissociate. This complex is then excreted by the kidneys. Narcotic poisoning, or overdosage, is characterized by severe respiratory depression and is treated by the intravenous administration of naloxone, followed by use of respiratory support as necessary until the crisis has resolved. Acetaminophen, also known as Tylenol, poisoning may cause severe toxicity to the liver. Acetylcysteine inactivates toxic metabolites of acetaminophen and greatly reduces the incidence of liver toxicity. Thus, acetaminophen toxicity is treated by induction of emesis of gastric lavage, or stomach pumping, followed by doses of acetylcysteine at 4-hour intervals for several days, until such time as the total absorbed amount of acetaminophen is metabolized and the toxic potential is eliminated. Scopolamine and atropine poisoning are treated specifically with drugs that inhibit the enzyme acetylcholine esterase. Such drugs increase total body acetylcholine and overcome the blockade of acetylcholine receptors produces by poisoning with these anticholinergic agents. Physostigmine, an example of this acetylcholine esterase inhibitor, effectively antagonizes atropine and scopolamine poisoning. Cyanide poisoning may result in severe tissue hypoxia. A cyanide antidote kit comes with Amyl nitrite for inhalation and one in a solution. The nitrite reacts with hemoglobin, in turn, complexes with cyanide to form cyanomethemoglobin, and preserves the integrity of cytochrome oxidase, an enzyme that otherwise would be bound and inactivated by the cyanide. The functional integrity of cytochrome oxidase is essential for preserving cellular respiratory capacity and thus oxygenation of body tissues. Sodium thiosulfate to enhance the detoxification of cyanide to thiocyanate by liver enzymes. Other specific antidotes are available for certain insecticides, such as the organophosphate acetylcholinesterase inhibitors, and certain rodenticides, such as those containing the anticoagulant warfarin. Hospital poison control centers are equipped to handle such emergencies with supportive therapy until specific treatment can be started. Carbon monoxide poisoning results from inhalation of carbon monoxide produced from incomplete combustion of organic chemicals such as gasoline. Carbon monoxide inhalation because of improper venting of automobile and furnace fumes causes many deaths each year. Toxicity results from the combination of carbon monoxide with hemoglobin, which produces carboxide hemoglobin, a form of hemoglobin that does not carry oxygen to body tissues. Treatment of carbon monoxide poisoning is directed toward providing oxygen to the tissues and hastening elimination of the carbon monoxide. Transferring the victim to fresh air is essential. CPR is needed if respiration has ceased. If poisoning is severe, treatment in a hyperbaric chamber is indicated. If this is unavailable, 100% oxygen is given at hospitals.

Oxytocin

Hormone of the posterior lobe of the pituitary Potent stimulant of the pregnant uterus during and after delivery Used clinically to: induce labor at term induce therapeutic abortion To prevent postpartum or postabortion hemorrhage Hyperstimulation of the uterus Oxytonin, like vasopressin, is a hormone of the posterior lobe of the pituitary. It is composed of a chain of eight amino acids, six of which are identical to those of vasopressin. Unlike vasopressin, oxytonin has little ADH effect and much less effect on blood vessels and blood pressure. Oxytonin also is a potent stimulant of the pregnant uterus during and after delivery. As such it is used clinically to induce labor at term, to induce therapeutic abortion, and to prevent postpartum or postabortion hemorrhage. Because hyperstimulation of the uterus can lead to reduced uterine blood flow, infant trauma, and even lacerations or a rupture of the cervix or uterus, close fetal and maternal monitoring is essential.

Legal Factors

History Harrison Act Crime Adulteration 1-methyl-4-phenyl-1,2,5,6-tetrahydro-pyridine (MPTP) Low availability Enforcement of narcotic laws in the US Legal issues around the world Up until the early 1900s, it was possible to obtain any drug available over the counter for a relatively small price. A wide variety of tonics and medicine contained unknown mixtures of alcohol, opium, cocaine, and other psychoactive substances. We can assume that, with such easy access to these mixtures, dependence was widespread. But we can also assume that the dependence was rather mild, because the common route of administration was oral. With the recognition of increasing dependence associated with these drugs a number of governments around the world became concerned about the ramifications of this problem. In 1914 the U.S. legislated the Harrison Act to deal with it. In essence, it classified a number of drugs as narcotics and made it illegal for them to be sold except by prescription obtain from a physician, who could only prescribe them during the course of professional practice. Initially, this restriction presented no problem to those dependent on opium or heroin, because they simply went to their local doctor for a prescription. However, before long some law officials began prosecuting physicians for prescribing narcotics to dependent persons, because addiction was not viewed as a disease and, therefore, prescribing narcotics solely to alleviate the symptoms of withdrawal was not an acceptable medical practice. Physicians soon stopped prescribing narcotics to their addicted patients. Immediately, some enterprising individuals recognizing the ready market for narcotics, set up shop and started dispensing narcotic drugs—at somewhat inflated prices. The law's attempt to prosecute these individuals, as well as to legislate more severe penalties for the sale and possession of narcotics, started a vicious cycle that escalated for more than half a century. With higher and higher prices for narcotics individuals turned to crime to support their habits. Little money went for proper nutrients and the physical health of the average adult began to decline. More and more misrepresentation of drugs in terms of quality, quantity, and type of drug, and the addition of adulterants led to increased toxicity and lethality in the addicted population. The danger of adulteration was illustrated in the 1980s by the discovery that the sloppy lab practices attempting to synthesize analogues of the narcotic mepheridine for street sale in northern California resulted in the chemical 1-methyl-4-phenyl-1,2,5,6-tetrahydro-pyridine or MPTP. The substance has been found to metabolize in the brain into a compound that kills midbrain dopaminergic cells whose axons project neurons into the basal ganglia. This effect produces clinical symptoms essentially identical to those of Parkinson's disease. This phenomenon was first described in 1979 in the case of a 23-year-old graduate student who had developed a Parkinson-like condition after injecting a demerol-like drug that he had synthesized in his own lab. In taking shortcuts in his manufacturing process the student contaminated his chosen product with MPTP. Unfortunately, the student was not the only one who used this adulterated substance, and several dozen young users of this synthetic opiate succumbed to a similar fate,—a lifetime of tremors, partial or complete paralysis, and abnormal posture. Low availability of narcotics also eventually led to the more dangerous intravenous method of administration. Problems with the injection procedure were compounded by the failure to protect against infectious diseases, in part because of lack of education. Finally, vigorous enforcement of narcotics laws in the US. allowed organized crime to strengthen itself with the immense profits associated with narcotic sales. That is, the greater the penalties for sale, the higher the price and the greater profit for selling. This phenomenon persists to this day. The basic problem is that the majority of the money spent to buy illicit drugs goes to the bottom level of the market —to the street and near-street sellers. Only a small portion of the final price goes to the production and smuggling sector. As a result, seizures of big drug shipments, which may cost the government —to the street and near-street sellers. Only a small portion of the final price goes to the production and smuggling sector. As a result, seizures of big drug shipments, which may cost the government on the order of $1 million per drug seizure, have almost no impact on buyers and thus no impact on demand or on the huge profits to be made. In essence, what started out as an effort to protect consumers from becoming mildly dependent on relatively nontoxic substances resulted in their becoming strongly dependent on very toxic and lethal substances. Around the time the U.S. legislated the Harrison Act, Great Britain was instituting its own similar legislation. However, it viewed dependence from a less moralistic perspective, as something to be treated. Thus, narcotic addicts in Great Britain were able to obtain heroin and other narcotics by prescription from their family physicians, while the law attempted to keep illicit narcotics out of the hands of nonaddicts. Thus, illicit trade in narcotics was minimized and the population of addicts was maintained at a fairly constant level until the 1960s. Unfortunately, some physicians were rather lackadaisical in their prescription practices, and more narcotics were being prescribed than was necessary to maintain just the addicted population. This excessive prescribing led to a change in policy in 1968, whereby only specifically licensed physicians are allowed to prescribe heroin, some other abused opiates, and cocaine to addicts on a maintenance basis. In addition, until 1996 addicts treated by these physicians had to be reported to what is called the Home Office. Most of these physicians are affiliated with special drug treatment centers although any physician can apply for a license to write prescriptions for these drugs for their addicted patients. Over the past 3 decades, there has been a trend in Great Britain to emphasize oral methadone as the most appropriate drug treatment for heroin addiction, and any medical physician in the United Kingdom is permitted to prescribe methadone for the purpose of treating opiate dependence. Due to a variety of reasons, the true addict population is two to 10 times the actual number reported.

Barbiturate Mechanism of Action

Hyperpolarize neurons Enhance GABA activity Open Chlorine ion channels Allows chlorine ions to flow into neurons Prolongs the duration of open channels Results in hyperpolarization Increase level of most neurotransmitters Effects on the brain The general tendency of these drugs is to decrease the excitability of neurons throughout the nervous system. Although barbiturates depolarize some neurons, their predominant action throughout the nervous system is to hyperpolarize these neurons. The inhibitory influence of barbiturates is due to their ability to enhance GABA's activity at the GABAA-type receptor, which results in the opening of chloride channels, allowing chloride to flow into neurons and hyperpolarizing them. The primary action of barbiturates appears to be one of prolonging the duration that these channels remain open. Accompanying these activities is an increase in the levels of most neurotransmitters, in all likelihood because of their decreased utilization. The rate of oxygen consumption and cerebral glucose metabolism in all areas of the brain is reduced with these drugs.

Drugs used for Hypertension

Hypertension is one of the significant risk factors in the long-term development of such serious cardiovascular disorders as congestive heart failure, coronary artery disease, heart attack, stroke, and kidney failure.

Effects of Opiates Withdrawal

Hyperthermia Increase in blood pressure Mydriasis Diarrhea Yawning and panting Sneezing Spontaneous ejaculation and orgasms Restlessness and insomnia Pain and irritability Depression

Amphetamine & Methamphetamine Background Information

Initially synthesized in the late 1800's, but medical uses for it were not developed until the late 1920's. Initially marketed in the form of inhalers for asthma treatment. Gained popularity for its potent CNS effects. Discovered to be made up of two isomers, L and D amphetamines. D found to be more potent and marketed as Dexedrine. Minor modification yielded methamphetamine. Methcathinone newest of the potent amphetamine. Just as addictive. Originally synthesized in Germany. Regulated as a Schedule I drug in 1993. Effects are similar to cocaine and methamphetamine. Slight changes to amphetamine can abolish both stimulant and appetite suppressant effects. Others may decrease only the profoundly enhanced MAO-inhibiting properties of the compound.

Treatment for Opiate Dependence

Interventions Treatment: Residential Self-help groups Therapeutic communities Triggers Blocking the effects with other drugs Narcotic substitution Environmental Although some chronic opiate users eventually stop on their own accord, for the most part dependence on opiates is so strong that some type of intervention is required in order to overcome it. Most of the psychological, approaches for dealing with alcoholism have been employed in the treatment of narcotic addiction, such as residential in-patient and out-patient treatment, self-help group, and therapeutic communities. Their efficacy in achieving abstinence for some period of time is dependent on a multitude of factors like age, length of opiate use, educational and occupational level, use of alcohol, or other drugs of abuse, comorbidity with other mental disorders, etc. However, regardless of their success in achieving abstinence, narcotic addicts inevitably experience cravings for narcotics that are a major factor in relapse. Thus approaches for dealing with these cravings have been extensively explored. The finding that abstinent opiate abusers experienced intense drug craving and withdrawal symptoms when exposed to drug-related stimuli has led to attempts to eliminate these responses through the process of extinction. This process basically involves exposing the person to the conditioned stimuli that provoke the craving without allowing the person to experience the drug. This has been found to virtually eliminate the conditioned craving and withdrawal symptoms within 20 hour-long treatment sessions. How long these reductions last and how well they generalize to other related stimuli after the patients' discharge remains to be determined. Some of the more common treatments for narcotic addicts involve the use of drugs that either block narcotic effects or are substitute narcotics with less disruptive effects than those on which the person is dependent. One of the first drug treatments for narcotic dependence involved the administration of narcotic antagonists, thereby theoretically breaking up the relationship between the drug-taking behavior and the reinforcing effects of these drugs. Initially, nalorphine and cyclazocine were used. While these drugs did block the effects of heroin and morphine, they had a number of properties that prevented them from being practical tools in the treatment of narcotic dependence. These drugs sometimes induced psychic side effects, and then chronically, they were capable of inducing a mild physical dependence. The disadvantages of naloxone were its short duration and its ineffectiveness when taken orally. These problems were surmounted with the subsequent development of naltrexone, which is not only more effective when taken orally but also has opiate-blocking actions for up to 3 days, thus eliminating the need for several daily administrations. While the use of pure opiate antagonists like naltrexone in the treatment of opiate abuse and dependence sounds great in theory, it is not an approach that is likely to be very effective in the treatment of most compulsive opiate users because these drugs do not deal with the major motivating factor behind the narcotic use; that is, they do not eliminate the psychological craving for narcotics. Therefore, without any further intervention, these individuals will probably stop taking the antagonist and go back to taking narcotics. In addition, unlike the opiate methadone, which can be administered at any stage of addiction, treatment with opiate antagonists, such as naltrexone, typically would not begin until after the addict has been detoxified and all signs of abstinence have dissipated because these drugs would induce a rapid onset of abstinence symptoms that could be quite severe. It is argued that these drugs would only be useful in highly motivated individuals. These concerns have been supported by a study indicating that only 27% of naltrexone-maintained narcotic addicts remained in treatment for the 12-week observation period, whereas 87% of methadone-maintained addicts remained in treatment. However, opiate-addicted professionals who routinely have access to opiates make excellent candidates. Perhaps one of the most successful drug treatments for narcotic dependence is not really a treatment at all, in that it involves substituting one narcotic for another with the substitute narcotic having more socially acceptable qualities and fewer disruptive effects on the individual. The first of these narcotics to be employed was methadone, a synthetic narcotic developed by Nazi Germany during World War II. Although it is a very effective analgesic, it did not come into the U.S until the late 1960s.

Chronic Use

Liver is one of the organs most likely to be affected -Alcohol-induced liver disease is primarily restricted to the fatty -Alcoholic hepatitis, -Cirrhosis Brain damage -Brain shrinkage and a number of functional deficits in cerebral and cerebellar function -Mechanisms for cellular death with respect to the CNS are also not well understood -Impairment in learning and memory have traditionally been attributed to malnutrition -Large portion of the alcoholic's diet is derived from alcohol -Poor diet associated with chronic alcohol intake can also depress appetite and prevent proper absorption of nutrients Sexual functions Alcohol-induced liver disease is primarily restricted to the fatty liver and is a benign and asymptotic condition. However, after years of alcohol abuse, a minority of alcoholics suddenly develop the potentially lethal condition called alcoholic hepatitis, characterized by cellular death and organ inflammation. Although liver damage associated with alcohol consumption was once believed to be primarily due to malnutrition, research has shown that excellent nutrition does not prevent the development of alcoholic hepatitis or its progression to cirrhosis. Chronic alcohol consumption has also been associated with brain shrinkage and a number of functional deficits in the cerebral and cerebellar function. Alcoholics suffering from these conditions can show some recovery when abstinence is maintained over periods of weeks to many months, with similar improvements occurring regardless of gender or family history of alcoholism. Rapid recovery may be attributed to the resolution of the alcohol withdrawal syndrome—a biochemical process—whereas gradual functional improvement may have a structural basis, a reversible atrophy indicative of the plasticity in the Central Nervous System. The mechanisms for cellular death with respect to the CNS are also not well understood, although there is clear evidence that a great deal of damage is directly due to alcohol consumption. Much of the alcohol-associated brain damage and the resulting impairment in learning and memory have traditionally been attributed to malnutrition, especially thiamine deficiency, rather than to the direct neurotoxic effect of ethanol. These problems come about because a large portion of the alcoholic's diet is derived from alcohol, which happens to be very high in calories but contains no other essential nutrients, and the consumption of proper amounts of proteins, vitamins, and essential nutrients is low. Poor diet associated with chronic alcohol intake can also depress appetite and prevent proper absorption of nutrients from the G.I. tract. Therefore, treatment of these neurological disorders with thiamine and glucose is generally helpful, although it will not reverse symptoms that are the result of neuronal loss. Chronic alcohol consumption can also severely affect numerous sexual functions. Male alcoholics, with or without overt liver disease, exhibit certain underactive gonadal functions, including testicular atrophy, impaired sperm production, impotence, and decreased libido, as well as abnormalities in the metabolism of sex hormones. Much of the evidence suggests that these deficits are due to increased activities of the drug-metabolizing enzymes in the liver resulting from chronic alcohol exposure, which, in turn, severely reduces testosterone levels.

Cannabis Background Information

Medicinal herb Recreational uses Marijuana coined from Mexican Spanish word Public officials Marijuana Tax Act Amotivational Syndrome The leaves and buds of the Cannabis sativa plant have been used as an intoxicant and as a medicinal herb for centuries, perhaps as far back as 2700 B.C. Only for about the last 100 years or so have the recreational uses of this plant been emphasized. Its medicinal use gradually declined, partially because other drugs with more selective actions were developed and partially because the shelf-life of the active ingredients is short. About the same time, its recreational use began to increase gradually. Because its use changed from a medicinal one to a recreational one, certain public officials, like one of the commissioners of the Federal Bureau of Narcotics by the name of Harry Anslinger, became concerned with its use. In the 1930s, Anslinger and other officials began to circulate stories about marijuana causing permanent brain damage and insanity, enhancing criminal and aggressive tendencies, and inducing sexual perversion. In reaction to these allegations, Congress enacted the Marijuana Tax Act of 1937, which made possession of marijuana without having paid a specific tax on it a federal crime. A number of people were still skeptical of the potential damaging effects of marijuana. One of these was New York City Mayor Fiorello La Guardia. In the early 1940s, he set up a special commission of experts to determine the actual consequences of marijuana use on people. The final report of La Guardia's panel suggested that marijuana was a fairly mild intoxicant with few side effects, even when used to excess. Despite the findings of these presumably objective and unbiased observers, the report had little impact on the opinions of the majority of the people in the U.S. In most cases the report was ridiculed and criticized for its lack of rigor and its methodology- particularly by Anslinger, who effectively undermined the results of the report well before its publication. In the 1950s, the beliefs about marijuana's effects changed somewhat. Its use supposedly resulted in a strong psychological dependence, led users to escalate their use to more potent and dangerous drugs, induced a so-called amotivational syndrome, and was a cause of permanent brain damage. A plethora of empirical research on the effects of marijuana in the late 1960s and early 1970s dispelled some of these beliefs but led to speculation over new, potentially detrimental effects. In one report, the findings suggested that irreversible brain damage was associated with its use which was quickly and severely criticized for its methodological deficiencies. Other researchers suggested that heavy marijuana use was the cause of severe personality changes. However, contrary to the notions that marijuana caused one to become a sex maniac, studies suggested that marijuana might actually cause sexual impotence and sterility in males due to reductions in the male sex hormone, testosterone. Chromosomal aberrations, decreases in certain kinds of white blood cells and immunity, and alterations in the DNA potentially leading to cancer were suggested by studies to be associated with cannabis use. The reliability and potential ramifications of these findings are still being debated today.

Narcotic Effects on Pregnancy & Babies

Lower birth weights More excited More irritable Development of the nervous system Mother to baby interactions There may be a significant damage, to a fetus and neonate if a woman is chronically exposed to narcotics during pregnancy. Newborns of narcotic-dependent women tend to have lower birth weights and be more excitable and irritable, than normal babies. Some of these symptoms are probably due to their experiencing narcotic withdrawal at birth. Symptoms that persist for several weeks or months, or longer, may be due to a number of factors. Prior to birth, the developing of the nervous system may be particularly sensitive to the periodic withdrawal that the mother probably undergoes. Or there may be alterations in the endorphin systems of, the fetus during development. After birth, the mother-infant bonding may be disrupted, inadequate maternal care or nutrition may be provided, and dependent mothers may perform less adaptively, in areas of intelligence, personality, and parenting behaviors. For example, a study assessing 2-year-old children born to methadone-using women during that mother-infant interactions following, birth were a factor in the child's development outcome, but that methadone exposure alone did not have a negative impact on the developmental measures studied.

Amphetamine & Methamphetamine Effects of Chronic Exposure

Malnutrition Non-healing Ulcers High blood pressure Meth mouth Brain damage from restricted blood flow to the brain Irreversible neuronal damage Gray-Matter deficits

LAAM & Buprenorephine

Longer durations than methadone Efficacy is comparable to methadone Cost saving compared to methadone Addicts may feel like long lasting narcotic treatments are not working The success of methadone has led to the development and evaluation of other opiate drugs in narcotic addiction with even more favorable qualities. These drugs include Levo-Alpha Acetyl Methadol or LAAM and buprenorphine. LAAM is a narcotic agonist similar to methadone, and buprenorphine is a mixed opiate agonist-antagonist. Both of these have even longer durations of action than methadone. Thus, they induce a much more stable effect on mood and psychological processes and induce a very mild withdrawal when drug administration is terminated. The efficacy of both of these drugs has been shown to be comparable to that of methadone in terms of suppressing addicts' use of heroin, effectiveness in withdrawal detoxification, blocking the effects of other opiates, and satisfying their cravings for opiates. They have advantages over methadone specifically with regard to only requiring one to three doses weekly, possible cost savings, and possible improved clinic-community relations. LAAM was approved for the management of opiate dependence in 1995, but its manufacturer discontinued its sale and distribution in 2003 due to increasing reports of severe cardiac-related adverse events associated with its use and the availability of less toxic treatment alternatives that have recently been approved for the same purpose, like Subutex and Suboxone. Subutex contains only buprenorphine and is recommended for use during the first few days of treatment, while Suboxone contains naloxone to guard against misuse and is recommended for use during the maintenance phase of treatment. Subutex and Suboxone are the first narcotic drugs available for the treatment of opiate dependence that can be prescribed in a physician's office, which will allow more patients the opportunity to access treatment. At the present time methadone can be only dispensed in a limited number of clinics that specialize in addiction treatment. Also, as patients progress in therapy, their doctor may write a prescription for a take-home supply of the medication. Only qualified physicians with an identification number required by the DEA will be able to start in-office treatment and provide prescriptions for ongoing methadone treatment. One of the advantages of buprenorphine over other opiates is the absence of dangerous respiratory depression—even at 100 times those necessary for inducing analgesia. Preliminary studies have found buprenorphine to be acceptable to heroin addicts who will not accept methadone maintenance treatment, either because they view methadone as "just another addicting drug" with less desirable effects than heroin or have experienced methadone effects as aversive. Buprenorphine maintenance treatment in opiate-dependent pregnant women has also shown to be well accepted by them, and is associated with a low incidence of neonatal abstinence syndrome. One potential problem with the use of very long-acting narcotic is that, after a history of taking other narcotics daily or several times daily, addicts may not feel subjectively that the longer-acting substance is actually working. Therefore, they may feel some psychological discomfort with a compound that only needs to be taken once or twice a week. On the other hand, research with LAAM indicated that many opiate addicts preferred LAAM over methadone because they needed to attend a clinic less frequently, experienced fewer side effects and felt that LAAM had a better maintenance effect. In summary, many users of narcotics never seek treatment. Those who do not are less likely to have severe non-drug-related problems than those who do. Many of those who do not seek treatment may eventually become abstinent on their own—a process called "maturing out." While maturing out tends to be a time-related phenomenon, it is less likely to occur in addicts who are deeply involved in crime and drug dealing.

Cocaine Consequences of Use

Lower productivity Financial losses Family disruptions Legal difficulties Neurological problems Seizures and tremors Headaches Sensory loss Visual impairment Fatalities Many of the problems attributed to cocaine, such as a lower productivity, financial losses, family disruptions, legal difficulties, and so on, are indirectly related to its use. These problems come about because of the user's preoccupation with the drug or the U.S. legal system's views on its possession and use. However, unlike opiates, where most of the problems with their use are due to these factors rather than to direct effects on the body, cocaine also has several potential direct adverse consequences. As noted previously, the adverse effects of heavy amphetamine use-for example, psychosis, profound irritability, misperception, paranoid thoughts, impaired interpersonal relations, and impaired eating and sleeping disturbances-have also been well-documented to occur with heavy cocaine use. Cocaine also has been shown to precipitate panic attacks, which may subsequently reoccur without further cocaine use. Cocaine can produce a variety of neurological problems, including seizures, headaches, and transient symptoms such as sensory loss on one side of the body, visual impairment, and tremors. Other than seizure activity, which is dose related, there does not appear to be a correlation between the neurological problems and the dose, or route of administration, or prior cocaine patterns of use. Although neurocognitive impairments may precede cocaine use and may be a factor in its initial use, there is considerable support for the conclusion that subgroups of cocaine-abusing, patients may demonstrate sustained and persistent neurocognitive deficits that are consequences of their cocaine use. Statistics regarding fatalities attributable to cocaine use are not particularly reliable, but it does appear that only about ¼ of deaths are actually due directly to the recreational use of cocaine. The majority of cocaine-associated deaths can be attributed to suicide induced by or facilitated by cocaine; accidental overdoses. For example, the person swallowed cocaine for smuggling purposes or to elude detection when arrested; homicides; death from natural causes; or the combination of cocaine with other drugs primarily opiates. For most individuals, the lethal dose of cocaine-approximately 1 to 2 grams in an hour-would be quite expensive. Cocaine use may cause sudden death because of cerebral hemorrhaging or bleeding within the brain, convulsions, lethal cardiac arrhythmias, or acute myocardial infarction or, sudden insufficiency of blood to the heart muscles, even in individuals with no preexisting arterial dysfunctions. The mechanism behind sudden deaths is still obscure, but evidence suggests that even low doses of cocaine can lead to inflammation of the muscular walls of the heart in certain individuals. Also, contrary to what is commonly believed, intranasal cocaine can lead to sudden death.

Naltrexone

More potent than Naloxone Orally effective 24 to 48 hrs duration

Methadone

Methadone as a treatment method; Drs. Dole & Nyswander Metabolism research Heroin to Morphine to Methadone Advantages Readily and reliably absorbed orally Long duration Eliminate injections Cross tolerance Maintenance program Narcotic reduction program The way in which methadone came into use for the treatment of narcotic dependence is an interesting story. It came about somewhat by accident through the combine efforts of Dr. Vincent Dole, a specialist in metabolic disorders, and Dr. Marie Nyswander a psychiatrist who specialized in the treatment of narcotic addicts. Dole was interested in establishing whether narcotic addicts had a metabolic disorder that resulted in their craving for narcotics and Nyswander was interested in pursuing alternatives to the multiple approaches to the treatment of addiction that were being used in the 1960s, and that almost always failed. To pursue the metabolism research, a few heroin addicts were first maintained on morphine. This required several injections per day and kept the patients in a generally lethargic and inactive state. For detoxification purposes, the patients were given methadone, which was known to produce a more protracted, but less intense, withdrawal. However, rather than immediately beginning to decrease the dose of methadone, the patients were maintained on rather high doses so that the metabolic studies could be repeated with methadone. Although the metabolic research did not turn up anything notable the researchers noticed a number of other developments in their patients. First, the patients' craving for narcotics was eliminated, and second, they began to engage in socially relevant activities. Follow-ups with more patients revealed other developments. There was a dramatic decrease in their heroin use and drug-related crimes, and an increase in their ability to function in the community. Patients began attending school, receiving passing grades, maintaining a family, and working at a job. In summary, Dole and Nyswander concluded that, despite most of their patients' preexisting disadvantages of low socioeconomic levels, poor education, prison records, and years of addiction, the majority of those individuals maintained on methadone became self-supporting, law-abiding citizens. Furthermore, the longer they were maintained on methadone, the more probable this scenario became. Since that report, a large number of studies have led to essentially the same conclusion—that is of all treatments for heroin dependence, methadone maintenance treatment has the most evidence of benefit in terms of reducing heroin use, as well as other illicit drug use, mortality, criminal activity and risk of HIV infection, and of improving social rehabilitation. The primary advantage of methadone over other narcotics are that it is readily and reliably absorbed orally and has a relatively long duration of action—approximately 24 hours. These characteristics eliminate the hazards of the injection method and, although it has some mood-elevating effects, methadone induces a more gradual and stable effect on the individual than heroin or morphine does. Tolerance develops to methadone, and through cross-tolerance, methadone blocks the effects of other narcotics unless they are taken in very high amounts. Because it is active at opiate receptors, it gradually reduces the craving for narcotics generally experienced by addicts and reduces their motivation for returning to their original drug-taking behavior. The side effects of methadone—namely, constipation and impotence—are qualitatively the same as those of other narcotics. Using sufficiently high daily doses of methadone is a critical factor in its efficacy. Higher methadone dosages may be necessary in individuals with higher degrees of psychopathological symptoms, regardless of their heroin-use history. Also, exposure to high-quality medical and psychosocial services, clear orientation toward social rehabilitation and treatment retention, and a slow detoxification regimen of well-stabilized patients are all factors contributing to better efficacy with methadone treatment. Methadone is used either as a maintenance drug, or as a drug that can be administered in smaller and smaller doses to gradually reduce the addict's physical dependence on narcotics. Most studies indicate that the former approach is more satisfactory in decreasing illicit narcotic use. Further decreases in illicit drug use can be obtained if the dose of methadone is made contingent on drug-free urinalysis. While methadone does decrease the use of illicit narcotics, it does not eliminate their use in a large portion of addicts. They often get into methadone treatment, gradually reducing their dose until their tolerance to narcotics decreases, and then return to their original drug-taking activities. Addicts under methadone are also more likely to have higher employment rates than nontreated addicts and are less likely to engage in criminal activities. However, access to methadone does not eliminate criminal behavior entirely, since most addicts in the U.S. have developed over the years a number of skills, such as selling drugs and stealing, that may still be useful to them, even though they may not be needed for obtaining narcotics any more.

Anticholinergics

Most common: Atropine Scopolamine l-hyoscyamine Effects: Confusion, slurred speech, disorientation similar to alcohol intoxication Psychotic behavior Hallucinations primarily consisting of brightly colored objects and pleasant sounds Drowsiness and fatigue Amnesia One of the oldest known groups of hallucinogens is called the anticholinergics because these drugs are pharmacological, competitive antagonists of a class of acetylcholine receptors called muscarine receptors. Thus, they are often, and more appropriately, termed antimuscarinics. Their blocking action at the acetylcholine receptors activated by nicotine is very weak. The early writings of Homer describe potent agents with properties similar to those of the anticholinergics. These drugs are often called belladonna alkaloids because at one time women used one of these compounds to dilate their pupils and enhance their beauty. At the present time, anticholinergics are not schedule-controlled substances, even though they can only be purchased through prescription, nor is there any law preventing, the cultivation of plants containing these alkaloids, primarily because the recreational use and the abuse potential for these drugs is currently very minimal. They have a number of side effects that reduce their reward value, and there are other drugs available with similar euphoriant properties that do not have these side effects. The three most common anticholinergics are atropine, scopolamine, and l-hyoscyamine. These drugs are discussed because of their ability to induce hallucinatory experiences at sufficiently high doses, but they have a myriad of effects that are heavily dose dependent. The effects of anticholinergics resulting from their CNS activity include the following: confusion, slurred speech, disorientation similar to alcohol intoxication; psychotic behavior; hallucinations, primarily consisting of brightly colored objects and pleasant sounds; drowsiness and fatigue; and amnesia, whereby the person may forget the entire episode of intoxication. At extremely high doses, coma can result. Although these drugs can be lethal and have been used as poisons in the past, their margin of safety is actually very large. Deaths attributed to them nowadays generally involve abusers who might wander off into heavy traffic or fall into swimming pools, and children who ingest berries or seeds containing belladonna alkaloids.

LAAM

Narcotic agonist Approved in 1995 Discontinued sale and distribution in 2003 Severe cardiac effects Subutex and Suboxone

Cocaine Routes of Administration

Oral Intravenous Intranasal Smoking The South American Indians generally chew the coca leaf, which contains very small amounts of cocaine. Since cocaine in the coca plant is an alkaloid that is slowly absorbed from the G.I. tract, very little cocaine accumulates in the brain. North American users administer a highly concentrated form of cocaine intranasally, intravenously, or, most recently, through inhalation- all of which result in a rapid and, high concentration of the drug in the brain. South American Indians have traditionally administered cocaine in its untransformed alkaloid form by chewing the leaves with an alkaloid substance, so that absorption through the oral mucous membranes is enhanced. Apparently, there are very few cases in this practice that results in acute overdosage, psychosis, neglect of one's responsibility, or extensive focus on cocaine use. More recently, some young South Americans in urban areas have begun to mix the cocaine paste, which is extracted from the leaves for subsequent synthesis into cocaine hydrochloride, with tobacco and smoke it. In some individuals, the same patterns of pathological states, neglect of work, and preoccupation with cocaine use seen in North American users are found. In North America and other developed countries, cocaine hydrochloride is commonly self-administered by sniffing it so that it is absorbed through the nasal membranes. This leads to a somewhat faster onset of action and higher brain concentrations than when ingested orally. The local vasoconstrictive properties of cocaine results in slower absorption and longer effects when the drug is snorted as opposed to smoked. Cocaine's vasoconstrictive properties in the nose also lead to tissue degeneration because of ischemia, or low blood source. Although much higher brain concentrations of cocaine can be achieved when administered intravenously, this mode of administration is uncommon in the vast majority of user, perhaps because users recognize the hazards of injections- particularly the development of HIV and later, AIDS. Also, since users generally have had experience with smoking marijuana, they do not have to learn a new drug administration procedure. Because cocaine hydrochloride is volatilized at temperatures that degrade it, in order for it to be effective when smoked, it must be reconverted chemically to its alkaloid state. This practice is generally called free-basing, and in its crystalline form the compound is commonly referred to as crack. In this mode it is easily volatilized in an active form at relatively low temperatures. Due to the efficiency with which cocaine gets into the brain via smoking, crack requires low doses to be effective, which makes it relatively inexpensive- a moderate day's use, can be financed for $10 to $20- while producing a rapid-onset, intense high, which makes it extremely addictive. Unfortunately, the toxic and lethal effects of cocaine, as well as the profound dependency, are just as readily induced by smoking the drug as with intravenous administration. Because of incomplete absorption, the potency of smoked cocaine is somewhat lower than the intravenous cocaine, but several of the positive subjective effects of cocaine, may actually be greater when it is smoked than when it is administered intravenously, even when the cocaine plasma levels are similar.

Buprenorphine

Opiate agonist-antagonist Absence of respiratory depression Use in pregnancy

Alcoholism Treatment

The first step in any treatment for alcoholism is getting into treatment! Various methods of treating alcoholism Chemical treatments for maintaining abstinence Psychologically based treatments, Behavior modification techniques Group therapies Coping and social skills training Anxiety and stress management, Behavior Change Alcoholics Anonymous (AA) Abstinence Controlled drinking training International vs. U.S. Treatments Categories of drinkers with distinct pathways to remission Those who resolve to abstinence through the use of treatment services Those who "mature out" of this stage in their life The first step in any treatment for alcoholism is getting the alcoholic into treatment. Unfortunately, persons with alcohol or other drug problems typically are in denial. When their difficulties do become obvious to them, their problems may be too extreme or too much for them to handle. However, there are strategies to get individuals into treatment before this happens. For example, coercion techniques or receiving "alternative consequences" has been shown to be highly effective for engaging and retaining alcoholics in treatment. Clients who have been coerced by their employer or the judicial system to enter treatment may be just as successfully treated as those who have entered treatment voluntarily. There are a multitude of ways of treating alcoholism, none of which has had universal success with all individuals. One thing is clear: for any of them to work, the alcoholic must not be physically dependent. Since withdrawal from alcohol can be lethal, medical intervention is advisable. Once the physical dependence phase is over with, other interventions can be applied. Chemical treatments for maintaining abstinence have ranged from drugs that induce nausea when accompanied by alcohol to drugs that attempt to promote insight into the causes of one's drinking. Among the psychologically based treatments, a number of traditional psychodynamic approaches, behavior modification techniques, and group therapies have been applied to the treatment of alcoholism. Empirical research has suggested may be helpful in the treatment of alcoholism include self-help groups, coping and social skills training, anxiety and stress management, and behavior modifications utilizing social, recreational, family, and vocational reinforcers. Cue exposure therapy, in which patients are exposed to potential conditioned stimuli associated with alcohol's reinforcing effects in order to extinguish alcoholics' conditioned craving for alcohol, has produced some promising results in terms of reducing alcoholics' responsitivity to alcohol cues. However, its long-term efficacy for achieving and maintaining abstinence remains to be established. Perhaps one of the most accepted approaches to dealing with alcoholism is the one taken by Alcoholics Anonymous (AA). This organization, founded by a group of alcoholics in 1935, believes that alcoholism is a disease, that abstinence is required to deal with the disease, and that faith in a higher spiritual being is important in the recovery process. From a psychological perspective, this group provides peer education about alcoholism and its consequences for the individual, and provides support through the testimonials of many individuals who share their problems of alcoholism. These individuals also serve the vital function of being able to respond to the denials and rationalizations that inevitably occur in the alcoholic and, that prevent the alcoholic from accepting that he or she has a problem. The general conclusions from a variety of studies are that the sooner one participates in AA after diagnosis of an alcohol-use disorder and the longer the duration of participation and the more frequent the participation, the more likely one will abstain from drinking, the lower the incidence of drinking problems, and the higher the overall level of functioning. However, the duration of treatment is a much better predictor of positive alcohol-related outcomes than is the frequency or intensity of treatment. Unfortunately, there is considerable difficulty in determining the actual effectiveness of AA, since the group is reluctant to give researchers access to their records or members. Furthermore, participation in AA is almost always voluntary. Research suggests that problem drinkers who choose to participate actively in AA experience more favorable outcomes than those who just attend meetings—that is, those who are mandated or coerced to attend meetings by the court or by employers—for whom controlled studies have found no unique efficacy of AA. Virtually all strategies involved in the treatment of alcoholism in the U.S. focus on abstinence as the goal—primarily due to the belief that once an individual becomes an alcoholic, it is not possible for that individual to return to moderate drinking. However, there are a number of authorities who have suggested that controlled drinking training may still be a viable alternative for those individuals exhibiting less, severe forms of alcoholism—that is, problem drinkers who have not developed a heavy physical dependence on alcohol. As mentioned earlier, there is some concern that many problem drinkers will simply not seek treatment if abstinence is the only option. The fact is, many individuals who receive extensive treatment for their alcoholism return to what can be considered controlled drinking following the period of abstinence required while they are in treatment. For example, in long-term follow-up studies of alcoholic patients treated in abstinence-oriented programs, controlled drinkers constituted 10% to 30% of the treated sample and, abstainers constitute an additional 10% to 30%, with relapses often comprising the largest outcome group. Those who return to moderate drinking are more likely to have received some type of training in controlled drinking, such as self-recording of drinking and blood alcohol levels; setting daily and weekly consumption limits; pacing drinking by sipping and alternating alcoholic and nonalcoholic beverages; learning about the antecedents of drinking; learning how to refuse drinks; changing drinking environments and companions; and learning alternatives to drinking. Whereas there is a considerable resistance to the implementation of controlled drinking strategies into U.S. and Canadian treatment programs, where it is commonly believed that abstinence is the only acceptable outcome for patients, controlled drinking training is widely accepted in the UK as a viable treatment for alcoholism. The success of controlled drinking programs is still unclear, with some studies finding uncontrolled drinking frequently following a period of moderate drinking, and others finding that moderate drinking was sustained for follow-up periods of a year or longer. No single personal characteristic has been consistently predictive of long-term success of controlled drinking treatments, but there is convincing evidence that a lower severity of dependence and, a persuasion that controlled drinking is possible are associated with controlled drinking after treatment. Although it may be argued that the majority of alcoholics who undergo behavioral self-control training will drink problematically or in excess of the controlled drinking limit at some time after their follow-up, it is important to note that the distribution of approximately equal abstinent and nonabstinent successful limit at some time after their follow-up, it is important to note that the distribution of approximately equal abstinent and nonabstinent successful drinking. Only about 15% of alcoholics ever receive formal treatment; many end up in jail, die of traffic or other accidents, or die of medical complications. Depending on the criteria used for assessing treatment outcomes, somewhere between one-third and two-thirds of alcoholics who are treated can be viewed as successes. Interestingly, numerous studies have indicated that many alcohol abusers are able to positively change their use patterns without the assistance of formal treatment. Factors associated with successful self-change include a high level of motivation and commitment to change, public announcements, social support, alterations in one's social and leisure-time activities, general lifestyle changes that decrease exposure to conditioned craving cues. Development of stress-coping strategies, and the generation of negative expectations over continued use and positive expectations concerning continued abstinence. A recent epidemiologic-based sample of individuals who remitted from alcohol abuse or alcohol dependence suggests that there may be two primary categories of drinkers with distinct pathways to remission: (1) those who experience significant problems for an extended period of time but then resolve to abstinence through the use of treatment services; and (2) those who drink heavily at some point in their lives experience some problems, and then "mature out" of this stage in their life and take on other life roles.

Dissociative Anesthetics

PCP Katamine

Insomnia

Sleep Disorder: The real or perceived inability to get to sleep or to stay asleep at night The chronic inability to maintain the amount and quality of sleep necessary for efficient daytime functioning Complaints of poor sleep, unrefreshing sleep, and sleep punctuated by abnormal restlessness Sedative-hypnotics Induce sleep Liabiltiies Supress REM sleep Psychodepenence potential Lethal withdrawal effects Examples: Dalmane Ambien Insomnia is a sleep disorder that involves (1) the real or perceived inability to get to sleep or to stay asleep at night, resulting in subjective feelings of fatigue; (2) the chronic inability to maintain the amount and quality of sleep necessarily efficient for daytime functioning; and (3) complaints of poor sleep, unrefreshing sleep, and abnormal restlessness. Chronic insomniacs not only report higher rates of difficulty with concentration, memory, and ability to cope with minor irritations, but also have two and a half times more fatigue-related automobile accidents than do good sleepers. In doses somewhat higher than those needed to sedate, the sedative-hypnotics induce sleep, and for many years barbiturates were the most common treatment for insomnia. However, the use of barbiturates for this purpose has virtually ceased, primarily due to safer drugs. It has long been recognized that the barbiturate sedative-hypnotics have numerous liabilities. Among these are their relatively low therapeutic index, their strong tendency to suppress REM sleep, their high psychodependence potential, and their potentially lethal withdrawal effects when physical dependence develops. Furthermore, there is a relatively fast tolerance development to their sleep-inducing eff ebated, it is clear that, once the suppressing factors have been removed, REM activity increases dramatically for a few days and the dream content tends to be very bizarre and emotionally unsettling. Because of these properties, drugs in the benzodiazepine class, such as flurazepam or Dalmane, became a popular treatment for insomnia. These drugs have considerably higher therapeutic indexes, have minimal effects on REM sleep, have less psychological dependence potential, and are less likely to induce severe physical dependence and withdrawal effects. However, benzodiazepines do not have characteristics that make them less than ideal treatments for insomnia. They can raise the arousal threshold to such an extent that outside noises that should wake a person up, such as a smoke alarm, do not do so. Also, there is evidence that benzodiazepine disrupt the deeper stages of sleep, an effect that may prove to be just as significant as REM inhibition. On the other hand, this may be a factor in the efficacy of benzodiazepines in the treatment of sleepwalking and night terrors which are most commonly observed to occur during the deeper stages of sleep. All of the benzodiazepines used in the treatment of insomnia have a number of problems in common. They are all synergistic with alcohol and other CNS depressants; their combination with alcohol or other CNS depressants is one of the major causes of "overdose" deaths. In the elderly, who traditionally complain and suffer from insomnia, the diminished alertness that can come about with the use of these drugs can be confused with dementia. The fact that these drugs do effectively induce sleep may prevent a patient from dealing with the problems causing insomnia. Ambien is a nonbenzodiazepine that was approved for treatment of insomnia in the U.S. in 1992 and is now the most commonly prescribed hypnotic. It has demonstrated efficacy equal to that of benzodiazepines, in terms of shortening sleep latency and prolonging total sleep time in insomniacs, and has actions resembling the latter class of drugs, but its advantages are that it appears to have low potential for inducing rebound insomnia or tolerance and withdrawal effects with chronic use. Furthermore, unlike benzodiazepines, Ambien has little effect on the stages of sleep in normal human subjects. At therapeutic doses, Ambien infrequently produces residual daytime sedation or amnesia, and the incidence of other adverse effects is also low. As is the case with benzodiazepines, Ambien does not produce severe respiratory depression with large doses, unless other sedative-hypnotic type agents are also ingested. While the available data indicate that under most of these circumstances the risk of abuse or dependence with Ambien is minimal, there are several case reports of Ambien dependence and abuse. Although this newer nonbenzodiazepine hypnotic seems to be equally efficacious as the short-acting benzodiazepines in the treatment of insomnia and has a better adverse-effect profile, neither it nor any drug treatment for insomnia should be used as the sole treatment, but should be used in conjunction with nonpharmacological techniques, such as adherence to good sleep practices, sleep restriction, stimulus control, and biofeedback.

Drugs and the Kidney

The kidneys, a pair of bean-shaped organs that lie at the rear of the abdominal cavity on either side of the vertebral column. The nephron is the basic unit of the kidney, and there are about 1 million nephrons in each of them. Each nephron consists of a renal capsule and it's attached to the renal tubule. The renal capsule is composed of two parts-a clump of capillaries, called the glomerulus, surrounded by an expanded, double-walled cup, called the Bowman's capsule, which covers the capillaries of the glomerulus. The first step in urine formation is glomerular filtration, which occurs in the renal capsule. Such filtration is estimated to be about 120 ml per minute, enough to dehydrate a person within minutes if most of the fluids are not reabsorbed in other portions of the nephron.

Urinary Stones

Treated by Dietary restriction Copious fluid intake Treatment of underlying infections Administration of selected drugs that may reduce stone formation. Allopurinol Reduces uric acid levels by decreasing uric acid production Stones in the urinary tract are treated by dietary restriction, copious fluid intake, treatment of underlying infections, and administration of selected drugs that may reduce stone formation. The most common kidney stones are composed of uric acid. Allopurinol reduces uric acid levels by decreasing uric acid production. It does this by inhibiting one of the enzymes involved in the steps of uric acid production. Since uric acid deposits also cause symptoms of gout, allopurinol is one of the drugs of choice for treating this disorder.

Phencyclidine

Typical Effects: Anesthesia Distortions in body image Feelings of depersonalization Sense of timelessness Mimics schizophrenia Low doses Moderate doses Chronic Use One of the most predominant effects of PCP and ketamine is profound anesthesia. Because patients anesthetized with these drugs are awake but appear disconnected from their environment, perhaps the simplest term to be used to describe the drug is dissociative anesthetic. In the 1950s, while searching for new psychoactive drugs with therapeutic properties, chemists synthesized PCP, which psychopharmacologists immediately recognized as having very unique effects in animals. It was this anesthetic action that was most promising for therapeutics, since most drugs with general anesthetic activity also have a strong lethal potential-due to the depression of the body's vital functions-at doses approximately double the anesthetic dose. With PCP, the lethal dose was approximately 10 times the anesthetic dose. At appropriate doses, PCP induced insensitivity to pain while increasing blood pressure and heart rate. Also, unlike any other general anesthetic, the human remained awake with the eyes open. When PCP was tested in humans, it soon became apparent that it had profound properties. However, unlike LSD, with its definitive visual distorting properties, PCP prompted distortions in body image, feelings of depersonalization, and a sense of timelessness, a transient feeling of being in outer space or dead or not having any arms or legs. In approximately a third of the individuals, the drug also prompted symptoms that mimicked very closely those of schizophrenia, which, in some cases, persisted for several days or weeks. Behaviorally in humans, low doses of PCP produce a drunken state, or "floating" euphoria, with numbness in the hands and feet. Persons often describe their experiences as involving grotesquely distorted body shape, unreal size of body parts, and sensation of floating or hovering in a weightless condition in space, or a leaving of the body. Radiantly colorful visions that include images of moving from one room to another and glowing geometric patterns and figures are also reported, and the user may experience a complete absence of time sense. Intriguingly, the verbal reports of subjective experiences induced by PCP and ketamine are very similar to the reports of individuals claiming to have a "near-death experience", resulting from various types of brain trauma, which suggests that the later experiences have a neurobiological explanation. Moderate doses induce analgesia and anesthesia, and an excited, confused intoxication can develop. Communication is definitely impaired. A body position may be rigidly maintained over extended periods of time. Larger doses of PCP induce a definite psychosis and, in rare cases, convulsions. Death is rarely directly caused by PCP because of its moderately high therapeutic index. PCP may also produce mild physical dependence, because abrupt withdrawal from PCP after chronic use may be followed by fearfulness, tremors, and facial twitches. Alterations in PCP receptors with chronic PCP exposure do not appear to play a major role in the production of PCP dependence. Some craving after stopping PCP may also be experienced by chronic users.

Antibiotics

A drug that kills or slows the growth of bacteria. Used to treat many different bacterial infections Antibiotics Terms: Bactericidal vs. Bacteriostatic Broad-spectrum vs. Narrow-spectrum Gram-positive vs. Gram-negative Problems: Walled-off abscesses usually are poorly penetrated by antibiotics Depressed defense mechanisms Bacteria can develop resistance to antibiotics Certain toxicities are associated with the use of antibiotics The word "antibiotics" comes from the Greek anti or "against" and bios or "life". An antibiotic is a drug that kills or slows the growth of bacteria. Antibiotics are one class of antimicrobials, a larger group which also includes anti-viral, anti-fungal, and anti-parasitic drugs. Antibiotics are chemicals produced by or derived from microorganisms. The first antibiotic was discovered by Alexander Fleming in 1928 in a significant breakthrough for medical science. Antibiotics are among the most frequently prescribed medications in modern medicine. Antibiotics are used to treat many different bacterial infections. Antibiotics cure disease by killing or injuring bacteria. Bacteria are simple one-celled organisms that can be found, by the billions, all around us: on furniture and counter-tops, in the soil, and on plants and animals. They are a natural and needed part of life. Bacteria cause diseases and infection when they are able to gain access to more vulnerable parts of our bodies and multiply rapidly. Bacteria can infect many parts of the body: eyes, ears, throat, sinuses, lungs, airways, skin, stomach, colon, bones, and even the genitals. By definition, antibiotics exert a selective toxicity against invading bacteria and inhibit a process essential for their survival but not that of the host, the person taking the antibiotic. Bacteriostatic activity refers to the ability of an antibiotic to inhibit growth of an organism; bactericidal activity refers to its ability to kill the bacteria. Antibiotics may be classified conventionally as being of either type, although they are more frequently classified by their chemical origin and spectrum of action. When two bactericidal antibiotics exert a greater killing effect than either can singly, their effect is said to be synergistic. In contrast, when a bacteriostatic antibiotic reduces the killing effect of a bactericidal agent, such an effect is said to be antagonistic. Such considerations obviously govern drug selection when serious infections that require two or more drugs for the eradication of the treated individual. The range of effectiveness of given antibiotics against infections caused by various types of bacteria. For many years, bacteria have been divided into two groups according to their ability, or lack thereof, to be stained by a violet-colored dye. Gram-positive bacteria contain cell walls that have a permeability barrier to removal of the dye by an alcohol wash, while gram-negative bacteria have membranes that do not retain the violet dye when washed with alcohol. Again, gram-positive bacteria contain cell walls that retain the dye, while gram-negative bacteria have membranes that do not retain the violet dye. It is interesting to note that antibiotics frequently are differentiated by their ability to destroy selectively either gram-positive or gram-negative bacteria. Therefore, based on the Gram stain, bacteria have been divided into two groups: gram-positive and gram-negative. Some antibiotics, such as many penicillins, have a narrow spectrum of action, while others, such as chloramphenicol and the tetracyclines, are effective against many organisms, although no antibiotic is universally effective against all microorganisms. In general, the narrower the spectrum of action, the more effective a drug is for an identified organism. Some antibiotics can be used to treat a wide range of infections and are known as 'broad-spectrum' antibiotics. Others only effective against a few types of bacteria are called 'narrow-spectrum' antibiotics. There are many problems associated with antibiotic therapy. First, large, walled-off abscesses usually are poorly penetrated by antibiotics and surgical drainage is necessary before effective antibiotic therapy can be initiated. Second, patients with depressed defense mechanisms are at increased risk of infection and may respond poorly to different antibiotics. Third, bacteria can develop resistance to antibiotics to which they were previously sensitive. For example, some staphylococci, gonococci, and pneumococci produce an enzyme called "penicillinase' that inactivates certain penicillins. This makes treatment of the disease caused by these organisms much more difficult. Fourth, certain toxicities are associated with the use of antibiotics. Some produce specific damage, such as effects on the auditory nerve or the kidneys, and many, such as the penicillins, are capable of inducing an allergic response.

Facts of Alcoholism

Alcoholism is found in all classes of society and in all walks of life Men are more likely to consume alcohol than women Incidence of alcoholism is disproportionately much higher in men than in women Males with an early onset of alcoholism and whose pattern of drinking is fairly continuous. Types of Alcoholism Type 1 vs. Type 2 Males vs. Females Factors: Genetics Biological and behavioral characteristics Environmental factors Cultural Factors Children are exposed to alcohol early in life Served in small or diluted quantities Abstinence is socially acceptable and excessive drinking is not Drinking is not viewed as proof of adulthood Well-established ground rules for drinking behavior Alcoholism is found in all classes of society and in all walks of life. While men are more likely to consume alcohol than women, the incidence of alcoholism is disproportionately much higher in men than in women. For example, national surveys in the United States indicate that while approximately 13% more men than women are current drinkers, the incidence of alcohol dependence is approximately three times higher in men than women. There is no consistent evidence to indicate that a particular personality type develops the disorder; however, individuals high in antisocial characteristics, as measured by a variety of personality tests, have been consistently shown to be more prone to alcoholism. Such individuals are generally males with an early onset of alcoholism and whose pattern of drinking is fairly continuous. They often engage in thrill-seeking behavior, fights, and criminal activities; rarely binge drink; display little guilt or anxiety over their drinking; and are low in the need for social rewards. Individuals with these characteristics are sometimes designated as type 2 alcoholics. Conversely, type 1 alcoholics develop symptoms later in adulthood and are much more likely to abstain from drinking for periods of time and then binge once they start drinking. They tend not to engage in thrill-seeking and antisocial activities, they have high social reward dependence, and they often feel guilty or fearful about their alcohol dependence. Female alcoholics are more likely to display type 1 characteristics, but many male alcoholics also share these characteristics. Many studies have indicated that there are specific genetic bases for many forms of this disorder. First of all, numerous studies assessing the acute responses of normal humans to alcohol have shown some degree of genetic control in a wide variety of responses. As a result, these individuals experience a more intense reaction to alcohol, with some reactions being pleasant and overs being aversive, which may contribute to their lower tendency to drink excessively. Within-race, genetically controlled differences have been shown to occur with respect to rates of absorption, metabolism, EEG alterations, heart rate, and blood pressure. Over the years several studies have suggested that there are a number of biological and behavioral characteristics or markers of alcoholics. Most of these studies looking for biological differences between alcoholics and nonalcoholics have been retrospective; that is, these characteristics were noted after alcoholism was evidenced. Thus, it is not clear whether these characteristics were preceded by heavy alcohol use or were caused by it. To circumvent the problem, researchers have attempted to determine whether non-alcohol-abusing young adults with a family history of alcoholism differ, in terms of their reactions to alcohol, from those without a family history of alcoholism. The general findings in these studies are that young adult males with a family history of alcoholism, when given alcohol, are more sensitive to alcohol's effects during, the rising arm of the BAC curve and exhibit reduced effects as the BAC level falls, compared with those without a family history males, despite the fact that the groups do not differ in their BAC curves. This suggests that males at risk for alcoholism find alcohol more rewarding because of the pleasurable, excitatory aspects at the early stage of intoxication are accentuated and, the dysphoric feelings—anxiety and depression—that predominate as BAC levels drop are attenuated. On the other hand, there is evidence that individuals at risk for alcoholism experience more frequent and intense hangover effects than do low-risk individuals, which may be a factor in their initiating further drinking to relieve these aversive symptoms. Environmental factors also are implicated in the vulnerability to alcoholism. One-third of alcoholics have no family history of alcoholism and only 17 percent to 25 percent of sons of alcoholics become alcoholics themselves. Not surprisingly, exposure to stressors and trauma has commonly been linked to alcoholism, and stress-relief drinking has been suggested to be one of several prominent, factors in the etiology of alcohol abuse and dependency. While many early studies investigating this hypothesis did find support for it, many did not. In some cases, it was the subjects' expectations as to whether alcohol would reduce or increase tension that was critical to the element in their response to alcohol. Alcoholics typically report more acute and chronic stressors and fewer social resources than do nonproblem-drinking adults. Perhaps as many as a third of alcoholics are raised in homes with an alcoholic parent. Numerous studies have indicated that having an alcoholic parent greatly increases the likelihood of experiencing a wide range of childhood stressors. For years environmental factors have been assumed to explain the findings of studies showing that different cultures have different alcoholism rates that are not easily tied in with per capita consumption of alcohol. For example, in France, where per capita consumption of alcohol is high, there is a high rate of alcoholism. However, in Italy, where per capita consumption of alcohol consumption is high, the rate of alcoholism is low. In the United States and Sweden, which have relatively low per capita consumption of alcohol, alcoholism is relatively high. In viewing the drinking habits and attitudes of these cultures, it appears that the lowest incidence of alcoholism occurs when (1) the children are exposed to alcohol early in life; (2) alcohol is served in small or diluted quantities; (3) abstinence is socially acceptable and excessive drinking is not; (4) drinking is not viewed as proof of adulthood or virility; (2) alcohol is served in small or diluted quantities; (3) abstinence is socially acceptable and excessive drinking is not; (4) drinking is not viewed as proof of adulthood or virility; Although considerably speculative, there is some evidence that environments that contribute to alcoholic vulnerability (1) do not promote impulse control; (2) view drunkenness as acceptable behavior; (3) reduce a person's cognitive ability to appraise information that might limit alcohol consumption or (4) do not provide nondrinking alternative sources of gratification.

Peptic Ulcer Disease

Gastric Antacids Treatment of gastric and duodenal ulcers Aluminum, calcium, or magnesium salts react with the hydrochloric acid Systemic Sodium bicarbonate or baking soda Nonsystemic salts containing aluminum and magnesium Anticholinergic Drugs Slightly reduce the secretion of hydrochloric acid from the stomach wall H2 Receptor Antagonists Used to reduce the volume and acidity of stomach secretions. Zantac Reduction of gastric acidity both promotes the healing and reduces the symptoms of ulcers occurring in either the stomach or the duodenum, the upper portion of the small intestine. Pharmacological therapy of gastric and duodenal ulcers utilizes three classes of drug-gastric antacids, anticholinergic drugs, and H2 receptor antagonists. Gastric antacids have been, and continue to be, the most important class of drugs in the treatment of gastric and duodenal ulcers. These aluminum, calcium, or magnesium salts react with the hydrochloric acid secreted from the stomach wall to form less acidic or even neutral products. This process of neutralization markedly reduces the pain and discomfort associated with peptic ulcer disease and facilitates healing of the ulcer. Antacids may be sub classified as either systemic or nonsystemic, depending on the amount of drug absorbed from the GI tract. Sodium bicarbonate (baking soda) is the only systemic antacid, but it is unwise to choose to use this drug since large amounts of sodium and bicarbonate ions are absorbed into the systemic circulation. While sodium bicarbonate effectively neutralizes gastric acids, such absorption produces excessive salt load, altered plasma pH, and, with prolonged use, possible acid rebound, loss of appetite, mental confusion, and muscle weakness. For these reasons, this product is not considered an appropriate drug for clinical use. The gastric antacids of choice are nonsystemic, or poorly absorbed, antacids. For long-term use, the various salts containing aluminum and magnesium generally are preferred over the calcium-containing antacids such as Tums. Side effects of nonsystemic agents are relatively minor and include diarrhea with the magnesium-containing products and constipation with large doses containing calcium or aluminum. These products all contain widely varying amounts of sodium. In patients in which this is a concern, such as those on a low-sodium diet for the treatment of hypertension, products with the least sodium should be chosen. Such information can be obtained from physicians or pharmacists, as product formulas are currently being revised to reflect increasing concerns over this problem. Anticholinergic drugs very slightly reduce the secretion of hydrochloric acid from the stomach wall. They were used for the treatment of peptic ulcers for many years, but the advent of the H2 receptor antagonists has made them relatively obsolete. Side effects of dry mouth, blurred vision, urinary retention, and tachycardia limit their use. Dosage usually is titrated upward until the appearance of side effects and then maintained at as high a dose as the patient can tolerate. H2 receptor blockers or antagonists are used to reduce the volume and acidity of stomach secretions. It is significantly more effective in the treatment of gastric and duodenal ulcers than either antacids or anticholinergic drugs. A long acting H2 receptor antagonist has been introduced recently. Zantac's longer duration of action allows for twice daily dosage and perhaps, greater patient compliance. Minimal side effects have also been reported.

Alcohol Background

General Characteristics -Bulky drug -Water-soluble -Calories General Problems -Liver damage -Brain damage -Poor nutrition Margin of Safety -Vomiting -Passing out If you were to pick 20 American adults at random, the odds are that 14 of them drink moderately or occasionally, two drinks to the point at which their drinking may be considered by others to be a problem, and one drinks excessively and chronically to the point at which we can consider him or her to be an alcoholic. Alcohol, technically ethyl alcohol or ethanol, has a number of characteristics that make it somewhat unique in comparison to most other drugs. First, it is a rather bulky drug, requiring several grams to exert noticeable effects, rather than the milligram amounts needed with other drugs. A limit of 0.08 blood alcohol content is used for determination of legal intoxication in terms of driving was established by federal legislation in 2000, which requires states to impose this standard or lose federal funds for highway improvement. A person can achieve this level by consuming one drink for every 50 pounds of body weight in one hour. Unlike many drug molecules, the ethanol molecule is a relatively small, neutrally charged molecule. These characteristics make it readily absorbed from all compartments of the G.I. tract. In contrast to many psychoactive drugs, it is highly water-soluble. Therefore, its onset of action is rather quick and its duration of action rather short. Its low fat solubility also generally results in females achieving somewhat higher plasma concentrations than males, even when the same amount of alcohol is ingested and they weigh the same, because females have more body fat proportionally than males. Unlike most other drugs, whose rate of metabolism is proportional to their concentration, alcohol is metabolized at a fairly constant rate. Finally, alcohol is high in calories that is almost always ingested orally as a beverage. Thus, it provides the body with a ready source of calories. The alcohol in wine is derived through the interaction of yeast and sugar or fermentation in fruits, whereas beer and distilled spirits are derived through the interaction of yeast and sugar in grains. The alcohol content of these beverages is generally specified in terms of proof, which is exactly double the actual percentage of ethanol they contain. For example, 90-proof whiskey is 45% ethanol. To some extent, these characteristics contribute to some of the unique problems associated with alcohol. For example, chronic users of alcohol often suffer from liver damage, partially because the liver spends a lot of time and energy trying to metabolize alcohol, and brain damage, partially because the individuals are consuming a large portion of their calories in alcohol and neglecting to eat proper amounts of other foods containing proteins, vitamins, and minerals essential for neuron maintenance. Considering its widespread use, one would hope that the relative margin of safety of alcohol would be high. Unfortunately, it is not. The BAC of persons who have died of acute alcohol exposure is typically around 0.5%. Fortunately, there are two built-in mechanisms that generally prevent lethal levels from being reached. If one approaches a BAC of around 0.12% rapidly enough, vomiting may occur, because of local irritation of the G.I. tract, disturbances in vestibular functioning, or the accumulation of acetaldehyde in the brain. Past this point, most persons pass out when a BAC is around 0.35%. Therefore, the lethal limit would only be achieved in those who consume alcohol rapidly enough to achieve higher concentrations before they pass out.

Effects of Opiates Administered

Hypothermia Decreased blood pressure Flushed warm skin Miosis Drying Secretion Constipation Respiratory depression Decreased sex drive Relaxation Analgesia Euphoria

Psychological Effects of LSD

entirely subjective and depends on self-reports effects are very dependent on the context and on the expectations of the person Prominent effects: Slightly heighted arousal Slight elevated blood pressure Increased heart rate State of inactivation, tiredness, and drowsiness Impairments in alertness Cognitive performance Dose-dependent alterations in sensory perception Complex scenic hallucinations The psychological effects of LSD and other hallucinogens are very difficult to describe because they are almost entirely subjective and depends on self-reports. Furthermore, the effects are very dependent on the context and on the expectations of the person. The person may express deep religious feeling at the moment, sexual feelings another, and extreme sadness, anxiety, and paranoia at another moment. Bizarre thoughts and feelings may represent a major break with reality and may lead to the person to believe that he or she can fly, stop automobiles by stepping in front of them, or perform some other amazing feat. Occasionally, these feelings can lead to self-destructive behavior, such as attempting suicide or jumping out of windows. The most prominent psychological symptoms of monoamine-related hallucinogens are indicative of slightly heighted arousal, slight elevated blood pressure, and increased heart rate, although the individual often experiences state of inactivation, tiredness, and drowsiness. Not surprisingly individuals in the influence of these drugs display impairments in alertness and cognitive performance and are confounded by the individual's, lack of motivation to perform well in tasks requiring attention and cognitive effort. Individuals administered LSD or psilocybin under controlled conditions have reported predominately positive emotional states ranging from heightened mood to euphoria associated with derealization and depersonalization. In many instances, users report that they develop insights that never occurred to them before or that they see things regarding themselves or others that they have never seen before. In some cases, this transcendental experience can leave them feeling quite at peace with themselves and their world, while in others it can be very disturbing. LSD and similarly acting hallucinogens induce dose-dependent alterations in sensory perception, including colorful visual illusions, and complex scenic hallucinations, as well as alternations in perception of time, space, and self. Perceptual alterations are usually visual, auditory, or tactile and may involve extreme distortions of the physical environment, or with higher doses, actual hallucinations. With the eyes closed, the person experiences a virtual kaleidoscope of changing patterns and intense colors. Dysphoric reactions, often referred to as bad trips, generally occur if users take a larger than usual dose of these substances and suddenly get the feeling that they, are completely losing control over the experience and that they may never return to normal. People and objects in the environment, as well as the person's own body image, may become so distorted that they are grotesque and threatening. Anxiety, panic, and paranoia are very common with this drug. Although these acute effects dissipate rapidly, a very small minority of individuals continue to experience psychotic-like effects, such as mental confusion, perceptual distortions, and poor concentration beyond this time- in some cases for days or weeks. In very rare cases, individuals have complained about mental and emotional disturbances several years after being exposed to LSD.

Incidence of Poisoning

2.5 million human exposures a year 74% are unintentional 9% were of undetermined intent 71,000 children under 18 were seen in Emergency Departments 80% were cases of unsupervised children found and consumed medicines 93% of unintentional poisoning deaths were caused by drugs The incidence of poisoning in the United States has been estimated to be about 2.5 million human poisoning exposures a year. A single substance is implicated in 93% of these poisonings. In 2007, 74 percent of poisoning deaths in the United States were unintentional, and 9 percent were of undetermined intent. Unintentional poisoning was second only to motor vehicle crashes as a cause of unintentional injury death in 2007. Among people 35 to 54 years old, unintentional poisoning caused more deaths than motor vehicle crashes. In 2009, unintentional poisoning caused about 700,000 Emergency Department visits. 22 percent of these visits resulted in hospitalization or transfer to another facility. Between 2004 and 2005, an estimated 71,000 children under the age of 18 were seen in emergency rooms because of medication poisonings excluding abuse and recreational drug use. Over 80 percent were because an unsupervised child found and consumed medicines. In 2007, 93 percent of unintentional poisoning deaths were caused by drugs. Opiate pain medications were most commonly involved, followed by cocaine and heroin. Among those treated in Emergency Departments for nonfatal poisonings involving nonmedical use of prescription or over-the-counter drugs in 2008, opioid pain medications and benzodiazepines, such as Valium, were most frequently reported. Among those who died from unintentional poisoning in 2007: Men were twice as likely as women to die as a result of this poisoning; Native Americans had the highest death rate, followed by Whites and then Blacks. The peak age was 45-49 years of age, and the lowest mortality rates were among children less than 15 years old. Among people who unintentionally poisoned themselves, received treatment in emergency departments in 2009: Men were 1.5 times more likely than women to make such a visit. The highest rates were in the 45-49 year old age group. Among children, emergency department visits for medication poisonings are most common in children under the age of 6. One out of about 200 two-year-olds visits an emergency department for a medication poisoning. Improved safety packaging of aspirin and prescription vials, along with increased parental awareness of the hazards of household chemicals, have contributed to a decrease in both the incidence and the severity of accidental poisoning in children.

Cannabis Sativa Plants

400 different chemicals Cannabinoids Active compounds Delta-9-tetrahydrocannabinol Cannabinol Cannabidiol Marijuana is not a drug itself; the word actually refers to the plant material, which contains over 400 different chemicals, and more than 60 of which are specific to the cannabis plant. These chemicals are referred to as cannabinoids. Most of these are not psychoactive even in high doses. The molecular structure of cannabinoids, which have no nitrogen atom and are not alkaloids, are very different from those of other classes of hallucinogens. It appears that cannabinoids possess complex and particularly unique properties, even though they induce effects similar to numerous other drugs. The major psychoactive chemical in marijuana is delta-9-tetrahydrocannabinol, or THC for short. Two other cannabinoids, cannabinol and cannabidiol, may be active at high doses. Although these drugs may have minimal effects in the amounts found in street marijuana, research has indicated that they may interact with THC to modify its effects.

Tolerance and Dependence

A low to moderate degree of tolerance develops Chronic user must take larger and larger amounts Therapeutic index for the drug gets smaller and smaller Cross-tolerance Tolerance Mechanism of Acton: Adaptive changes in the GABA Type A receptor may have a more significant relationship Up-regulation of brain NMDA receptors appears to play a significant role in both tolerance development and withdrawal Due to behavioral compensation CNS hyper-excitability during withdrawal Symptoms after cessation of larger doses High degree of arousal associated with weakness, tremor, anxiety, and elevated blood pressure, pulse rate, and respiratory rate. Severe reactions convulsions may occur Toxic psychosis Delirium tremens Hangovers A low to moderate degree of tolerance develops to most of the behavioral and mood-altering effects of alcohol, such that the chronic user must take larger and larger amounts in order to obtain the desired effects. Minimal tolerance develops to the lethal effects of alcohol, so that, in effect, the therapeutic index for the drug gets smaller and smaller. There is cross-tolerance among alcohol and all the sedative-hypnotic drugs. There is evidence that pharmacodynamics tolerance occurs with respect to ethanol's actions at GABAA receptor and up-regulation of NMDA receptors. The adaptive changes in the GABAA receptor system may have a more significant relationship to the development of ethanol tolerance than to withdrawal, whereas the NMDA receptors appears to play a significant role in tolerance development as well as many of the symptoms associated with ethanol withdrawal. Some of alcohol's acute biological effects appear to be the result of an increase in fluidity and chemical composition of cell membranes, whereas enhanced membrane rigidity with chronic alcohol exposure is believed to be a result in cellular tolerance to alcohol. This enhanced rigidity occurs as a consequence of a compensatory shift in the composition of the cell membrane whereby polyunsaturated fats are replaced by saturated fats and cholesterol, rendering the membrane less susceptible to fluidization. Much of the tolerance to alcohol is believed to be due to behavioral compensation; that is, the individual learns to compensate for the detrimental effects of the drug on behavior. Several of the mechanisms that result in tolerance to ethanol's effects are linked to its ability to induce physical dependence with chronic, heavy use. Downward-regulation of dopamine input into various limbic areas may be the cause of dysphoric mood and increased anxiety. The previously mentioned up-regulation of NMDA receptors and the down-regulation of GABAA receptors, which occur with chronic ethanol exposure, most likely contributes to the CNS hyper excitability during withdrawal. After cessation of larger doses, the symptoms may be evidenced as a high degree of arousal associated with weakness, tremor, anxiety, and elevated blood pressure, pulse rate, and respiratory rate. In severe reactions, 12 to 48 hours after the person stops drinking, convulsions may appear, and a toxic psychosis may appear with symptoms such as irritability, headaches, fever, nausea, agitation, confusion, and visual hallucinations. This latter syndrome is referred to as delirium tremens or the D.T.s, which typically appear 2 to 4 days after drinking stops. Withdrawal-related symptoms have been noted in numerous clinical studies to become increasingly more severe after repeated exposures of alcohol intoxication and withdrawal, perhaps through a "kindling" process, in which each episode of withdrawal "sensitizes" the brain toward progressively more intense withdrawal responses. Although physical dependence on alcohol generally requires several months or years of exposure to alcohol to develop, many experts believe that a single day's exposure to a large quantity of alcohol can induce an abstinence syndrome, which is commonly experienced as a hangover. The fact that re-exposure to alcohol can "cure" a hangover supports this belief. Some of the symptoms of a hangover may be related to a buildup of acetaldehyde in the brain, depletion of norepinephrine, lack of sleep, dehydration, and low blood sugar. In addition, by-products of fermentation in alcoholic beverages called congeners—many of which are toxic to the body—may enhance a hangover. This is probably why some alcoholic beverages induce greater hangovers than others.

Poison Control Centers

American Assiciation of Poison control Centers 61 AAPCC in U.S. 1-800-222-1222 At present, there are 61 poison control centers in the United States. The 1 800 number for the American Association of Poison Control Centers is 1-800-222-1222. This number should be near a telephone in homes with children and should be saved within cell phone address books in case you need to use it.

Benzodiazepine Mechanism of Action

Activation GABA enhance the activity of this inhibitory neurotransmitter Cerebral Cortex, limbic structures, cerebellum Indirect agonists Do not bind Appear to occupy sites that enhance binding and activating recpetors Minimal effects on the drug-metabolizing enzymes of the liver Inhibition Flumazenil Displace from specific binding sites There are a number of differences between the benzodiazepine anxiolytics and earlier compounds used in the treatment of anxiety-related disorders. The most striking difference is their high therapeutic index. Very few deaths are attributed to overdoses of benzodiazepines by themselves, although they have been involved in a number of deaths when combined with other sedative-like drugs, because of their additive effects. Their high therapeutic index is probably due to their specific ability to enhance the activity of an inhibitory neurotransmitter, GABA, as opposed to the more generalized neuronal suppressive effects of other sedative-hypnotic drugs. This may also account for why benzodiazepines have minimal general anesthetic effects except at very high doses. Another advantage is that they have minimal effects on the drug-metabolizing enzymes of the liver, and therefore do not enhance the hepatic metabolism of themselves or other drugs. Part of the more selective action of the benzodiazepines is due to the fact that there are binding sites for them on GABAA receptors that mediate their action in the central nervous system. These benzodiazepine sites are highly specific for benzodiazepine agonists and antagonists and for some nonbenzodiazepine compounds with similar psychoactive properties. The highest concentrations of these sites are found in the cerebral cortex, limbic structures, and the cerebellum. Although the function of these sites is unclear, the action of benzodiazepines at these sites has been suggested to be once facilitating the activity of GABA, which predominantly enhances the flow of Cl- ions into neurons and hyperpolarizing them. Benzodiazepines are indirect GABA agonists, as they do not bind directly to GABA binding sites, but appear to occupy sites that enhance the ability of GABA to bind to and activate the type A receptors. As a result, the degree of effect of benzodiazepines depends on the concentration of GABA; that is, they produce marked effects at low GABA concentrationsand minimal effects when high GABA concentrations are present. The action and thus the effects of benzodiazepines can be blocked completely with flumazenil. Flumazenil acts by competitively displacing benzodiazepines from their specific binding sites. In addition to its valuable use in locating and identifying specific benzodiazepine receptor sites, flumazenil has been used to rapidly reverse the effectsof benzodiazepines used in surgical procedures, as an antidote in cases of benzodiazepine poisoning, and to reverse benzodiazepine comas.

Bronchospasm

Adrenergic Stimulants Most stimulate both the beta1 and beta2 receptors. Bronchial relaxation is accompanied by cardiac stimulation and hypertension Ephedrine Epinephrine Isoproterenol Theophylline Produces bronchodilatation by inhibiting the enzyme phosphodiesterase Increases the activity of cyclic AMP. Produces bronchodilatation and tachycardia, Cromolyn Sodium Stabilizes the membranes of the mast cells Prevents episodes of allergic asthma Steroids Most potent and most effective of the antiasthma drugs Systemic effects are restricted to patients who do not respond adequately to other drugs Relief of bronchospasm is essential for the treatment of asthma. Although the ideal adrenergic stimulant would be selective for beta2 receptors in the lung, most stimulate both the beta1 and beta2 receptors. Bronchial relaxation, therefore, generally is accompanied by cardiac stimulation and hypertension. Ephedrine also is available in oral form for more long-lasting effects. The use of epinephrine and isoproterenol in acute attacks of severe asthma is legendary and frequently life-saving; the accompanying tachycardia is considered to be an unavoidable consequence. Theophylline, the prototypical xanthine bronchodilator, produces bronchodilatation by inhibiting the enzyme phosphodiesterase and thus increasing the activity of a substance called cyclic AMP. This result is the same as if it would occur if the drug were to stimulate beta-adrenergic receptors directly, thereby relaxing bronchial smooth muscle. Administered either orally or intravenously, theophylline produces bronchodilatation and tachycardia, which is consistent with the beta1 and beta2 stimulation. Sustained-release preparations of theophylline make twice or three times daily dosage possible for long-term prevention of bronchospasms. At therapeutic levels, gastrointestinal upset, tachycardia, and CNS stimulation are the most frequently occurring side effects. Cromolyn sodium helps prevent bronchospasm by stabilizing the membranes of the mast cells of the lungs so that histamine release in susceptible individuals is reduced. It is quite effective, therefore, in preventing episode of allergic asthma. Cromolyn sodium is available as a powder that is inhaled through the mouth and for use in children, as a solution that is nebulized and inhaled. Steroids are among the most potent and most effective of the antiasthma drugs. However, their systemic effects are of such importance that their use is restricted to patients who do not respond adequately to other drugs. Steroids reduce the inflammation and edema associated with bronchitis and bronchospasm, and they potentiate the effects of sympathetic stimulants and theophylline.

Depressant vs. Sedative Hypnotic

Alcohol Barbiturate Benzodiazepine The term sedative-hypnotic is used because, in most individuals, the lower doses of these drugs have a psychological calming effect, and somewhat higher doses have a hypnotic, or sleep-inducing, effect. The term hypnotic in this context should not be confused with the state induced by hypnosis, which is a state in which the individual is actually very much awake. These drugs are also commonly called CNS depressants, or central nervous system depressants, because their predominant tendency is to inhibit the excitability of neurons. Alcohol is the most used and abused recreational depressant drug in U.S. society, and barbiturates and benzodiazepines are among the most frequently abused prescription sedative-hypnotics. In addition, there are many drugs with very similar properties, including Vistaril, Ambien, chloral hydrate, Placidyl, Doriden, and Quaalude, many of which are no longer on the market because of their abuse potential. For the most part, all of these drugs differ primarily in the latency of onset, the intensity of effect, and the duration of action. Lower doses induce sedation; moderate doses induce sleep somewhat similar to natural sleep, in which the person is still responsive to pain; high doses induce sleep to the point of anesthesia; and successively higher doses can cause coma, respiratory arrest, and death. In the lower dose range, excitement, increased activity, gregariousness, and aggression may occur in some individuals. This phenomenon has completely been attributed to the disruption of neural pathways of higher cortical origin that play an inhibitory function on subcortical centers in the brain, a phenomenon commonly referred to as disinhibition.

Mechanism of Action

Alcohol is believed to act directly on neuronal membranes -Altering their basic semisolid structure and making them more "fluid" -High doses can interfere with the ability of the neuron to generate and conduct action potentials -Lower doses directly or indirectly affects the function of a wide variety of neurotransmitter systems in the brain Two key receptors: -GABA Type A -Allows chloride ions to flow into neurons and hyperpolarizes them -enhances the activity of GABA Type A -NMDA -Allows calcium ions to flow into neurons and depolarizes neurons. -inhibits NMDA receptors Consistent with its designation as a CNS depressant, studies have indicated that acute ethanol administration induces marked decreases in metabolic activity throughout the human brain, e.g., reduced glucose metabolism or cerebral blood flow. Normalizing for these global effects also reveals that there are marked changes in the patterns of regional metabolism, with relative increases in some areas and decreases in others, which may be correlated with the different behavioral effects of alcohol. Alcohol is believed to act directly on neuronal membranes by altering their basic semisolid structure and making them more "fluid-like". At high doses, this fluidizing action may inhibit the movements of the Na+ and K+ ions across the membranes and interfere with the ability of the neurons to generate and conduct action potentials. At lower doses they lead to intoxication. Ethanol directly or indirectly affects the function of a wide variety of neurotransmitter systems in the brain. This makes it particularly difficult to determine which ones are most relevant to intoxication, tolerance, dependence, and withdrawal, as well as which ones might be targets for drug therapy in dealing with alcoholism. However, two key receptors that appear to be particularly relevant to ethanol's subjective effects and the development of tolerance and dependence with chronic use are the GABAA and the NMDA receptors. Activation of GABAA receptors allows Cl- to flow into neurons and hyperpolarize them, whereas activation of NMDA receptors allows Ca++ to flow into neurons and depolarizes neurons. Ethanol enhances the activity at GABAA receptors and inhibits NMDA receptors. Ethanol's ability to enhance Cl- conductance via GABAA receptors may be due to its ability to elevate levels of a neuroactive steroid that is a potent modulator of this receptor subtype. It should be apparent from the preceding discussion that the liver is one of the organs most likely to be affected by chronic alcohol consumption.

Mineralocorticoids

Aldosterone released from the adrenal cortex is stimulated by Reduction in the volume of circulating blood Reductions in plasma sodium, Response to the presence of angiotensin Acts to increase the reabsorption of sodium ions Increases in plasma sodium Results in water retention Aldosterone released from the adrenal cortex is stimulated by reduction in the volume of circulating blood, by the reduction of plasma sodium, and in response to the presence of angiotensin. It acts directly on the cells of the distal tubules of the kidneys to increase the reabsorption of sodium ions at the expense of potassium excretion. This produces an increase in plasma sodium, which results in water retention. The resulting increases in plasma volume, cardiac output, blood pressure, and peripheral vascular resistance are all detrimental to patients with hypertension or congestive heart failure.

Psychological Effects of Cocaine

Amphetamines vs. Cocaine Effects Duration of Drugs Potency Because of the similarities of the neurochemical effects of cocaine and those induced by amphetamines, it is not surprising that their mood-altering and behavioral effects are also quite similar. With few exceptions, the effects of amphetamines mentioned in the previous lecture apply to cocaine. These effects include euphoria, enhanced arousal and vigilance, reversal of fatigue-induced deficits in performance, and increases in blood pressure and heart rate. Although users of cocaine and amphetamines will often assert the effects of the two drugs are different, most studies have found that, when users of cocaine and, amphetamine are administered these drugs intravenously, they are unable to distinguish between them, except for the duration of the drug's effect. The time course for amphetamines is approximately 2 to 3 hours, whereas cocaine's effects dissipate in only 30 minutes. Also, after chronic exposure to either substance, those effects exhibiting tolerance to one will sometimes confer tolerance to the other. On the other hand neither is cross tolerant with opiates like morphine. High doses of cocaine induce the same psychopathological effects noted earlier with respect to amphetamines: suicidal thoughts, irritability, anxiety, rebound depression, and paranoid ideation. The most common of the perceptual changes and pseudohallucinations induced by cocaine are tactile disturbances, in which there is a sensation of bugs running all over the skin, which are called coke bugs, and visual disturbances. There are some other differences between cocaine and amphetamine. Although the potency of cocaine is about 60% of amphetamines when administered intravenously, cocaine is considerably less potent when administered orally. Oral cocaine, because of its alkaloid nature and the effects of the G.I. secretions, is not well absorbed, whereas amphetamine is readily absorbed from the G.I. tract. There is also a difference between them when taken intranasally; cocaine has local anesthetic properties, whereas amphetamines do not. This local anesthetic action also appears to make it difficult for cocaine users to distinguish cocaine from other local anesthetics with minimal central nervous system actions. Perhaps some of the subjective differences between amphetamine and cocaine are due to reputation, expectation, and setting, all of which are potent factors in many so-called drug-induced effects. Despite the South American Indians' long-term use of cocaine, there are no reports of them suffering from any unpleasant side effects or toxicity. On the other hand, in the late 1980s in the U.S., we began to experience an epidemic of use and abuse of, and extreme dependence on, cocaine. Why is there such a difference in the use of cocaine in these two cultures. Basically, the difference lies in the way in which the drug is administered.

Prolactin

Anterior pituitary hormone Stimulate milk production after delivery Under hypothalamic control Dopamine is the major CNS inhibitor of prolactin secretion Prolactin deficiencies Excesses of prolactin The primary function of prolactin, an anterior pituitary hormone, is to stimulate milk production after delivery. Like other hormones of the anterior pituitary, secretion of prolactin is under hypothalamic control. This control is unique, however, in that it is primarily inhibitory in nature, which results in prolactin-inhibitory hormone. Dopamine is the other major CNS inhibitor of prolactin secretion and, indeed, it may be the major PIH released by the hypothalamus. Prolactin deficiencies are rare and probably of no clinical significance except that they result in a woman's inability to secrete milk after delivery. Excesses in prolactin may result in nonstimulated mild production, menstrual irregularities, and infertility. Pituitary tumors that might cause milk secretion are treated surgically or by irradiation. Bromocriptine can be used both for a trial of pharmacologic therapy and to prevent postpartum lactation if such is desired.

Beta Lipotropin

Anterior pituitary hormone met-enkephalin Betatropin is an anterior pituitary hormone that contains the sequence for several of the "endogenous opiates," the most important of which is met-enkephalin. Whether beta lipotropin is the source of CNS enkephalins is unclear and probably unlikely. It may be the source of hormone fragments released from it or it may serve other, as yet unidentified, functions.

Drugs used for Cardiac Arrhythmias

Antiarrhythmic drugs are useful both in the acute treatment and in long-term prevention of disorders of cardiac rhythm.

Antidepressents

Anxiety and depression frequently coexist Selective Serotonin Reuptake Inhibitors (SSRIs) Clinical use Anxiety OCD Panic disorder GAD Social Phobia Posttraumatic Stress Disorder Anxiety disorders share a common affective state characterized by high psychological arousal, ranging from excessive worry to anxiety to fear. Thus, it would seem that these disorders would be most amenable to treatment with the types of drugs we have previously discussed. However, other drugs not commonly viewed as anxiolytics have been shown to be equally or more effective in the treatment of these disorders. In clinical settings, anxiety and depression symptoms frequently coexist. Thus, a variety of antidepressants have been used in the treatment of patients with anxiety with some degree of success. Several of the long-acknowledged antidepressant drugs, have been shown to be effective treatments for panic and phobic disorders, with an efficacy rate comparable to benzodiazepines such as Xanax. Since 1987 another class of antidepressants, collectively called "selective serotonin reuptake inhibitors," or SSRIs, have come into clinical use. Their use has broadened dramatically, and they are being used in the treatment of a wide variety of disorders, including several in the anxiety category. The first of these was OCD, for which it was found that a variety of SSRIs were superior to placebo, with approximately 60% to 70% of patients exhibiting at least moderate relief from their OCD symptoms. The SSRIs were shown to be more effective in the treatment of OCD than antidepressant drugs that did not have selective serotonergic properties. In good responders, maintenance therapy with SSRIs for up to 2.5 years has been shown to provide substantial protection against OCD symptom worsening, compared to patients not receiving active medication, even when the maintenance of SSRI dose is half that of the acute dose. These findings eventually led to several pharmaceutical companies applying for, and being granted, FDA approval for their SSRI drugs for the treatment of OCD. The SSRIs also have demonstrated clinical efficacy in the treatment of panic disorder, generalized anxiety disorders, social phobias, and PTSD. In most of these disorders, the efficacy of SSRIs is comparable to, or in some cases better than, the efficacy of more established anxiolytics.

Anxiolytics

Anxiety disorders Most observed mental disorder in adults Induce a dissolution or loosening of anxiety Some have similar properties of alcohol and barbiturates Some have a higher efficacy rate and are less prone to abuse Minimal potential for inducing death from an overdose At their core, anxiety disorders involve unrealistic, irrational fears or anxiety of disabling intensity. There are several primary types of anxiety disorders. Collectively, these disorders are the most frequent observed type of mental disorders in adults. For centuries, alcohol and to some extent opiate-type drugs were commonly used to reduce the symptoms of anxiety disorders; the barbiturates were subsequently used in their treatment. However, because of the high abuse potential and toxicity of these drugs, along with the development of drugs with more selective actions, the use of the former drugs in treating anxiety disorders has virtually ceased, with perhaps the exception involving those individuals who use them for "self-medication" purposes. Anxiety disorders are now treated with drugs that are collectively referred to as anxiolytics, because they induce a "dissolution" or "loosening" of anxiety. A number of these drugs have pharmacological and behavioral properties similar to alcohol and barbiturates—differing only in matter of very slight degrees. In many cases, these drugs have a higher efficacy rate, are less prone to abuse, and generally have minimal potential for inducing death through overdose.

Respiratory System

Autonomic nervous system regulates the tone of vascular smooth muscle in the nose Reductions in vascular tone produce increased resistance to airflow through the nose, Exposure to cold Common cold Inflammation or irritation of the nasal vasoconstrictors Nasal decongestants Antihistamines Bronchospasm Considered to be a medical emergency Asthma Bronchodilators Chronic bronchitis Emphysema The autonomic nervous system regulates the tone of vascular smooth muscle in the nose. Reductions in vascular tone produce increased resistance to airflow through the nose, as is observed during exposure to cold, the common cold, inflammation or irritation of the nasal vasoconstrictors such as cocaine. Drugs used to treat nasal congestion are often those that stimulate the sympathetic nervous system or, less frequently, block the parasympathetic division of the autonomic nervous system. Most nasal decongestants stimulate alpha-adrenergic receptors on the blood vessels in the nose, constricting them and reducing both blood flow and edema in the swollen, engorged tissues. This improves the passage of air and the drainage of the sinuses. Antihistamines frequently are added to cold medications, although their roles in nasal congestion are unclear. The anticholinergic side effects of antihistamines provide a drying action which may help alleviate stuffiness. Acute spasm of the smooth muscle of the bronchi or bronchospasm characterizes lower respiratory tract disorders. Bronchospasm is considered to be a medical emergency, since air in the trachea reaches the gas-exchange membranes of the lung-thereby oxygenating blood-only after it passes through the bronchi. Narrowing or occlusion of the bronchial air passages prevents the movement of air from trachea to blood. Such bronchospastic disorders are term as "asthma". The bronchial smooth muscle is dually innervated by the parasympathetic and the sympathetic nervous systems the former causing increased tone or bronchoconstriction and the latter reduced tone or bronchodilation. Bronchodilators therefore either stimulate closely related processes or block cholinergic receptors. Those that act by the first mechanism are therapeutically more effective. Besides asthma, other causes of airflow obstruction in the lower respiratory tract include chronic bronchitis, which is associated with excessive mucus production and chronic cough, or emphysema, which involves irreversible damage to lung tissue. Smoking is the most usual cause of bronchitis and emphysema. Advanced states lead to reduced oxygenation of the blood, respiratory difficulty, wheezing, pulmonary hypertension, and heart failure. Therapy is aimed at withdrawal from cigarettes, reducing secretions, relieving bronchospasm, and managing any infections or heart failure present. In severe cases of emphysema, supplemental oxygen may be necessary.

Cannabis Therapeutic Uses

Available for medical use in oral form in the U.S. Some states allow smoked marijuana rapid onset of effect and users is able to control the THC concentrations needed to produce the maximal benefits Canada was first country in the world to allow individuals with chronic illnesses to legally grow and use marijuana Cancer, AIDS, muscle spasms, arthritis pain, Tourette's syndrome, glaucoma On the other side of the coin, cannabinoids have been suggested to have some therapeutic value, an issue that is the subject of growing debate in the medical community. THC within the prescription Marinol is available for medical use in oral form in the U.S. Smoked marijuana does not share this legal position, although several states have passed initiatives that would allow, contrary to federal regulations, the sale and use of smoked marijuana for a variety of medical indications. In 2001, Canada became the first country in the world to allow individuals with chronic illnesses to legally grow and use marijuana. The primary advantages of smoked marijuana come from the ability to achieve a rapid onset of effect and of users to control the THC concentration needed to produce the maximal benefits, whereas oral THC produces a slower onset of effect, with greater variability in degree of effect. Advocates cite anecdotal and clinical evidence that cannabinoids can reduce nausea and vomiting associated with chemotherapy for cancer, reverse the wasting syndrome associated with AIDS, ease muscle spasms in the paralyzed, reduce arthritis pain, reduce the tics and obsessive-compulsive behavior of individuals with Tourette's syndrome, and significantly reduce the pressure in the eye associated with glaucoma. Although cannabinoids generally are not superior to other medications used in these problems, they may prove useful in certain patients for whom these drugs are ineffective. Other doctors and federal health officials, however, say there is sufficient evidence to prove that marijuana is not beneficial; some suggest that smoking it could be harmful, particularly for AIDS patients vulnerable to lung ailments. Because of the development of synthetic cannabinoid compounds with fewer intoxicating qualities and concerns over the potential harmfulness of marijuana, in 1992 the U.S. government stopped accepting new participants in its medicinal marijuana program, which, for some 15 years, had been supplying government-grown marijuana to patients suffering from cancer, glaucoma, and AIDS.

Cocaine Street Names

Blow Charlie Coconut Ice Marconi and cheese Flamethrower Primo Speedball cociane mixed with herion Some other names you might have heard of include cocaine and some other drug mixed together. Here are only a few: Flamethrower, which is cigarette laced with cocaine and heroin. A primo is a mixture of marijuana and cocaine, and it is smoked. While a speedball is cocaine mixed with heroin, and speedballing is referred to when smoking the mixture.

Cannabis Street Names

Blunt Doobee Ganja Hydro Lid Matchbox Dips Killer weed Fry stick Love boat Some street names for marijuana include Blunt, which is marijuana rolled in a cigar; Doobee; Ganja; Hydro weed, is marijuana that has been grown in a hydroponic system. One ounce would be considered a lid. A Matchbox is ¼ ounce or 6 marijuana cigarettes, while a sandwich bag is $40 worth of marijuana and many more. I highly recommend reviewing the reading from the midterm section of the course that describes the names of illegal drugs. Some other names you may have heard of include marijuana mixed with some other drugs. Here are a few, but this list is not inclusive. Dips, happy sticks, or killer weed are joints that also include PCP in some form and then smoked. A fry stick is a marijuana cigarette dipped in embalming fluid and can also be laced with PCP. And lastly, love boat is a blunt missed with marijuana and heroin.

Antibiotic Resistance

Bacteria are capable of developing resistance Internal mechanism Gene coding Problem: Resistance is worsened when antibiotics are used to treat disorders in which they have no efficacy Infectious diseases are becoming more difficult to treat Antibiotics are extremely important in medicine, but unfortunately bacteria are capable of developing resistance to them. Antibiotic-resistant bacteria are germs that are not killed by commonly used antibiotics. When bacteria are exposed to the same antibiotics over and over, the bacteria can change and are no longer affected by the drug. Bacteria have number of ways how they become antibiotic-resistant. For example, they possess an internal mechanism of changing their structure so that the antibiotic no longer works, they develop ways to inactivate or neutralize the antibiotic. Also, bacteria can transfer the genes coding for antibiotic resistance between them, making it possible for bacteria never exposed to an antibiotic to acquire resistance from those which have. The problem of antibiotic resistance is worsened when antibiotics are used to treat disorders in which they have no efficacy, like infections caused by viruses, and when they are used widely as a prophylaxis rather than an actual treatment. Resistance to antibiotics poses a serious and growing problem, because some infectious diseases are becoming more and more difficult to treat. Resistant bacteria do not respond to antibiotics and continue to cause infection. Some of these resistant bacteria can be treated with more powerful medicines, but there are some infections that are difficult to cure with new or experimental drugs.

Penicillins

Bactericidal Inhibit the formation of cell wall Penicillin G vs. Penicillin V Used to treat: Skin infections Dental infections Ear infections Respiratory tract infections Uninary tract infections Gonorrhea Side effects Clinically, the penicillins are important, highly effective antibiotics of low toxicity. They presently are drugs of choice for the treatment of many infectious diseases. The mold Penicillium chrysogenum produces penicillin G, the only naturally produced penicillin. All other penicillins are semisynthetic derivatives of the basic penicillin nucleus. All penicillins inhibit cell wall formation in susceptible bacteria; therefore they are bactericidal in nature. Again, penicillins are bactericidal in nature. Penicillin G is used widely in parenteral form primarily to treat infections caused by gram-positive organisms, including pneumococcal, streptococcal, meningococcal, gonococcal, and other organisms. Penicillin V has the same spectrum of activity as penicillin G, but is much more stable in gastric acid and, therefore, much better absorbed orally. It is widely available in tablets, drops, and in suspension forms. There are five semisynthetic penicillins that are not destroyed by the penicillinase released by the straphylococci and gonococci drugs. These drugs, therefore, are used primarily for infections known to be caused by the penicillinase-producing organisms. Available drugs in this category include methicillin, oxacillin, cloxacillin, dicloxacillin, and nafcillin. Of these, methicillin and nafcillin are absorbed poorly in oral form and are recommended primarily for injection. The other three are acid stable and primarily administered orally. Of these, methicillin and nafcillin are absorbed poorly in oral form and are recommended primarily for injection. The other three are acid stable and primarily administered orally. The penicillin's are the oldest class of antibiotics. Penicillin's are used to treat infections of the skin, dental infections, ear infections, respiratory tract infections, urinary tract infections, and gonorrhea. Penicillins are among the least toxic drugs known. The most common side effect of penicillin is diarrhea. Nausea, vomiting, and upset stomach are also common. In rare cases penicillin can cause immediate and delayed allergic reactions - specifically, skin rashes, fever, and anaphylactic shock.

Cephalosporins

Bactericidal Inhibit the formation of cell wall Used to treat: Pneumonia Strep throat Staph infections Tonsillitis Bronchitis Skin infections Gonorrhea Urinary tract Infections Diverse class of antibiotics First generation Second generation Third generation Forth generation Side effects Cephalosporins have a mechanism of action identical to that of penicillins. However, the basic chemical structure of penicillins and cephalosporins differ in other respects, resulting in some difference in the spectrum of antibacterial activity. Like the penicillins, cephalosporins have a beta-lactam ring structure that interferes with the synthesis of bacterial cell wall, so they are bactericidal. Cephalosporins, again, a bactericidal antibiotic, are used to treat pneumonia, strep throat, staph infections, tonsillitis, bronchitis, otitis media, various types of skin infections, gonorrhea, and urinary tract infections. Cephalosporins are among the most diverse classes of antibiotics, they are grouped into "generations" by their antimicrobial properties. Each newer generation has a broader spectrum of activity than the one before. The first generation of cephalosporins possess generally excellent coverage against most gram-positive pathogens and variable to poor coverage against most gram negative pathogens. The second generation cephalosporins also kill bacteria that are gram-positive in spectrum, like the first generation cephalosporins. These agents have expanded gram negative spectrum. Enough variation exists between the first generation and second generation cephalosporins in regard to their spectrums of activity against most species of gram negative bacteria, that susceptibility testing is generally required to determine their sensitivity. Third generation cephalosporins have much expanded gram negative activity. However, some members of this group have decreased activity against gram-positive organisms. They have the advantage of convenient drug dosing schedules, but they are expensive. The fourth generation cephalosporins are extended-spectrum agents with similar activity against gram-positive organisms as first-generation cephalosporins. They also have a greater resistance to beta-lactamases than the third generation of cephalosporins. Many fourth generation cephalosporins can cross the blood brain barrier and thus are effective in meningitis. Cephalosporins generally cause few side effects. Common side effects associated with these drugs include: diarrhea, nausea, mild stomach cramps or upset stomach. Approximately 5-10% of patients with allergic hypersensitivity to penicillin will also have cross-reactivity with cephalosporins. Thus, cephalosporin antibiotics are contraindicated in people with a history of allergic reactions to penicillin.

Aminoglyosides

Bacteriocidal Stop bacteria from making proteins Used to treat: Septicemia Complex infections within the abdominal cavity Severe urinary tract infections Hospital acquired respiratory infections Side effects In 1943, Selman Waksman, together with his co-workers, discovered that a fungus Streptomyces griseus produced an antibiotic substance which they named "streptomycin." Waksman was awarded the Nobel Prize in Physiology or Medicine in 1952 for his discovery of streptomycin. The aminoglycoside antibiotics are important drugs used to treat serious infections caused by gram-negative organisms. The mechanism behind their bactericidal action involves their interference with protein synthesis by their binding to protein subunits. This action ultimately results in disruption of the formation of cytoplasmic membranes located just inside the rigid bacterial cell wall. This effect is bacteriocidal. Aminoglycosides work quite well, but bacteria can become resistant to them. Since aminoglycosides are broken down easily in the stomach, they can't be given by mouth and must be injected. Generally, aminoglycosides are given for short term periods of time. They are used to treat septicemia, complex infections within the abdominal cavity, severe urinary tract infections, and hospital acquired respiratory infections. The major irreversible toxicity of aminoglycosides is audio toxicity, that is, damage to the ear and hearing. Another important concern with aminoglycoside antibiotics is nephrotoxicity, that is, kidney damage.

Fluroquinolones

Bacteriocidal interfering with their ability to make DNA difficult for bacteria to multiply Newest class of antibiotics. Synthetic antibiotics Used to treat: Urinary tract infections Skin infections Respiratory infections Side effects Fluoroquinolones are the newest class of antibiotics. Their generic name often contains the root "floxacin". They are synthetic antibiotics, and not derived from bacteria. Fluoroquinolones belong to the family of antibiotics called quinolones. The older quinolones are not well absorbed and are used to treat mostly urinary tract infections. The newer fluroquinolones are broad-spectrum bacteriocidal drugs that are chemically unrelated to the penicillins or the cephalosporins. Because of their excellent absorption fluroquinolones can be administered not only by intravenous use but also orally. Fluoroquinolones are used to treat most common urinary tract infections, skin infections, and respiratory infections, such as sinusitis, pneumonia, and bronchitis. Fluoroquinolones inhibit bacteria by interfering with their ability to make DNA. This activity makes it difficult for bacteria to multiply, thus the effect is bacteriocidal. Fluoroquinolones are well tolerated and relatively safe. The most common side effects include nausea, vomiting, diarrhea, abdominal pain. Other more serious but less common side effects are central nervous system effects such as headache, confusion and dizziness. All drugs in this class have been associated with some convulsions.

Macrolides

Bacteriostatic Binding with bacterial ribosomes to inhibit protein synthesis. Used to treat: Respiratory tract infections Genital infections Gastrointestinal tract infections Skin infections Side Effects The macrolide antibiotics are derived from the Streptomyces bacteria, and got their name because they have a macrocyclic lactone chemical structure. The macrolides are bacteriostatic, binding with bacterial ribosomes to inhibit protein synthesis. Erythromycin, the prototype of this class, has a spectrum and use similar to penicillin. Newer members of the group, azithromycin and clarithyromycin, are particularly useful for their high level of lung penetration. Macrolide antibiotics are used to treat respiratory tract infections, such as pharyngitis, sinusitis, and bronchitis, genital and gastrointestinal tract infections, as well as skin infections. Side effects associated with macrolides include nausea, vomiting, and diarrhea. Infrequently, there may be temporary auditory impairment. Macrolide antibiotics should be used with caution in patients with liver dysfunction.

Effects of Barbiturate Use

Behaviors Perceptual processes Mental activites Sleep REM Tolerance A wide variety of behaviors, perceptual processes, and mental activities are affected when low doses of these drugs are used for their calming and sedative effects. Although they are used for enhancing or inducing sleep, the pattern of sleep induced is not really what one would consider normal. In general, during an 8-hour night of sleep, we go through several stages of sleep. These stages differ with respect to how easy it is to awake the person, how psychologically aroused the body is, the mental context, and the person's eye movements. All stages have been presumed to have some functional significance, but there is no consensus as to what specific functions they have. Most nonbenzodiazepine sedative-hypnotics tend to prolong the deeper stages of sleep and reduce the stage known as REM, or rapid eye movement. REM is the stage in which vivid dreams are most common. However, the ability to suppress REM sleep is not restricted to the sedative-hypnotics. This characteristic has been noted to occur with many other types of drugs as well, including stimulants and marijuana. The mechanisms for inducing tolerance to alcohol apply to barbiturates, although the latter appear to have a greater effect than alcohol on the drug-metabolizing enzymes of the liver. Cross-tolerance occurs with all of these substances, and the psychological and physical dependence associated with them is quite similar. The faster acting compounds, which also have more intense effects and shorter durations, are more likely to be abused, and the abstinence syndrome associated with them is likely to be more intense.

PCP Mechanism of Action

Binding to the NMDA site: PCP prevents calcium ion and sodium ion flow through the channel and into the neuron. Antagonize NMDA-type glutamate receptor activity appears to be a major factor in its ability to increase extracellular dopamine concentrations in the nucleus accumbens, prefrontal cortex, and basal ganglia. Dopamine-enhancing effects may be responsible for some of PCP's rewarding properties. Has been shown to potentiate the effects of electrical stimulation of the brain The CNS actions of PCP are quite complex and probably involve a wide variety of neurotransmitter systems. Almost all of these sites appear to be located deep within an ion channel regulated by the NMDA receptor for the excitatory amino acids glutamate and aspartate; by binding to this site, PCP prevents calcium ion and sodium ion flow through the channel and into the neuron. PCP's ability to antagonize NMDA-type glutamate receptor activity also appears to be a major factor in its ability to increase extracellular dopamine concentrations in the nucleus accumbens, prefrontal cortex, and basal ganglia. Although these dopamine-enhancing effects may be responsible for some of PCP's rewarding properties, as is the case with most drugs of abuse, PCP has been shown to potentiate the effects of electrical stimulation of the brain. With such a confusing array of pharmacological effects, it is not clear what accounts for PCP's popularity. The majority of PCP users report that they enjoy the intoxication state, viewing it as a novel experience that provides an escape from anxieties, depression, and other external pressures. To this outside observer, these effects seem a little like the effects from a combination of a sedative-hypnotic, a monoamine-related hallucinogen, and an opiate.

Effects of Chronic Use

Body damage Poor nutritional practices Non-sterile syringes Mix of other drugs Immune system effects Lifestyle of abuser Although the chronic use of narcotics might be expected to lead to significant deterioration in the body, many studies have found no major damage to any of the body that is, solely due to the presence of narcotics- even heroin. Most of the damage that is found is due to poor nutrition practices of addicts, the use of adulterated drugs under nonsterile conditions, concomitant use of other drugs, and the general lifestyle of the addicts. Also their narcotic use decreases their ability to recognize pain that is normally present when something is pathologically, wrong with them, and thus they fail to seek treatment. Their recognition that medical treatment may also reveal their addiction and lead to termination of their drug use may also be a factor in failing, to seek treatment. If pure narcotics are taken under sterile conditions and proper nutritional practices are followed, there is little damage to the body. It is possible for chronic exposure to, narcotics to permanently alter the body's synthesis or regulation of endorphins and their receptors, so that normal psychological processes that are believed to be associated with them, like pain, perception, mood, and pleasure, may be affected for the remainder of the person's lifetime. It has long been observed that opiate addicts have increased susceptibility to infections. Whether this is a result of the addict's lifestyle or a direct result of opioid exposure is not clear, since opiates have been shown to exert detrimental effects on the immune functions of the body. For example, opiate agonists such as morphine and fentanyl tend to suppress antibody production, alter the ability of white blood cells to respond to substances that stimulate white blood cell, transformation, and decrease the toxicity of other types of natural killer cells. Many of these effects are mediated through opiate receptors in the midbrain.

Tetracyclines

Broad-spectrum Bacteriostatic agents Inhibit bacterial protein synthesis. Used to treat: Microorganisms: Rickettsia Amebic parasites Infections Respiratory tract Sinus Middle ear Urinary tract Skin Intestines Gonorrhea Rocky Mountain spotted fever Lyme Disease Side effects Tetracyclines got their name because they share a chemical structure that has four rings. They are derived from a species of Streptomyces bacteria. Tetracycline antibiotics are broad-spectrum bacteriostatic agents that inhibit bacterial protein synthesis. Tetracyclines may be effective against a wide variety of microorganisms, including rickettsia and amebic parasites. Because of their broad spectrum, tetracyclines have been overused, and such use has led to both bacterial resistance in previously sensitive bacteria and to superinfections from organisms not sensitive to the drug. In general, these broad-spectrum, bacteriostatic agents are best replaced whenever possible by narrow-spectrum, bactericidal agents for sensitive pathogens. Tetracyclines are variably absorbed when taken orally, ranging from 30 percent of the administered dose of chlortetracycline and 100 percent for minocycline. Calcium salts and gastric antacids bind to tetracyclines in the stomach and prevent their absorption. Milk products and antacids should be avoided when taking tetracyclines. Tetracyclines have relatively long half-lives, and high concentrations are found in bone, the liver, and the kidneys. They readily cross both the blood-brain barrier and the placental barrier. Excretion is through the liver and the kidneys. Tetracyclines are used in the treatment of infections of the respiratory tract, sinuses, middle ear, urinary tract, skin, and intestines. Tetracyclines are also used to treat gonorrhea, Rocky Mountain spotted fever, and Lyme disease. Toxicities to tetracyclines are significant. Gastrointestinal side effects include nausea, vomiting, diarrhea, colitis, and bacterial, yeast, and fungal superinfections. Some host cells are affected by tetracyclines, and liver damage, and an antianabolic action have been postulated. Tetracyclines can be deposited in developing teeth, with the risk being greatest between the neonatal period and about 7 to 8 years old. When taken during this time, teeth will develop a permanent brown discoloration. The intensity of discoloration appears to be dose-dependent. Tetracyclines also are deposited in the bony skeleton of the fetus, infants, and young children, which produces depression of bone growth. Thus, tetracyclines should be avoided in pregnant women and in children up to 8 years old. Other toxicities include photosensitivity of the skin and possible renal damage.

Urinary Incontinence

Can result from many physiological and psychological factors Anticholinergic drugs Block the actions of acetylcholine on the bladder Increase the bladder's capacity by reducing the stimulus to bladder contraction Adrenergic stimulants Urinary incontinence can result from many physiological and psychological factors. Thus, its pharmacologic treatment is approached from several points of view. Anticholinergic drugs block the actions of acetylcholine on the bladder and increase the bladder's capacity by reducing the stimulus to bladder contraction. As might be expected, the use of anticholinergic drugs to decrease bladder tone is accompanied by the anticholinergic side effects including constipation, dry mouth, blurred vision, and tachycardia. The parasympathetic and sympathetic nervous systems reciprocally innervate most of the body's organs, including the bladder. One would think, therefore, that if inhibition of the cholinergic system were effective in treating incontinence, adrenergic stimulation should produce a similar effect. Indeed, adrenergic stimulants such as ephedrine and phenylpropanolamine may have some efficacy. Adrenergic stimulants must be used with caution in hypertensive patients.

Cathartics and Laxatives

Cathartics and laxatives assist the process of defecation by increasing the hydration of the intestinal contents Cathartics cause a rapid, fluid evacuation of the bowel Laxatives form soft, easily passed fecal contents. Mechanism of Action Increase the water content of feces reduce the transit time of the intestinal contents by several mechanisms Drug types: Bulk-forming Laxatives Increase the water content volume of the stool Magnesium hydroxide or Milk of Magnesia is another bulk cathartic. Contact Cathartics Act directly on the wall of the intestine by reducing the absorption of water from the GI tract into plasma Mineral Oil Penetrates and softens the stool May interfere with the absorption of water from the GI tract. Glycerin Suppositories Facilitate fecal evacuation Soften and lubricate hard feces Cathartics and laxatives assist in the process of defecation by increasing the hydration of the intestinal contents. Although their mechanism of actions are similar, that is, both increases the water content of stool, their results differ: cathartics cause a rapid, fluid evacuation of the bowel; laxatives form soft, easily passed fecal contents. There are relatively few indications for the use of laxatives and cathartics. The use of cathartics and laxatives by the lay public can be curtailed by patient education, improved dietary habits, and increasing the ingestion of bulk-containing foods. The self-diagnosis of chronic constipation is not an indication for the continual use of these substances, as a "laxative habit" can easily result. Laxatives and cathartics increase the water content of feces and reduce the transit time of the intestinal contents by several mechanisms. First, the retention of water will, by hydrophilic and osmotic forces, cause an increase in the bulk of the intestinal contents and increase the rate of transit. Second, the drugs may act directly on the walls of the GI tract to block absorption of electrolytes and water and to increase the secretions of the GI tract. Third, the lubricants and stool softeners act by incorporation to fecal material, retaining water and increasing the ease of evacuation. A diet rich in fiber is an appropriate method for the prevention and treatment of most forms of constipation. The bulk-forming laxatives increase the water content volume of the stool, which thus decreases transit time. The increased mass usually reaches the rectum within about 1 to 3 days. Irritant or stimulant contact cathartics act directly on the wall of the intestine by reducing the absorption of water from the GI tract into plasma. These compounds also may stimulate the contraction of the large intestine, which reduces transit time. Contact cathartics' continuous use occasionally may produce bowel irritation or severe diarrhea that can result in dehydration and a variety of electrolyte and protein abnormalities. Such agents are best used only for short periods of time. Mineral Oil is a mixture of liquid hydrocarbons obtained from petroleum. The oil is indigestible and thus very poorly absorbed. It penetrates and softens the stool and may interfere with the absorption of water from the GI tract. Although it formerly was used widely, it is used less now that bulk-forming laxatives and salts have become available. Glycerin suppositories facilitate fecal evacuation within 30 to 60 minutes of insertion into the rectum. They do this by softening and lubricating hard feces located in the rectum. Glycerin suppositories are not intended for prolonged use, as more efficient stool softening can be achieved with the use of other agents.

Insulin

Consists of two chains of amino acids Metabolized in the liver and the kidneys. Insulin preparations Beef insulin Pork insulin Human insulin Hypoglycemia Other Side Effects Insulin is a hormone consisting of two chains of amino acids. Its half-life is about 10 minutes, and its metabolization occurs in the liver as well as the kidneys. An appropriate amount and dosage form must be chosen for use by injection by diabetic patients. Dosage is calculated in units of the drug. The standardization of units is based on the ability of the drug to lower blood glucose levels in laboratory animals. Most commercial insulin preparations are now packaged with 100 units of insulin per milliliter of injected liquid. Insulin preparations used to replace endogenous insulin commonly consist of extracted and purified hormones from the pancreas glands of cattle, which is known as beef insulin, or hogs, which is also known as pork insulin. Most diabetics use insulin made from a mixture of beef and pork insulin. Human insulin is now available and is used increasingly. Beef and pork insulin have one or more amino acids that differ from those of human insulin, which is a factor that occasionally leads to allergic reactions. Pork insulin differs from human insulin by only one amino acid and is less effective than beef preparations. Synthetic human insulin is identical to the insulin produced by the human pancreas. Excessive doses of insulin, especially when accompanied by reduced caloric intake, cause hypoglycemia, a fall in the level of blood glucose. Signs of hypoglycemia include fatigue, weakness, headache, confusion, sweating, nausea, increased respiration, and hypertension. Low blood sugar may lead to convulsions, coma, and brain damage if sugar is not given rapidly. Eating sugar or a sugar-sweetened product usually will correct the problem and prevent its further progression. Other side effects include allergy, usually to the beef or pork insulin products; gradual development of insulin resistance, which is generally controlled by losing weight and exercising; and atrophy of subcutaneous fat at the site of repeated injections.

Cannabis Tolerance and Dependence

Continued use may result in: More sensitivity to the effects Psychological dependence Physical dependence Abstinence syndrome irritability, restlessness, decreased appetite, sleep disturbance, sweating, tremor, nausea, vomiting, and diarrhea Many users of marijuana report that continued use of it results in their becoming more sensitive to its effects. This phenomenon may be due to the novice user exposed to low doses of THC learning to be more aware of marijuana's subjective effects, or to drug accumulation, since cannabinoids are stored in fat. However, the vast majority of studies include that tolerance can develop to most of the psychological effects, but as is the case with most drugs, tolerance development to THC is dose dependent. Apparently, the usual patterns of marijuana smoking by North Americans, on the order of a joint or less a day, is such that tolerance to marijuana's effects does not develop. However, with sufficiently higher dosages, tolerance to most of THC's effects is likely to occur. Considerable evidence suggest that much of the tolerance phenomena observed in humans is due to the learned adaptations to marijuana's disruptive effects on the behavioral and perceptual processes. Dependence on marijuana is primarily psychological- that is, it is due to its mood- and cognitive-altering properties. Although in some ways it is like comparing apples with oranges, most experts would probably agree that psychological dependence associated with cannabinoids is of a considerably lower degree than that associated with alcohol and other sedative-hypnotics, opiates, or the many different stimulants. Physical dependence as a result of social use of marijuana is even more atypical; until the mid-1970s most experts even denied its existence. However, studies conducted in the late 1970s and early 1980s demonstrated that cessation of extremely high dosage chronic marijuana use by humans can precipitate an abstinence syndrome that may include one or more of the following: irritability, restlessness, decreased appetite, sleep disturbance, sweating, tremor, nausea, vomiting, and diarrhea. More recently, signs of withdrawal were shown in humans following 4 days of smoking 4 marijuana cigarettes a day. Interestingly, none of the participants in this study requested to be terminated from the study during the abstinence periods, suggesting that the withdrawal symptoms were not particularly uncomfortable. This is consistent with reports by heavy marijuana users that when withdrawal symptoms do occur, they tend to be very mild. Although there has been a recent increase in the number of people entering treatment programs with a primary diagnosis of marijuana dependence, most of these are multiple drug abusers, who also report problems with alcohol, cocaine, amphetamine, tranquilizers, or even heroin.

Vitamin Background

Definitions: Catalyst Enzyme Organic catalyst Coenzyme Most vitamins act as coenzymes and catalysts The 13 vitamins essential for the life and health of humans Fat-soluble vitamins Vitamins A, D, E, and K Water-soluble vitamins Vitamin C and the eight B vitamins Fat vs. Water Soluble A catalyst is a substance necessary for the performance of a chemical reaction but which remains unchanged or is regenerated while performing its task many times. An enzyme is a protein that acts as a catalyst for biochemical reactions in the body. In general, an enzyme can be referred to as an organic catalyst. A coenzyme is a partial protein that combines with another partial protein to form a complete, functional enzyme. Most vitamins act as coenzymes. In addition, they are catalysts, since they are essential for the formation, and therefore the activity, of an enzyme and do not change during the chemical reaction they foster. This explains why vitamins are required in only minuscule amounts and why their absence from the diet is associated with specific disease states. The 13 vitamins essential for the life and health of humans can be divided into two groups: fat-soluble vitamins and water-soluble vitamins. Vitamins A, D, E, and K are fat-soluble; vitamin C and the eight B vitamins are water-soluble. The importance of fat solubility versus water solubility lies in the ability of the body either to store or excrete vitamins in excess. The fat-soluble vitamins are stored in great quantity because they are soluble in such body tissues as fat, cell membranes, and in the liver. The water-soluble vitamins are stored in only miniscule amounts, and their excesses are excreted in the urine, usually without adverse effects. Because they cannot be stored, they need to be consumed more frequently so that saturation of tissues is maintained. Since all vitamins are obtained by the ingestions of foods, and since all vitamins are essential for health, lack of intake of any vitamin will result in specific deficiency disorder that is reversible when the vitamin is resupplied. The deficiency state associated with each vitamin will be discussed in the next few slides.

Poison Treatment

Diagnosis Appropriate reactions Immediate Assistance Treatment Termination of Ezposure Topical Exposure Oral Ingestion Bases and Acids Pertroleum Distillates Unconscious pateitns Injection Drug Therapy The diagnosis of poisoning is very difficult. Physical signs may vary from unconsciousness to convulsions. Central nervous system involvement is common and cardiovascular instability may be present. Hysteria on the part of the discoverer of the patient may preclude rational reactions. Appropriate reaction includes assessment of the poisoned individual, including his or her level of consciousness, respiratory accuracy, and presence of palpable pulses; identification of the poison ingested; and assessment of the surroundings in which the individual is found. One must seek assistance immediately from professionals trained to handle these crisis situations. This means that one should immediately contact both the nearest poison control center and the paramedics. The mainstay of treatment is supportive care of vital organs. Assessment and maintenance of both respiration and circulation by basic CPR techniques will prolong the life until assistance arrives. Early termination of exposure to the poison is essential for optimal treatment. Topical exposure to caustic chemicals necessitates prompt removal of all contaminated clothing, and copious flushings with tap water at low force. When the eyes are involved, flushing should be maintained for at least 15 to 20 minutes by the clock. When the skin or hair is involved, mild soap will aid in the cleansing. When poisoning results in oral ingestion, emptying the stomach to prevent further absorption is essential and may be lifesaving. Indeed, induction of emesis or vomiting is indicated after poisoning by oral ingestion of most drugs and chemicals. Exceptions include: poisoning caused by the ingestion of strong acids or alkalis, such as lye or drain cleaner. These will cause even more damage to the esophagus when vomited. Another exception is the ingestion of certain petroleum distillates, such as kerosene and gasoline, as well as some furniture polishes. These may result in severe pulmonary damage if vomited and inhaled into the lungs. Poisoning in patients who are unconscious, convulsing, in shock, and semi-comatose, or whom coma appears to be imminent. Such patients are at an increased risk for aspiration of vomitus. When over dosage results from injection of a drug, nothing can be done to prevent its absorption. Hospital treatment will be aimed at supportive care, increased renal elimination of the drug, and the administration of any antidotes, if indicated. In rare instances of poisoning, about 2% of cases, specific drug therapy may be considered to treat the poisonings.

Glycosides

Digoxin and the other cardiac glycosides: Increase the contractibility of the heart muscle Increase cardiac reserves More complete emptying of the ventricles Reduction in the physical size of the failing heart Mechanism of action: Inhibition of the enzyme sodium-potassium-activated adenosine triphosphatase Active transport of sodium and potassium ions across cardiac cell membranes Increase in intracellular sodium Induced ATPase inhibition Effects of Cardiac Glycosides on the Electrophysiology of the Heart Effects of Digoxin Outside the Heart Effects of Toxicity The classic drugs used to treat congestive heart failure are glycosides. Digoxin and other cardiac glycosides increase the contractibility of the heart muscle, thereby increasing cardiac reserves. The increased force of contraction results in more complete emptying of the ventricles and thus a reduction in the physical size of the failing heart. As a result, tension in the myocardial fibers decreases, and both the energy requirements and the rate of oxygen consumption of the heart cells are reduced. The mechanism of action appears to involve inhibition of the enzyme sodium-potassium-activated adenosine triphosphatase, which leads to an increase in intracellular calcium concentrations. This enzyme is involved in the active transport of sodium and potassium ions across cardiac cell membranes. Its inhibition leads to an increase in intracellular sodium and a decrease in intracellular potassium. An increase in intracellular sodium is crucial since the intracellular calcium normally is exchanged for extracellular sodium along gradient-dependent transport systems. When intracellular sodium is increased as a result of induced ATPase inhibition, the exchange of extracellular sodium for intracellular calcium is diminished, and the concentration of intracellular calcium increases. This process most likely leads to increased stores of calcium in the muscle fibers; at each electrical impulse the greater quantities of calcium released augment contraction of myocardial muscle fibers. Cardiac glycosides have important therapeutic and toxic effects on the electrophysiologic properties of the conducting system of the heart. Digoxin slows conduction of electrical impulses through the AV node, which reduces the numbers of atrial impulses that can be conducted through the node to the ventricles. At therapeutic doses, digoxin and the other cardiac glycosides primarily affect the heart. As blood levels of the drug increase, however, significant systemic effects may be observed. Gastrointestinal effects are manifested as nausea and loss of appetite. Neurologic symptoms may include altered vision and a toxic psychosis. The diuretic effect are the increased cardiac output, improved circulation, and decreased aldosterone release and is considered to be part of the therapeutic effect of digoxin in relieving fluid retention and edema. Symptoms of mild toxicity may include vomiting, loss of appetite, bradycardia, visual disturbances, and mild cardiac arrhythmias. More severe toxicity results in increased incidence of virtually every type of cardiac arrhythmia, the most dangerous being ventricular in origin because it can lead to ventricular fibrillation and death. Elderly patients and patients taking diuretics, which cause potassium loss, are especially prone to digitalis intoxication. Drug interactions with digoxin are extremely common. All patients taking cardiac glycosides should be closely monitored, and no additional medications should be taken without advice of a physician.

Antihypertensive Drugs

Diuretics Promote the excretion of sodium though the kidneys Directly Acting Vasodilators Dilate either arteries or veins Reduce vascular tone Calcium Channel Blockers Dilate the smooth muscle of arterioles Angiotension Antagonists Enzyme renin is synthesized and stored in the kidneys Released in response to a decrease in blood flow to the kidneys Sympathetic Depressant Drugs Exert a depressant action on the heart Reduce the tone of vascular smooth muscle Types: Beta-adrenergic blockers Depress myocardial contractility Relax vascular smooth muscle Peripheral alpha-adrenergic receptor blockers Blockade of these receptors relaxes blood vessels Ganglionic blockers Diuretics, which promote the excretion of sodium though the kidneys, are important as a first-line treatment of essential hypertension because sodium is thought to be somehow involved in the pathogenesis of the disease. Also, as salt is excreted, it carries water with it, thereby reducing the volume of fluid in the plasma and body tissues. Drugs that dilate either arteries or veins reduce vascular tone and decrease blood pressure as a result of their decrease in overload or preload. Nitroglycerin is an example of a venodilator. Because of calcium channel blockers' ability to dilate the smooth muscle of arterioles, they often are used in the treatment of hypertension. It appears to be most effective when combine with diuretics and a sympathetic blocking agent. However, it also appears to be useful in patients who cannot tolerate the side effects associated with sympathetic blockade. The enzyme renin is synthesized and stored in the kidneys and released in response to a decrease in the blood flow to the kidneys. When released into the blood, it is a very potent vasoconstrictor. Surgical correction of renal artery narrowing, with restoration of normal renal blood flow, reduces the process of renin release, angiotensin II formation, vasoconstriction, and rise in blood pressure. This is one of the few surgically correctible causes of hypertension. Drugs that interfere with the function of the sympathetic nervous system either exert a depressant action on the heart or reduce the tone of vascular smooth muscle. These drugs can be classified as centrally acting antihypertensives, beta-adrenergic receptor antagonists, alpha-adrenergic antagonists, and ganglionic blocking drugs. The beta-adrenergic blockers depress myocardial contractility and relax vascular smooth muscle. They are effective in treating hypertension. Indeed, this is their most widespread use today. When combined with a diuretic, they effectively reduce blood pressure while producing fewer side effects than most other antihypertensive combinations. Peripheral alpha-adrenergic receptor blockers are seldom used as clinical antihypertensive agents today, having been largely replaced by the beta-adrenergic blockers. Aplha-adrenergic receptors are found in most blood vessels, especially those of the skin and internal organs. Blockade of these receptors relaxes the vessels and decreases blood pressure. The ganglionic blocking drugs are also seldom used today because of their high incidence of side effects when used chronically andbecause there are much more effective agents available on the market.

Hallucinogens General Information

Drug examples Drug effects Small doses Large doses Psychedelic Brief History Since hallucinations are one of the more striking symptoms associated with drugs such as LSD, Mescaline, and THC, many authors commonly refer to this class of drugs as hallucinogens. Drugs referred in this fashion rarely induce a condition that mimics the types of psychoses naturally found in humans-namely, schizophrenia and mania. At the same time, doses of some drugs that do mimic natural psychotic states, such as large doses of cocaine and amphetamines, are not voluntarily taken for this expressed purpose. The term psychedelic, for mind-expanding, -manifesting, -clarifying, or -revealing, has also been applied to these drugs, but the functional meaning of this term is also unclear. Many have been intrigued by the hallucinogens for a variety of reasons. For centuries, a variety of aboriginal groups have used hallucinogen-containing plants in their rituals and ceremonies for healing and sacramental purposes to promote group cohesiveness, spirituality, and mystical experiences. For example, the peyote sessions of the Native American Church, yage or hoasca ceremonies of the South American Amazon tribes, or ingestion of sacred mushrooms by a number of Indian tribes in Mexico. In many cases, these practices are still conducted today, with evidence that they may contribute to the reduction of psychopathological characteristics of the participants. Over the past 50 years, a number of conventional psychotherapists have proposed the use of hallucinogens as adjuncts in the treatment of a variety of mental disorders. Our society has been deeply concerned over their recreational use, abuse, and potential toxicity that most of them are controlled substances and are schedule 1 drugs.

Properties of Benzodiazepines

Four categories: Ultra-short acting Status epilepticus Short acting Insomnia Status epilepticus Intermediate acting Anxiety related symptoms for alcohol detoxification Long acting Seizure disorders As a family, benzodiazepines differ primarily in terms of their properties, which in turn are a factor in their therapeutic uses, as well as their liability for abuse and dependence. Basically, there are four categories: (1) ultra-short-acting; (2) short-acting; (3) intermediate-acting; and (4) long-acting. Ultra-short acting benzodiazepines are typically used in preanesthetic and intraoperative medications and for treatment of status epilepticus. Short-acting benzodiazepines are commonly used for the treatment of insomnia and status epilepticus. These have a high abuse liability, and if used frequently and chronically, they could trigger severe withdrawal symptoms upon abrupt cessation of use. Intermediate-acting benzodiazepines are commonly used in treating anxiety-related symptoms for alcohol detoxification; although less likely to be abused, they can trigger withdrawal following chronic use. Long-acting benzodiazepines are used primarily for the treatment of seizure disorders and have limited abuse liability and withdrawal effects. As is the case with other drugs with sedative-hypnotic properties, tolerance develops to some of the pharmacological actions of benzodiazepines, and cross-tolerance may occur. However, the rate of tolerance may be slow, fast, or nonexistent.

Amphetamine & Methamphetamine Mechanism of Action

Effect on Catecholamines Epinephrine, norepinephrine, dopamine Enhance levels of catacholamines in synaptic cleft Effect on Monoamines Catecholamines plus serotonin increase extracellular concentrations of the monoamines Enhance dopaminergic activity in a part of the limbic system called the nucleus accumbens Little activity appears to be due to a direct agonist action at these receptor sites. Agonist effect occurs when a substance mimics the action of a neurotransmitter thus directly activating the receptor. Instead of amphetamines being an agonist, amphetamines have properties that enhance the level of epinephrine, norepinephrine, and dopamine in the synaptic cleft, which then increases catecholamine receptor activation with the cleft. Cause more of the neurotransmitters to be released. Amphetamines also increase extracellular levels of serotonin, but this action appears to play minimal role in most of its behavioral effects. Amphetamines and related drugs increase extracellular concentrations of the monoamines through two primary mechanisms. Both of the mechanisms that increase the extracellular concentrations of the monoamines involve the protein transporters that normally terminate the action of monoamines via reuptake. The first mechanism binds to these transporters and inhibit monoamine reuptake into neurons; and secondly, they promote reverse transport of the monoamines. Methamphetamines are roughly equipotent in promoting release and inhibiting reuptake and are more potent in affecting the dopamine and norepinephrine transporters than the serotonin transporter. Amphetamine also has a mild, temporary, inhibitory action on the enzyme MAO and redistributes monoamines from the synaptic vesicles to the cytoplasm, so there are more monoamines to be released. The primary reward properties of these drugs are due to their ability to enhance dopaminergic activity in a part of the limbic system called the nucleus accumbens.

Effects of Nicotine

Effects are variable Enhance task performance Memory Cognition Mood Who, where, and when potential factors: Whether the person being tested is a tobacco user or not The degree of nicotine dependence and deprivation level at the time of testing The route of administration, which influences the onset and duration of effects The dose The predrug psychological state of the person The type of task used The effects of nicotine on performance are typically subtle and variable. Various lines of evidence, suggest that nicotine can enhance task performance, memory, cognition, and learning in some individuals, in some situations, some of the time. The problem in determining the who, where, and when is that there are so many potential factors involved. Some of these factors include whether the person being tested is a tobacco user or not; the degree of nicotine dependence, and deprivation level at the time of testing; the route of administration, which influences the onset and duration of the effects; the dose; the predrug psychological state of the person; the type of task used; and so forth. Furthermore, nicotine can affect mood, cognition, or arousal, all of which can interact in complicated ways; for example, cognition could be enhanced, directly by nicotine or it could be enhanced because nicotine improves the person's mood.

Absorption Barriers

Emetic Drugs Apomorphine Ipecac Chemical Absorbent Activated Charcoal Two agents available to stimulate emesis or vomiting are apomorphine and ipecac. Apomorphine is seldom used today, since it is not available in homes and must be given by injection, but can also cause central nervous system sedation and respiratory depression that occasionally requires naloxone for reversal. However, apomorphine has a rapid onset and is extremely effective in inducing regurgitation of gastric and upper intestinal contents. Its mechanism of action involves direct stimulation of the chemoreceptor trigger zone in the brainstem. sysyrup acts within 15 minutes; the dose may be repeated if emesis is not produced within that time. Failure of two doses to produce emesis indicates that stomach pumping should be performed by trained personnel. Ipecac syrup can be kept at home for emergency use, is inexpensive, and is quite safe. A glass of water administered after the ipecac syrup aids in inducing emesis. But activated charcoal should not be given at the same time as ipecac syrup because it adsorbs the ipecac and nullifies the vomiting effect. When given after the vomiting has ceased, the charcoal functions to adsorb any residual poison. Ipecac's mechanism of action involves local irritation of the GI tract. A 0.5 or 1 oz bottle of ipecac syrup should be kept in all homes with small children where accidental poisonings may occur. Activated charcoal, a potent absorbent for most poisons, acts to tightly absorbing poison to the surface of particles. Since the charcoal particles are not absorbed from the stomach into the circulation, poison absorption is blocked, and the toxicity of the drug is greatly reduced. The poison-charcoal is excreted in the feces. The recommended dose is 5 to 15 teaspoons in a glass of water. Since activated charcoal absorbs any drug reaching the intestine, it also is useful in increasing the body's elimination of drugs such as tricyclic antidepressants, diazepam, and glutethimide that undergo entropichemateoic circulation. Such drugs are secreted from bile into the intestine are absorbed again, pass through the circulation into the liver, and eventually pass into the bile, and the cycle is repeated.

Cannabis Mechanism of Action

Endocannabinoids Postsynaptic neuron then releases endocannabinoids from its membranes Travel "backwards" across the synaptic cleft, where one or two seconds later they activate receptors Undergo reuptake into neurons and glial cells and are degraded by intracellular enzymes Excitatory vs. Inhibitory Before we take a look at the mechanism of action for THC, we need to briefly discuss endocannibinoids. Recent psychological, pharmacological, and high-resolution anatomical studies indicate that endocannabinoids serve as retrograde neurotransmitters. Endocannabinoids are a group of receptors and lipids in the nervous system that are involved in a variety of physiological processes including appetite, pain-sensation, mood, and memory. In other words, following the release of classical neurotransmitters from a presynaptic terminal and the activation of receptors on a postsynaptic neuron, the postsynaptic neuron then releases endocannabinoids from its membranes. These endocannabinoids then travel "backwards" across the synaptic cleft, where one or two seconds later they activate receptors on the presynaptic terminal, which reduces calcium ion channels influx into the presynaptic terminals and inhibits the release of neurotransmitters from the presynaptic terminal for up to several seconds. However, sites other than presynaptic terminals may also be affected in a similar fashion. Endocannabinoids then undergo reuptake into neurons and ganglial cells and are degraded by intracellular enzymes. Numerous neurotransmitters are affected by this process, including the inhibitory transmitter GABA and the excitatory transmitter glutamate. Thus, endocannabinoids induce a mixture of excitatory and inhibitory effects on neurons. THC appears to work in the same fashion, except that THC exerts longer actions and suppresses neurotransmitter release without the first step or the postsynaptic receptor activation. In other words, rather than postsynaptic neurons signaling the presynaptic neurons that a message has been received, indicating that no further neurotransmitter needs to be released for a while, THC signals the presynaptic neurons that they have sent a message when they have not. For example, THC may induce some of its disruptions in human cognition and memory, through its inhibition of acetylcholine release in the hippocampus, a major area involved in memory formation and the retrieval process. The fact that THC exerts both excitatory and inhibitory effects, in different areas of the brain could account for its ability to induce a variety of excitatory and depressant psychological effects, such as sedation and euphoria. Cannabinoid receptors are widely distributed in the brain, but the pattern is uneven. The highest levels are found in the cerebral cortex, hippocampus, hypothalamus, and the amygdala. These areas are critically important for higher mental processes, memory formation, primary drive regulation, and emotional expression- all of which are altered to some degree by cannabinoids.

Alcohol Effects

Enhances social and physical pleasure Enhances sexual performance and responsiveness Increases power, social assertiveness, and aggression Reduces tension Depress psychological processes Disrupted learning and memory processes Increases blood circulation to the skin Heart rate and blood pressure Increase in blood glucose levels Criminal activity Family violence Work Related Accidents Amnesia and blackouts Death The most notable and global expectancy about alcohol is that it serves as a positive transforming agent that enhances social and physical pleasure; enhances sexual performance and responsiveness; increases power, social assertiveness, and aggression; and reduces tension. Individuals may acquire these beliefs even before beginning to drink, and they appear to be powerful predictors of both adolescent drinking status and adult alcoholism. Heavy drinkers generally expect more positive and fewer negative consequences than do light drinkers. It is well established in humans that alcohol has both positive and negative social consequences that are highly dependent on the context the person is in. For example, one study indicated that people who consumed alcohol in the presence of others were more likely to perceive increased feelings relative to sociability and more likely to exhibit objective indicators of sociability compared with those who consumed a placebo beverage in that setting. However, those who consumed the same amount of alcohol in a solitary setting reported significantly more physiological changes compared with those consuming the placebo, and demonstrated few effects related to sociability. These effects, in turn, are reflected in more of the undesirable consequences of alcohol, such as engaging in criminal activity and family violence. Statistically, alcohol consumption is the single most common denominator to all of these activities; in approximately half of all these examples, either the perpetrators or, the victims were determined to be under the influence of alcohol. A substantial proportion of deaths from unintentional injury also involve alcohol. Over 20% of work-related accidents are likely to involve alcohol use. It has been estimated that consuming alcohol is a factor in up to 77% of deaths from falls, 47% of drowning deaths, and 86% of deaths involving fires and burns. About 40% of all fatal traffic accidents in North America and Europe are alcohol-related, and the risk of a fatal car accident increases exponentially when the driver's BAC increases. Alcohol tends to disrupt ongoing psychological processes in a dose-dependent manner. In general the types of faculties affected by increasingly larger doses of alcohol are depressed in the reverse order in which they were originally developed: first, complex cognitive skills; then fine learned motor skills; then gross learned motor skills; and finally, visual accommodation and unconditioned reflexes. Although alcohol induces sleep, it is not exactly a natural sleep, since REM is considerably reduced. Various processes involved with learning and memory are also disrupted by alcohol. Attention to relevant stimuli, ability to encode new information, and short-term memory all decrease. In the most extreme case, these processes may be so affected that the person may experience blackouts—that is, complete amnesia regarding events that took place over much period of time of intoxication. These dose-related blackouts occur in approximately a quarter of social drinkers and may occur in up to 90% of problem drinkers and alcoholics. Alcohol has numerous effects on tissues other than the brain. It increases blood circulation to the skin, causing a warm, flushing sensation. However, this change increases the rate of loss of body heat when exposed to the cold. Heart rate decreases, although in some individuals the initial effect of alcohol is to increase blood pressure, heart rate, and blood sugar level. After an hour or so, these activities often decline below normal. Alcohol stimulates production of acid and pepsin in the stomach, and this effect could explain why some people's appetites are enhanced by alcohol. Alcohol inhibits the release of antidiuretic hormone from the hypothalamus, causing water to be eliminated at a high rate. Thus drinking alcoholic beverages to relieve thirst is counterproductive.

History of LSD

Ergot Albert Hofmann Three phases of interest: Potential use for revealing the biochemical basis of psychosis Proposed to be a potentially useful adjunct to various psychotherapeutic techniques unable to decide how LSD should be used in therapeutic process US government passed a law that banned the use of LSD Became just another class of abused drugs that mainstream culture attempted to suppress LSD is a derivative of the ergot-producing fungi and produces a wide variety of neuropsychiatric and vascular symptoms. We know that in 1938 a pharmacologist named Albert Hofmann, synthesized LSD while working with several derivatives of ergot. Five years later, Hofmann was the first to describe its profound effects on consciousness, after he accidently ingested the compound while working in his laboratory. As Hofmann also found out rather quickly after purposely taking about one-quarter of a milligram and experiencing a psychotic reaction, it is one of the most potent pharmacological agents. It can exert subjectively detectable effects in most people with doses as low as 50 micrograms, about the weight of a grain of salt. It is up to 10 times more potent than our own hormones at the sites of action. Following Hofmann's discovery of LSD, interest in it went through three distinct phases. First there was an interest in LSD's potential use for revealing the biochemical basis of psychosis, a phase that began to wane in the mid-1950s, primarily because it was determined that its effects did not mimic the symptoms of any natural psychosis. The second phase began in 1953 when it was proposed to be a potentially useful adjunct to various psychotherapeutic techniques. Therapists, who often took LSD themselves so that they could better understand the therapeutic process in their clients was also used to treat other disorders such as alcoholism, drug addiction, and emotional distress and physical pain of terminally ill patients. For example, in the 1960s, one study over 100 alcoholics found that half of the high-dose LSD treatment participants reported abstinence 6 months after treatment, in comparison to one third of those on low-dose LSD group and only 12 percent in conventionally treated group. Other research in the 1960s indicated that a majority of cancer patients suffering from anxiety, depression, and uncontrollable pain showed improvement in their physical and emotional status after LSD treatment. The researchers also observed that many of these LSD-treated patients reported that their desire for addictive pain medicines, such as morphine, diminished or vanished along with the pain. In fact, at the time the National Institute of Mental Health recognized the use of LSD in these types of patients was legitimate. The LSD therapy phase began to wane in the mid-60s for two primary reasons. First, the psychiatric community was unable to decide how LSD should be used in the therapeutic process or to document its efficacy scientifically and non-medical use of LSD, especially by young people, lead to the belief that LSD had become a public health problem. As a result, the U.S. government passed a law that banned the use of LSD, as well as peyote, mescaline, and several similar drugs by the public. At that point, legitimate research on its effects on humans and on it potential therapeutic uses declined- not only because of the legal difficulties and maze of bureaucratic procedures required, but also because psychedelic research with humans was not viewed as reputable by the vast majority of those in the scientific community. In the third phase, LSD and similar drugs became just another class of abusable drugs that the mainstream culture attempted to suppress. In the 1990s the FDA sought ways to allow human studies to test LSD and other Schedule I psychedelic drugs to assess their potential medical usefulness and has granted IND status to several of drugs. The IND status meant that the drugs have been studied in the laboratory for their major physical and chemical properties and tested in laboratory animals for their pharmacological and toxic effect. The National Institute on Drug Abuse funds some of these studies. It is still difficult for researchers to conduct human research with psychedelic drugs but at least this type of research has returned to some degree of respectability.

Amphetamine & Methamphetamine Psychological Effects

Euphoria Excitement Exhilaration Rapid flight of ideas Increased libido Rapid speech Motor restlessness Hallucinations Delusions Psychosis Insomnia Reduced fatigue or drowsiness Increased alertness Heightened sense of well being The specific behavioral effects of amphetamine and related compounds depend to a great extent on the task requirements, the normal frequency of the behavior, the dose, and individual characteristics. Effects are less intense after oral ingestion than following smoked or intravenous use. Although stimulants are commonly believed to have effects in hyperactive children that are different from those observed in normal children or adults, empirical evidence indicates that other than the magnitude of the observed effects, amphetamines produce qualitatively similar effects in all three groups. After the drug wears off for a while, a person can feel restless, agitated, nervousness, paranoia, they may become violent or aggressive, and have a lack of coordination. May also experience pseudo-hallucinations and have a craving for the drug.

Nicotine

Every year thousands of young people take up smoking tobacco. Over time their use changes from sporadic to occasional to use that is continuous during the day. On the other hand, thousands of people who have smoked for years try to stop; in most cases these attempts fail because the process is so aversive. In fact, several years ago the Surgeon General of the United States, issued a report that stated that the pharmacologic and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine. Most smokers and nonsmokers recognize that there are costs for smoking. Although cheap in comparison to most other drug habits, smoking is not inexpensive. "Pack-a-day" smokers currently, spend around $2,000 a year for their habit. However, this expense is a drop in the bucket compared to the potential health costs of lung cancer, emphysema, cardiovascular dysfunction, and other diseases associated with cigarette use. The problems are compounded by the fact that cigarette smoking is prominent among most abusers of other drugs; for example, more than 90 percent, of alcoholics are smokers. This smoking behavior exacerbates their health risks and complicates their treatment.

Hallucinogen Classes

Four major classes: Monoamine-related Dissociative anesthetics Anticholinergics Cannabiniods Although hallucinogens are used occasionally in a clinical context, the predominant use of these substances is recreational. There are four major types of hallucinogens: The monoamine-related substances, whose molecular structures and biochemical activity suggest that their effects are mediated by, alterations in the activity of serotonin, dopamine, and norepinephrine in the central nervous system. Dissociative anesthetics, which are analgesic-anesthetic drugs with hallucinogens and hallucinogenic effects. Anticholinergics, which block acetylcholine activity in the brain. The cannabinoids, which is a derivative of the Cannabis sativa or the marijuana plant, which will be discussed in the next lecture. Before beginning a discussion on hallucinogens, I want to point out that research on most hallucinogens over the last three decades, particularly with humans, has been very limited, primarily because of government restraints and a lack of funding for this type of research. Furthermore, since many of these substances are classified as Schedule 1 drugs, researchers have to apply for a special DEA license to conduct research with these drugs. Some of the restraints have come about because of public wariness over the potent consciousness-altering properties of these drugs. In some cases the early research was conducted without proper controls, with subjects who were not sufficiently informed of the type of research being conducted. Some subjects experienced very dysphoric, and occasionally long-lasting, reactions. During the 1960s, literally thousands of people experienced the effects of hallucinogens, either in clinical settings or as a potential therapeutic tool as well as in recreational settings. Unfortunately, information from these individuals consists mostly of self-reports that are highly variable in nature. Because present ethical concerns limit the type of research conducted with hallucinogens in humans, much of the research with these substances is done with animals. Many of the questions we would like to address concerning hallucinogens are somewhat limited by the nature of the primary properties of hallucinogens. That is, animals cannot communicate about the highly subjective drug-induced experience, so their role is primarily one of determining what the neuropharmacological and biochemical actions of these drugs are. Unfortunately, trying to relate these actions to the cognitive and perceptual effects of hallucinogens in humans is exceedingly difficult.

Inhalants

Gases Solvents Effects: Inhalation Dizziness Intoxication Euphoria, hallucinations, empowerment, loss of coordination, nausea, decreased heart rate Chronic Use Inhalants consist of a wide variety of gases (ether, halothane, nitrous oxide, and chloroform and industrial solvents(for example, toluene, a compound of some glues) that have sedative-hypnotic properties. Others are used for their intoxicating and euphoric properties. Inhalants, although not necessarily illicit drugs, are often used illicitly to get "high," particularly by young individuals; for example, approximately 16 percent of eighth graders in 2003 reported having used these at least once. Inhalants comprise one of the "gateway" drugs to further illicit drug use, but unlike almost all other substances that are used to get high, use of inhalants actually declines from the eighth grade to the end of high school. Typically, after several minutes of inhalation, dizziness and intoxication occur. The characteristics of this high commonly include euphoria, visual and auditory hallucinations, a sense of empowerment, loss of motor coordination, nausea, and decreased heart and respiratory rates. Following the high, a period of drowsiness and stupor may persist for several hours. Few of the many compounds of this nature have been systematically studied. Therefore, little is known about their intoxicating properties. Some of them have been shown to have addictive qualities. Tolerance occurs with those substances that have been tested, but cross-tolerance may occur between some of these but not others. Therefore, little is known about their intoxicating properties. Some of them have been shown to have addictive qualities. Tolerance occurs with those substances that have been tested, but cross-tolerance may occur between some of these but not others. Clinical problems associated with chronic use of many of the inhalants—for example, toluene—include cardiac arrhythmias, bone marrow depression, cerebral degeneration, and damage to the liver, kidney, and peripheral nerves. Deaths have occasionally been attributed to inhalant abuse; most of these are associated with heart failure, suffocation, or accidents.

Pancreas and Anti-diabetic Drugs

Glandular structure located in the mid-abdomen Two predominant cell types Alpha cells secrete glucagon Beta cells elaborate the hormone insulin Powerful effects on glucose metabolism Deficiency results hyperglycemia Release is stimulated primarily by increases in plasma glucose levels The pancreas is a glandular structure located in the mid-abdomen. It has two predominant cell types, alpha and beta, each of which synthesizes and excretes a specific hormone. Alpha cells secrete glycogen, a hormone with glucocorticoid like effects in that it promotes increases in plasma glucose. Beta cells elaborate the hormone insulin, which is a key regulator of metabolic processes, by lowering blood glucose levels and stimulating the formation of energy storage compounds. Insulin exerts powerful effects on glucose metabolism; its deficiency results not only in hyperglycemia, or elevated blood glucose, but in many other serious derangements of fat and protein metabolism. Its increase is stimulated primarily by increases in plasma glucose levels and, to a lesser extent, by certain amino acids, ketones, and hormones. Insulin acts directly on specific receptors on cell membranes to increase glucose transport across those membranes, lowering plasma levels of glucose and increasing its intracellular concentration.

Heart Failure

Heart's inability to pump sufficient quantities of blood to meet the demands of the body tissues Decreased contractility of the cardiac muscle Reduced cardiac output Higher-than-normal pressures Accompanied by decreased strength of heart muscle contraction Reduced cardiac output leads to: Increased activity of the sympathetic nervous system Increased force of contraction Increased total peripheral resistance Reduced blood flow to the kidneys. Formation of edema Characteristics of heart failure include a decreased contractility of the cardiac muscle, a reduced cardiac output, and higher-than-normal pressures in either the left or the right atrium as forward failure of pumping leads to increased backward pressure. Heart failure is accompanied by decreased strength of heart muscle contraction. As contractile strength is lost, cardiac output fails, and several of the body's compensatory responses come into play. Reduced cardiac output leads to increased activity of the sympathetic nervous system-causing an increase in heart rate, force of contraction, and total peripheral resistance-as well as reduced blood flow to the kidneys. The increase in peripheral vascular resistance places additional load on the left ventricle, which can further aggravate heart failure. Reduced perfusion of the kidneys leads to the secretion of aldosterone from the adrenal cortex, which causes water retention and plasma volume expansion. The combination of reduced cardiac output, increased plasma volume, and reduced venous return leads to the formation of edema, especially in the lungs, which can cause congestive heart failure, and the lower extremities. Thus, breathing may become difficult and the ankles may become swollen. In summary, heart failure is manifested by reduced cardiac output, increased sympathetic tone of blood vessels, fluid retention, increased intravascular volume, edema of the lungs and lower extremities, myocardial dilatation, and loss of cardiac reserve.

Reflux Esophagitis

Heartburn Regurgitation of acid material Inability of the esophagus to clear the refluxed material back into the stomach Relief achieved by ingesting antacids Cimetidine is an H2 receptor inhibitor Reduces the secretion of gastric acid Metoclopramide Increases the tone of the gastroesophagial sphincter Stimulates gastric emptying into the small intestine Reflux esophagitis, or heartburn, appears to result both from regurgitation of acid material from the stomach into the esophagus through the gastroesophageal sphincter, and an apparent inability of the esophagus to clear the refluxed material back into the stomach. Numerous nonpharmacologic treatments help relieve heartburn, including sleeping with the head elevated, losing weight, wearing loose garments, reducing meal size, and eliminating certain foods such as coffee and alcohol. Relief from heartburn also has been achieved by ingesting antacids that neutralize much of the gastric acidity, although these do little to correct the underlying disorder. Cimetidine is an H2 receptor inhibitor that reduces the secretion of gastric acid and, for long-term therapy, is significantly more effective than either intermittent or continual ingestion of antacids. Metoclopramide both increases the tone of the gastroesophagial sphincter and stimulates gastric emptying into the small intestine. These actions account for its clinical efficacy. Metoclopramide stimulates gastric emptying without affecting acid secretion. Its efficacy is augmented by the concurrent administration of either antacids or cimetidine. An interesting drug interaction occurs between metoclopramide and cimetidine.

Kava

Herbal remedy Prepared form the oceanic kava plant Used in south pacific Treatment of anxiety Severe hepatic toxicity Liver failure Liver transplants The use of herbal preparations as alternative medical treatments has increased dramatically over the past several years in the U.S. and other parts of the world. Kava, a beverage prepared from the oceanic kava plant and is used extensively throughout the South Pacific for recreational and medicinal purposes, is one plant-based therapeutic option for treating anxiety. In 1998 it was among the top-selling herbs in the U.S. based on one report of its calming influence. Several double-blind and randomized, placebo-controlled trials of its efficacy have been conducted. Virtually all of these trials suggested that, relative to the placebo, kava extract can significantly reduce anxiety. Unfortunately, since 1999, health-care professionals in a number of countries have reported the occurrence of several hepatic toxicity possibilities associated with the consumptionof products containing kava, with some individuals who used kava products experiencing liver failure and requiring subsequent liver transplants. Although liver damage appears to be rare, in response to five such case reported, in 2002 the FDA issues a consumer advisory that advised consumers and health-care providers about potential risks for hepatic toxicity associated with the use of kava-containing products. Several countries have restricted the sale of kava-containing products based on the occurrence of the hepatic adverse events associated with kava products.

Amphetamine & Methamphetamine Physiological Effects

Increased heart rate increased blood pressure increased respiration rate Elevated temperature Heart palpitations Irregular heartbeat Dry mouth Abdominal cramps Appetite Dilated pupils A faster reaction time Increased strength Low to moderate doses tend to facilitate performance of tasks dependent on sustained attention or those requiring quickness and strength. High doses interfere with performance of these tasks. After drug wears off effects may include, fatigue, sleepiness with sudden starts, itching/picking/scratching, normal heart rate, and normal to small pupils which are very light reactive.

Dependence on Amphetamines

Historical perspective "Crashing" Effects opposite of taking the drug Abstinence syndrome Depletion of dopamine and norepinephrine Decrease in the sensitivity of postsynaptic catecholamine receptors Beginning in the mid-1970's, the use of amphetamines gradually decreased for many reasons. -First, the government began to exert legal pressures on pharmaceutical companies to decrease their production. -Second, the number of legitimate medical uses was drastically reduced. -Third, the general population and physicians became more educated about potential hazards and misuse. -Fourth, compounds with less abuse potential, and more specific actions with respect to major mood depression were developed. For example, antidepressants. -Finally, cocaine, which users were led to believe was much less harmful than amphetamine, came on the scene to replace it as a drug for recreational use. Unfortunately, in the 1990's there was a resurgence in the illicit use of amphetamine, in this case methamphetamine, with the expected consequences of earlier amphetamine epidemics, an increase in violence, criminal behavior, death, psychotic behavior, and extreme addition. Making the situation worse is the fact that the quality of methamphetamine has improved drastically over the past several years, due to refinements in manufacturing process, and marketing factors—apparently so much is available that dealers aren't cutting the drug as much as they used to. Despite the dysphoric effects of high doses or chronic use, the dependence liability of amphetamine and similar-acting drugs is considered to be among the highest of all drugs. There is no question that when individuals stop taking amphetamines after a few days of moderate to heavy amphetamine exposure, they generally "crash"; that is, they experience exhaustion, depression, lethargy, and hunger. All symptoms which are opposite to the direct effects of the drug. However, rather than being signs of an abstinence syndrome, these symptoms may be due to lack of decent sleep, low blood sugar, or depletion of dopamine or norepinephrine, among other things. Some users go for months or years before becoming daily users, whereas others report such an intense positive response with the first dose that addiction occurs almost immediately.

Buspirone

History Properties Lacks hypnotic, anticonvulsant, and muscle-relaxant properties Takes 1 or 2 weeks of daily treatment before the onset of its anxiolytic effects is noted Is much less likely to induce drowsiness and fatigue Does not impair psychomotor or cognitive function Has no potential for abuse and dependence Has no synergistic effect with alcohol Is not cross-tolerant with benzodiazepines and does not help reduce with benzodiazepine withdrawal Adverse effects GAD For centuries, people have used alcohol and opium or its derivatives to reduce the consequences of stress and relieve the symptoms of anxiety. Then from the mid-1800s through the mid-1900s, thousands of barbiturates and similar drugs were synthesized for the use of the same purposes. Then the benzodiazepines took over in the 1960s. All of these drugs had anxiolytic qualities, but they were accompanied by side-effects of impaired motor coordination, disruptions in working memory and alertness, and had the potential for abuse and dependence. That all changed with the development of buspirone, or BuSpar, in the early 1980s. After 20 years of umpteen different variations on the basic benzodiazepine molecule, pharmacologists finally synthesized this novel anxiolytic agent, which was unrelated to the benzodiazepines and other sedative-hypnotics in structure and pharmacological profile. As is typical in this field, the drug was originally developed for something other than what it may actually be used for. Initially, it looked like it might have antipsychotic properties. However, extensive clinical studies have shown buspirone to be comparable to the benzodiazepines diazepam and clorazepate in the treatment of anxiety. It is also effective in patients with mixed anxiety and depression. However, buspirone may be more effective in reducing the psychic problems of anxiety. Unlike benzodiazepines, buspirone (1) lacks hypnotic, anticonvulsant, and muscle-relaxant properties; (2) takes 1 to 2 weeks of daily treatment before the onset of anxiolytic effects is noted; (3) is much less likely to induce drowsiness and fatigue; (4) does not impair psychomotor or cognitive function; (5) has no potential for abuse and dependence; (6) has no synergistic effect with alcohol; and (7) is not cross-tolerant with benzodiazepines and does not help reduce benzodiazepine withdrawal. Pharmacokinetic interactions of buspirone with other coadministered drugs seem to be minimal. The most frequently reported adverse events with buspirone treatment are dizziness, headache, and nausea, although adverse effects are typically mild and do not generally lead to treatment discontinuation. Since its approval for use for generalized anxiety disorder or GAD by the FDA in 1986, numerous studies have examined the efficacy and safety of buspirone for patients with other symptoms and disorders. Although relatively few placebo-controlled trials have been conducted on patients with problems other than GAD, an ever-growing body of research suggests that buspirone may be beneficial in the treatment of a variety of disorders

Ketamine

Identical effects as PCP Mechanism of action: Antagonizes NMDA receptor-sensitive glutamatergic neurotransmission in the brain Popular for its dissociative, sedative, and hallucinatory effects Joined the list of popular club drugs Intranasal vs. intravenous Except for their duration, the psychological effects of ketamine are identical to those of PCP. In healthy volunteers, ketamine has been shown to produce dose-dependent impairments in episodic, recognition, and working memory and procedural learning, as well as a slowing of the systemic processes. Essentially the same perceptual distortions in vision, audition, body image, sense of time, and the like, noted with PCP can occur, during the recovery period following ketamine anesthesia, but to a lesser degree. Furthermore, like PCP, ketamine has been shown to induce positive and negative symptoms of schizophrenia in both healthy subjects and schizophrenic patients. The symptoms in these schizophrenic patients were strikingly similar to those exhibited by the patients during active episodes of their illness. After noting the many effects of PCP, chemists synthesized a number of analogues of PCP. Ketamine was found to have the most therapeutic value as an anesthetic. While possessing the desirable characteristics of PCP, it did not induce convulsions and was shorter-acting than PCP. Ketamine's actions are identical to those of PCP; that is, it antagonizes NMDA receptor-sensitive glutamatergic neurotransmission in the brain. Unfortunately, since the 1980s,ketamine has gained popularity for its dissociative, sedative, and hallucinatory effects by recreational drug users, and it has joined the list of popular club drugs, with which ketamine is often combined. Ketamine is used recreationally in a variety of settings apart from the club or rave environments, where it is usually administered intranasally. However, it is not uncommon for it to be injected, which produces more reliable and intense dissociative effects than when taken orally or intranasally. Ketamine is also considered one of the "date-rape" drugs due to its colorless, odorless, and tasteless nature, as well as its ability to immobilize individuals, disorientate them, and induce amnesia. Concerns over its abuse led to its being classified as a Schedule III drug by the DEA in 1999.

Diuretics

Increase renal excretion of water and sodium chloride Clinical uses Congestive heart failure Hypertension Renal failure Acute states of increased intracranial pressure and in neurosurgical procedures Hepatic failure Glaucoma Diuretics increase the renal excretion of water and sodium chloride. Most diuretics decrease renal tubular reabsorption of sodium chloride and water either by the glomerular filtration of a substance that the renal tubules cannot reabsorb or, more commonly, by blocking the tubular reabsorption of sodium chloride. Some of the clinical uses of diuretics include the treatment of Congestive heart failure, as an adjunct to glycoside therapy. Hypertension, either as a sole therapy or in combination with other antihypertensive drugs. Renal failure, to increase the excretory function of failing kidneys. Acute states of increased intracranial pressure and in neurosurgical procedures where osmotic diuretics reduce intracranial extracellular volume and intracranial pressure. Hepatic failure, to aid in the excretion of intra-abdominal fluid that can result from such failure. Glaucoma, where carbonic anhydrase inhibitor diuretics reduce the formation of intraocular fluids, which lowers intraocular pressure.

Chronic Exposure to Cocaine

Induce a very strong psychological dependence 5-6% of users become dependent in the 1st year 15-16% of users develop dependence within 10 years of 1st use Smoking vs. intravenous use Although most reports prior to 1980 indicate that cocaine had relatively benign effects on most individuals, the majority of reports in the 1980s and 1990s indicate, considerable concerns over cocaine's dependence liability and toxicity. These reports indicated that, particularly when administered intravenously or through smoking, cocaine may induce a very strong psychological dependence. For example, cocaine addicts report that virtually all thoughts are focused on cocaine during binges; nourishment, sleep, money, loved ones, responsibility, and survival lose all significance. It is estimated that 5-6% of cocaine users in the U.S. become cocaine dependent in the first year of use and that 15-16% of users develop a cocaine dependence within 10 years. The risk of addiction is significantly higher for smoking cocaine or intravenous use than intranasal use. Until recently there was some question whether tolerance occurred with cocaine use. There is now considerable evidence that tolerance does develop to many of the physiological and subjective rewarding effects of cocaine, and in some cases it develops very rapidly. Some acute tolerance to cocaine's effects may be due to the activation of negative-feedback systems, that is, autoreceptor activation, which reduces monoamine neurotransmitter release, whereas long-term tolerance with chronic cocaine exposure may be related to the depletion of monoamines and/or down-regulation of monoamine receptors. In cases in which cocaine disrupts task performance, lowers reinforcement ability, or increases exposure to adverse stimuli, the learning of compensatory behaviors has long been viewed as a mechanism for tolerance development. In humans, panic attacks and seizures may also develop with chronic use. However, research has shown that doses of cocaine are much lower and the length of exposure is much shorter than the dose typically reported by street abusers, acute tolerance to the subjective and cardiovascular effects is commonly observed. Withdrawal-like effects do occur after extensive cocaine use.

Use of Thyroid Hormones

Iodine or iodide salts are used to treat simple goiter Have no place in the treatment of obesity Grave's Disease Dietary iodide from seafood or iodized salt is concentrated enough by the thyroid gland, which results in concentrations of 30 to 20 times those found in plasma. Lack of iodine in the diet reduces the blood levels of iodine and the synthesis of T3 and T4. This results in increased release of TSH from the pituitary gland, which causes stimulation of the thyroid gland which is now unavailable to manufacture the hormone. The gland then swells and results in a simple or nontoxic goiter. Reduction in thyroid size with restoration of normal function is achieved quickly with administration of exogenous iodine or iodide salts. Iodine or iodide salts are used to treat simple goiter. About 0.1 mg per day of iodine is needed to avoid a deficiency state. Thyroid hormones have no place in the treatment of obesity, despite the fact that they increase caloric utilization and have been promoted as agents that "burn fat". The dangers of excessive thyroid hormone intake and thyroid-pituitary-axis dysfunction far outweigh any temporary benefits obtained. Adverse effects of excessive levels of thyroid hormone result either from the administration of excessive doses of thyroid hormone drugs or from excessive secretion of thyroid hormone by the gland. Diseases associated with the latter include Grave's disease, toxic nodular goiter, and thyroiditis. They may represent autoimmune disorders that are characterized by excessive thyroid stimulation.

Alcohol Metabolism

It takes approximately one hour for 90% of the alcohol in a drink to get into the bloodstream. -Rapidly and readily absorbed from the stomach -Accumulation in the brain is rapid enough to exert noticeable effects within minutes -Carbonated alcoholic beverages tend to enhance the absorption Alcohol is metabolized at a rate of approximately 1.0 to 1.5 ounces of 80-proof liquor per hour. -Liver accounts for approximately 90% of the alcohol metabolized -First metabolite is acetaldehyde Interferes with the normal metabolic activities of the liver -Reduces the rate at which the liver forms glucose, oxidizes fats, and releases complex fats -Liver cells may rupture or become isolated and die -Some individuals eventually develop cirrhosis Chronic exposure It takes approximately one hour for 90% of the alcohol in a drink to get into the bloodstream. However, because alcohol is rapidly and readily absorbed from the stomach, its accumulation in the brain is rapid enough to exert noticeable effects within minutes. Carbonated alcoholic beverages tend to enhance the absorption of alcohol because the carbonation forces the alcohol into the small intestine, where there is greater surface area for the absorption to take place and, thus, more rapid accumulation of alcohol in the brain. Alcohol is metabolized at a rate of approximately 1.0 to 1.5 ounces of 80-proof liquor per hour. The liver accounts for approximately 90% of the alcohol metabolized. The first metabolite is acetaldehyde, a highly toxic substance capable of inducing nausea, headache, and high blood pressure, as well as causing liver damage. Acetaldehyde is then rapidly metabolized into acetic acid, which is further metabolized into carbon dioxide and water, which are then excreted. Alcohol also interferes with the normal metabolic activities of the liver because of its own metabolism. Alcohol reduces the rate at which the liver forms glucose, oxidizes fats, and releases complex fats. As a result, when there is extensive exposure to alcohol, the liver accumulates fat, and blood sugar levels are depressed. Free fatty acids are not broken down and are deposited into the liver cells themselves. Thus, early stages of chronic alcohol consumption are characterized by fatty livers. Eventually, the cells may rupture or become isolated and die. Cell death is followed by the formation of fibrous connective tissue, which is nonfunctional, at least with respect to what the liver is supposed to do. Some individuals eventually develop cirrhosis. Chronic exposure to ethanol can significantly change its rate of metabolism and alter its BAC levels. Initially, ethanol induces greater synthesis of the enzymes responsible for its metabolization, thus enhancing the rate at which ethanol is metabolized. However, in those individuals who use large doses of alcohol chronically and develop liver damage, the rate at which alcohol is metabolized can dramatically reduce, which increases ethanol levels and prolongs its stay in the body—the ramifications of which should be apparent.

LSD Mechanism of Action

LSD and several other monoamine hallucinogens appear to induce their subjective effects via a variety of mechanisms effects are most likely linked to serotonergic systems in the brain structural similarities between LSD and the 5-HT serotonin molecule Observed to inhibit the spontaneous firing of serotonergic neurons of the reticular activating system LSD is absorbed within 30 to 60 minutes after oral administration, and its high lipid solubility allows it to rapidly penetrate the blood-brain barrier and stay in the body for up to 15 hours. The potency of LSD is even more emphasized by the fact that there is general distribution of the drug throughout the body, which relatively low levels are found in the brain, whether there is widespread regional distribution of LSD binding sites. Despite its potency with respect to perceptual, emotional, and cognitive alterations, there is only a single documented case of fatal poisoning by LSD. LSD and several other monoamine hallucinogens appear to induce their subjective effects via a variety of mechanisms, but many of their effects are most likely linked to serotonergic systems in the brain. Because of structural similarities between LSD and the 5-HT serotonin molecule and because LSD was observed to inhibit the spontaneous firing of serotonergic neurons, of the reticular activating system, in the early 1970s it was proposed that LSD acted on the serotonergic receptors.

Calcitonin & Calcium Regulation

Major portion of body calcium is located in bone Calcium plays essential roles in: Nerve function Muscle contraction Cardiac contractility and excitability Blood coagulability Cell membrane integrity unction in bone Calcitonin: Release from the thyroid gland Stimulated by a rise in the concentration of calcium in plasma Lowers plasma calcium Disorders of calcium metabolism: Hypocalcemia Hypercalcemia The major portion of body calcium is located in bone. However, calcium plays essential roles in nerve function, muscular contraction, cardiac contractibility and excitability, blood coagulation, and cell membrane integration. Note that calcium's metabolic roles have priority over its structural function in bone. Thus, so that adequate plasma levels of calcium are maintained, deficits will be compensated for the reabsorption of calcium from bone. Other regulatory mechanisms for calcium availability include gastrointestinal absorption and renal excretion of the compound. The regulation of these adjustments is complicated and involves calcitonin, parathyroid hormone, and vitamin D. Calcitonin release from the thyroid gland is stimulated by a rise in the concentration of calcium in plasma. Calcitonin lowers plasma calcium by decreasing calcium reabsorption from bone and by increasing the renal excretion of the substance. Disorders of calcium metabolism involve either hypocalcemia, decreased levels of calcium and hypercalcemia. Hypocalcemia, as one can predict from the discussion above, can result from inadequate calcium in the diet, vitamin D deficiency, or other, more subtle dysfunctions. Increased calcium intake or the addition of vitamin D, or both, often corrects the disorder, although severe disorders may require that calcium be administered intravenously. Hypercalcemia may be caused by increased secretion of vitamin D excess, certain cancers, or other diseases. Osteoporosis and renal dysfunction may manifest themselves as toxic symptoms of excessive vitamin D, resulting in hypercalcemia.

Antidiarrheal Agents

Management of diarrhea: Elimination of the cause Administration of sufficient quantities of fluids and electrolytes. Symptomatic treatment Prolonged diarrhea may necessitate hospitalization Drug Types: Diphenoxylate Loperamide or Imodium Bulk Antibiotics The causes of diarrhea are many and beyond the scope of the current discussion. However, severe diarrhea can cause water and electrolyte depletion and may lead to dehydration and serum electrolyte abnormalities. Reduced serum potassium can produce profound weakness and debility. Persistent diarrhea leads to severe discomfort and perianal irritation. The management of diarrhea is based on the elimination of the cause, whenever possible, and the administration of sufficient quantities of fluids and electrolytes. The symptomatic treatment of diarrhea is justified so that temporary relief is provided until the cause is identified or the infection (usually viral) spontaneously subsides. Prolonged diarrhea may necessitate that the sufferer be hospitalized to correct the fluid and electrolyte imbalances. Diphenoxylate is an opiatelike drug that is clinically useful as an antidiarrheal agent. Since the drug is virtually insoluble in water, it is poorly absorbed orally. Clinically used doses exert an antidiarrheal effect, by acting directly on the bowel without causing significant morphinelike systemic effects. Loperamide or Imodium, an antidiarrheal drug whose action is similar to that of diphenoxylate, prolongs transit time, increases water absorption, and reduces fecal volume. It is nearly insoluble in water and does not cross the blood-brain barrier. Because even very high doses fail to elicit the pleasurable effects typical of opiates, its overall abuse potential is lower than that of diphenoxylate. The bulk laxatives for the treatment of constipation bind water and have limited efficacy in the treatment of water diarrhea. While the amount of stool is not decreased, frequency is reduced and stools increase in bulk. While many of the other compounds available in over-the-counter preparations appear to do little good, they are not considered to be harmful unless they are used for prolonged, periods of time or unless they delay the evaluation of potentially serious GI disorders that may underlie the cause of the diarrhea. Common sense should dictate the rational approach to self-prescribed therapy. A pharmacist can often be of valuable assistance for prescribing these types of therapies. For infectious diarrheas, such as those encountered as travelers' diarrhea, certain antibiotics may be used to rid the intestine of the causative organism. Because data concerning their efficacy is limited, however, and because it is possible to create antibiotic-resistant strains of bacteria, antibiotics' use should be limited to the more severe, carefully diagnosed cases. Careful evaluation by a physician is indicted before such therapy is initiated.

Beneficial Effects

Moderate drinking Less than 2 ounces of ethanol per day is not associated with any poor health consequences for the user May have some health benefits. Can lead to longer life Former drinkers Characteristics that could enhance their mortality Alcohol induces a variety of effects that users find pleasurable or beneficial to them. Furthermore, despite all that I said about alcohol up to this point, there is no evidence that chronic exposure to less than 2 ounces of ethanol per day is associated with any poor health consequences for the user. In fact, drinking of these amounts—often described as moderate drinking—may have some health benefits. Moderate drinking leading to longer life may be overstated, because many of the studies investigating this link ignored factors such as the participants' socioeconomic status and overall health, or lumped together two kinds of individuals—lifelong teetotalers and former drinkers—to form their nondrinker reference group. Evidence suggests that former drinkers exhibit risk characteristics that could enhance their mortality, and that, compared with light or occasional drinkers or lifelong teetotalers, these individuals may have the highest risk of mortality from all causes.

Nalmefene

More potent than Naloxone Orally effective Acts fast Last long

Opiate Antagonists

Naloxone, naltrexone, and nalmefene Reverse the effects of narcotics in acute overdose cases preventing overdoses associated with illicit narcotic use assessing the actual degree of physical dependence in opiate-abusing individuals determine the appropriate dose of methadone for detoxification or maintenance purposes Before we look at this section of the lecture in depth, let's review the definition of antagonist. In this instance opioid antagonists bind to the opioid receptors with high affinity then agonists but do not activate the receptors. The action of the antagonist effectively blocks the receptor which prevents the body from responding to opiates. For over two decades, the relatively pure opioid receptor antagonists naloxone and naltrexone have been the mainstays of research and treatments associated with the opioids and their receptors. Naloxone is fast acting, with a short duration of action and is poorly absorbed when taken orally. Naltrexone is more potent that naloxone and is quite effective when taken orally, and its duration of opiate-blocking action is between 24 and 48 hours. Nalmefene is a relatively new, pure opiate antagonist that is structurally similar to naloxone and naltrexone. Compared with naloxone, nalmefene is more potent in blocking opiate receptors, more readily absorbed when taken orally currently being used primarily for their ability to reverse the effects of narcotics in acute overdose cases. From a harm-reduction perspective, one area in which naloxone would be particularly useful is in preventing overdoses associated with illicit narcotic use. A typical opiate-related overdose fatality occurs in a long-time heroin user who uses heroin after a period of abstinence and also uses alcohol or other drugs. Most overdoses occur with other people around, but because of fear of police, they fail to call for help. Naloxone may also be used as a diagnostic tool for assessing the actual degree of physical dependence in opiate-abusing individuals, to determine the appropriate dose of methadone for detoxification or maintenance purposes. Naltrexone and nalmefene are being used as a prophylactic measure in opiate addicts who have terminated their opiate use but are concerned that they may relapse. Should they do so and administer a narcotic such as heroin, they are aware that they would not experience any of the effects and that it would be a waste of money. Opioid antagonists may have a variety of other potential uses outside the scope of drug dependence. With the discovery of a variety of endogenous opioid peptides in the body, there has been much speculation as to their function. Obviously, one of these is in the area of pain regulation, but there are many other areas. It has been speculated that endogenous opioids are involved in a variety of psychopathological conditions including autism, self-injurious behavior, schizophrenia, obsessive-compulsive disorders, eating disorders, sleep apnea syndrome, and attention deficit disorders.

Amphetamine & Methamphetamine Clinical Use

Narcolepsy ADHD One of first clinical uses: narcolepsy. Only two disorders which most experts agree amphetamines may be legitimately prescribed, although there are a number of other uses for them-most notably in the treatment of obesity.

Smoking Cessation

Nicotine is addictive! Success of cessation is low and relapse is common. Cessation aids: Gum Patch Prescriptions Smokeless inhalers In summary, despite the inconsistencies in the evidence, there is a very strong case that nicotine, is addictive. Patterns of use by most smokers are consistent with compulsive use. Although a majority of chronic smokers report the desire to quit, the likelihood of success in a cessation attempt is low, relapse is a common occurrence, and nicotine replacement enhances outcomes in smoking cessation. There is evidence of both tolerance development to nicotine's effects and symptoms upon cessation. Nicotine has both positive enhancement of mood or performance and negative relief of abstinence symptoms. Finally, nicotine shares some discriminative properties with cocaine and amphetamine, and many of its biochemical actions are shared by a variety of other addictive drugs. While many people "mature out" of their drug use habits because their drug use ceases to match a change, in their lifestyle- for example, marriage, job, or parenthood, hardly anybody matures out of cigarette smoking, but not through the loss of interest. Quitting requires determination. The most promising aids to quitting are medicines that contain nicotine, such as chewing gum or nicotine-containing skin patches, which release a constant, small amount of nicotine, into the bloodstream and presumably lessen the craving for cigarettes. After a few weeks patients can chew less gum or receive smaller patches that release less nicotine until they are, weaned off the substance. When used in conjunction with appropriate interventions, these nicotine-replacement therapies roughly double the rate of quitting smoking, in comparison to, the placebo treatments. For example, in over a dozen studies, nicotine patches produced 6-month abstinence rates of 22% to 42%, compared to 5% to 28% with placebo patches. These nicotine-replacement systems reduce most, but not all, nicotine withdrawal symptoms, including the craving for cigarettes, negative moods, and increased appetite. In addition, the satisfaction and good taste of cigarettes appear to decrease in subjects using nicotine-replacement therapies. The evidence for their efficiency and safety has been deemed sufficient for, both types of nicotine-replacement systems to be approved as nonprescription drugs. When nicotine-replacement therapy may be most appropriate is mostly dependent on individual preferences. The nicotine patch may be the more effective treatment because it is easier to use and comply with than gum and causes fewer side effects than other options such as smokeless inhalers. It should be emphasized that while using these aids, smoking tobacco should be avoided, because of nicotine's potential cardiovascular toxicity at high doses.

Nicotine Mechanism of Action

Nicotinic receptors normally activated by acetylcholine Receptors in adrenal gland trigger the release of adrenaline into the blood stream Leads to increases in heart rate and blood pressure Peripheral Nervous System The psychological effects occur because of nicotine's ability to stimulate nicotinic receptors normally, activated by acetylcholine. Which of the particular nicotinic receptors normally activated by acetylcholine are most important is not clear, since they are found throughout the nervous system. In the peripheral nervous system, activation of these receptors produces sympathetic effects, primarily because of the receptors are found in the adrenal gland trigger the release of adrenaline, from the adrenal gland into the bloodstream. Adrenaline, in turn, is transported to adrenergic receptors in the heart and blood vessels, leading to an increase in heart rate and elevated blood pressure. Although adrenaline may potentially affect CNS function, it is unlikely to have much effect because it does not cross the blood-brain barrier very well. Despite these multiple PNS effects, they are probably not of major importance in reinforcing smoking because they can be blocked without appreciably altering the psychological effects of nicotine in humans. Following chronic tobacco exposure, nicotine may also be reinforcing because it immediately stops withdrawal symptoms, indicative of the physical dependence on nicotine that many believe exists. The onset of withdrawal symptoms may occur within hours of the last cigarette. In addition to a craving for tobacco, these symptoms may consist of decreased heart rate, irritability, increased hunger, sleep disturbances, gastrointestinal disturbances, drowsiness, headache, and impairment of concentration, judgment, and psychomotor performance.

Antianginal Drugs

Nitroglycerin Reduction of venous tone Reduces return of blood to the heart Decrease peripheral vascular resistance Oral Nitrates Produces vasodilatation Beta-Adrenergic Blockers Reduce both heart rate and the force of contraction Calcium Channel Blockers Controls vascular tone in the smooth muscle of both the coronary and the peripheral blood vessels Nitroglycerin is a liquid that is adsorbed to a tablet for convenience of sublingual administration, or right under the tongue. It is the drug of choice for acute angina attacks. In unopened, darkened glass bottles, its shelf-life is about 6 months; when the bottle is opened, the medication deteriorates within a few weeks. Onset of activity with sublingual use occurs within 1 to 3 minutes and effects may last from 10 to 20 minutes. Nitroglycerin's reduction of venous tone results in a pooling of blood in the peripheral veins. Nitroglycerin also reduces return of blood to the heart, which reduces the volume of blood in the ventricle and thus decreases the tension on the walls within these ventricles. Its ability to decrease peripheral vascular resistance reduces arterial blood pressure, thereby decreasing the resistance against which the left ventricle must pump. A degree of coronary artery dilation may also be involved. Nitroglycerin is available in tablets for sublingual use, as I previously mentioned; a liquid for intravenous infusion; in ointments for topical use; and in transdermal "patches" that release the drug continuously through the skin over a 24-hour period. The oral compounds have a longer duration of action than the sublingual preparations and when used for long-term prevention of classic angina, can improve exercise tolerance and reduce the need for sublingual nitroglycerin. They are well absorbed from the stomach, but because they are quite rapidly metabolized by the liver, rather large doses may be required to achieve therapeutic effects. Side effects encountered with these agents, and with nitroglycerin, include headaches, flushing, dizziness, hypotension, and reflex tachycardia—all of which can be explained by the vasodilatation produced. The beta-adrenergic blockers are widely used in the treatment of classic angina pectoris. Their effectiveness is due to their ability to reduce both the heart rate and the force of contraction, thus reducing the oxygen demands of the heart. The relief of symptoms of angina must be balanced carefully against the possible detrimental effects of cardiac function in patients with borderline cardiac reserves who rely on sympathetic stimulation to maintain a level of activity. In general, the beta-adrenergic blockers are important in the long-term management of angina pectoris, significantly reducing the amount of nitroglycerin patients must consume. Because these agents and nitroglycerin reduce cardiac work by different mechanisms, they have a synergistic effect on the heart in reducing its oxygen requirement. Because the beta blockers also reduce heart rate and contraction force, they tend to prevent or reduce the reflex tachycardia that follows the vasodilatation and the fall in blood pressure induced by nitroglycerin. The cardiac depressant effects of calcium channel blockers make them useful as antiarrhythmic agents. In addition, calcium movement across cellular membranes controls vascular tone in the smooth muscle of both the coronary and the peripheral blood vessels. Such calcium movement may be blocked by the calcium channel blockers. Clinically, these drugs appear to be most effective against variant angina, the type most refractory to long-term beta blocker therapy. Their interference with calcium entry into the vascular smooth muscle results in coronary vasodilatation, relief of coronary artery spasm, and reduction in peripheral vascular resistance—all of which are beneficial to the patient. In summary, the four classes of drugs I just discussed—nitroglycerin, oral nitrates, beta-adrenergic blockers, and calcium blockers—all contribute to the beneficial supply and demand ratio either by reducing myocardial work or by increasing myocardial oxygen supply. Nitroglycerin remains the first drug of choice for acute attacks and the other three classes of agents are added as tolerants to reduce nitroglycerin requirements, reduce the severity of angina attacks, and improve exercise tolerance. Once again, close physician guidance is imperative and patient education regarding the goals and limitations of therapy, as well as a reduction in risk factors, must be an important part of the overall therapeutic plan.

Typical Opiates

Not all drugs classified as narcotics have identical effects Natural Opiates Synthesized Potency Heroin vs. Morphine Methadone vs. Morphine Codeine vs. Morphine Considering the various, types and subtypes of opioid receptors, it should not come as any surprise that not all drugs classified as narcotics have identical effects. In some cases, drugs with narcotic-like effects, by themselves may actually block the effects of other narcotics. In addition to the natural opiates, derivatives and semisynthetic opiates, like heroin, malorphine, and hydromorphine, have resulted,from minor modifications in structure. A number of other drugs with very similar properties, but very dissimilar molecular structures, have been synthesized, including meperidine, fentanyl, propoxyphene, and methadone. In addition to having somewhat different pharmacological effects, these drugs differ with respect to potency, intensity, duration of action, and oral effectiveness. For example, heroin is considered to be one of the most potent of the nonendogenous types of opiates. It is approximately two to four times more potent than morphine when injected. Because of this difference in potency, many individuals have campaigned to make heroin, which is presently a Schedule I drug, a legally available medication in the US for the treatment, of severe pain in terminally ill patients. However, what most people do not realize is that the differential potency is due to pharmacokinetics and not to efficacy at the receptor site. First, the potency of heroin and morphine is equivalent when taken orally. Second, the heroin molecule is simply a slight modification of morphine. This modification allows heroin to penetrate the, blood-brain barrier much more rapidly than morphine does. This characteristic allows it to accumulate in the brain much more quickly. Once in the brain, heroin is metabolized into morphine, but because it gets there so much more quickly, its effects are exerted at a much more rapid and intense rate. Administered subcutaneously in humans, methadone has approximately the same potency as morphine, and approximately half the potency of heroin for inducing comparable effects. With respect to its ability to suppress opiate withdrawal symptoms, methadone is about twice as potent as heroin, and four times as potent as morphine. At the same doses administered orally, methadone is much more effective than either heroin or morphine and has an action approximately three to four times longer, than that of heroin or morphine. Codeine is approximately 12 times less potent than morphine when injected, primarily due to the fact that codeine needs to be metabolically converted into morphine to, become effective. However, it is more readily absorbed through oral administration than morphine. Since they are weak alkaloids that become ionized in acidic media, neither heroin nor morphine is, readily absorbed orally, heroin administered orally is about 100 times less potent than when it is administered intravenously. The endogenous opioid peptides are far more potent than heroin, but they are rapidly inactivated by enzymes throughout the body. Fentanyl is one of the most potent of the nonendogenous opiates. Its short duration of action makes it useful for, an adjunctive treatment during surgical procedures, but its potency can lead to lethal overdoses in individuals who believe they are injecting heroin.

Narcotics Background

Oldest psychotropic drugs Began as extract and move to purified forms Most effective pain relievers Narcotic: Most popular term for morphine Refer to as a class of drugs that promote sleep and induce analgesic effects Layperson often thin if narcotics as any highly abusive and addictive drug Some of the oldest psychotropic drugs used by humans are morphine and codeine; their use may go back 7,000 years. Originally these drugs were used in the form of extracts from the poppy plant, which contains opium, and in purified form they are still used. They belong to a class of drugs that includes the most, effective pain relievers available, so they are the most commonly used analgesic treatments for moderate to severe pain. Since users often experience euphoria, drowsiness, and mental clouding-perhaps, resulting in the feeling that all their problems are trivial-these drugs are also used recreationally and are highly subject to abuse. The most common term for morphine and similar-acting drugs is narcotic. Unfortunately, the term narcotic has taken on many unwarranted connotations. It has been used primarily to refer to a class of drugs that promote sleep and induce analgesic effects, but many laypersons, often think of narcotics as a highly abusable or addictive drug. From this perspective, drugs that have little similarity to morphine, in terms of their neurochemical actions or their physiological, actions, they have been designated as narcotics for legal purposes. However, pharmacologically, only a drug with the following qualities can be appropriately classified as a narcotic: 1) It generally has, sedative-hypnotic and analgesic properties; it acts stereospecifically on endorphin/encephalin receptors; and its actions are antagonized by naloxone. In essence, narcotics are restricted to extracts of, opium(opiates), opiate derivatives, and synthetic drugs with opiate properties. Perhaps because of the confusion around the term narcotic, many authorities now refer to these substances as opioids. Routinely throughout this lecture, I will refer to these substances as narcotics, opiates, and opioids interchangeably.

Narcotics Mechanism of Action

Opioid receptors act through G-protein secondary messenger systems Inhibit cyclic AMP presynaptic axon terminals inhibit the Calcium ion influx postsynaptic membrane hyperpolarizes the membrane by enhancing potassium ion flow out of neurons Reduce transmission in neuronal pathways Indirectly activate dopaminergic systems Inhibits neuronal excitability and the release of neurotransmitters Opiates depress the rate of neuronal, firing in most areas of the brain, but some groups of neurons increase their rate of firing. Opioid receptors act through G-protein secondary messenger systems to inhibit cyclic AMP which is an important, intracellular second messenger that mediate hormonal effects. Activation of opiate receptors on the presynaptic axon terminals inhibit the calcium ion influx that underlies release of neurotransmitters. At the postsynaptic membrane, their activation hyperpolarizes the membrane by enhancing potassium ion flow out of neurons. In some cases these two processes appear to operate independently, and in others they appear to work synergistically to reduce transmission in neuronal pathways. The euphoria, tranquility, and other mood changes induced opioid agonists have been linked to their ability, to indirectly activate dopaminergic systems via stimulation of opioid receptors. Since opioid receptor stimulation generally inhibits neuronal excitability and the release of neurotransmitters, it is unlikely that opiates directly induce the release of dopamine. Rather it appears to be a classic case of activation by way of inhibition.

Cannabis Routes of Administration

Orally Smoking Marijuana is most commonly administered by smoking a "joint". However, most cannabinoids are highly lipid-soluble and are also readily absorbed orally. Because of the stomach acid degradation, enzyme alterations, and slow absorption, oral THC is about one-third as potent as THC that is smoked. Since, at most, only half of the original THC in the smoked cannabis is actually delivered and absorbed, inhalation may be five to 10 times as effective as a mode of administration. However, if one takes sufficient amounts of THC orally in order to achieve the same peak intensity effects of smoked THC, because of the slower accumulation of the drug in the blood, the effects last considerably longer than when THC is smoked. Initial metabolism of cannabinoids in marijuana smoke occurs in the lungs, whereas orally administered cannabinoids are metabolized in the G.I. tract and by the liver. There are more than 30 metabolites of THC, and over 20 each of cannabinol and cannabidiol metabolites. Many of these metabolites are also psychoactive. One of the principal psychoactive metabolites of THC is 11-hydroxy-delta-9-THC, which crosses the blood-brain barrier more rapidly than THC, and therefore may be more active than THC. However, because of the multitude of biotransformation pathways and metabolites and the complex interaction of the cannabinoids, no particular method has been developed for determining levels of intoxication based on detectable cannabinoids and metabolites. What is quite apparent about cannabinoids is that their extremely high lipid-solubility results in their persisting in the body for long periods of time. Studies have shown that after a single administration of THC, detectable levels are found in the body for weeks or longer, depending on how much was administered and the sensitivity of the assessment method. A number of investigators have suggested that this is an important factor in marijuana's effects, perhaps because cannabinoids may accumulate in the body, particularly in the lipid membranes of neurons. However, it is most likely that the major site of accumulation is the adipose tissue, which means that these drugs would have no significant psychological consequences.

Disorders Treated with Anxiolytics

Phobias Species Environmental Social Panic Disorders Agoraphobia Generalized Anxiety Disorder Post Traumatic Stress Disorder Phobias are characterized by a present and disproportionate fear of some specific object or situation that presents little or no actual danger to the person. When persons with phobias encounter a feared object or situation, they often experience the flight-or-fight response, which prepares them for escaping from the situation. Specific phobias generally involve fears of other species (for example, snakes, spiders) or fears of specific features of the environment, like large bodies of water or height. Social phobias involve fears of social situations in which the individual feels exposed to the scrutiny of other people, such as during public speaking, and is afraid of acting in a humiliating or embarrassing way. Panic disorder is related to phobias but is much less common. It is characterized by recurrent panic attacks, which are accompanied by heart palpitations or chest pain, a choking or smothering feeling, dizziness, numbness and tingling in the hands or feet, sweating, and trembling. The symptoms come on quite suddenly and unpredictably. The individual is persistently worried over experiencing a panic attack and "going crazy" or losing control. Long-term sufferers may begin to feel anxious in anticipation of an attack. Agoraphobia is a common complication of a panic disorder (although it can occur without experiencing prior panic attacks), in which the individual fears being in places or situations from which escape would be difficult or embarrassing should they experience a panic attack or something bad happen to them. In extreme cases, agoraphobics don't even venture outside of their homes. Generalized anxiety disorder (GAD) is characterized by the occurrence of unwanted and intrusive obsessive thoughts or distressing images. These are accompanied by compulsive behaviors that may temporarily neutralize the obsessive thoughts or images or prevent some anticipated dreaded event or situation. Both obsessions and compulsions may occur in the disorder, or they may occur separately. Individuals diagnosed with OCD typically recognize that these symptoms are excessive and unreasonable. Posttraumatic stress disorder (PTSD) is characterized by a pathological re-experiencing of prior traumatic events in the form of intrusive thoughts, flashbacks, and dreams; avoidance of situations reminiscent of trauma; and numbed responsiveness to the environment, manifested as diminishing interest in significant activities, detachment from others, as well as symptoms of hyperarousal, including hypervigilance, exaggerated startle response, sleep disturbances, and impairment of concentration.

Hormones of the Pituitary Gland

Pituitary gland Anterior pituitary synthesizes and releases at least seven major hormones Thyroid stimulating hormone and its releasing factor Corticotropin and its releasing factor Lutenizing hormone Follicle-stimulating hormone and their respective releasing factors Growth hormone Prolactin Beta lipotropin Posterior pituitary synthesizes and releases vasopressin and oxytocin The pituitary gland is anatomically and physiologically divided into two parts- the anterior pituitary and the posterior pituitary. The anterior lobe of the pituitary gland synthesizes and releases at least seven major hormones, all of which are under control of releasing factors produced in the hypothalamus. Four of these hormones and their respective factors have already been discussed, which include thyroid stimulating hormone and its releasing factor; corticotropin and its releasing factor; and lutenizing hormone and follicle-stimulating hormone and their respective releasing factors. The remaining three growth hormones, prolactin, and beta lipotropin will be discussed within the next few slides. The posterior lobe of the pituitary gland synthesizes and releases vasopressin and oxytocin, two important hormones. These compounds have important vasoactive, antidiuretic, and uterine-stimulating properties. Vasopressin and oxytocin are not regulated by hypothalamic releasing factors; rather, each is synthesized in cells of the hypothalamus and then transported down axons to the posterior lobe, of the pituitary gland where they are stored in axon terminals for later release by appropriate and sometimes by inappropriate stimulation.

Smokeless Tobacco

Primarily used by males Declining use Smokeless tobacco is not harmless Oral and pharyngeal cancer Dental and gum problems Cardiovascular abnormalities Although smoking tobacco is the most common route of nicotine administration, smokeless tobacco is used by a substantial percentage, of adolescents, primarily males, although use has declined considerably over the past decade in twelfth graders from approximately 30% in 1990 to 17% in 2003. The perception by most users is that, smokeless tobacco is safer and more socially acceptable than cigarette smoking, and that smokeless tobacco enhances athletic performance. While the health risks of smokeless tobacco use are indeed, much lower than those associated with smoking tobacco, smokeless tobacco is not harmless. Its use has been associated with oral and pharyngeal cancer, numerous dental and gum problems, and cardiovascular, abnormalities related to elevated blood pressure and heart rate. Also, smokeless tobacco does not appear to facilitate performance, since differences between users and nonusers of smokeless tobacco have, not been observed with respect to neuromuscular reactivity or perceptual-motor task performance.

Cocaine Mechanism of Action

Plasma half-life Metabolite detection Increased Plasma levels and formation of cocaethylene Inhibit the reuptake of the monoamines Dopamine-reuptake-inhibiting properties The dependence liability of cocaine with either of these modes of administration may actually be greater than that of amphetamine, because the subjective "crash" following smoking, or intravenous administration of cocaine which is more noticeable than amphetamines. This outcome is probably related to cocaine's very short duration of action. Once in the body, cocaine is widely distributed throughout the body and is rapidly metabolized. Minimal amounts of cocaine are excreted in an unmetabolized form. Although cocaine's plasma half-life is around 30 to 90 minutes, several metabolites can be detected by way of urinalysis for up to 2 to 5 days after a cocaine binge, with the major metabolite being detectable in the urine of heavy users for up to 10 days following a binge. Use of alcohol along with cocaine, a common occurrence in users, results in increased plasma concentrations of cocaine and the formation of a psychoactive metabolite, cocaethylene, both of which enhance and prolong the subjective euphoria and cardiovascular effects of cocaine. These phenomena potentially play a role in the toxicity and abuse associated with the drug combination. Although cocaine has local anesthetic properties because of its ability to block neural conduction, its CNS effects are mediated primarily by its potent ability to inhibit, the reuptake of the monoamines, that is, serotonin, norepinephrine, and dopamine from the synaptic cleft. Unlike amphetamine, cocaine is very weak in promoting monoamine release through the uptake transporters. which with acute exposure to cocaine results in large increases in extracellular levels of dopamine. There is, however, debate over the primary region of the brain that is responsible for the rewarding actions of cocaine- with some evidence favoring the nucleus accumbens and, other evidence favoring the medial prefrontal cortex. Both of these areas are primarily terminal areas for dopaminergic input originating in the ventral tegumental area of the midbrain. The neurochemical effects of cocaine are similar to those of amphetamine and some antidepressants, although in many cases there are subtle, but potentially important, differences. Although some anti-depressants, such as tricyclics and SSRIs, share cocaine's monoamine-reuptake-inhibiting properties, they do not elevate mood until after several days of exposure, nor do they elevate mood in nondepressed individuals. Some of these differences may be due to these drugs having considerably weaker effects at the dopamine-uptake-binding site than cocaine.

Cannabis Psychological Effects

Pleasure Dysphoric reaction Appetite Sexual experiences Mental Health Memory Flashbacks The acute effects of marijuana or being stoned generally consist of an increasing dose-dependent impairment of memory and cognitive functions, such as attending, speaking, problem solving, and concept formation. The person's speech is fragmented, suggestive of disjointed thought patterns, and the speaker often forgets what he or she and others have recently said. Sometimes the person under the influence of marijuana gains insights of great importance. Unfortunately, while under the influence, the person's ability to reflect or to analyze the quality of these insights is greatly impaired, and when the intoxication phase is over, the great insights often turn out to be mundane or unworkable ideas. One of the primary effects of marijuana is interference with short-term memory. This is found to occur with both verbal and graphic material. Marijuana also disrupts long-term memory retrieval. This effect is more predominant with recall than with recognition. Much of the memory disruption appears to be due to the increase in imagery and thought flow coming out of the intrusion of irrelevant associations. However, there is little evidence that, once the person returns from the intoxicated state, retrieval of information learned prior to the intoxication state is affected. Although there are no studies directly assessing the effects of marijuana on classroom learning experiences, the similarity between the types of activities relevant to such settings, and those observed in the laboratory is so close as to strongly suggest that marijuana interferes with classroom functioning and knowledge acquisition. This is an important factor considering the extent of marijuana use among high school students today. The detrimental effects of marijuana on complex psychomotor skills in the laboratory have also been observed in real-life situations of driving and flying. While marijuana may be less detrimental to driving performance than alcohol is, it nevertheless is a potential causal factor in accidents that occur while driving or engaging in similar activities. Some of the detrimental effects on performance may persist for some time, possibly up to 24 hours, beyond the period of subjective intoxication. One factor that contributes to alcohol's detrimental effects on driving is its tendency to provoke risk taking, whereas in simulated and actual driving tests, marijuana typically makes drivers more cautious, and drivers under the influence of marijuana consciously attempt to compensate for its detrimental effects.

Use of Hallucinogens

Popularity is a function of this general characteristic of stimulus seeking They seem to increase the capacity of the human brain to respond to: Fine gradations of stimulus input To enhance our responses to stimulation at both the upper and lower levels of perceptual processing To remove the constraints imposed by the different sensory pathways In addition to the setting, the person's attitudes, motivations, cognitive set, and expectations play such a large role in the experience We are built to process stimuli, and an important aspect of our living is our seeking the stimuli process. The popularity of hallucinogens is a function of this general characteristic of stimulus seeking. The central property of any of the hallucinogens is the enhancement of experience. They seem to increase the capacity of the human brain to respond to fine gradations of stimulus input, to enhance our responses to stimulation at both the upper and lower levels of perceptual processing, and to remove the constraints imposed by the different sensory pathways through which stimulation is received. They produce new perceptions, alter our ways of looking at the world, and in some cases induce hallucinations. The experience can be very exhilarating or very frightening. In contrast, the sedative-hypnotics and narcotics reduce our attention to sensory input, although these substances may induce dreamlike states. Stimulants may enhance endurance, improve mood, and increase alertness, but they do not alter our attention to sensory input as do hallucinogens. However, in order for the enhanced capacity for experience to occur with hallucinogens, an adequate range of stimuli must be available, because exposure to them under conditions of sensory deprivation seems to reduce their effects considerably. On the other hand, as the complexity of the stimulus increases, the variability of the experiences and perceptual reactions also increases. Furthermore, in addition to the setting, the person's attitudes, motivations, cognitive set, and expectations play a large role in the experience that it is impossible, to predict in advance the type of experience one may have with these substances. This unpredictability may, in fact, be the other reason why humans use them.

Rohypnol

Rophy Not marketed in the US Sleep aid 5 to 10 times more potent than Valium Small amounts are effective Impairs judgment and motor skills Induce amnesia "Date Rape" drug One benzodiazepine that has gained considerable notoriety for its uses is Rohypnol. Although not marketed in the U.S., there has been an increase in the illicit use and abuse of this drug, which is used clinically primarily as a sleeping aid. The fact is that it is quite potent—five to 10 times more potent than Valium—thus requiring very small amounts to be effective, coupled with its propensity to impair judgment and motor skills and to induce amnesia—particularly when combined with alcohol. This has led to this drug termed the "date rape" drug. Its amnesia-inducing effects may prevent users from remembering how or why they took the drug or even having taken it, making investigation of sexually related offenses associated with its use very difficult. Because of its reputation for abuse, the DEA has recently classified it as a Schedule I drug. This is the first benzodiazepine to be classified in this schedule.

Angina Pectoris

Principal symptom of ischemic heart disease Manifested by sudden and severe pressing chest pain Often radiates to the left shoulder and down the left arm Attacks of classic angina: Temporary ischemia of heart muscle Chest pain caused by both types of angina Treatment: Antianginal drugs Nitroglycerin Cessation of smoking Weight loss may produce Dietary modifications Control hypertension Attacks of classic angina are the result of temporary ischemia of heart muscle; that is, the flow of blood through the coronary arteries to the heart muscle does not meet the oxygen requirements of the heart muscle. The chest pain caused by types of angina is relieved quickly by nitroglycerin. Although nitroglycerin and other drugs also may afford more long-term relief, they do not correct the underlying causes of reduced coronary artery blood flow. Treatment with antianginal drugs is only part of a general program to alleviate symptoms and reduce risk factors that predispose to coronary artery disease. Cessation of smoking is essential, and in obese patients, weight loss may improve symptoms of angina. Dietary modifications, especially efforts to reduce blood cholesterol levels, may be advantageous in the situation as well. Control of hypertension leads to a decrease in myocardial work and therefore to decreased myocardial oxygen demands. This alone may relieve angina. Young adults with a family history of coronary artery disease and "heart problems" would be wise to reduce their risk factorslong before the symptoms of angina indicate the presence of coronary artery disease.

Benzodiazepines

Reduce anxiety symptoms without inducing undesired effects Examples: Meprobamate Chlordiazepoxide or Librium Diazepam or Valium Oxazepam or Serax Clorazepate or Tranexe Lorazepam or Ativan Alprazolam or Xanax Over the years, a number of drugs have come into clinical use with claims of being highly selective in their ability to reduce anxiety symptoms without inducing other undesirable effects. In the 1950s meprobamate was highly touted as one of these. However, it did not quite live up to its reputation in subsequent clinical tests and was not found to be significantly different from other sedative-hypnotic compounds. The introduction of chlordiazepoxide or Librium into clinical use in 1961 ushered in the era of a new class of drugs called the benzodiazepines, and they essentially took over, primarily for safety reasons. These drugs are also sometimes referred to as "minor tranquilizers," because they are used predominantly in minor or less severe cases of pathology. Of the 3,000 benzodiazepines synthesized, about three dozen are in clinical use in various parts of the world. In the United States the most commonly prescribed benzodiazepines for anxiety are chlordiazepoxide, diazepam (Valium), oxazepam (Serax), clorazepate (Tranexe), lorazepam (Ativan), and alprazolam (Xanax). Over the years, a number of drugs have come into clinical use with claims of being highly selective in their ability to reduce anxiety symptoms without inducing other undesirable effects. In the 1950s meprobamate was highly touted as one of these. However, it did not quite live up to its reputation in subsequent clinical tests and was not found to be significantly different from other sedative-hypnotic compounds. The introduction of chlordiazepoxide or Librium into clinical use in 1961 ushered in the era of a new class of drugs called the benzodiazepines, and they essentially took over, primarily for safety reasons. These drugs are also sometimes referred to as "minor tranquilizers," because they are used predominantly in minor or less severe cases of pathology. Of the 3,000 benzodiazepines synthesized, about three dozen are in clinical use in various parts of the world. In the United States the most commonly prescribed benzodiazepines for anxiety are chlordiazepoxide, diazepam (Valium), oxazepam (Serax), clorazepate (Tranexe), lorazepam (Ativan), and alprazolam (Xanax). For many years Valium was the most popular drug of this group, but Xanax has replaced it as the most commonly prescribed anxiolytic, probably because of growing fears of addiction with Valium, competition from generic forms of diazepam, and limited evidence that Xanax may possess somewhat better antidepressants, antipanic, and antiphobic effects. The properties of benzodiazepines are very similar to those that I just described for the sedative-hypnotics. For example, they are effective anticonvulsants and muscle relaxants, they reduce a variety of aggressive tendencies, and they decrease anxiety. However, the actions of these drugs are hypothesized to be more specific than barbiturates and similar compounds in affecting the limbic system at doses that do not affect the reticular activating system or the cerebral cortex. In contrast to barbiturates, the benzodiazepines are not effective as general anesthetics.

Urinary Retention

Reduced ability to urinate can be caused by many factors Cholinergic stimulants facilitate emptying of the bladder primarily by increasing contractility The reduced ability to urinate can be caused by many factors. Cholinergic stimulants and other drugs used to treat urinary retention facilitate emptying of the bladder primarily by increasing contractility. The cholinergic stimulant bethanechol is widely used and clinically effective in the treatment of urinary retention.

Drugs and the Respiratory System

Respiratory and pulmonary disorders can be divided into those that affect the upper or the lower portions of the respiratory tract. The upper portion extends from the nose to the trachea, and the lower portion involves the bronchi and the alveoli of the lungs. The nose functions both to warm and to humidify inspired air and to trap inhaled particulate matter.

Cocaine Withdrawal

Several Phases (1) First few hours: Feelings of depression and agitation, lacks appetite, and experiences high cocaine craving (2) Next several hours or days: Extreme hunger, although cocaine craving is absent and need for sleep is overwhelming (3) Next several days: Sleep patterns and mood return to normal, and little cocaine craving (4) Several weeks: Mood and pleasure response return to normal, and experiences only episodic cocaine cravings If a person begins taking cocaine again at any point, he or she generally returns to the first phase Furthermore, reports from cocaine-dependent persons suggest that withdrawal involves several phases, with mixtures of different dependence-inducing processes being implicated. During the first few hours after a binge, the user feels depressed and agitated, lacks appetite, and experiences high cocaine craving. In the next several hours or days, the user experiences extreme hunger, although the cocaine craving is absent. In some individuals there is also a strong abhorrence for cocaine during this time period, and the need for sleep is overwhelming. During the next several days, the user's sleep pattern and mood return to normal, and there is little cocaine craving. However, subsequently the user experiences anxiety, a lack of energy, an inability to enjoy normal activities, and a high cocaine craving that is exacerbated by, environmental cues previously associated with cocaine use. After several weeks, the user's mood and pleasure response return to normal, and he or she experiences only episodic cocaine craving, which again is most common in the presence of specific environments. If the person begins taking cocaine again at any point, he or she generally returns back to the first phase. Whether or not the discomfort following extensive cocaine use is due to an actual physiological abstinence syndrome, it probably plays a minimal role in motivating drug-seeking users. In most cases withdrawal symptoms are maximal 1-2 days after cessation of drug use, whereas the susceptibility to relapse may continue to grow for weeks or month. However, the intensity and presence of cocaine craving following cocaine exposure is a major factor behind its abuse and relapse, with higher levels of cocaine craving being reported by cocaine-dependent persons when they are experiencing negative mood states. Cue-induced craving has been found to be associated with increases in activity in areas of the limbic system and decreases in the basal ganglia. Interestingly, both pleasant and unpleasant conditioned responses can be elicited in cocaine-dependent persons. Any aspect of a drug that may increase its likelihood of being used on subsequent occasions may be a factor in its being a positive reinforcement and being abused. Cocaine has a reputation of enhancing a person's subjective self-worth, competence, and performance, and we would expect this to be a factor in the maintenance of cocaine drug use. Cocaine has been shown to enhance the performance of sleep-deprived individuals, but evidence that cocaine can enhance the learning or performance of non-fatigued individuals is weak.

Hypertension

Significant risk factors in the long-term development of such serious cardiovascular disorders Excessive salt intake Obesity Blood pressure: 120/80 mmHg Systolic pressure Diastolic pressure achieved during cardiac filling. 90 mmHg or greater 95 mmHg or greater Hypertension can contribute to premature death and disability. Excessive sodium chloride intake and obesity both appear to play an important role in the genesis of "essential hypertension". Weight control, reduction of salt intake, as well as pharmacologic agents to treat hypertension are mainstays of the current hypertension therapy. Hypertensive patients may improve the quality and length of their lives by achieving strict control of blood pressure, maintaining ideal body weight, reducing salt intake, adhering to the pharmacological recommendations of their doctor, and controlling other risk factors associated with cardiovascular disease, such as stopping smoking, lowering blood cholesterol, and increasing physical conditioning. An ideal blood pressure is 120/80 mmHg, with 120 mmHg being the systolic pressure achieved during the period of cardiac contraction and 80, the systolic pressure achieved during cardiac filling. Such patients are candidates for a trial of management without drugs that employs weight loss, dietary salt restriction, and exercise. A strong family history of hypertension and cardiovascular disease, however, may sway judgment to early pharmacologic therapy. At levels of 95 or higher, pharmacologic therapy should be strongly considered and monitored by your physician.

Monoamine-related Drugs

Similarity with the molecular structures Serotonin Dopamine Norepinephrine Examples: LSD Psilocybin DMT DET DMMA MMDA General Effects Papillary dilation Increases in blood pressure and heart rate Exaggeration of deep tendon reflexes Tremor Nausea Increased body temperature Monoamine-related drugs are also named because they share a basic similarity with the molecular structures of the monoamine neurotransmitters serotonin, dopamine, and norepinephrine. Examples of these drugs include LSD; psilocybin and psilocin, found in a specific type of mushroom; bufotenine, found in the glands of certain toads; DMT, and DET. Examples of the catecholamine-type hallucinogens are mescaline, found in peyote cactus; DMMA, the main ingredient in the street drug known as STP; 3,4-MDA; and MMDA. The subjective effects of the monoamine-related hallucinogens in the dose ranges that are effective are quite similar and often indistinguishable in both humans and animals. However, their potency may vary tremendously. For example, LSD is approximately 100 times more potent than psilocybin and approximately 4,000 times more potent than mescaline in humans. They may also differ in terms of their durations of action; for instance, the effects of LSD may last for several hours, whereas the effects of DMT may dissipate within 1 hour. The durations of action of mescaline, psilocin, and psilocybin are in between these two. Most drugs in this category induce fairly rapid tolerance to both their mental and sympathetic effects; tolerance appears to be complete after three or four daily exposures. They are also cross-tolerant with each other, but do not appear to exhibit cross-tolerance with drugs in the other three hallucinogen classes. The one exception seems to be DMT, in which tolerance in humans has not been shown to develop. In most cases, tolerance is lost after a few days of no drug exposure. As far as we know, there are no signs of an abstinence syndrome following chronic exposure to any of the monoamine-related hallucinogens. In addition to the similarity of the subjective effects of the monoamine-related hallucinogens, as one might expect of drugs with some of the properties of the stimulants, they share the tendency to produce bodily effects largely sympathetic in nature. These may consist of papillary dilation, increases in blood pressure and heart rate, exaggeration of deep tendon reflexes, tremor, nausea, and increased body temperature. As I will discuss later in this lecture, the other classes of hallucinogens share these characteristics in some respects but differ greatly in other respects. For example, anticholinergics may increase heart rate and blood pressure and produce papillary dilation, but unlike the monoamine-related hallucinogens, the papillary dilation is not responsive to light. While the monoamine-related hallucinogens induce signs of heightened arousal, anticholinergics and cannabinoids tend to induce sedative-like effects, drowsiness, and fatigue. You should be able to note fundamental differences in the effects of the other hallucinogens by the end of this lecture.

Arrhythmias

Sinus Arrhythmias Sinus bradycardia Sinus tachycardia Atrial Arrhythmias Premature atrial contractions (PAC) Paroxysmal atrial tachycardia (PAT) Nodal rhythm Atrial flutter Atrial fibrillation. Ventricular Arrhythmias Occasional premature ventricular contractions (PVCs) Ventricular tachycardia Ventricular flutter Ventricular fibrillation Cardiac arrhythmias may be relatively benign in patients who can maintain normal cardiac output, or they may be associated with very high rates of fatality. The SA node usually functions as the pacemaker for initiation of the cardiac electrical impulse. The normal sinus rate is between 55 to 100 beats per minute. Irregularities in rhythm or rates outside the normal range typically are classified as arrhythmias. Sinus bradycardia refers to a regular rhythm with a rate below 55 beats per minute, and sinus tachycardia refers to a regular rhythm with a rate above 100 beats per minute. Sinus bradycardia does not require treatment if cardiac output is normal. Trained athletes, for example, often have rates below 50 beats per minute at rest and can greatly increase their cardiac output with only the modest increase above this. If bradycardia results in failure to supply sufficient cardiac output to meet the body's demands, atropine may increase the sinus rate temporarily. For permanent relief an implanted battery-operated pacemaker may be needed. Non-SA node arrhythmias arising in ectopic foci of the atria include premature atrial contractions, or PAC; paroxysmal atrial tachycardia, or PAT; nodal rhythmia arising in the AV node; atrial flutter; and atrial fibrillation. PAC or nodal rhythm usually is innocuous, often requires no pharmacologic treatment, and usually responds to the elimination of their principal cause, such as the excess use of caffeine, nicotine, or alcohol. Control of congestive heart failure with digoxin generally controls the PAC associated with this disorder. PAT refers to the rapid heart rate in which the impulse originates in the atria, outside the AV node. PAT is thought to be caused by reentry mechanisms or self-supporting "circus movement" of impulses around the atrial muscle. Numerous drugs have been used to treat PAT. Currently, the calcium channel blockers are playing an increased role as first-line treatment of a persistent PAT. Ventricular arrhythmias include occasional premature ventricular contractions or PVCs, ventricular tachycardia, ventricular flutter, and ventricular fibrillation. Occasional PVCs in patients without coronary artery disease or underlying heart disease usually are of little clinical significance and generally do not require treatment. Frequent PVCs, however, are associated with an increased risk of sudden death due to their progression to more serious ventricular arrhythmias. Ventricular tachycardia is a serious disorder because it may lead to reductions in cardiac output, decreased coronary artery perfusion, ventricular fibrillation, and possibly, death. Antiarrhythmic drugs are used to treat persistent episodes of ventricular tachycardia and to prevent their reoccurrence. Agents used to treat rapid onset, life-threatening ventricular tachycardia include lidocaine and procainamide. Several drugs used for long-term suppression of serious ventricular arrhythmias include quinidine, procainamide, and beta blocking agents.

Amphetamine & Methamphetamine Routes of Adminstration

Snorted Oral Injected Smoked Relatively high in lipid-solubility and very well absorbed when taken orally or inhaled as a vapor. Intravenous administration results in brain penetration within seconds. Most amphetamines are not sufficiently volatile to vaporize when smoked, a form of methamphetamine hydrochloride has been developed so that it can be inhaled when smoking. Has rapid onset and its effects last much longer.

Cocaine History

South American Indians Introduction to Europe Sigmund Freud Karl Koller South American Indians have been using cocaine for centuries to increase their endurance and reduce fatigue and hunger. The early European explorers of South American, who essentially enslaved the natives, soon found the natives' fondness of the coca leaf, but when introduced in Europe there was very little fanfare. In the mid-1800s, cocaine was isolated from coca extracts, but its general use did not begin until the late 1800s. Earliest leading proponent of cocaine's clinical use was Sigmund Freud. Between 1884 and 1887 Freud performed the functions of a psychopharmacologist by testing the various mood- and behavior-altering properties of cocaine, primarily on himself and a few friends. Freud initially believed that cocaine had many beneficial characteristics, such that it could be used to enhance mood, alleviate depression, reduce effects of fatigue, and enhance sexual potency. He felt it could be a potential treatment for morphine and alcohol addiction, numerous psychological disorders such as hysteria and hypochondria, and a variety of physical disabilities. Finally, he suggested that its local anesthetic properties might be of value. His work with cocaine may have led to its use by an eye surgeon, Karl Koller, as a local anesthetic in the eye. It was the first drug physicians had for this purpose. Cocaine was later used as a therapy for asthma and colic. Although Freud's work with cocaine ceased, he continued to use cocaine regularly until at least 1895, and probably quite a bit longer. Many have speculated that his cocaine use not only was a factor in his prodigious writings, but also may have played a casual role in the early development of his psychoanalytic, theories by facilitating his capability or capacity for introspection and self-analysis.

Methamphetamine Street Names

Speed Bikers Coffee Poor Man's Cocaine Trash Yellow Barn

Cocaine Prenatal Consequences

Studies have shown that female cocaine users: Are more likely to be poor and undereducated May differ considerably in the amount, frequency, and time of cocaine use Commonly use other drugs, such as alcohol, nicotine, marijuana, and heroin, that may also compromise prenatal development May under- or over report their drug use May practice other poor health behaviors, such as inadequate nutrition and pre- and postnatal care. Effects of prenatal cocaine exposure on language and cognitive functioning of children Unfortunately, the true extent of the severity and incidence of the harmful effects of prenatal cocaine exposure in humans is simply not known because of a number, of methodological problems in the studies addressing the issues. Among many problems, for example, the women in these studies are more likely to be poor and undereducated. They may differ considerably in the amount, frequency, and time of cocaine use; commonly use other drugs, such as alcohol (by itself a potent teratogen), nicotine, marijuana, and heroin, that may also compromise prenatal development; may under- or over report their drug use; and may practice other poor health behaviors, such as inadequate nutrition and pre- and postnatal care. Recent analyses of a large number of studies suggest that the effects of prenatal cocaine exposure on language and cognitive functioning of children are more subtle than previously assumed. However, these effects can have profound consequences for the success of these children in school and for the cost of special education services. If the estimates of 375,000 cocaine-exposed children being born each year are correct, the additional number of children necessitating special education services would range, from around 1,700 to 38,000 and the additional monetary costs would range from $4 million to $80 million per year. Since the mothers' cocaine use often occurs in the context of poverty and other known risks to children, including tobacco, alcohol, and other drugs, these children's prenatal exposure to cocaine compounds their problems. A recent longitudinal study assessing long-term cognitive effects of prenatal cocaine exposure in preschool children detected even smaller full-scale IQ deficits along with small, but significant deficits on several subscales. A notable finding from this study was that these cocaine exposed children who were raised in homes with more stimulating environments and caregivers with better vocabulary scores, attained full-scale and performance IQ scores that were essentially the same as those of the noncocaine-exposed children. This suggests that exposure to a better home environment can significantly improve cognitive deficits associated with prenatal cocaine exposure.

Vasopressin

Synthesized in cells of the hypothalamus Carried in axons to the posterior lobe of the pituitary gland Stored in nerve terminals Released in response to alterations in plasma osmolality. Major function: Maintain body fluid osmolality Acts directly on the renal tubules Has the ability to constrict blood vessels Vasopressin is a hormone containing eight amino acids. It is synthesized in cells of the hypothalamus, carried in axons to the posterior lobe of the pituitary gland, stored in nerve terminals, and released in response to alterations in plasma osmolality. Its major function is to maintain body fluid osmolality within a narrow range by regulating the excretion of water by the kidneys. Vasopressin acts directly on the renal tubules to increase the reabsorption of water by increasing the permeability of the distal tubules and collecting ducts to water. The hormone also has the ability to constrict blood vessels, which is an action that works in conjunction with the increased water reabsorption to maintain plasma volume and blood pressure.

The Thyroid Gland

Synthesizes and releases three important hormones Thyroxine (T4) Triiodothyonine (T3) Calcitonin T3 & T4 Production of calories Synthesis of body proteins Regulation of body temperature Deficiency Reduced metabolic rate Reduced growth and development of several organ systems Alters the function of the CNS, skeletal muscles, heart, liver, kidneys, circulation, and reproductive systems. The thyroid gland synthesizes and releases three important hormones, two of which, thyroxine and triiodothyonine, are involved in energy metabolism and protein formation and are essential for normal growth and development. The third, calcitonin, is important for the maintenance of body calcium. The fundamental actions of the two major thyroid hormones, T3 and T4, are related to the following: Production of calories for energy utilization and expenditure, synthesis of body proteins for normal growth and development, and regulation of body temperature by increasing cellular metabolism. Deficiency of thyroid hormone results in reduced metabolic rate, reduced growth and development of several organ systems, and altered function of the CNS, skeletal muscles, heart, liver, kidneys, and reproductive systems. Deficiencies are treated effectively by the administration of an exogenous thyroid hormone.

Why is Marijuana Rewarding?

THC can enhance the release of dopamine in reward-relevant areas of the brain Cognitive and memory disruptions Intrusions into thought What makes the marijuana experience rewarding. We really don't know. The ability of THC to enhance the release of dopamine in reward-relevant areas of the brain may be one factor. The transient cognitive and memory disruptions associated with marijuana may account for its popularity in some, but by not means all, humans. That is, new and unrelated intrusions into thought, the loosening of traditional or learned associations among stimuli and responses, the encoding of new information subject to associative links that normally would be inhibited, the ambiguity and variability in the perceptual experience, and so forth, result in novel experiences, feelings of creativity, and insightfulness. Those individuals who are not particularly anxious, about the unfamiliar or the unconventional or about to lose control and the unpredictability of their world may find such effects pleasurable, as long as they can retain control over time and the degree of these effects. Those who are anxious about these may find such effects unpleasurable. Other drugs may have similar properties, but marijuana's effects are relatively short-lasting and are easier to control; tolerance to them develops relatively slowly, and the immediate side effects associated with marijuana are less troublesome. Again, I know that I presented a lot of new information about marijuana and THC within this lecture

Cannabis Consequences of Use

Tachycardia Reddening of the eyes Increased blood pressure Blurred vision Headaches Inflammation Edema Cell injury to lungs Reproductive functioning There are a number of other potential consequences of marijuana use. Acute marijuana intoxication effects are minimal and consist predominantly of tachycardia or rapid heart rate and reddening of the eyes. There may be a slight increase in blood pressure with low doses and a slight decrease with high doses. Some individuals may experience blurred vision or headaches. Following acute intoxication, there are generally no residual physiological effects, unless particularly large quantities are used. Numerous studies have indicated that marijuana smoking produces inflammation, edema, and cell injury in lung tissues of smokers and may be a risk factor for lung cancer, although there is no empirical evidence for lung cancer related to solely marijuana smoking. Studies have also shown that smoked cigarettes containing THC indicate that marijuana smoke may be a source of cell injury and dysfunction in the lungs of smokers. Comparisons of heavy, habitual smokers of marijuana alone, smokers of marijuana plus tobacco, regular tobacco, but not marijuana smoking is associated with greater annual rates of decline in lung function than is nonsmoking. Some studies have suggested that reproductive functioning may be impaired with marijuana use which may be reflected in lower testosterone levels, reduced sex drive, and less vigorous sperm motility in males and in interference with fertility in females. Most studies, however, have failed to show any significant effects of chronic marijuana use on the reproductive hormones of either men or women.

Narcotics Receptors

The definition of a narcotic has become more confusing and complex since the discovery, of a multitude of substances with opiate properties. Three distinct families have been identified thus far: the enkephalins, the endorphins, and the dynorphins. However, as mentioned previously, these are all categorized in a general sense as endorphins. Each family is derived from different precursor polypeptides, more than 200 amino acids long, with different anatomical distributions. Each precursor contains a number of biologically active opioid and nonopioid peptides, which are cleaved at specific sites by specific enzymes to produce the active agents. Enkephalins Endorphins Dynorphins

Types of Diuretics

Thiazide Diuretics Increase the urinary excretion of sodium chloride and water by inhibiting the reabsorption of sodium Increase the urinary excretion of other ions, the most prominent of which is potassium Loop Diuretics Block the active reabsorption of sodium chloride in the ascending limb of the loop of Henley Produce a much greater diuresis, with both the urine volume and the total sodium excreted being much greater Potassium-Sparing Diuretics Increase sodium and water excretion while conserving potassium. Not as potent as either the loop or the thiazide diuretics. Osmotic Diuretics Closely resemble that of glucose Filtered by the glomeruli of the kidney but unlike glucose Carbonic Anhydrase inhibitors Increase sodium excretion by reducing the reabsorption of sodium bicarbonate in the proximal tubules of the kidney The thiazide diuretics are considered the most reliable, best tolerated, and most useful orally administered diuretics. Many thiazides are available, and they differ primarily in potency and duration of action. These agents increase the urinary excretion of sodium chloride and water by inhibiting the reabsorption of sodium mainly in the distal tubules, possibly also with some effect on the proximal tubules. They also increase the urinary excretion of other ions, the most prominent of which is potassium. The thiazides usually are ineffective in patients with renal failure and may actually cause further deterioration of kidney function. Loop diuretics block the active reabsorption of sodium chloride in the ascending limb of the loop of Henley, the site of greatest reabsorption of water and salt. Reabsorption at this site is much more effective than which occurs in the distal tubules. Drugs that block sodium reabsorption in the loop have a much greater inherent activity than those that act on the tubules. Thus, the loop diuretics produce a much greater diuresis, with both the urine volume and the total sodium excreted being much greater. These potent agents usually are reserved for patients with more severe disorders that cannot be controlled by thiazides, such as renal failure, acute pulmonary edema, and hypertensive crises. The diuretics discussed so far cause losses of potassium in addition to those of sodium and water. The potassium-sparing diuretics increase sodium and water excretion while conserving potassium. They do this by blocking a process in the distal renal tubule in which sodium is reabsorbed from the fluid in the lumen of the nephron in exchange for potassium. Since only small amounts of sodium are normally reabsorbed in the distal portions of the distal convoluted tubules, the potassium-sparing diuretics are not as potent as either the loop or the thiazide diuretics. When combined with thiazide or loop diuretics, however, they reduce potassium losses, exert an effective diuretic effect, and are better tolerated than are potassium supplements. Osmotic diuretics closely resemble that of glucose and, like glucose, it is filtered by the glomeruli of the kidney but unlike glucose, it is not reabsorbed by the tubules into plasma. Consequently, an osmotic equivalent of water passes through the renal tubules to increase the volume of urine excreted. Carbonic Anhydrase inhibitors increase sodium excretion by reducing the reabsorption of sodium bicarbonate in the proximal tubules of the kidney. Thus, sodium bicarbonate is excreted along with a volume of water. Little or no chloride is excreted at all. Tolerance develops to the diuretic action within a few days. It is the result of excess excretion of bicarbonate, which alters acid-base balance in the body and limits the drug's diuretic effects.

Barbiturates

Thiopental Secobarbital Amobarbital Phenobarbital Barbiturates have become the dinosaur of drugs; they enjoyed a century of use as sedative and hypnotic agents, but have only a few specialized uses today. Furthermore, these and other drugs in the sedative-hypnotic class have effects so similar to alcohol's effects that little further discussion is needed, except to note that long-term alcohol exposure probably has more toxic physiological consequences. Sedative-hypnotic compounds without the barbiturate structure, such as methaqualone and glutethimide, but their actions are indistinguishable from those of other barbiturates. Barbiturates differ from each other primarily in terms of pharmacokinetics, which determines how quickly the drugs act, their intensity of action, and their duration of action. All three of these properties are tied together. The differences in these properties are a major factor in determining what these drugs are used for. Representative barbiturates are thiopental, a fast-acting, ultrashort-duration (approximately 15 minutes) drug used primarily as an anesthetic; secobarbital, a short-duration (approximately 1.5 hours)in which this drug is used to induce sleep; pentobarbital and amobarbital, short- to intermediate-duration (approximately 4 hours). These drugs are used for either their sedative or sleep-inducing qualities; phenobarbital is a a relatively long-acting (approximately 6 hours) drug and is used as a sedative or an anticonvulsant. The medical uses for these drugs have declined considerably over the past 3 decades, primarily because of the development of newer compounds with less toxicity or dependence liability. The primary advantage of the barbiturates at present is their cost because many are no longer under patent, and thus they are very inexpensive.

Withdrawal from Nicotine

Tolerance: Nicotinic acetylcholine receptor sites undergoing desensitization and inactivation Withdrawal: Slowly recovering to functional states from various levels of desensitization and inactivation Are symptoms psychological? Some of these withdrawal symptoms may be mediated, by changes in nicotinic acetylcholine receptor sites that may occur with chronic nicotine exposure. In general, long-term nicotine exposure induces functional up-regulation of nicotinic acetylcholine, receptor sites -opposite to what one might normally expect from an agonist-receptor interaction. Thus, aspects of nicotine tolerance could be explained by nicotinic acetylcholine receptor sites undergoing, desensitization and inactivation, and withdrawal could be explained by their slowly recovering to functional states from various levels of desensitization and inactivation. Also, the increased number of nicotinic acetylcholine receptor sites could account for why the first smoke of the day in chronic smokers is particularly enjoyable. However, different models that can, account for the acute and chronic effects of nicotine on the nicotinic acetylcholine receptor sites have been developed, and more research is needed to determine which of these is most likely to be, responsible for nicotine's psychological effects and its properties to induce addiction. Furthermore, observations that none of these symptoms may occur, that they may be delayed for several days, or that they may wax and wane over a period of months suggest that many of these symptoms may be more psychological than pharmacological. In other words, if the symptoms were purely physiological, in origin, they would be strongly and inversely related to how much the person had been smoking recently and how long it had been since the person's last cigarette. If this were the case, all heavy smokers would undergo withdrawal every morning, because nicotine plasma levels are essentially zero at this time; yet some do not start smoking until the afternoon. Conversely, if these, symptoms were psychological in origin, they would be directly related to the type of environment, social setting, and mood states that regularly have accompanied cigarette smoking, as well as the, person's expectations and attitudes about cigarette withdrawal. The fact that these vary considerably within and among individuals more easily accounts for the variety in the degree of discomfort, and the times when it occurs. For example, one study found that smokers in a treatment program who believed they were getting nicotine gum, but actually were receiving a placebo, reported fewer, withdrawal symptoms and smoked fewer cigarettes during the first week of quitting smoking than those smokers who thought they were getting a placebo. Also, there was no relationship between the, actual nicotine content of the gum and reported withdrawal symptoms or eventual relapse rates. Unfortunately, once the underlying conditioning factors take place and the expectations develop, their presence may be felt for the rest of the person's life.

Glucocorticoids

Under the influence of hormones released from the pituitary gland Catabolism Suppress the inflammatory response may mask the signs and symptoms of diseases and delay proper diagnosis Reduce the immune response Lowering resistance to infection and promoting its spread. Special Comments Do not cure any disease. The inflammatory response is the body's first line of defense against infection. Beneficial when used short term as anti-inflammatory agents Abrupt cessation Inflammatory disorders The synthesis and secretion of several body hormones, including the glucocorticoids, are under the influence of hormones released by the pituitary gland. The adrenal glands store very little cortisol. The most important metabolic effect of cortisol is to provide increased availability of energy in the form of glucose. This is a major factor in the total body response to stress. Cortisol functions to protect glucose-dependent cerebral functions by increasing the formation of glucose from body proteins, by promoting its storage in the liver as glycogen, and by decreasing its peripheral utilization. Catabolism, the breakdown of body protein, and the inhibition of the formation of new protein are the major sources of material for glucose formation. Excesses in cortisol, as seen in Cushing's syndrome, result in wasting of skeletal muscle and the loss of protein matrix of bone. Thus, these metabolic effects are the opposite of the effects of insulin. Doses greater than the equivalent amount of cortisol secreted per day, the glucocorticoids suppress the inflammatory response, alleviating the swelling, pain, and cellular destruction associated with it. There are several mechanisms responsible for such action, involving white blood cells, reduced capillary permeability, inhibition of prostaglandin formation, and membrane stabilization. Such reduction in inflammatory response may mask the signs and symptoms of diseases and delay proper diagnosis. It also may reduce the immune response, lowering resistance to infection, and promoting its spread. Therapeutically, this reduction in immune responsiveness has led to the use of glucocorticoids to reduce the rejection of transplanted organs. Glucocorticoids do not cure any disease. In Addison's disease, they promote replacement therapy. In all other states, they merely suppress the inflammatory response. I also want to point out a few notes about glucocorticoids. The inflammatory response is the body's first line of defense against infection. Glucocorticoids can cause the spread of infections and can suppress the signs and symptoms of this spreading infection. The presence of bacterial or viral infections may be a reason for discontinuing glucocorticoid therapy. Cessation, however, can be a problem. Glucocorticoids are particularly beneficial when used short term as anti-inflammatory agents or for acute flare-ups of inflammatory or asthmatic disease. For chronic therapy, they are much more difficult to use and possess only limited effectiveness. Abrupt cessation of glucocorticoid therapy may result in adrenal crisis and acute exacerbation of the disease for which the drug was prescribed. Despite their disadvantages and limitations, glucocorticoids are of great therapeutic importance in inflammatory disorders, especially those that are chronic and disabling, as well as those that fail to respond to other therapies.

Upper Airway Disorders

Upper respiratory tract illnesses include: Common cold Nasal stuffiness Membrane inflammation with cough Bronchitis. Drugs for Treatment: Sympathetic Stimulants Nasal decongestants Provide temporary relief of nasal stuffiness and inflammation and sinus congestion A generalized sympathetic stimulation results Antihistamines Drying effect Typically induced an unwanted sedation effect Anti-Cough Preparations Function to expell foreign material from the respiratory tract. Expectorants Mucolytics Antitussives Narcotic Nonnarcotic Upper respiratory tract illnesses include the common cold, nasal stuffiness, membrane inflammation with cough, and bronchitis. Drugs used to treat these ailments include decongestants, cough suppressants, and cold preparations. The majority of nasal decongestants are sympathetic stimulants. These drugs increase vascular tone, reduce tissue edema, increase the cross-sectional area for air passage, decrease the resistance to airflow, and improve sinus drainage. Sympathetic stimulants are widely used for the temporary relief of nasal stuffiness and inflammation, as well as sinus congestion associated with the common cold, hay fever, allergic rhinitis, and other acute and seasonal disorders. Taken orally, a generalized sympathetic stimulation results and may include cardiac stimulation and hypertension. This response is quite unusual when these agents are applied topically as drops or as sprays. Antihistamines occasionally are used as decongestants, probably for their drying effects, but they are included more commonly as components of mixtures that include a sympathetic stimulant. Antihistamines generally have little beneficial effect and only unwanted sedation. One should not drive or operate machinery while taking antihistamine-containing preparations, as the sedation may impair judgment and motor performance. Coughing serves as a protective function by expelling foreign material from the respiratory tract. It is also a reflex initiated by inflammation, irritation, or thick secretions. Antitussive therapies aim to relieve unwanted coughing by depressing the cough reflex. Expectorants aim to increase mucus formation, and mucolytics to liquefy thickened secretions. These drugs are available as syrups, lozenges, tablets, and so on. Antitussives usually are classified as narcotic or nonnarcotic. Opiate narcotics all alleviate cough through a depressant action on the cough centers in the brainstem. Their analgesic and sedative effects also contribute to a feeling of well-being. Codeine and related narcotics obviously carry all of the dependency liabilities of narcotics in general.

Narcotics Tolerance and Dependence

Users can become very tolerant High doses Cross tolerance Drug Metabolizism Neurotransmitter inhibition Up-regulation or sensitization Immune system Withdrawal effects Psychological vs. physiological After continued use of an opiate, especially if it is, taken often and in fairly high doses, the user becomes very tolerant to many of its effects, and cross-tolerance occurs to all of the narcotics, including the endorphins. After several months, of heavy use, some users can administer 40 to 50 times the dose that would kill a nontolerant individual. Tolerance occurs to some but not all effects of narcotics. The rush and euphoria probably, show the fastest tolerance, whereas there is little or no tolerance developed to the constipation and pupil constriction. Many of the mechanisms for inducing tolerance have been involved in tolerance, developed to narcotics with chronic exposure. Although pharmacological changes, such as a slight elevation in the drug metabolizing enzymes in the liver, which could lead to faster metabolic inactivation, of opiates, has been shown, these probably play a minor role in tolerance and none in withdrawal and craving. On the other hand, a wide variety of nonassociative, pharmacodynamics changes in neuronal, systems are believed to be responsible for the neuroadaptations that take place with acute and chronic opiate exposure. These can account for both tolerance development as well as withdrawal effects, and long-term drug craving. Since opiates inhibit the release of several types of neurotransmitters, the receptors for these neurotransmitters may exhibit adaptation in terms of up-regulation, or sensitization, which could also account for some of the physical withdrawal symptoms that occur with opiate use. Research has suggested that continual stimulation of opiate receptors may, gradually increase the activity of anti-opioid peptide systems that counteract opiate effects. These systems could also account for some tolerance and dependence phenomena associated with opiate use. Several studies have also demonstrated that a variety of treatments that suppress the immune system significantly reduce the severity of withdrawal signs in morphine-dependent animals. Thus, at least with opiates, it appears that the immune system may play a role in the abstinence symptoms. In addition to these pharmacodynamic processes that we just discussed, learning processes can, account for some tolerance and dependence associated with chronic opiate use. Due to the disruptive effects of opiates on task-related performance, it is not surprising that individuals may learn compensatory, behaviors to these disruptive effects. However, while some studies indicate that environmental cues associated with the drug effects can be a factor in tolerance to some opiate-induced effects, others suggest that environmental cues can have an additive effect. The symptoms of withdrawal from opiates are essentially opposite of the direct effects of these drugs, you can refer to slide 6, for more information about the effect of withdrawal. The intensity and duration of the abstinence syndrome are directly correlated with the intensity and duration of the particular drug's effects. For example, the withdrawal from heroin, which induces rapid and intense effects of short duration, is relatively intense but dissipates within a few days. On the other hand, withdrawal from methadone, which induces gradual and mild effects of long duration, is relatively mild, but the syndrome takes several days to weeks to subside. For this reason, many opiate addicts find methadone withdrawal to, be more disruptive and disturbing than heroin withdrawal. The opioid withdrawal syndrome can be very unpleasant, consisting of symptoms much like those experienced during a bad case of the flu. It begins 6 to 12 hours after the last dose of a short-acting opiate like heroin and may be delayed up to 72 to 84 hours after a long-lasting opiate. Several investigators have suggested that many of, the physical complaints are really of psychological rather than physical origin, in which case they would be very context-specific. Unlike the withdrawal associated with the depressants, and alcohol which we will discuss later in this module, opiate withdrawal is rarely life-threatening, unless there are preexisting cardiovascular problems that could result in stroke, or heart failure during the heightened sympathetic nervous system activity. For a number of years, many experts believed that the physical dependence on opiates was the primary motivating factor in, continued drug taking. However, study after study has noted that even after abstinence syndrome has long since dissipated, the vast majority of addicts, if left without further treatment, eventually start taking opiates again. Addicts often report the craving for opiates may be present even after several months of abstinence. Studies demonstrating how the context, can trigger reactions that could promote the craving. Continued abstinence symptoms have been shown to develop when organisms undergo physical withdrawal when opiate actions, are terminated rapidly in specific contexts. Thus, the view is now that the psychological dependence on opiates is far more powerful factor, in the long run, in maintaining opiate drug-taking behavior. All forms of dependence-primary and secondary psychological, as well as physiological, have been documented to occur with narcotics. Other than these effects, heroin and other narcotics are not, particularly damaging as far as the body is concerned. However, they have such primary reinforcing value that people will engage in some maladaptive behaviors to obtain them and experience their effects. The high incentive value of narcotics may also decrease the person's desire for engaging in socially acceptable activities.

Effects of Cocaine

Varying based on the individual Low dose: Mood-elevating Increases alertness Increased energy Increased cognitive functions Increased heart rate and blood pressure High dose: Insomnia Restlessness Muscle tenseness Anxiety or panic attacks Cardiac problems Effects with alcohol Effects with nicotine The effects of caffeine vary, considerably among individuals in terms of wakefulness, psychomotor coordination, mood alternations, and the autonomic nervous system response. Two cups of coffee, which contains on average about 150 mg, of caffeine, have the mood-elevating and fatigue-relieving properties of threshold doses of some amphetamines. However, larger doses generally do not have more of a mood-elevating effect, and 7 to 10 cups of coffee may cause insomnia, restlessness, mild sensory disturbances, or muscle tenseness, or someone may experience anxiety or panic attacks. Caffeine typically raises blood, pressure slightly in both men and women, but apparently have different mechanisms. Similarly, increases in heart rate can occur with some caffeine doses, but with others it may actually decrease. Persons who consume low to moderate doses of caffeine typically display dose-dependent improvements in arousal, daytime alertness, vigilance, and some aspects of psychomotor performance. It can also increase cognitive functions, such as reaction time, sustained attention, and information processing. Again, with low to moderate doses of caffeine, individuals may experience predominately, positive subjective effects on mood, characterized by increased well-being, energy, and concentration. These beneficial effects are particularly evidenced when the individuals are tested under, conditions of caffeine deprivation or total abstinence in regular caffeine use has been shown to significantly improve auditory vigilance and visual reaction time. Caffeine can produce an increased, capacity for both muscular work and sustained intellectual effort, but it can also disrupt arithmetic skills and task performance when delicate muscular coordination and accurate timing are required. However, in terms of subjective feelings of drunkenness, such as manual dexterity, balance, numerical reasoning, and verbal fluency-the effects of alcohol intoxication are not reduced by caffeine. Thus, an intoxicated driver, after consuming a few cups of coffee, might feel more alert, but he or she will still be impaired in terms of the motor coordination and decision making required, for properly driving a motor vehicle. Caffeine also exhibits some interesting interactions with nicotine. In this case, the evidence suggests that caffeine can enhance the reinforcing, and subjective stimulant qualities of nicotine in humans. On the other hand, cigarette smokers, who generally consume more coffee than nonsmokers, metabolize caffeine at an accelerated rate. Upon smoking cessation, consumption of caffeinated substances can increase caffeine plasma levels on average more than 200 percent-an effect that may persist for as long as 6 months. This in turn could increase the person's "jitteriness" and be a contributing factor in tobacco withdrawal symptoms. These drug interactions, plus the possibility that the consumption of, caffeine-containing beverages can serve as a conditioned stimulus triggering tobacco craving, suggest that the effectiveness of programs to treat nicotine addiction might be improved by, eliminating the use of caffeine prior to the start of treatment.

Fat-Soluble Vitamins

Vitamin A Essential for vision Necessary for the health and development of the skin Needed for other cellular linings of the body Essential for bone growth, sexual reproduction, and fetal development. Vitamin D Promotes the absorption of calcium from the intestine Regulates the metabolism of both calcium and phosphorus Vitamin E Known to act as an antioxidant effect Contribute to the maintenance of cell-wall integrity, muscle metabolism, and pregnancy Vitamin K Essential for the normal biosynthesis of several factors required for the clotting of blood Vitamin A has a number of important functions in the body. It is essential for vision, especially in connection with adaptation to the dark, and for the structural integrity of the eye. Vitamin A is necessary for the health and development of skin as well as other cellular linings of the body. It is also essential for bone growth, sexual reproduction, and fetal development. The average adult receives half of his or her daily intake of vitamin A as performed vitamin and the remainder as precursors to vitamin A formation. Retinol is found in the liver, butter, cheese, whole milk, egg yolk, and fish. Carotenoids are present in various yellow or green fruits and in vegetables. Fish liver oils contain extremely high levels of vitamin A, and excessive ingestion of such oils can lead to toxicity. Deficiencies of vitamin A can produce night blindness; thick, rough, and dry skin; increased susceptibility to respiratory infections; dryness and thickening of the conjunctiva; and blindness. The role of vitamin D in promoting the absorption of calcium from the intestine was discussed earlier. It should be added that vitamin D also regulates the metabolism of both calcium and phosphorus. The major sources of vitamin D are the livers or liver oils of fish. Other sources include tuna, salmon, herring, egg yolk, and dairy products. Today, the fortification of milk with vitamin D provides enough of the substance to meet daily requirements. Rickets is the disease associated with vitamin D deficiency. In adults, vitamin D deficiency results in osteomalacia, a disease characterized by a generalized decrease in bone density much like that seen in osteoporosis. Vitamin E is known to act as an antioxidant effect; vitamin E may contribute to the maintenance of cell-wall integrity, muscle metabolism, and pregnancy. Other functions and therapeutic applications are largely conjectural at the present time. Vitamin E is widely found in foodstuffs, especially in vegetable oils, vegetables, fruits, grains, and dairy products. Vitamin K is essential for normal biosynthesis of several factors required for the clotting of blood, the most important of which is the production of prothrombin by the liver. Vitamin K is widely found in nature, and its highest concentrations are in leafy green vegetables, liver, grains, egg yolks, and dairy products. Now, lets move on to water soluble vitamins.

Water-Soluble Vitamins

Vitamin C Acts either as a coenzyme or as an antioxidant. Functions : Normal synthesis of collagen and other connective tissues. Formation of normal teeth, bones, and blood capillaries. Synthesis of steroids in the adrenal cortex and certain neurotransmitters. "B complex" Thiamine (B1) Necessary for the breakdown of certain keto-acids into forms that can be used to produce energy Essential for normal neuromuscular transmission and the synthesis of the transmitter AcH Maintain cardiac muscle tone, probably as an intermediary in energy production. Riboflavin (B2) Essential for certain reactions of intermediary metabolism involving cellular respiratory and energy producing processes Niacin (B3) Necessary for many metabolic processes essential for cellular energy production. Pyridoxine (B6) Essential metabolic utilization of amino acids, synthesis of neurotransmitters, formation of bile acids, and the development of the brain Cyanocobalamine (B12) Combines with an "intrinsic factor" secreted but the stomach that is essential to the absorption of the vitamin Folic acid Protein and nucleic acid synthesis Required for blood cell production, growth and development of body tissues, and the normal functioning of the CNS and GI tract. Biotin Important in normal growth and the maintenance of nervous system tissue, skin, hair, muscle, bowel, and blood. Pantothenic acid (B5) Cofactor for several reactions Vitamin C, in the form of limes, lemons and oranges, has been used to prevent and treat scurvy since the mid-1500s. In about 1930, the antiscurvy substance in citrus fruits was identical as ascorbic acid, a six-carbon compound structurally related to glucose and other sugars. Ascorbic acid is obtained from citrus fruits, tomatoes, strawberries, green vegetables, currants, and potatoes. Orange and lemon juices contain about 15 mg/ounce. Ascorbic acid functions in many biochemical reactions; it acts either as a coenzyme or as an antioxidant. Vitamin C is necessary for the normal synthesis of collagen and other connective tissues; the formation of normal teeth, bones, and blood capillaries; the synthesis of steroids in the adrenal cortex; the synthesis of certain neurotransmitters; and, the ability to aid in wound healing and maintains the structure of blood capillaries and gingiva by increasing collagen formation. Megadoses have been postulated to aid in treating a variety of illnesses ranging from the common cold to states of advanced cancer. These allegations remain unproved. The "Vitamin B complex" comprises many vitamins, all of which are involved in numerous metabolic activities. These vitamins, although separate types, usually are grouped together since they originally were isolated from the same common sources, notably liver and yeast. The B vitamins consist of either recognized substances: thiamine (b1), riboflavin (b2), niacin (b3), pyridoxine (b6), cyanocobalamine (b12), folic acid, biotin, and pantothenic acid (b5). All are water soluble; therefore, excesses are excreted rapidly. In addition to these eight compounds, several other substances have been alleged to be B vitamins, which are essential for health. Thiamine functions in carbohydrate metabolism and is necessary for the breakdown of certain keto-acids into forms that can be used to produce energy. Thiamine is essential for normal neuromuscular transmission and is involved in the synthesis of the transmitter AcH. Thiamine also is involved in maintain cardiac muscle tone, probably as an intermediary in energy production. Foods rich in thiamine include pork, organ meats, yeast, and grain. Many cereals and flour are enriched with thiamine. Riboflavin or Vitamin B2 is essential for certain reactions of intermediary metabolism including cellular respiratory and energy producing processes. Riboflavin is abundant in most dairy products, organ meats, and yeast. It is also present in enriched breads, and cereals. Niacin or Vitamin B3 is a coenzyme necessary for many metabolic processes essential for cellular energy production. Its role is essential in the Krebs cycle. The integrity of this process is essential for biochemical conversion of carbohydrates, fats, and proteins for useable energy. Niacin is readily obtained from liver, meat, poultry, fish, white grains, and enriched breads and cereals. The amino acid tryptophane, found in milk and eggs can be converted in the body in to small amounts of niacin. Lack of niacin in the diet leads to the clinical condition called pellagra. Characteristics of pellagra include diarrhea, dermatitis, redness and swelling of the tongue and dementia. Such deficiency is commonly seen in people suffering from chronic malnutrition and alcoholism. Pyridoxine or vitamin B6 is essential as a coenzyme for numerous reactions involving the metabolic utilization of amino acids, the synthesis of neurotransmitters, the formation of bile acids, and the development of the brain. Pyridoxine is commonly found in meat, liver, fish, whole-grain cereals, and vegetables. Vitamin B12 is not absorbed orally unless it combines with an "intrinsic factor" secreted but the stomach that is essential to the absorption of the vitamin. Humans are dependent on dietary sources of vitamin B12 to avoid pernicious anemia. Large quantities are found in meats, and especially livers. Egg yolk and seafood's contain lesser amounts. The vitamin is absent in vegetable products which places vegetarians at risk for developing deficiencies unless they take b12 supplements. Folic acid is a coenzyme required for several biochemical reactions involving protein and nucleic acid synthesis. It is therefore required for blood cell production, the growth and development of body tissues and the normal functioning of the CNS and the GI tract. Most foods are rich in folic acid, especially fresh green vegetables, liver, yeast, and beans. Lack of folic acid produces an anemia identical to that produced by vitamin b12 deficiency. The nervous system is rarely, if ever, effected. Other symptoms of deficiency include weight loss, diarrhea, and sore tongue. Biotin is a cofactor in carbohydrate and fat metabolism. As such, it is important in normal growth and the maintenance of the nervous system tissue, skin, hair, muscle, bowel, and blood. Biotin is found widely in organ meats, egg yolk, peanuts, and some vegetables. Egg white contains none and indeed raw egg white contains a substance that binds to biotin with great affinity and prevents its absorption. Deficiency of this element is characterized by neuromuscular disorders; severe skin irritation, loss of hair, muscle pain, and depression. Pantothenic Acid or Vitamin B5 is required as a cofactor for several reactions involving the metabolism of carbohydrates, the syntheses of glucose, the synthesis and breakdown of fatty acids, and the synthesis of steroid hormones. Vitamin B5 is found in organ meats, beef, egg yolk, bran, and peanuts. Deficiency in pantothenic acid is associated with neuromuscular degeneration, adrenal cortical insufficiency, and some infections.

Vitamins

Vitamins are organic substances that must be provided dietarily in small amounts to increase the rate of biochemical reactions within the body. Vitamins, therefore, are exogenous compounds required for the maintenance of life and of health.

Caffeine Tolerance

Withdrawal symptoms: Adult: Headache Increased fatigue Sleepiness Laziness Decreased alertness Neonatal Irritability Jitteriness Vomiting Tolerance develops to many of the effects of caffeine, most likely due to up-regulation of adenosine receptors in the brain. Withdrawal symptoms are uncommon, except following heavy use. Caffeine withdrawal may include headaches, increased fatigue, sleepiness, and laziness, and decreased vigor and alertness. A neonatal withdrawal syndrome, consisting, of irritability, jitteriness, and vomiting, may occur in infants born to mothers who consume large amounts of caffeine during pregnancy. However, the dependence liability of caffeine is very low, and classical clinical indicators of dependence, such as difficulty in stopping the use of caffeine and use despite harm, have not been documented.

Chronic Use of Benzodiazepines

Withdrawal: -Moderate Doses Anxiety Agitation Increased sensitivity of light and sound Muscle cramps Twitches Sleep disturbances Dizziness -High Doses Panic Depression Seizures Delirium -May not appear for a week or so after abrupt discontinuation of these drugs Toxic Reactions Increase in hostility and irritability Following chronic usage of moderate dosages of benzodiazepines, abrupt discontinuation of use induces withdrawal symptoms consisting of anxiety and agitation, increased sensitivity to light and sound, strange sensations, muscle cramps and twitches, sleep disturbances, and dizziness. Following high-dosage usage, panic attacks, depression, seizures, and delirium can develop. The severity of withdrawal is inversely related to the plasma half-life of the benzodiazepine used. However, since many benzodiazepines, and their active metabolites, accumulate and persist in the body for several days, withdrawal symptoms after chronic use may not appear for a week or so after abrupt discontinuation of these drugs, and the withdrawal symptoms are generally less intense than those occurring with other sedative-hypnotics. Furthermore, high doses must be given for a considerable length of time before marked withdrawal symptoms develop. Withdrawal following chronic benzodiazepine exposure can also be triggered by the administration of the benzodiazepine antagonist flumazenil. As might be expected, chronic exposure to benzodiazepines is associated with progressive development of GABAA receptor desensitization. The toxic reactions and side effects of benzodiazepines are similar to those of the barbiturates. In some cases, a paradoxical increase in hostility and irritability, and even anxiety may accompany benzodiazepine use. Other potential side effects of benzodiazepines include amnesia, hallucinations, skin rashes, nausea, headaches, vertigo, light-headedness, sexual impotence, lowered white blood cell count, and menstrual irregularities.