Unit 7

Factors that contribute to drug abuse: Social factors

Desire for social status/approval is common reason for initiating drug use. Similarly, desire for status/approval is common reason for repeating use after initial exposure, ** which is often unpleasant **

Alcohol pharmacology: CNS effects

Two acute effects when ETOH interacts to increase GABA and decrease glutamate (depressant effects) and spur serotonin to release dopamine (reward): 1. General depression of CNS function 2. Activation of reward circuit

Drug abuse

Using a drug in a fashion inconsistent with medical or social norms. Varies from culture to culture. More of a social science question than a pharmacological question.

Nicotine pharmacology: CNS effects

Nicotine is a stimulant. Increases alertness, facilitates memory, improves cognition, reduces aggression, suppresses appetite. Releases dopamine in same way as other highly addictive drugs.

Nicotine pharmacology: CV effects

Nicotine promotes release of epinephrine and norepinephrine, which constrict blood vessels, increase HR and contraction, which elevates BP and increased cardiac work.

DEA schedule I drugs

No approved use. Not prescribed. ** Table 37-3, pg. 436, Lehne. **

Factors that contribute to drug abuse: Reinforcing properties of drugs

Occurs in two ways: 1. Drugs give the individual an experience that is pleasurable 2. Drugs can reduce the intensity of unpleasant experience (e.g. anxiety and stress) Studies show that pre-existing psychopathology is NOT necessary for drug abuse to develop due to reinforcing properties of drugs.

Factors that contribute to drug abuse: Physical dependence

Physical dependence can cause a person to keep abusing drugs as a motivator to avoid withdrawal symptoms. Degree of physical dependence largely determined by: 1. dosage 2. duration of use - Opioids and CNS depressants = substantial physical dependence - Psychostimulants, psychedelics, marijuana = less prominent physical dependence

Factors that contribute to drug abuse: Psychologic dependence

Psychologic dependence makes people feel strongly that their sense of well-being is dependent upon continued drug use. When drug is unavailable, a sense of "craving" is felt.

DEA schedule V drugs

Rx: Oral, written or electronic Refills: Up to 5 times within 6 months of original order. * Special: Schedule V drugs may be dispensed WITHOUT Rx provided the following conditions are met: 1. Drug dispensed by pharmacist 2. Amount dispensed is very limited 3. Recipient is at least 18 years old and can prove it 4. Pharmacist writes and initials a record indicated date, name and amount of drug, and name and address of recipient 5. State and local laws do not prohibit dispensing Schedule V drugs without Rx. ** Table 37-3, pg. 436, Lehne. **

DEA schedule III drugs

Rx: Oral, written or electronic Refills: Up to 5 times within 6 months of original order. ** Table 37-3, pg. 436, Lehne. **

DEA schedule IV drugs

Rx: Oral, written or electronic Refills: Up to 5 times within 6 months of original order. ** Table 37-3, pg. 436, Lehne. **

DEA schedule II drugs

Rx: Typed, written in ink/indelible pencil and signed by prescriber or submitted electronically. Oral OK in emergencies but must be followed by written within 72 hours. Refills: No. But multiple prescriptions can be written on the same day for the same patient and drug to be filled sequentially for up to 90 days. ** Table 37-3, pg. 436, Lehne. **

Alcohol pharmacology: Acute overdose

S/S: vomiting, coma, hypotension (leading to renal injury and shock), respiratory depression.

Principles of addiction treatment

See Table 37-2, page 435 of Lehne. - Ultimately goal: Complete cessation of drug use. But often treatment that changes drug use from compulsive to moderate will permit increased productivity, better health and decrease in socially unacceptable behavior. Note: tobacco, alcohol and opioid abusers are rarely capable of "sustained moderation." - Relapse does not mean treatment has failed. It just means that at least one more treatment episode is needed. - Treatment program should address: drug use, along with any related medical, psychologic, social, vocational and legal problems.

Alcohol pharmacology: Drug interactions

- CNS depressants: Additive - NSAIDS: Increased risk for GI mucosa injury - APAP: Increased risk for liver injury - Disulfiram: Variety of adverse affects - Antihypertensive drugs: Counteractive effect unless consumed in moderation, then a possible thereapeutic affect

Factors that contribute to drug abuse

- Reinforcing properties of drugs - Physical dependence - Psychologic dependence - Social factors - Drug availability - Vulnerability of the individual

Alcohol pharmacology: Therapeutic uses

- Topical: cooling in febrile patients, disinfectant, ulcer prevention - Oral: aid to digestion in bedridden patients - IV: provide calories and fluid replacement - Local injection: nerve blog and pain relief

Alcohol pharmacology: NIAAA list of those who should avoid ETOH

- pregnant or trying to conceive - plan to drive or perform activities that require attention and coordination - taking antihistamines, sedatives, or other drugs that will increase ETOH affects - recovering alcoholics - people under age 21

Cross-dependence

Ability of one drug to support physical dependence of another drug. Example: Drug A will prevent withdrawal in a patient physically dependent on Drug B, and vice versa. Generally existgs among drugs of same pharmacological family.

Alcohol pharmacology: Absorption

Absorbed by stomach (20% and dependent on food) and small intestine (80% and independent of food).

Factors that contribute to drug abuse: Drug availability

Abuse can flourish only in environments where drugs can be readily obtained. When procurement is difficult, abuse is minimal.

Alcohol pharmacology: Liver

Acute ETOH causes reversible fat and protein build-up in liver. Chronic ETOH can lead to hepatitis and then fatal cirrhosis.

Factors that contribute to drug abuse: Vulnerability of the individual

Some individuals are more prone to becoming drug abusers than others. Several factors have been associated with drug abuse tendencies: - impulsiveness - lower tolerance for frustration - rebellious against social norms - depressive/anxiety disorders - antisocial personality - genetics

Alcohol pharmacology: Physical dependence

Chronic consumption produces physical dependence. Abstinence syndrome will develop with sudden withdrawal.

Alcohol pharmacology: Tolerance

Chronic consumption produces tolerance. However, very little tolerance to respiratory depression develops. Therefore, moderate and heavy drinkers face the same risk of fatal respiratory depression.

Nicotine pharmacology: Dependence

Chronic smoking results in dependence. Prominent symptoms of abstinence syndrome: craving, nervousness, restlessness, irritability, impatience, increased hostility, insomnia, impaired concentration, increased appetite, weight gain. Begins 24 hours after cessation, lasts weeks to months.

Addiction

Chronic, relapsing brain disease that is characterized by compulsive seeking and use, despite harmful consequences. Addiction is NOT equal to physical dependence. Physical dependence can CONTRIBUTE to addiction but is not necessary nor sufficient for addiction to occur.

Alcohol pharmacology: Lactation

Concentration of ETOH in breast milk parallels concentration in blood. Can adversely affect infant's feeding and behavior.

Alcohol pharmacology: Sexual function

Conflicting psychologic and physiologic sexual affects. 1. Psychologic: Release of inhibitions known to motivate sexual activity 2. Physiologic: ETOH significantly decreases capacity for sexual responsiveness.

Withdrawal syndrome

Constellation of S/S that occurs in physically dependent individuals when they discontinue drug use. Often symptoms are opposite to effects that drug produced before withdrawal (e.g. CNS depressant withdrawal = CNS excitation).

Alcohol pharmacology: Distribution

Distributes well to all tissues and body fluids. Crosses blood-brain barrier with ease, as well as placenta.

Alcohol pharmacology: Cancer

ETOH (even moderate) associated with increased risk of cancer of the breast, liver, rectum, aerodigestive tract (lips, tongue, mouth, nose, throat, vocal cords, esophagus/trachea).

Alcohol pharmacology: Pancreas

ETOH associated with pancreatitis.

Alcohol pharmacology: Effect on sleep

ETOH disrupts sleep when drinking late in the evening. It can: - alter sleep cycles - decrease total sleeping time - reduce quality of sleep - exacerbate sleep apnea

Alcohol pharmacology: Bone health

ETOH increase bone mineral density.

Alcohol pharmacology: Kidney

ETOH is a diuretic by inhibiting ADH from pituitary.

Alcohol pharmacology: Glucose metabolism

ETOH may decrease risk for Type 2 diabetes by lowering fasting levels of both glucose and insulin and suppressing gluconeogenesis.

Alcohol pharmacology: Pregnancy

Effects of ETOH on developing fetus are dose dependent. Risk greatest with heavy doses, lower with light drinking. Heavy drinking can result in: stillbirth, spontaneous abortion, alcohol-dependent infant. ** Conflicting data on whether light drinking is safe during pregnancy, but women are recommended to abstain completely as the risks far outweigh the benefits **

Nicotine pharmacology: Pregnancy and lactation

Exposure can harm fetus and nursing infant. Currently considered medically reasonable to use nicotine therapy to help pregnant woman quit smoking, as pharmaceutical nicotine is safer than tobacco smoke.

Alcohol pharmacology: FASD vs. FAS

FASD: Fetal Alcohol Spectrum Disorder. Reference to full range of mild to severe outcomes of drinking while pregnant. FAS: Fetal Alcohol Syndrome. Reserved for most severe cases of FASD, characterized by craniofacial malformations, growth restriction, neurodevelopmental abnormalities.

Alcohol pharmacology: Stomach

Heavy ETOH can cause erosive gastritis. Mechanisms: 1. ETOH stimulates secretion of gastric acid 2. High doses of ETOH can injure gastric mucosa directly

Neurobiology of addiction

In a nutshell: Drugs cause molecular changes in the brain that promote further drug use. How: Drugs activate brain's "reward circuit." The major neurotransmitter is dopamine, which gets released and promotes pleasure and therefore reinforces behavior (normally in response to sex, eating, etc). But because drugs spur the release of 2-10X the normal amount of dopamine, the brain goes through "down-regulation." The reward circuit is activated so excessively that the brain responds by 1) producing less dopamine and 2) reducing the number of dopamine receptors. As a result, the natural stimuli to activate the reward circuit is reduced, and also the response to drugs is reduced. Thus, the addict is left feeling flat, lifeless and depressed.

Psychologic dependence

Intense subjective need for a particular psychoactive drug.

Alcohol withdrawal

Low dependence: S/S include disturbed sleep, weakness, nausea, anxiety, mild tremors, all lasting less than a day High dependence: cramps, vomiting, hallucinations, intense tremors, increased in HR/BP/temp, seizures, disorientation, loss of insight. Delirium tremens: severe hallucinations that disconnect addict from reality

Alcohol pharmacology: Impact on cognitive function

Low-to-moderate drinking helps preserve cognitive function in older people and may protect against development of dementia.

Alcohol pharmacology: Metabolism

Metabolized by liver and stomach at constant rate that is unchanged by amount consumed (except for heavy drinkers, then metabolism becomes faster). Consumption of 1 drink per hour will result in ETOH build-up.

Alcohol pharmacology: Longevity

Moderate doses: Data show it can prolong life over those who abstain, but nobody currently recommends those who abstain to start drinking. Heavy doses: Higher mortality rate than population at large (cirrhosis, respiratory disease, cancer, fatal accidents.)

Alcohol pharmacology: CV system

Moderate doses: May experience less ischemic stroke, coronary artery disease and myocardial infarction as a result of increase in HDL cholesterol, anticoagulant effects and reduced inflammation. Heavy doses: Direct damage to myocardium, hypertension, increase in risk of heart disease and stroke ** Benefit of moderate drinking associated with people who otherwise lead unhealthy lifestyles **

Alcohol pharmacology: Respiration

Moderate doses: Negligible respiration depression Heavy doses: Respiratory depression can be fatal

Nicotine pharmacology: GI effects

Nicotine increases gastric acid and augments tone and motility of GI smooth muscle. Also can induce vomiting.

Tolerance

State in which a particular dose elicits a smaller response than it did with initial use. Results from regular drug use.

Physical dependence

State in which an abstinence syndrome will occur if drug use is discontinued. Result of neuroadaptive processes that take place in response to prolonged drug exposure.

Cross-tolerance

State in which one drug confers tolerance to another. Usually with drugs of particular class. Example: tolerance of heroin (opioid) confers cross-tolerance to other opioids (e.g. morphine) but not CNS depressants, nicotine, etc.

Alcohol use disorder

Table 38-4, pg. 444, Lehne Alcohol use disorder, commonly called alcoholism or alcohol dependence, is a chronic, relapsing disorder characterized by impaired control over drinking, preoccupation with alcohol consumption, use of alcohol despite awareness of adverse consequences, and distortions in thinking, especially as evidence by denial of a drinking problem. Development and manifestations are influenced by genetic, psychological and environmental factors.

Nicotine pharmacology: Tolerance

Tolerance develops to nausea and dizziness but very little tolerance develops to CV effects.

Alcohol pharmacology: Chronic effects

When consumed chronically and in excess, ETOH can produce severe neurological and psychiatric disorders. Injury to CNS caused by direct actions of ETOH and by nutritional deficiencies. 1. Wernicke's encephalopathy - Thiamin deficiency - S/S: confusion, nystagmus, abnormal ocular movements. Treat with thiamin. 2. Korsakoff's psychosis - S/S: polyneuropathy, inability to convert short-term memory to long-term memory, confabulation (unconscious filling of gaps in memory with fabricated facts and experiences). Irreversible. 3. Enlargement of cerebral ventricles - S/S: impairment of memory and intellectual function. Can be partially reversible.