Drugs and Behavior Test 2 (6,7,8,9,13,14)

Off-Label Uses of Antipsychotics

Atypical Antipsychotic Ability was the second best selling drug in 2015. Zyprexa and Seroquel also big sellers. Together they produce more than $16 billion -Odd, because schizophrenia is relatively uncommon (1% of population) -Off-Label (Unapproved) uses include depression, dementia, sleep disorder, stress, OCD. -Limited support for theres uses - Lilly fined 1.4 billion in 2009 for of label zyprexa ads

Cocaine in the 1970's-1990's

-"Cocaine is not an addictive or especially dangerous drug. It should be legalized" -Glamorized drug -Cocaine is still used for facial surgeries because it helps clot the blood (vasoconstriction) and it's a mild anesthetic (unfortunately, that also decreases cocaine absorption, meaning that capillaries are all clamped down, you won't absorb drug as officially ) -If you have the money to spend on cocaine, you will spend it all -The George Jung Story (Blow: The story behind the movie) -Led to Colombian Cartels -Medellin: Pablo Escobar (killed in 1993) Alternative group emerges: Cali Civil war between Cali and Medellin Now, twelve years later, the textbooks read "Cocaine is the most dangerous drug on earth"

What is depression? Differentiate between endogenous and exogenous depression. Consider theories of the etiology of depression. What are the types of drugs used in the treatment of depression and how they are thought to work? In particular, be able to differentiate the MAOI's, the tricyclics, and the SSRI's. Consider the major effects of depressant drugs. What is meant by the terms anxiolytic; Sedative-hypnotic? General anesthetic?

-20% of US will experience depressive episode, 10% in given year -Endo is caused by genetics or bad brain chem, -Exo is from traumatic life events or environment. Symptoms: dysphoric mood, loss of interest, sleep disturbance, withdrawal, difficulty concentrating Depression results from deficiency in catecholamines (particularly norepinephrine) and serotoninin 1.Cyclic antidepressants: Block uptake of amines (More commonly prescribed) 2.MAOI's: Prevent the breakdown of neurotransmitters Monoamine oxidase inhibitors (Parnate, Marplan, Nardil) 3. Newer antidepressant meds (Effexor, Celexa) Monoamines: Norepineprhine, serotonin, dopamine -MAO would normally be breaking down mono amides -Results of MAOI's are not as impressive as cyclics -Cyclics: Third most commonly prescribed drug class taken by 13% in 2017 -Blocks reuptake of serotonin receptors (Doesn't effect norepinephrine) -Bupropion (Wellbutrin) dopamine reuptake anxiolytic- inhibits anxiety sedative hypnotic- reduces irritability anesthetic- loss of consciousness General Anesthesia: The reduction of pain by rendering the subject unconscious -First depressants discovered were drugs used for general anesthesia -Nitrous Oxide used almost solely for anesthesia

Alcohol

-Known manufactured and used for longer than nicotine or caffeine -Depresses central nervous system (Alters cell membrane's anatomy by entering their internal structure) -Affects cell membranes, all neurichemical systems, all endocrine systems -Formally classified as a food - 60% of Americans drink alcohol, a minority drink heavily America's "Love-hate" relationship with alcohol The largest drug business in the world: >$400 billion dollars/year in USA (double check this number) 65% high school seniors report drinking Students are targets of alcohol advertising (Sex sells) Alcohol advertising targets virtually everyone in our society (Especially youth) One in 12 will develop alcoholism or alcohol abuse disorder Ethyl Alcohol or ethanol is what we consume Other types of alcohol are toxic: 80 people died due to methanol (Wood alcohol) poisoning in India, Feb 2019

What is Erythroxylum coca? Where does it grow?

-Low shrub bush called the coca bush or coca tree, the leaves produces powerful stimulant cocaine -Grows in Bolivia, Ecuador, northern Argentina, and Peru (Northern South America)

Why is Ginkgo biloba used?

-Marketed as "smart drug" -Supposedly enhances memory and concentration -Might actually be helpful for patients wit cognitive impairments/ Alzheimers

Passive Smoking

-Second hand smoking. Living or working in a environment where you are constantly exposed to smoking also increases the risk of these diseases (Still an active killer) -Kills 600000 people globally per year

BAC - Drinks - Effects Consider the effects of alcohol across various doses (Table 9.5)

0.04% 1-2 Relaxed, skin may flush, mild impairment in motor skills 0.08% 3-4 High (Motor coordination measurably impaired, exaggeration of emotional response, definition of driving under the influence) .15% 7-10 drinks = Drunk (major impairment in balance and movement, large impairment in judgement and perception, increase in reaction time) .30%. 11-15 Dead drunk (confusion and stupor, loss of consciousness, difficulty comprehending .40% 16-20 Dead (typically unconscious, alcohol has become anesthetic) LD50 for alcohol is about .45-.5 (25 drinks in an hour) Protracted tolerance from daily drinking can lead to higher BAC (Mostly functional tolerance, meaning you might feel sober, but BAC says otherwise)

What are the sensorimotor effects of alcohol?

0.05% and Up: Vision decreases in acuity, taste and smell not so sensitive 0.08-.1% pain sensitivity decreases .1% and up: Simple reactions time begins to slow significantly Complex reaction time may be impaired in both speed and accuracy at BAcs of .05% or even lower At BAC .06% body sway is impaired by 40% -Alcohol impairs psychomotor skills at .03% and up At .15% or more, there is clear abnormality in gross motor functions like standing and walking (Neural messages not being sent to the muscles) 29% of all traffic fatalities caused by person with BAC at 0.08 or greater National academy of sciences 2018 report recommends reduce limit to 0.05% Decline in performance is measurable at 0.05% Estimates 11% decrease in alcohol fatalities at 0.05% limit Utah placed a 0.05% DUI limit in effect Jan 2019 Young people more likely to crash Many states call "measurable" BACs higher than 0.02% Young men (18-34) seem most likely to b e intoxicated, driving, and in accidents From 1982-2015, alcohol related traffic fatalities fell 51%

6. What are the physiological effects of caffeine? 7. What are the effects of caffeine on mood and performance? 12. What are the therapeutic effects of the methylxanthines?

6. Acute effects: Contraction of straighted/heart muscle, relaxation of smooth muscle, metabolism stimulation (stimulation of gastric acid), diuretic effects on the kidneys 7. Mood: CNS stimulation action of caffeine elevates mood, feeling energized, creative, efficient, confident, and alert Performance: improves task performance by decreasing fatigue and increasing vigilancse so performance does not drop below what is normal. Caffeine impairs the decision-making part of the task but improves the motor component (reaction time) -Decreases motor skills 12. -Caffeine is used in variety of prescription and over-the-counter medications -Often used for headaches and colds -Cerebral stimulation = caffeine (coffee), coronary dilation = theophylline (tea), Appetite suppresant/diuresis= theobromine (cocoa), and respirator stimulant for premature infants = caffeine) -Treatment for pain and Parkinsons

What is a "crack baby"? What is the prognosis for these children?

A child born to a mother addicted to crack. -Low birth weights, baby more likely to die -Difficult to separate crack effects from effects of up bringing -Lower IQ's, but is it caused by crack? Premature birth and some birth defects can happen but the child usually does OK, but will have to undergo withdrawal if they are born addicted

How is tolerance to alcohol related to ethnicity (note the Asian flushing response)

A physical reaction that occurs with drinking alcohol, it consist of cutaneous flushing and sometimes other symtoms such as palpitations, tachycardia, perspiration, and headaches (only occurs in Asians) -due to deficiency in aldehyde isozyme, which leads to build up of acetaldehyde -Unpleasant, leads to drinking in moderation -Japan: Biological reaction + cultural customs = no epidemic of alcohol problems -In Japan, moderate alcohol use is valued and excessive drinking is not

What is kratom and why has it recently become controversial?

A plant that produces sedative effects. Although kratom is now illegal in Malaysia and Thailand, largely due to concerns about addiction, it is not scheduled in the United States. -Produces pain relief similar to opiates -Produces euphoric state -Can relieve opiate withdrawal -Associated with tolerance and withdrawal symptoms

Bath Salts

A psychoactive "designer drug" that is synthesized from various amphetamine-like chemicals and can be inhaled, swallowed, smoked, or injected Synthetic analogs of cathinone, found in plant called khat

What is St. John's wort (Hypericum) used for? Does it work? What about valerian

Antidepressant (Non-drug therapy, herbal) -Yellow flowered plant, aka goatweed -Treatment for mild to moderate depression -Increases production of liver enzyme, speeds elimination of many common drugs/some cancer drugs may be less effective -Some debate on whether or not it works (Controversial) -May produce side effects Valerian: Treatment for insomnia and anxiety for 1000 years -Studies find mixed results

Depressant Drug Action

Anxiolytic < Sedative < Anesthetic (As in general anesthesia) < Death

Benzodiazepines: Anxiolytics/Hypnotics What are benzodiazepines? Consider their mechanism of action. How are benzodiazepines used in psychotherapy? Why are they preferred to other depressants?

Barbituates, benzodiazepines, non-barbiturate sedatives and general anesthetics all can depress CNS and behavior (common mechanism o f action Currently the most widely prescribed anxiolytic drugs -1950's -Work by enhancing neural inhibition in the GABA system Largely replaced barbiturates since they are considerably safer(although issues with dependence and withdrawal are still present) Benzodiazepines: Often labelt as anxiolytic (anti anxiety) drugs, larger doses produce sedative hypnotic effects (Prescribed as sleeping pills) First Benz = Chlordiazepoxide (Librium) in 1960 >48 hrs Diazepam (Valium) >48 hrs These were first to be discovered -Most important class of drugs for treating anxiety and sleeping disorders Clonazepam (Klonipin) >12 hrs Alprazolam (Xanax) > 12 hrs Lorazepam (Ativan) >12 hrs Often use for alcohol withdrawal Triazolam (Halcion) >4 hours Most potent: Midazolam (Versed) 1 hour -Used for short surgical procedures -Anxiolytic Effects, also prescribed for insomnia -Sedative Effects without the hangover! -Rebound insomnia is less of a problem than with barbituates -Tolerance (develops slowly), cross tolerance does occur too -Synergy (Don't combine sleeping pills/alcohol), cross tolerance and cross dependence -Withdrawal symptoms are pretty rare and not severe Adverse Effects: Drowsiness, motor impairment, Anterograde amnesia (interference with the storage of memories/ loss or limitation of ability to form new memories) -Roofies are Benzos All depressant drugs, including alcohol, can lessen anxiety at low levels, produce intoxication at moderate levels, induce sedation/sleep at higher levels, produce general anesthesia at very high doses, and can eventually lead to coma/death

Why are synthetic cathinones often called "bath salts" or "plant food"? What are some frequently used synthetic cathinones? What law banned sales of the main synthetic cathinones?

By giving these psychoactives these names and labeling them as not for human consumption you can get away with legally selling them. Some examples are khat, mephedrone, methylone, and MDPV, methicathinone. The 2012 Synthetic Drug Abuse Prevention act has banned these substances.

Adenosine Hypothesis

Caffeine blocks adenosine receptors as its mech of action because caffeine effects are opposite to those of adenosine. Adenosine is chemical body produces (Inhibitory neurotransmitter) -Leads to behavioral sedation, dilation of blood vessels Cafeine occupies adénosine recentres and then block the action of that transmitter Neural mechanism: blocks the inhibitory transmitter adenosine. It is not a particularly abundant in the body. Very different from amphetamines which activate monoamines, in particular dopamine.

How is caffeine absorbed into the body? What about tolerance, withdrawal and dependence on caffeine?

Caffeine is rapidly absorbed from the gastrointestinal tract, it quickly reaches the brain because it can pass through the blood-brain barrier -Half life ranges from 3-7 hours Metabolism and Excretion: Metabolized by liver, excreted by kidneys The usual picture for drugs is the reverse: They can induce tolerance without dependence but rarely dependence without tolerance Withdrawal: Clear withdrawal symptom has been identified: headache and fatigue mostly, but also depression, decreased alterness and energy, increased irritability (Begin within 12 to 24 hours of cessation of caffeine) (last about a week) (Only 11% report withdrawal) Tolerance: effects on renal function, sleep, and other physiological functions, such as blood pressure and heart rate -Little tolerance seems to develop to cafeine stimulant effects -Possible explanation: One reason people are heavier or lighter caffeine users is their individual ability to tolerate caffeine

Atypical Antipsychotics (New generation of antipsychotics)

Clozapine (Caused agranulocytosis) Risperidone (Risperdal) Olanzapine (zyprexa) Quetiapine (Seroquel) Bind to dopamine receptors that are effective to treat symptoms, but do't bind to dopamine receptors in motor pathways with as great an effinity. Less likely to produce shakes and bad symptoms -Linked to weight gain/diabetes

Stimulants

Cocaine Amphetamines Stimulant Withdrawal symptoms = depression Stimulant Mechanism of Action: Block reuptake of monoamines : Dopamine, serotonin and norepinephrine (mostly cocaine) Amphetamines and methylphenidate also increase the release of dopamine and norepinephrine Mesolimbic dopaminergic pathway-short cut to the pleasure center Long term effects = Monoamine depletion in withdrawal (Body doesn't recycle monoamines, they are broken down by enzymes = body runs low on dopamine/serotonin= cocaine has less effect) Depressive-abstienance syndrome is longer lasting for amphetamine users than cocaine users, but same pattern

What about tolerance to and dependence on cocaine and amphetamines? What are the chronic effects of stimulant abuse?

Cocaine = acute tolerance (Dissapates quickly) Studies to protracted tolerance to cocaine and stimulants have not yielded consistent results -Crash: sleep a long time -Depression -Extinction: not craving all the time but during center stimulants and increase craving -most relapse after 6 months -According to some there is no physical withdrawal Chronic effects= tolerance and dependence "Dependence may develop after chronic use of cocaine, amphetamines, or synthetic cathinones. The abstinence syndrome is characterized primarily by depression and craving with few measurable physiological effects. Thus, a drug that does not cause severe physical withdrawal symptoms can still be highly addictive"

What is contained in the combination birth control pill? What risks are associated with using the pill? What are the failure rates of the various methods of contraception?

Combination pill: Contains synthetic forms of both female sex hormones: Progesterone and estrogen -Tricks women brain into responding as if she were already pregnant -Missing dose can cause ovulation to occur -Does not prevent STDs Side Effects: Increased risk of blood clots (Can produce stroke or heart attack), mood changes, irritability, depression -Increased risk for heart attack and stroke -Alternate form of BC = Progestin pill (mini pill) and continuous birth control pills Failure rate with perfect use/typical use: -Vasectomy: .2/.2 -Patch, ring, combination BC pill: .3/9 -IUD: .2/.8 -Condom: 2/18 -Diaphragm + spermicide: 6/12 -Withdrawal: 4/22 -Rhythm, body temp: 5/24 -Chance: 85

Cocaine and crack in the 21st century

Crack and cocaine remain major dependence problems, but use is declining Coca in the 21st century 2000-2005: Cartels weaken in Colombia.... FARC (Marxist) takes over coca production Both cartels are weakened Marxist movement takes over parts of Colombia and takes over Coca production Bolivia's President, Evo Morales took office in 2006 with a pledge to decriminalize the cultivation of coca Defy the U.S, very populist movement Bolivian President Evo Morales chews coca during U.N speech on international drug law (MArch 2009) "Coca is not cocaine!"

Anti-Drug Abuse Acts of 1986 and 1988

Crack cocaine Penalties for sale: 1986 Penalties for possession: 1988 -5 year mandatory sentence for crack possession (Law repealed in July 2010) In hindsight, not very equatable (500 grams of cocaine vs crack 5 grams of crack receive same punishment) Didn't really affect big-time dealers who were transporting street cocaine, not crack Disproportionately affected poor african Americans (80%)

What are the current trends of alcohol consumption in the USA (Figure 9-1 and Table 9-2)?

Data includes drinkers and non drinkers at east 14 y/o -Huge increase from 1935 into 40's after prohibition -Increase from 1960-70's, decline in 80's, slight increase in 1990 -Rose slightly to about 2.33 gallons from 1995-2012 (per capita consumption) -6.5% reported heavy drinking in last month in 2015 -Highest for whites, males, and those aged 18-25 -65% of undergraduate drank in past month

Characterize the development of tolerance to alcohol. What types of tolerance develop?

Dispositional tolerance: Drinker must consume greater amounts of alcohol to maintain a certain BAC Functional tolerance: Greater practical influence Acute: Effects tend to be greater when BAC curve is rising compared to falling Protracted: requires and individual to drink greater amounts of alcohol to achieve an effect once achieved with less alcohol, person becomes more susceptible to serious health and other consequences- still results in high BAC Cross tolerance and cross dependence to CNS depressants

What types of treatments are available for helping people quit smoking and what kinds of results occur? Is formal treatment necessary? What is nicotine replacement therapy? What about varenicline (Chantix) and bupropion?

Divided into behavioral programs (huge relapse rates) and nicotine replacement therapies (Nicotine gum, patch, nasal spray, lozenges, E-Cigs) Combining the 2 is most useful Hypnosis, cognitive behavior therapy Bupropion (antidepressant) and Chantix (Varenicline) are two FDA approved treatments that do not work by replacing nicotine -Varenicline (nicotine-like compound) was developed for smoking treatment and works by competing with nicotine in binding to nicotine receptors in the brain (stimulates nicotine receptors, so if people do smoke, they feel reduced nicotine effects) 6 month follow-up: 80-90% relapse Mark Twain: "Quitting is easy, I myself have done it dozens of times!" Relapse: A term from physical disease; return to a previous state of illness from one of health. Formal treatment is necessary! But a large portion of ex-smokers quit on their own after a few tries • Quitting nicotine is linked to depression and suicide Quitting three step program 1. Switch brands, something with lower nicotine. People who do this tend to smoke more cigarettes, inhale more deeply and hold it in longer 2. Set a quit date- choose this carefully 3. Quit When a person quits their cravings occur at high frequencies every few minutes. After a few days frequency begins to drop, and after a few weeks the intensity drops significantly. Cravings may never go away entirely. If the person has even one cigarette during this time the cravings are right back to where they were at the beginning. Ads should target those who have not yet started smoking

Bath Salt Drug Effects:

Effects 15-45 minutes after oral ingestion and last approximately 2-7 hours Effects 5-30 minutes after intranasal administration and last approximately 2-3 hours High lasts 15-20 minutes with IV injection

Hangover

Episode of overindulgence, appear 4 to 12 hours after reaching the peak BAC and generally are not considered a pleasant alcohol effect Symptoms include: headache, dizziness, nausea, vomiting, increased heart rate, fatigue, and thirst -BAC is 0, but still reduced ability to perform complex tasks/drive -Can be "cured" by alcohol -Only dependable and safe cure is time or not over drinking

What is a blackout? Characterize the effects of alcohol on sleep and memory.

Failure to recall events that occurred while drinking even though there is no loss of consciousness. -Does not necessarily mean loss of consciousness

Combat Methamphetamine Epidemic Act

Federal law in effect 2006 All products containing ephedrine and pseudoephedrine sold behind counter Purchasers over 18 and must show ID and sign log, only limited quantities may be purchased

November 2018 FDA Rule on E-Cigs

Flavored E-Cigs (Except mint and menthol) banned in most stores Available only in stores that bar underage consumers These proposed regulations may make it impossible for up to 90% of producers to market E-Cigs in 2022

Formication Syndrome

Formication (ants) syndrome (Feeling of bugs or worms crawling on skin) Symptoms of itching and feeling as if insects were crawling under skin, caused by cocaine and amphetamine

Analog

Functionally/structurally similar chemicals, but not identical. Not identical, so they aren't illegal Bath Salts

Side Effects of ADD/ADHD Drug Treatments

Growth suppression/weight loss Loss of appetite Insomnia Drug and alcohol problems? Children with ADHD more likely to have SUDs later in life Higher rate of alcoholism and substance abuse disorder with adults that were diagnosed with ADHD as children BUT - those treated with stimulant drugs are LESS likely to have SUDs, than untreated children Many parents have their kids take "drug vacations"

Regulation of Tobacco

Historically, tobacco products were not regulated as a drug Until 2009, tobacco regulated by Bureau of alcohol Tobacco and firearms Suits against tobacco companies reveal nicotine added to cigarettes to make them more addictive Tobacco regulation moved to FDA in June, 2009 FDA bans flavored cigarettes (Sept, 2009) from USA 2012: FDA imposed graphic label requirement to begin Tobacco companies appeal this requirement (2011) Found unconstitutional Feb 2012; Still under appeal CVS voluntarily stopped selling cigarettes (October 1st, 2014) Walgreen's under pressure 2019.... Some stories don't sell cigarettes

History of alcohol use

Humans have used alcohol for thousands of years (First produced in Egypt in 6000 - 5000 BC) or for as long as 1000 years -Distilled spirits were last to be developed in China about 1000 BC -Alcohol has always been consumed in excess by some -18th century Europe: "Gin Lane" attributed social problems to alcoholic beverages -Colonial America adopted alcoholic beverage and many drinking customs from Western Europe ("Country of Drunkards") -1830: 5 drinks a day average -19th century US expansion westward = development of saloon (lots of whiskey) -Behavior associated with saloon led to rebirth of the temperance movement, which had been quieted somewhat by American Civil War (Saloon blamed for social ills) - Now argued for total abstinence, supported by captains of industry -WW1, anti alcohol drive gained power, led to prohibition (repealed in 1933) and Volstead Act

Attention Deficit Disorder/ ADHD

Hyperactivity and the "paradox?" First recorded example - 1937 (Bradley): Stimulant drug (Meth) calms hyperactive children Amphetamine (Adderall, Vyvanse) Methylphenidate (Ritalin, Focalin, concerta - extended release, Daytrana Patch) Methylphenidate: Not an amphetamine (Blocks reuptake of monoamines) Produces identical effects to amphetamines Are ADHD meds overprescribed? (Debatable, but prescriptions are soaring (Over 10 million prescriptions annually) Amphetamines enhance focus for everyone, so how do we diagnose ADHD Should everyone be taking ADHD meds? Is there a paradox? Do stimulants work? Teacher and parent ratings of performance are consistently improved BUT little evidence for term improvement in grades.... Diversion and abuse: 5-35% if college students report illicit use of ADHD medication

What impact has cocaine had on society in the USA and in Colombia in the past 25 years?

In Americas: Causes more hospital visits than any other illegal drug, and is the second most commonly used illegal drug in the United States besides marijuana which is the number one It is used as a localized anesthetic. Columbia was the world's leading producer of cocaine up until 2012. This is mostly from decreasing the power of the cartels through a less corrupt government and aid from the United States.

How did the use of cocaine change in the second epidemic of cocaine abuse?

In the 1970's, cocaine was the "champagne" of drugs, too expensive for normal people "Cocaine became one of the most frequently abused drugs in 80's and 90's with the introduction of an inexpensive smokable form - crack" Cocaine became cheap, widespread, and crack cocaine was a big thing Crack burst onto scene in 1986 Sniffing was major method of administration until 1980's Freebasing (vaporizing) cocaine became a thing

Metabolism and Excretion of Nicotine

Major organ for metabolizing nicotine = liver (Lungs and kidneys also important) Eliminated primary through urine (10-20% unchanged)

What are the acute physiological effects of alcohol?

Intoxication: Transient state of physical and psychological disruption caused by the presence of toxic substances, such as alcohol, in the CNS Disruption of sleep patterns - Alcohol suppresses REM sleep (Rapid eye movement, where dreams occur), when the dose is low it suppresses only the first half of REM but at larger doses it suppresses the entire REM Alcohol impairs memory (especially short term), blackout may occur which is thought to be failure in the transfer of information in short term to long term memory -Grayouts -Hangover Increased urination Increased body fat/weight gain Peripheral dilator (warm/red skin) Increases gastric secretion/stimulates appetite Increases release of corticosteroids

What is Gamma Hydroxybutyrate (GHB)? Why is it so controversial?

Marketed legally as supplement until medical complications and abuse led to schedule 1 status -Found in brain, thought to be neurotransmitter -Structurally related to GABA, depressant drug -Unconsciousness and coma frequently reported -Illegal in US -Tolerance and dependence -May be used as a date rape drug at higher levels -Approved for treatment of narcolepsy -Both a schedule 1 drug and approved schedule 3 medical drug

Computing BAC How is alcohol metabolized and what factors affect rate of metabolization?

Measured in milligrams of alcohol per 100 milliliters of blood Standard drink: The alcohol equivalent in a drink of beer, wine, or distilled spirits. 1 Standard drink = .5 oz (½ oz) pure ethanol!!!!!!!! 1 beer (12 oz) - Most beer 4-7% 4 oz wine - Most wine 12-15%) 1 oz 90-100 proof liquor - Most 45-50% Alcohol Metabolization 1 drink every 2 hours BAC goes down .01% every 40 minutes BAC = NSD (Number of standard drinks) X (.025%) - NHD (Number of hours drinking) X (.015%) Dont need to know that for test Fun fact, you can be convicted of drunk driving if your BAC is below .08 More than 90% of alcohol absorbed, mostly is metabolized in the liver -broken down to acetaldehyde by enxzyme alcohol dehydrogenase. Aceyaldehyde is broken down to CO2 and water. Release of energy or calories. CO2 is excreted from the body through air exchange in lungs and water is excreted in urine -Alcohol liberates about 75 calories per half ounce Nothing can increase the rate of metabolism -Rate that alcohol is metabolized is independent of the body's need of calories it could provide or of the amount of alcohol consumed (rate of alcohol oxidation is constant and averages 0.35 ounce per hour)

Khat

Middle East African Plant (Yemen, Ethiopia, Somalia) Chewing leaf produces mild stimulation Cathinone is major active ingredient Synthetic methcathinone (cat) is schedule I Numerous analogs of methcathinone have been synthesized Marketed as bath salts/Plant food: Methcathinones 1986 analog act designed to prevent this, so how could stores sell this? Based on intent (Can't prove what you are using it for) First encountered in Europe (Meow meow mephedrone in 1920's) Mostly unused until it was used as pesticide in Israel and people discovered stimulant properties Spring 2009: Law enforcement and ERs note increasing incidents with mephedrone and other bath salts 2010: British crime survey: 7% of adolescents and young adults report using bath salts 2010 clubbers survey (non-scientific) up to 42% using Legally obtained throughout europe online then distributed at clubs Made illegal in Britain in 2010 2011, about 5% report using Emerged in 2010 in U.S (Meow Meow): Legally available on web: Not for human consumption Calls to poison center for bath salts: 2009:0, 2010: 298, 2011: over 6,000, 2016: 437 Bath Salt Drug: Mephedrone, Methylone, MDPV (Don't need to know this) Similar to chewing a cocoa leaf • The leaves need to be consumed fresh because the active chemical denatures quickly Vitamin R- also known as Ritalin, used to treat ADHD

What are health consequences with moderate drinking? What is the French paradox?

Moderate drinkers are actually the healthiest.- lower risk of cardiovascular disease (1-3 drinks per day) -Conclusion remains controversial.... is it true..... Co-occurrence of a diet high in saturated fats and a low incidence of coronary heart disease (about moderate drinking) -2 glasses of red wine a day

Omnibus Tobacco Settlement

November 1998 The states settled their Medicaid lawsuits against the tobacco industry for recovery of their tobacco-related health-care costs, and also exempted the companies from private tort liability regarding harm caused by tobacco use. In exchange, the companies agreed to curtail or cease certain tobacco marketing practices, as well as to pay, in perpetuity, various annual payments to the states to compensate them for some of the medical costs of caring for persons with smoking-related illnesses. The money also funds a new anti-smoking advocacy group

Compare the pharmacokinetics of cocaine and the amphetamines.

Oral and intranasal routes require about 10-15 minutes for drug action to begin IV injections result in intense effects in 30 seconds When smoked in the form of crack or freebase, the onset of action is even faster Effects of cocaine dissipate in 20- 80 minutes (Detectable in urine for 2-3 days after) Amphetamines are longer acting Includes: Amphetamine (6-8 hours or 4-12 hours) Dextroamphetamine (8-10 hrs)- Adderall Methamphetamine (12+ hours) Synthetic Cathinones have typical duration of 3-4 hours

What is an over-the-counter drug? What do GRAS & GRAE mean?

Over the counter drugs are drugs you buy without a prescription, like asprin. Evaluated on safety and efficacy GRAS: Generally recognized as safe GRAE: Generally recognized as effective

Stimulant psychosis

Paranoid delusions (most common symptom) and disorientation resembling the symptoms of paranoid schizophrenia Caused by prolonged use or overdose of cocaine and or amphetamine A state of hallucinations and paranoia caused by stimulant overdose

Cyclic Antidepressents

Produces immediate elevation in serotonin/norepinephrine -Includes SSRI's Third most commonly prescribed drug class taken by 13% ebb 2017 Antidepressent action appears only after 1-5 weeks of daily use Side Effects: Drowsiness, dry mouth constipation, urinary difficulties, dizziness, weight gain, and sexual dysfunction, urinary difficulties, dizziness, weight gain and sexual dysfunction Withdrawl symptoms can include nauseas, headache, insomnia, flu-like symptoms, rebound depression (Is this part of the withdrawal or is this jus the depression retunring?) Include Luvox, Paxil, Prozac, Zoloft

What drugs are found in cold and allergy medications?

Pseudoephedrine (decongestant), Guaifenesin (Expectorant/breaks up phlegm), Antitussive (Cough suppressant), antihistamines (decongestant, good for fever and allergic reactions) -Often contains analgesics -Popular antitussive = dextromethorpan (antagonist of NMDA receptor), can be quite toxic/produce hallucinations -Diphenydramine: Major ingredient in OTC sleeping aids -Main ingredient in OTC stimulants is caffeine Side effects of antihistamines: dry mouth, dizziness, nausea

What was the effect of the 1994 Dietary Supplement Health and Education Act? What about GRAS and GRAE with respect to drugs covered by the 1994 Dietary Supplement Health and Education Act?

Reduced the authority of the FDA to regulate herbal and other biological products that often contain psychoactive drugs Changed definition of dietary supplement Made many preparations exempt from regulations that require testing for safety and efficacy As long as packages make no specific claims with respect to treating a disease, the supplement is not considered a drug "Health supplement" industry has boomed FDA has not evaluated herbal preparations with respect to GRAS or GRAE standards

What is "proof?"

Refers to alcohol content -Indicates ABV(alcohol by volume) it is twice the percentage of alcohol -43% alcohol by volume is 86. proof 100 proof comes from bootleggers during prohibiton: they would take the barrel of whiskey, poor half into another barrel and add water to fill both up, so speakeasies started demanding "proof" that alcohol was good. 50% or higher will light wet gunpowder (That was the test) 90 proof = 45% alcohol Alcohol content of a beverage may be expressed by volume or by weight

How was mental illness treated prior to the advent of chlorpromazine? How did chlorpromazine (thorazine) change our approach?

Roots of psychopharmacology based in 19th century Bloodletting, hot irons, flogging, revolving chairs, starvation, and sneezing powder 20th Century: CO2 inhalation, antihistamines, amphetamines, insulin shock, elctroshock, psychosurgery, and alkali metal lithium -Moreau de Tours used cannabis -Electroshock therapy, psychosurgery -1949: John Cade discovered lithium for mania 1950-1951: Charpentier synthesized Greatest advance in psychopharmacology: Chlorpromazine Profound effect on the field of psychiatry, patients appeared to be more calm and less chiaotic It took a number of hospitalized psychiatric patients out of the hospitals -Hospitalized patients in US in 1955 = 600,000 and today = 150,000 1950's were a frontier period for psychopharmacology -Decreased number of hospitalized psychiatric patients (Good and bad, many mentally ill left homeless/without treatment)

Major Psychiatric Disorders

Schizophrenia: hearing things/voices, delusions Depression Bipolar Disorder

What are "Roofies?" Why are they so controversial?

Slso known as flunizatripan, it is a benzo used as a powerful sleep aid. it is sometimes known as the date rape drug although cases of it actually being used for that purpose appear rare. Detecting the drug is difficult after a few days so it is hard to say for certain. Causes memory loss and blackouts Schedule 4 drug

How has smoking prevalence changed over the years in the USA? How do factors such as ethnicity, education, and employment affect smoking trend outcomes?

Smoking in America decreased rapidly but has since started to level off(but is still decreasing). Younger generations tend to smoke less than older ones, gender is about the same, American Indians smoke the most Whites smoke more from 12-25 but African Americans smoke more 26 y/o and up Lower education correlates to more smoking. Lower income and unemployment tend to correlate with smoking.

Stimulant Overdose/Cocaine Overdose

Stimulant Psychosis Death from: -Convulsions, seizures (result in respiratory collapse) -Cardiac failure -Stroke Sub lethal overdose: Confusion/anxiety Paranoid state Formication syndrome

Nicotine Paradox What neurotransmitter is influenced by nicotine?

Stimulant effects (mild stimulation) Relaxing/tranquilizing effects One drug having two different effects Hypothesis: Stimulate norepinephrine Release: Sympathomimetic (Heart rate and BP go up, blood shunting away from gut, reduced appetite) Increased HR and BP increase risk for heart disease Mimics acetylcholine (Binds to acetylcholine receptors in brain, but there are some receptors that acetylcholine binds to that nicotine doesn't bind to - Determined that not all receptors are identical))- Nicotinic receptors (Tranquilizing effects) Dopamine has 8 or 9 receptor subtypes (Nicotine doesn't seem to stimulate dopamine receptors, but you can measure increase in activity of pleasure center) Receptors for one neurotransmitters can have subtypes Neurotransmitter: Acetylcholine (ACH), nicotine is an agonist for ACH, ACH stimulates both Autonomic and Central nervous systems

Synthetic Cathinone Effects

Stimulate release and/or block reuptake of dopamine Sympathomimetic Alertness, arousal, mood elevation High doses: Confusion, paranoia, panic, seizures NIDA (2014) reports craving and dependence not unlike meth

Adverse effects of Bath salts

Tachycardia and elevated BP Anxiety and panic attacks Extreme paranoia, violent behavior, hallucinations Acute psychosis Self mutilation: But not cannibalism (Rudy Eugene, Miami Cannibal, was not on bath salts)

What are the potential effects of psychotropic drugs on pregnancy?

Teratogenic risks: Producing abnormalities as a fetus. -perinatal syndrome or neonatal toxicity, risk for negative long-term effects on childhood development -Hard to gather data... -The groups of medications with greatest apparent potential risks = anxiolytics (particularly benzodiazepines) and mood-stabilizing medications (Lithium carbonate, valproic acid, carbamazepine)

Cocaine

The effects of cocaine depend tremendously on the form of cocaine that is used/method of administration Form: Coca Leaf - Method: oral Coca Paste (basuco) - chemistry: Cocaine Sulfate - Method: smoking (Usually just a transition state into street cocaine) Street Cocaine: Chemistry: Cocaine hydrochloride (salt form) - Method: Injection (Soluble in water) or intranasal This type was mostly coming into U.S Crack: Chemistry = Freebase cocaine

What about newer antipsychotics such as risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify) etc? Why are they becoming so popular?

They all appear to help more patients control symptoms for a longer period of time without the other side effects, expect seem to increase risk of diabetes, may increase risk of cardia arrhythmias Abilify stabilized dopamine system, postive outcoemes and fewer less severe side effects

What are the acute effects of nicotine. Consider the issues of tolerance and dependence with regard to nicotine.

Tolerance develops quickly -Dispositional tolerance: Non-smokers metabolize the drug more quickly than non-smokers In 1988, surgeon general announced nicotine is addictive Withdrawal: Craving, irritability, anxiety, difficulty concentrating, restlessness, increased appetite, impatience, somatic complaints, insomnia Acute Effects: General CNS stimulant - Increases behavioral activity, may produce tremors, stimulates vomiting center in brain stem (tolerance develops quickly), stimulates release of antidiuretic hormones from hypothalmus, increasing fluid retention, reduces muscle tone by reducing activity of afferent nerves from muscles, enhances alertness, learning, and memory Increase heart rate, blood pressure, and contraction of the heart, initiates dilation of arteries -ACH-like effects Lower body weight from decrease in appetite and increase in energy that the body uses

What is the balanced placebo design?

Two groups are added to the traditional two-group placebo group design, The participants in each of the two additional groups are told they will not recieve a drug; then those in one group get the drug and those in the other group do not. That way comparisions can be made with a group of subjects who believe they are not getting and do not get a drug -Group 1 told they get alcohol and actually get it -Group 2 told they are getting alcohol ut achieve placebo -Group 3 told they are getting placebo but get alcohol -Group 4 told they are getting placebo and actually get it

Cosmetic Pharmacology

Use of psychoactive drugs to enhance one's personality (Peter Kramer) -Cognitive enhancers (Adderall) -Anabolic Steroids

Freud and Cocaine/Cocaine in the 19th Century

Used cocaine sample in 1884, decided it was miracle drug (Wrote "On Coca") Cocaine for depression and morphine addiction, local anesthetic (Only thing that turned out to be true), aphrodisiac.... Started experimenting with IV cocaine (more intense) Cocaine Psychosis (Fleischl-Marxow= first cocaine addict/formication syndrome) Led to cocaine epidemic of 1880's Inspired Dr. Jekyll and Mr. Hyde Coca caught on (Metcalf's Wine of Coca, Coca-Cola (Caught on especially during prohibition), Cocaine as mild anesthetic) At the time, Harrison Act and opioid epidemic were being thought about Annie C. Meyers: A "well-balanced Christian women" before becoming a "cocaine fiend" - Published paper on how cocaine turned her life upside down Cocaine included in 1914 Harrison Act Cocaine use dropped, but in years following harrison act, drug use amphetamines increased (1920's)

What is state-dependent learning?

When learning under the influence of a drug is best recalled when one is in the same "state"

Extra

Why do we only use males to test on? Fear of pregnancy Speed Kills (reference to psychological effects) -Effectively switched use of stimulants from speed to cocaine FDA Head Scott Gottleib resigns on March 5, 2019 One in 4 to 5 adults in US experience some form of mental disorder Psychotherapeutic drug use is more likely among women, older people, people living alone, more educated, and wealthier The elderly are the age group most likely to misuse psychotherapeutic drugs Alcohol in combination with the depressant drugs is the leading cause of drug overdose death in US water pipe smoking resulted in greater exposure to smoke and carbon monoxide and no difference in nicotine exposure compared to cigarette People tend to become dependent on nicotine quickly and before they are 20 years old. The younger someone is when they start smoking, the harder it is to quit (Teen brain more sensitive to effects of nicotine, impulsive and aggressive people more stimulated by nicotine) Nicotines calming effects are main reason for use Low tar cigarette are overall just as damaging Lasted research shows that typical doses of caffeine consumption by mothers pose little to no health risks to fetus In 2015, retail sales of alcohol in the US totaled about 220 billions dollars

What is the neurochemical mechanism for the actions of cocaine and amphetamines? How has this been related to the cocaine withdrawal syndrome? What are the causes of cocaine blues?

Works by blocking the reuptake of mono amines, particularly dopamine. When going into withdrawal the monoamines are severely depleted which causes depression, or the cocaine blues. The most common withdrawal symptom associated with cocaine is depression

Trace the early history of cocaine. How was it used by the Indian people of Peru and Bolivia?

-They engaged in the practice of chewing the coca leaf -Leaf had important religious significance and was used for medicinal and work related purposes as well

Binge drinking

-4-5 drinks in a single setting (3-4 hrs) -college students reported an average of 9 drinks in a typical binge episode -memory: blackouts -hangover: may be an alcohol withdrawal syndrome -overdose (LD50 is about 40%) consuming at least five (for men) or four (for women) drinks on at least one occasion -44% of college students reported engaging in binge drinking in last month -Associated with accidental death, injury/assault, vandalism/crimes, suicide, academic problems...

What receptors mediate alcohol's actions? What are some factors influencing alcohol absorption?

-Alcohol depresses the CNS -There is good evidence that alcohol acts on GABA-benzodiazepine receptors, and there is increasing evidence that alcohol enhances serotonergic and dopaminergic activity. -The most common way alcohol is absorbed is through the small intestine, which happens after drinking. If alcohol was vaporized it could be absorbed through lungs and subcutaneous sites. Pylorospasm: the shutting of the pylorus valve that occurs in some people when they drink very large quantities of alcohol (Prevents it from passing into intestines)

Consider theories of the etiology of alcoholism. Is it a disease?

-Biological model -Genetic predisposition in some cases (Children whose parent were alcoholics, but they were adopted, are still more likely to be alcoholics) -Psychological explanations = alcoholic personality (Emotionality, extraversion, impulsivity, sociability) -Sociological models of etiology -Cross cultural differences in drinking patterns/ demographic factors "Biopsychosocial" Approaches to Etiology -Multiple types of factors come together (Biological, psychological, sociological) High risk for developing alcohol use disorder = lower volume of brain orbital formation (OFC) -Disease: Identifiable physical disease that is pathological -Afflicted individual is not responsible -In 1957, American medical association classified alcohol use disorder as disease

Consider the many sources of caffeine in Table 8-1. What are the estimates of caffeine use around the world (Table 8-2)?

-Caffeine is different because it is a "cradle to grave drug" -used by young and old alike (Used by 50% of general population) -Estimates are that 90% of world consumes products that contain caffeine regularly (World most preferred drug) -When body weight is taken into account, children aged 1-5 have highest caffeine exposure after adults -Total caffeine consumption does not seem to vary by characteristics of people, except for age

What is nitrous oxide? How did it contribute to the discovery of anesthesia?

-First depressant compound other than alcohol to be used in 1776 -Began to be used in 1845 in surgery, but it was a blunder, replaced by Ether by Morton in 1846 Adverse effects reported from nitrous oxide use have included nausea, vomiting, and headache. In addition, heavy chronic use has occasionally been reported to resemble the sort of dependence that develops with other depressant drugs. With heavy use come more severe problems, including numbness of the extremities and permanent peripheral nerve damage. There have also been some reports of death by asphyxiation after using large amounts in a poorly ventilated space

Who uses inhalants? What kinds of substances are they? What are their effects? What sorts of problems are associated with them?

-Medical anesthetics: Halothane and nitrous oxide -Glue, paint, butane gas -Produce dizzy euphoria upon inhalation -Commonly used by younger ages -Hypoxia, inhaling vomit and cardiac arrest are risks -"Huffing" or "bagging" -Deaths due to cardiovascular collapse/suffocation -Chronic use: psychotic behavior, movement disorders, liver and kidney toxicity, brain damage -Nitrite inhalants: Amyl, butyl, and isopropyl nitrite (poppers, dilate blood vessels) -Side effects: headache, tachycardia, eye problems, sudden death -Adverse effects of nitrous oxide (laughing gas): Nausea, vomiting, headache -Dependence -nerve damage, numbness in extremities, asphyxiation

What is methaqualone (Quaaludes/Sopor)? Compare it with barbiturates.

-Non barbiturate sedative -1965 -Become major street drug in 70's (ludes/disco biscuits) -Discontinued due to high abuse potential, toxic at high doses, it is featured in the Wolf of Wallstreet

What is Areca (betel) and how is it used? DHEA?

-Similar to chewing tobacco, mild stimulants addictive, mouth damage DHEA- a hormone that occurs naturally secreted by adrenal glands, the supplement doesn't seem to do anything, may produce side effects similar to anabolic steroids, marketed as miracle drug

What is kava and what psychoactive effects does it have? What about melatonin? SAM?

-South Pacific Island root -Relaxing effects -Enhances neurotransmitter GABA -Similar effects as alcohol Melatonin: Naturally occurring hormone in Pineal gland -Thought to regulate biological rhythm/sleep -Good for sleep, but short half life and bad side-effects SAM: Marketed for emotional well being, may help with depression but has problematic side effects

What are anabolic steroids? Why do people take them? What adverse effects are associated with them?

-Tissue building drugs that produce masculinizing effects as well -Similar to testosterone in the body and increase protein content in cells. They cause aggression and mood swings, and causes cardiovascular problems, liver and kidney damage Synthetic drug that resembles male sex hormone testosterone -Can help build muscle (anabolic actions) and repair damage but also induces male secondary sexual characteristics (androgenic actions) Oral or injected Ethylestrenol, methandrostenolone, stanozolol, methandriol Developed in Nazi Germany in 1930's -Steroids allow you to benefit more from the same workout -Regular, randomized testing is needed

Anabolic Steroid Timeline

1976: Steroids banned in Olympic games 1988: Ben Johnson breaks 100 meter dash record in Seoul Olympics, but tests positive for stanozolol (Confirmed that steroids offer huge advantage) 1990 Anabolic steroid control act made anabolic steroids schedule III drugs when high school survey showed 3% using steroids 2002: Ken Caminiti 3-time all-star MVP in 1996 admitted to steroid use during MVP season (Estimates 50% major league steroid use) 2001 Barry Bonds breaks major league baseball record with 72 home runs (Tests free of steroids) 2003: Tetrahydrogestrinone (THG) surfaces (That's what Barry was taking) 2004 BALCO executives indicted (Caminiti and Canseco claimed 50-85% of MLB players used steroids) 2005 Senate investigation into steroids and sports 2006 Grand Jury indicts Bond's trainer 2007: Bond's trainer jailed, but refused to testify 2007: THG: Marion Jones admits THG use (stripped of 5 olympic medals) 2016: Jenrri Mejia lifetime ban from baseball after third positive test 2018: US swimmer Ryan Lochte banned from winter olympics in South Korea 2018: Entire russian team banned from winter olympics because of state-supported doping

E-Cigarettes

A heating element activated by a sensor detecting airflow A cartridge containing a nicotine solution is heated Nicotine is vaporized - an aerosol is generated and inhaled Over the years, devices have become less like cigarettes and more functional Juuling Many e-cigs are refillable and the packages usually label how much nicotine is in device Highschool nicotine use through cigarettes has decreased from 16% in 2011 to 14% in 2015, but E-Cig use jumped from 2% in 2011 to 16% in 2015 (2015 important year because e cigs surpassed cigarette use in high schoolers) - Up to like 30% in 2018 FDA had decided to not regulate E-Cigs Advertisement showing benefits to E-Cigs over cigarettes Nicotine levels vary widely; not clear how much nicotine is absorbed from vaping No tar should translate into reduced risk of cancer, but probably CHD not affected Other chemicals in Ecigs (propylene glycol) may pose risks E-Cigs were not regulated by the FDA until 2016 August 8, 2016: FDA issued a rule regulating electronic nicotine delivery All E-Cig products will have to apply for FDA approval of safety E-Cigs may continue to be sold through 2019 without FDA approval - Since extended to 2022 Small vape shops don't have the capital to do the test to prove safety 2016: Free samples no longer permitted and sales to minors (<18) are banned Smokeless Tobacco: Most commonly used among 18-25 y/o Mens usage exceeds those of women by over 10-fold

What are the amphetamines? Consider their history

A class of drugs first synthesized in the late 19th century - First medical applications developed in 1920's They are used as a treatment for cold and sinus symptoms (Introduced to medical community to reduce sinus drainage), obesity, narcolepsy, and paradoxically, attention deficit/hyperactivity disorder (ADHD). They have a high potential for abuse Soldiers during WW2 used these drugs for stimulant properties (Kept them awake and alert), they became a problem in the US when doctors proscribed them for those with heroin addiction In the 1940's they became used by students and the military Huge problem in Japan, not a big problem in U.S until 1960's (Not recognized as dangerous in US until 1960's) Working with heroin addicts by giving them amphetamines instead led to outbreak Those who don't learn are doomed to repeat their mistakes.........

What is neurogenesis and how is it linked to antidepressant action?

Link found between depression/stress/anxiety and atrophy and cell loss in hippocampus -Antidepressant treatment increases neurogenesis (New cell growth) in hippocampus -May block or reverse the effects of depression -New growth takes several weeks, may explain why antidepressants take several weeks to start working

Nicotine (Nicotiana Tabacum)

A species of tobacco plant found only in cultivation. It originated in the South America where indigenous people used it, mostly for religious ceremonies Biphasic: Stimulate ACH receptors at low doses but it retards neural transmission at higher doses (Depressant effects at high doses) In the 15th century Columbus and other explores found Native Americans in the New World smoking dried tobacco leaves - Quickly became popular in Europe In 1828, German chemists isolated nicotine By mid 19th century, medical use of tobacco had vanished and it was rarely used for pleasure Cigarette invented in early 20th century (Popular in 20's and 30's)(Most toxic way to smoke) 1940'a: Nearly 50% of American adults are smokers 1950's: Concerns about health..... Eve/Virginia Slims: 1960's-1970's: Cigarettes for women Peak of smoking in America = 1963 1965: Surgeon General: attach warning label 1965-1970: Removal of some cigarette advertisements 90's: keep the guys interested: Sex to sell cigarettes Smoking prevalence among U.S Adults: From over 40% in 1955 to around 15% in 2017 Most successful drug control program that exist (Most promising trend) Not just public information, but a change in culture Highest rate of current cigarette use among 18-25 year olds Rates are higher from men n the 18-25 y/o and higher in women 26 y/o and older. Rates for boys and girls 12-17 y/o differ little

What is Ephedra (Ma Huang), how is it used, and why is it so controversial?

A stimulant used in ancient chinese medicine, sometimes used as a performance enhancing drug but has negative side effects, mostly things you see with stimulant overdose -Psychoactive compound = ephedrine -Marketed to increase energy/decrease appetite -Banned after lined to deaths

Methamphetamines

AKA Crank, Crystal, Ice and Speed = Methamphetamine (Desoxyn), stimulant drug (meth) Return of Meth labs in 1990's West to East progression of meth use (Starting on West coast/Hawaii) In what parts of the US is meth use posing the biggest problems? California and Mexico -Rural American cities, like Upper Midwest, Southwest, and Northwest -Including both rural and urban sections of the South and Midwest -1996 Comprehensive methamphetamine Control Act increased penalties for meth, shifted meth labs into "kitchen" labs 2018: Most meth now comes through Mexico (Overall use declining) On the other hand, meth isnt being produced in U.S anymore, but now its being produced in Mexico -Most powerful, potent, and longest acting drug -Combat Meth Epidemic Act, federal law in effect 2006 Issues with Meth Production: -Higher crime rate -Fires from explosions in meth labs -Hazardous waste, meth labs produce chemical waste dumped into waterways and farmlands -Meth can cause long term brain damage and depression if used frequently (Damage to the dopaminergic pathways and may lead to Parkinson's disease)

Describe the absorption and distribution of nicotine

Absorbtion: absorbed through oral, buccal, nasal mucosa, gastrointestinal tract, and the lungs; absorption depends on both the site of absorption and how the nicotine is delivered. -Most readily absorbed by the lungs -Depends on site of absorption and how its delivered -Less acidic the medium = easier absorption -Longer contact = greater amount of nicotine absorbed (Snuff and chewing tobacco = lots of absorption) Nicotine Poisoning: A consequence of nicotine overdose characterized by palpitations, dizziness, sweating, nausea, or vomiting Distribution: blood distributes it to a number of sites of pharmacological action, it reaches the brain from the lungs in about 7 seconds (Faster than IV). -Takes 3-5 minutes to reach peak levels -Distribution half life is only 10-20 minutes It reaches the brain rapidly and there is an overlapping presence of nicotine doses in the brain with successive puffs on a cigarette Absorbed through the lungs and is passed almost directly into the brain The quickest way to reach the peak blood level for a dose of nicotine is by inhalation or smoking

What drugs are used as OTC analgesics? Compare them in terms of desirable and undesirable effects.

Acetylsalicylic Acid (Aspirin), acetaminophen, ibuprofen, naproxen Analgesic: Produces pain relief with out unconsciousness Pain killers and anti-inflammatory and antipyretic (reduces fever) effects -Aspirin relieves pain by blocking prostaglandin release Aspirin side effects: stomach irritation and bleeding (anti-coagulate), Reyes syndrome -Acetaminophen: Same effects as Aspirin except no anti-inflammatory effects, less stomach irritation, can cause liver problems Ibuprofen and Naproxen: Stomach irritation, liver and kidney damage, increased risk of heart failure in elderly

Physical side effects of steroid use

Acne Premature balding (testosterone linked) Atrophy of testes (reduction in sperm production) Breast enlargement Liver damage Jaundice Heart disease Premature bone fusion (Can stunt growth in adolescence) Reduced sexual desire Effects are usually reversible Side effects in women Facial and chest hair Baldness Deepening voice Breast shrinkage Clitoral enlargement (permanent) Menstrual irregularities Many effects are irreversible -Change cholesterol levels = increase risk of heart disease, liver damage/cancer, Children: premature bone fusion and stunted growth, abnormal pubertal development

Synthetic Drug abuse prevention act (2012)

Added three methcathinone analogs to schedule 1 Also added several THC (Spice) analogs and several hallucinogens to schedule Gave DEA emergency scheduling powers for up to two years

How does alcohol affect sexual responding?

Alcohol with certain BACs can retard sexual arousal, erection and ejaculation competence are inhibited or eliminated Behavior in women show that alcohol promotes promiscuity (They perceive increased sexual arousal even though physiological arousal is declining) .1% BAC and higher = erectional and ejaculatory competence are inhibited or eliminated .05-.1 = retarded sexual arousal At lower BACs, cognitive factors/expectancies may increase male libido (alcohol itself has no effect on measured arousal at .05% and below) Basically, high alcohol = no sex, low levels = increased sex but only because of increased confidence

Delirium Tremens (DTs)

Alcohol withdrawal is divided into 3 phases Phase 2: Within 24 hours of drinking cessation (seizures) Not everyone experiences all phases Phase 3 A severe withdrawal syndrome seen in alcoholics -Characterized by restlessness, anxiety, delirium -Parkinson's-like tremors (First symptom to appear) -Confusion and irritability -Hallucinations -Anxiety and insomnia -Seizures and convulsions (hyper stimulated brain activity) Alcohol withdrawal is the deadliest withdrawal (More deaths than any other withdrawal) -Can be treated with any depressant drug (like Xanax) -Detoxification: Cross dependence and cross tolerance with other depressants

What is rebound insomnia? REM rebound?

Associated with barbituates -rebound effect- after getting off a medication the symptoms come back Inability to sleep produced as withdrawal symptom associated with some depressant drugs rem rebound- patient spend more time in rem to make up for not getting it when medicated REM rebound: Increase in rapid eye movement ir REM stage of sleep when withdrawing from drugs that suppress REM time (vivid dreams) (Barbituates reduce amount of time in REM sleep)

What are barbiturates? Consider their history and development and their physiological and psychological effects. What are the other adverse effects associated with barbiturates?

Barbituates: Depressant drugs formerly used as sleeping pills, in high doses can be used in anesthesia and treatment for epilepsy, in low doses can be anxiolytic -Hypnotics -Not used often due to the high potential for overdose, they are sometimes used as anti convulsion and in euthanasia. -They are occasionally used in fast surgeries or as sleeping aids. -It works on GABA inhibitors in a really intense way making tolerance and fatal withdrawal likely. -First discovered in the 1862 from concentrated urine and were used to euthanize animals -Ends with suffix -al -Pentobarbital and secobarbital (2-4 hours, potent and short acting), amobartbital (intermediate), phenobarbital -Rapid onset and short duration of action is good for anesthesia, slower onset and longer duration of action good for epilepsy -Introduced to general medical practice in 1903 = first sleeping pills, use increased up until 1960's -Physiological effects: respiratory depression, lower HR and BP, gastrointestinal activity -Move away from barbituates due to tolerance and dependence -Require more and more to get sleep, similar withdrawal to alcohol, possibility of seizures, rebound insomnia -High risk of Fatal overdose

How are alcoholic beverages produced? What is beer made from? Wine? What about distilled beverages such as whiskey, rum and vodka? How do these vary in alcohol content?

Beer, wine, and hard liquor (distilled spirits) all depend on the process of fermentation and on the further process of distillation for hard liquor. Fermentation begins when sugar is dissolved in water and exposed to air, which creates the perfect environment for living organisms called yeast. Yeast multiply rapidly by eating the sugar which is then converted to ethanol and carbon dioxide by the yeast metabolic processes. Carbon dioxide bubbles to the top, leaving ethanol Distillation: to process by which heating of fermented mixture increases its alcohol content (Steam has greater alcohol content, it is cooled and condensed) What is beer made from? What is the alcohol content? Grains such as barely malt like rice or corn ; 4-8 % What is wine made from?What is the alcohol content? Red grapes and skinless grapes; Average of 12 % What is whiskey made from?What is the alcohol content? Grains brewed with water and distilled; 40-50 % What is rum made from?What is the alcohol content? Fermented molasses, 40-75 % What is vodka made from?What is the alcohol content? Distilled from potato or almost any other carbohydrate source ; 35-50%

Describe the general history of caffeine use. Where does caffeine come from? What are the other methylxanthines and where are they found?

Caffeine, theophylline (tea) and theobromine (chocolate) are methylxanthines that occur naturally in more than 60 species of plants History- Caffeine was used from coffee beans in the ancient mayans, and tea was discovered in ancient china. It was then isolated in the 1800s. -Europeans discovered coffee in Arabia, Turkey, and Ethiopia and found tea in China -Caffeine is an alkaloid and a central nervous system stimulant

Sympathomimetic effects of Stimulants / Stimulant Effects

Cocaine and amphetamine are virtually indistinguishable in their major physical and behavioral effects Sympathomimetic Effects: (Physiological) -Increase heart rate, blood pressure, and respiratory rate -Pupil dilation (Most visible symptom) -Changes in blood flow (Blood shunts away from gut towards big muscle groups like arms and legs and brain) -Increase sweating (Psychological) effects: -Increased sociability -Anorectic Effects (Loss of appetite) -sexual effects -Impairs performance in complex reasoning Insomnia (First used in WW2 to keep soldiers awake) Anorexia (appetite suppression) Dry mouth ("Meth mouth", bad dental hygiene) Mood elevation Alertness and arousal Sustained vigilance performance Amphetamines (not so much cocaine because its short-acting) increase ability to keep attention/maintain focus Reduced reaction time Increased strength and endurance Banned in all athletics Original performance enhancing drugs Effects on learning and cognition (Increase learning and cognition, but decreases accuracy)

Cocaine and Crack today:

Cocaine use down currently >4.8 million users Down 20% from 10 years ago Still led to >500,000 hospital visits Overdose deaths are increasing due to cocaine and opioids/synthetic narcotics

Cocaine and methamphetamine dependence and abstinence

Crash Depression Extinction (power of stimulus decreases) 70-80% relapse rate of cocaine and meth Relapse is the fundamental problem in drug treatment

2018 NAS Report on E-Cigs - Substantial Evidence that:

E-Cigs produce dependence on nicotine In addition to nicotine, E-Cigs contain other potentially toxic substances But, exposure to toxic substances is less for E-Cigs E-Cigs help smokers to reduce cigarette smoking But, young people who use E-Cigs are more likely to begin smoking cigarettes

What are the health consequences of chronic tobacco use? Consider the data of Woloshin, Schwartz & Welch (2002) on death rates among smokers and non-smokers. What diseases are linked to smoking?

Health risks: -480000 deaths in US annually attributed to smoking, 41,000 of which were from second hand smoke -Largest preventable cause of death in US -Smoking costs US 300 billion dollars/year Tar (Cancer causing), Nicotine, and Carbon Monoxide • Lung and other cancers- risk is elevated even after quitting for many years and is based on the smoke • Increased risk of CHD(coronary heart disease). As soon as you quit the risk drops because it is caused by nicotine in the system -Chronic obstructive lung disease • Emphysema: Disease of the lung characterized y abnormal dilution of its air spaces and dissension of its walls. Frequently, heart action is impaired The paper basically says that smoking is one of the most critical factors in potential life span -Smoker can expect to live ten years less than non-smoker Women: Higher risk of cervical cancer, unwanted side effect of using oral contraceptives, early menopause, higher risk of spontaneous abortion, preterm births, low weight babies, and fetal/infant deaths -Nicotine in mothers milk However, no double-blind studies have been done (For obvious reasons....) Correlational data When you smoke cigarettes, rate/ risk of cancer increases as a function of the years you have been smoking Tobacco companies proposed third variable causing cancer: Cigarette smokers are stressed, that's why they smoke. It's the stress that causes cancer, not the cigarettes. Supported by data that showed that stress led to increase in disease Supported by more stress = more cigarettes = more risk of disease But.... why is there no increased risk for other types of cancer, ilke skin cancer or pancreatic cancer, in cigarette smokers? Only increased rates of cancer in areas that cigarette smoke touches Risk of lung cancer and CHD drops when you quit smoking Tobacco use number 1 cause of avoidable death (455,000) in U.S The WHO estimates that at current rates of use, there will be over 1 billion deaths due to cigarette smoking during next 100 years Rates of cigarette smoking not decreasing in many other countries

Coca and the Inca How was cocaine introduced to Europe

Jaffee (1965): Led a medical team in south america - researched consequences of chewing coca leaf Found no meaningful differences Appeared that people weren't addicted to coca leafs Absorption is very slow and in small amounts -The Spanish conquistadors encountered the Incas using it as a religious use in 16th century (Mama Coca) -The Spanish came to control Inca access to the coca leaf by using it as a form of payment and levying taxes to be paid in coca leaves (believed it made them work harder)(Coca used as tool to control conquered population) -Spanish considered it a vice and did not use it for themselves nor encourage other Europeans to use it -1850's European chemists were able to isolate potent active agent in leaf, called cocaine Why do people in the Andean countries of South America chew coca? It produces a mild stimulant effect and has been a part of their culture for thousands of years

Bipolar Disorder

Lithium used to treat it (alkaline metal found in rocks) -Mood stabilizing properties discovered in 1940's -Lithium probably the only drug in psychiatry for which there is effective prophylaxis against disease recurrence -Enhances reuptake of serotonin and norepinephrine, decrease dopamine and norepinephrine effects -Normalizes mood of manic patients, not just offset mania through sedation -Small difference between therapeutic and toxic levels - Can cause drowsiness, blurred vision, ataxia, confusion, cardiac problems, seizures, coma Side effects of Lithium: Gastrointestinal problems, nausea, diarrhea, fine hand tremor, urinary frequency, dry mouth Mania: Pronounced elevation in mood and increased activity Anticonvulsant drugs (Lamictal) Atypical antipsychotic drugs (Ability)

Effects of Chronic Drinking

Liver damage: fatty liver (reversible), alcohol hepatitis (more serious but reversible, inflammation and death of liver cells), or cirrhosis (Most serious, not reversible, most dead within 5 years, chronic inflammatory disease, cell death and scar tissue, fails to metabolize various toxins and they accumulate in body, rare) Wernicke-Korsakoff Syndrome (Often seen in homeless population- caused by vitamin B12 deficiency, impaired cognitive functioning from nutritional deficiency, confusion, loss of memory, staggering gait) -Cognitive effects from chronic drinking seem to be reversible Greatly enlarged ventricles in the brain (reduction of brain mass) Increased risk of contracting several cancers Cause of gastritis and increased risk of pancreatitis Fetal Alcohol Syndrome: Physical deformities, small head, deformed face, mental retardation Increased susceptibility to several infectious diseases Increased mortality from coronary heart disease Sexual dysfunction: Both men and women suffer impaired reproductive functioning (Men may experience gynecomastia/breast formation) -Altering balence in hormones, less sexual desire, impaired sperm production, hypogonadism and eventual sterility in men Alcohol and brain: Poorer performance on neuropsychological tests (Longer and more a person drinks = greater cognitive functioning impairment, can be reversed with long abstinence) Relapse rate of 70% or higher following detox

Psychological Effects of Steroid Use

Mild euphoria/Mood elevation Increased energy levels/stimulant like effects Irritability/aggression Paranoia/violence Psychotic reactions Withdrawal: Lethargy, fatigue

What is the relationship between alcohol and automobile accidents? Agression?

Sensorimotor skills constitue a major part of driving and sensorimotor skills are impaired when drinking Motor vehicle accidents are the single most common nonnatural causes of death in US and leading cause of death for ages 15-24 in US Alcohol increases the risk of a car accident greatly .02-.03 increases risk of crash by 1.4X , .05-.09= 11.1X as likely, .1-.14 = 48X as likely, .15% and up = 380X as likely to crash 30% of automobile accidents involve alcohol At lower BAC = feeling elated and friendly when BAC is rising, opposite when BAC is falling When BAC goes above .1% = anger and hostility At .05% and up, short term memory worse, worse ability to estimate passage of time Alcohol+aggressioin especially prevalent at 18-30 -Alcohol involved in 25-50% of spousal abuse incidents -Alcohol does not CAUSE violent behavior -Alcohol=increase in successful suicide attempts -Controlled lab experiments do not support disinhibition theory that people are more aggressive when drinking (Much be combined with situational factors) -"Agression is a complex social behavior affected by the characteristics of the agrresor and situational factors, only one of which is alcohol consumption"

Benzodiazepine-Like-Compounds What is Ambien (zolpidem)? BuSpar (buspirone)? How are these drugs used?

Short acting, side effects are less severe Zolpidem (Ambien), Sonata, Lunesta (Most prescribed sleeping pills) Zolpidem is effective at inducing sleep and doesn't interfere as much with REM sleep, less likely to produce hangover or rebound insomnia (high dose will cause these though), works through GABA BuSpar: Affects serotonin neurotransmitter system instead of GABA, treatment for anxiety, no abuse potential or withdrawal. However, effects are delayed several weeks whereas Benzos are immediate, does not relieve insomnia, does not work for panic disorder Schedule four (Need prescription, but not hard to get one) Nearly 40 million prescriptions a year (Billions of dollars) Note: OTC Sleep aids are not benzodiazepines: -Most OTC sleeping pills are antihistamines or melatonin -Both produce drowsiness, but do not pose high risk for dependence -Main side effects are feeling sleepy/groggy the next day

Antidepressants What are the side effects of antidepressants? Are there special issues for children?

Side Effects of Cyclics: drowsiness, anticholinergic effects (dry mouth, constipation, difficulty urinating, blurred vision, orthostasis (Dizzy when standing), decreased libido, weight gain, and tachycardia, increased risk of bone breaks -More potential for lethal overdose, primarily with SSRI's (Assess risk of suicide, especially among children) -Need balance between risk of using antidepressants against leaving the illness untreated -Effexor, lexapro, Luvox, Paxil too risk for children under 18 in GB MAOIs: Drowsiness, dry mouth, dizziness, weight gain, insomnia, constipation, fatigue, positional low BP, impaired sexual functioning -MAOI's have dietary restriction: NO TYRAMINE -Not as effective as Cyclics Effective in children and adolescents Suicidal ideation and suicide attmmpts more common during first few weeks of SSRI treatment the ni general population B;acl boy warning for suicide risk required 2004-2007 study suggests suicide rates are higher in untreated depression

Crack

Smokable cocaine A freebase cocaine produced by mixing cocaine salt with baking soda and water. The solution is heated, resulting in brittle sheets of cocaine that are "cracked" into small smokeable chunks or "rocks"(super tiny) Method: Smoking (Taking street cocaine, mix it with volatile solvent, usually ether) Ether has a tendency to blow up, so it didn't catch on that much, until some random chemist in Miami discovered that there is another way to free cocaine base from the salt (Made like a brittle = crack) Created devastating epidemic Now users come to crack house, cocaine suddenly much cheaper, users would buy rock at house and use it there Shorter duration of action Acute tolerance (But tolerance effects different places in the body at different rates.... You may feel tolerant but your heart may not be) Theory: All the effects that you want, you develop rapid tolerance to, but the effects you don't want, you don't see rapid tolerance Once you start using, you are powerfully motivated to keep using Crack is less expensive More intense effects More risk of overdose Much higher rate of addiction (Thought to be more addicting) Less dangerous to produce. Produces strong cravings and dependence Freebase cocaine created by stripping the salt off of powder cocaine. It is usually smoked and create a intense euphoric high by releasing dopamine that lasts 5-10 minutes.

8. How does caffeine interact with nicotine and alcohol? 9. Describe the toxic effects of caffeine. 10. Can you overdose on caffeine? What about chronic effects of caffeine?

Smokers smoke fewer cigarettes after they drink coffee compared with when they have not had coffee -Nicotine increases the rate of excretion of caffeine from body (50% faster) -Smokers metabolize caffeine quicker than non-smokers -Drinking energy drinks with alcohol does not reduce alcohol related deficits -Can increase alcohol consumption -Alcohol's CNS depressant cation remains relatively untouched by caffeine (Caffeine gives the illusion of being less drunk) 9. Caffeine intoxication or caffeinism (generally occurs with more than 600 mg daily) -muscle twitching, rambling flow of thought, cardiac arrhythmia, periods of inexhaustibly and psycho motor agitation, ringing in ears, flashing lights.... 10. -Lethal dose = 10g for adults and 100mg/kg for children (75 cups of coffee (Not common)) Chronic Effects -relationship between the lifetime amount of caffeinated coffee consumed and osteoporosis in postmenapousal women -association between serum cholesterol levels and caffeine consumption (Related to atherosclerosis) (Caffeine-cholesterol link depends on how coffee is brewed) -Indigestion, palpitations, tremor, headache and insomnia -High rates of caffeine = lower rates of conception -No association between caffeine and cancer or heart attacks -Drug may exacerbate anxiety symptoms -coffee drinkers have a lower risk of dying from a variety of diseases, relative to people who drink little or no coffee -May help prevent over disease, Parkinson's, dementia, heart irregularities, type 2 diabetes...

Consider the antipsychotic or neuroleptic drugs. What is the disorder they are designed to treat? What are some of the major antipsychotic drugs?

They are designed to treat schizophrenia -Neuroleptic drug: Tranquilizing drugs used to treat psychoses, same as major tranquilizer -1950's -Primarily affect reticular activating system, limbic system, and hypothalamus -Dopamine hypothesis (psychosis caused by overactive dopamine - increased levels of dopaminergic activity induce psychoses, and most antipsychotic drugs block postsynaptic dopamine receptors) -Primary action of antipsychotics is central dopamine antagonists o Chlorpromazine (Thorazine)- usually made as a dye, these drugs were tried on schizophrenics and it was the first step towards doing something with these people other than locking them in a padded room all of their lives o Thioridazine (Mellaril) o Haloperidol (Haldol) • 2nd generation- they try to target specific dopamine receptors(D2) so they treat schizo with less severe motor defects o Clozapine(Clozaryl) o Risperidone(Risperdal) o Olanzapine(zyprexa) o Quetiapine(Seroquel)

How does alcohol interact with other depressant drugs? What sorts of drug interaction occurs when depressants are taken in combination?

potentiation- produce additive effects Alcohol interacts synergistically with other CNS depressants/barbituates/ benzodiazepines /marijuana / antihistamines Alcohol+barbituates= suicide Alcohol decreases the effects of certain prescribed medications, such as antibiotics, anticonvulsants, anticoagulants, and MAO inhibitors (Drug use to treat depression that inhibit the enzyme monoamine oxidase, which degrades the neurotransmitters of norepinephrine and serotonin) Alcohol causes slight respiratory depression at low doses. High doses are associated with the induction sleep, stupor, and possibly coma Overdose can cause cardiovascular depression (Dysfunction of medulla that controls breathing and heartbeat)

Coca Today (2019)

the cartels are gone, FARC and Colombian government have signed a historic cease-fire, but coca production has actually increased Coca production has also gone up in Bolivia and Peru Where is it going? MEXICO Controlled by the Sinaloa Cartel Now responsible for most of the cocaine (and meth and heroin) entering the US Cartel Chief "El Chapo" convicted Feb 12, 2019 on 10 counts of drug trafficking and related crimes El Chapo was accused of using hitmen to commit hundreds of murders as well as assaults, kidnapping, torture, and delivering 1 million bribe to former mexican president He escaped from an early prison sentence when the cartel through a tunnel The reach fo the cartel includes fleets of ships, private planes, and submarine, defying border interdiction DEA says that most of the drugs don't really come across where a wall will do any good. Most drugs come through border checkpoints, the traffickers are very good at disguising drugs, and don't forget, they have ships and planes.... Coca Today: 2019: Coca flour, tea and other products legal and readily available Legal coca cultivation in Peru (Purchased by government from farmers with permit)

Antipsychotic Drugs What is the mechanism of action for antipsychotic drugs? What side effects are associated with them? Note particularly tardive dyskinesia.

• Extrapyramidal: Origin in basal ganglia, cell bodies involved in movement -Motor disturbances -Dyskinesia: Disordered movements -Akinesia: Slowness of movement and under-activity -experienced by 50% of patients on anti-psychotics • Work by blocking dopamine- so it causes Parkinson's like symptoms such as tremors. • Extensive use over many years leads to permanent damage of the motor system called tardive dyskinesia. It causes very disturbing motor ticks and spasms particularly in the face and tongue (side effect of Long term use) • They seem to induce significant weight gain and diabetes Chlorpromazine (Thorazine) Thioridazine (Mellaril) Haloperidol (Haldol) *Not helpful at treating cognitive and negative symptoms *Relieve symptoms of schizophrenia, but its not a cure *Block dopamine receptors *Flattened affect/depression *Tardive Dyskinesia