Drugs & Individual Behavior Class Notes Week 5
Drugs & Individual Behavior Class Notes Week 5 PSYCH 3102
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This 7 page Class Notes was uploaded by McKenna Keck on Thursday September 22, 2016. The Class Notes belongs to PSYCH 3102 at University of Northern Iowa taught by Dr. Linda Walsh in Fall 2016. Since its upload, it has received 13 views. For similar materials see Drugs and Individual Behavior in Psychology at University of Northern Iowa.
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Date Created: 09/22/16
Drugs & Individual Behavior Week 5 Tuesday, September 20, 2016 Continued from families of CNS Depressants ○ NonBarbiturate SedativeHypnotics ■ Called then nonbarbiturates b/c there were so many problems w/ the barbs that they wanted to come up w/ something better ■ Several drugs were released claiming to be big improvements over the barbs (but they turned out not to be better) ■ Examples: ● methadone (Quaalude) ● meprobamate (Miltown) ● It just wasn’t the improvement they claimed it was. ○ It’s really not until drugs have been out for a long time that you know what it’s really like. ■ Turned out not to be significant improvements & one after another have been removed from the legal market ○ Benzodiazepines ■ “Minor Tranquilizers” or “Anxiolytics” ■ 15 different benzos currently available, main difference is half life/time course (just like for barbs) ● Examples: diazepam (Valium), alprazolam (Xanax), chlordiazepoxide (Librium) ■ Act via benzodiazepine receptor on GABA receptor, increasing the calming effects of GABA (they are sometimes called BZRAs: benzodiazepine receptor agonists) ■ Very commonly prescribed ● Several benzos are in the top drugs prescribed ■ Why might you want a short acting benzo? ● You need a sleep aid but don’t want to wake up groggy ■ Why might you want a long acting benzo? ● If you have epilepsy ● If you have muscle spasms ● If you’re going through alcohol detox ● If you have an anxiety disorder that bothers you all the time ■ Benzo benefits ● Somewhat more selective than barbs ● Wide safety margin (high LD) as long as other depressants aren’t used ● 2 antidotes for overdose are available: ○ Antagonist flumazenil (Romazicon) (short halflife, must be readministered) ■ Misplaces the benzo from the receptor they attach to so they can’t have an effect any more ■ Short halflife, so they might have to give it more than once if you overdose on something longacting ○ NEW!: narcotic antagonist Narcan (naloxone) that’s used for opiate overdoses can also help in benzo overdose! (but not good if person is opiatedependent) ● Less tolerance & dependence than barbs ● Less dangerous withdrawal (can be delayed several days & leaves more gradually due to longer halflife) ● Sleep somewhat more normal than w/ barbs (but still REM suppression) ■ After their introduction in the 1960s, benzodiazepines became THE most widely prescribed psychotherapeutic drugs until nearly the 1990s. ● Doctors got a little trigger happy on their prescribing. ■ Benzo Problems ● Great for short term use, but dependency & abuse still possible (Schedule IV) ● Significant cognitive/memory storage impairment ○ Sometimes used specifically for that reason, like for colonoscopies ● Driving impaired, interacts w/ alcohol; (low dose Xanax = like BAC .15) ● Dangerous interactions ○ Should never be paired w/ other CNS depressants or opioids ● Some increased risk of birth defects ● Overresponse in elderly common; idiosyncratic responses like agitation & rage possible ■ Benzo Withdrawal: Rebound Hyperexcitability ● Not as dangerous as barb withdrawal because it is naturally more gradual ● But rebound insomnia, anxiety, restlessness, agitation, & irritability making quitting difficult for dependent users. Taper dose over months to get the least withdrawal symptoms. ● In rare cases can get DTs (delirium tremens a delirious state) & seizure like barbs ● Even after withdrawal users are prone to relapse (like alcoholics) ■ Rohypnol a “daterape drug” ● “Roofies” contain a high potency bezo not marketed in the US, but similar to Halcion ● Actually any combination of alcohol + sufficient benzo could produce similar effects ● Impairs consciousness & memory of victim ● DAWN reports about 15,000/yr cases of such “intentional poisonings,” ⅔ in females, about 60% via tainted drinks ● There are products now to check if your drink has been tainted (there’s even a nail polish that’ll change colors if you dip it in your drink & it’s tainted). ● GABArelated Club Drug Gammahydroxybutyrate (GHB) ○ Not a benzo, but worth mentioning here. ○ A non benzo that that’s sometimes used as a daterape drug. ○ Potent depressant used as a general anesthetic in some countries & as daterape or club drug in others ○ Found in the CNS some GABA is converted into GHB ○ Overdose can be deadly nausea, vomiting, loss of consciousness, respiratory depression, possible seizures ○ DAWN reports 3,4005,000 overdoses per year, 72 fatal ○ Now a Schedule I drug & a Schedule III drug for improving nighttime sleep/decreasing daytime sleepiness in narcolepsy ○ When you get a drug on the street there’s really no way of knowing exactly what it is, how potent it is, etc. ■ Alternatives to Benzos & Barbs ● The Trend in Drug Development: Even More Selective Drugs ○ More “selective” drugs affect only a subgroup of receptors ○ Nonbenzodiazepine selective BZRAs the Z’s ■ zolpidem (Ambien) Mostly hypnotic & amnesic effects w/ little antianxiety, anticonvulsant, or muscle relaxing effects. More normal sleep, less insomnia rebound. Halflife 2 hrs; shortterm use only. ■ zaleplon (Sonata) halflife > 1 hr, so can be taken in middle of night (about 4 hour effect) ■ eszopiclone (Lunesta) halflife about 6 hrs approved for use up to 6 months ■ Take these at bedtime only; DO NOT DRIVE, may increase bizarre sleepwalking, sleep eating in some w/ no memory of event ■ Approved v. OffLabel Uses of a Drug: ● If a drug company wants to list a particular use for a drug in their materials and/or advertise their drugs for that use, the FDA require that they conduct & submit the extensive research necessary to demonstrate the drug is safe & effective for that use (approved). ○ It takes many years… Usually more than a decade. ○ When you research a drug you can see what a drug is actually approved for. ● But doctors aren’t limited to prescribing for these “approved” uses. You should always check (offlabel). ○ Did the FDA approve this drug for this use? If not, what research suggests it would be useful? ○ What alternatives are there? ● Brand name companies that produce Halcion, Restoril & Dalmane did the years of research necessary to get FDA approval to market their drugs as hypnotics & list this use in their package insert. This is a FDA approved use of these drugs. ● If doctors prescribe other benzos to promote sleep (ones that didn’t submit research related to sleep to the FDA), use for that purpose would be “offlabel” (those drugs can’t be marketed for that use & can’t list that use on their label or package insert). In this case, any benzo can make you sleepy, but sometimes “offlabel” use is really experimental. ■ Drug Abuse Warning Network (DAWN) ● Network of metropolitan hospitals w/ ER departments ● From ER medical records glean how many visits are associated w/ different drugs ● It’s not perfect information, because they don’t do blood tests to check to see if it’s the drug. They just go off of mentions. Thursday, September 22, 2016 Continued from Benzodiazepines… ■ Benzos may be following the barbs out of widespread popular use ● Benzos are being replaced by safer, more selective drugs for many, if not most, of their therapeutic uses ● Use for anxiety now being replaced by antidepressants & other drugs more than 50% decrease in benzo prescriptions ● Use for insomnia decreasing as well ● BUT: Swing to new drugs may be going too far ● Benzos still have their place & new drugs have their own problems. ○ Antiepileptics or “Anticonvulsants” Besides the Barbs & the Benzos ■ The majority of the many drugs used to control seizures work on the same transmitterenhancing the calming action of GABA. ■ We’ll come back to a few of the anticonvulsants being used as psychotherapeutic drugs later in the semester. ○ General Anesthetics ■ Exert dosedependent CNS depressant effects ■ Additional complication of inhaled anesthetics decrease/displace the inhalation of oxygen. Except in the hands of a trained anesthesiologist there is a very real risk of hypoxia & brain damage. ■ We won’t cover individual anesthetics except nitrous oxide & GHB as substances of abuse. ● Alternatives to CNS Depressants/Sedatives/Hypnotics ○ You might not want to prescribe a CNS Depressant b/c of substance abuse, alcohol use, recovery, etc. ○ Antihistamines (for sedative/hypnotic effects) ■ diphenhydramine (Benadryl) (OTC) ● The sedating antihistamine that’s in “PM” drugs (like Tylenol PM) ■ hydroxyzine (Atarax, Vistaril) prescription only ■ promethazine (Phenergan) prescription only ○ Melatonin (OTC supp) or a melatonin agonist (prescription) Rozerem (ramelteon) to help one fall asleep ○ Betablockers (decrease body signs of anxiety) ■ propranolol (Inderal), atenolol (Tenormin), metoprolol (Lopressor) ○ Antidepressants ■ trazodone (Desyrel), amitriptyline (Elavil), mirtazapine (Remeron) & doxepin (Sinequan) used for sleep ■ SSRIs now used for most anxiety disorders we’ll cover these later in the semester ○ AntiAnxiety Drug Not Working on GABA ■ Selective 5HT1A agonist buspirone (Buspar) (antianxiety but not CNS depressant) ● Delayed (24 weeks) antianxiety action without sedation, incoordination, memory problems, depressant interactions, dependency (good for those w/ abuse risk or drinking problem). May not be as effective for panic disorder. ● Side effects: headache, dizziness, nausea Alcohols ● Different Kinds ○ Beverage alcohol = ethanol or ethyl alcohol ○ Rubbing alcohol = isopropyl alcohol (also in antiseptics, aftershave, window washer fluid) ○ Methanol or Methyl alcohol = common industrial/chemical form of alcohol (antifreeze, Sterno, solvents, duplicating fluid) ○ All 3 are toxic to your body, but ethanol is the least toxic. ● Ethanol ○ Produced by the action of yeast on a sugary mixture (“fermentation”) ■ Or you could start w/ a starchy mixture that can be turned into sugar ■ Fermentation can only go up to (at max) a solution that’s 15% alcohol. Once it gets that high the alcohol itself kills off the yeast. ■ Distillation must be used to produce stronger spirits ● Alcohol boils at a lower temp than water. If you boil it off, the alcohol will evaporate 1st, collect the vapors, stopping before the temp where the water would boil off, & get a more concentrated alcohol. ● Distilled spirits can get up to 40% ● “Proof” is 2x the % ○ A lot of people use alcohol to ease their pain for a while, some people are totally against it, etc. ○ BAC (Blood Alcohol Concentrations) are how you measure the dose response for ethanol ■ .08% is considered the legal limit ○ Alcohol absorption ■ Fat & water soluble molecule easily gets into all tissues; no digestion necessary ■ Provides calories but no nutrients ● Alcoholics often have a lot of vitamin deficiencies ■ About 20% absorbed from stomach, 80% from intestines ■ Stomach contents, alcohol concentration, carbonation (speeds), gender, drug interactions (aspirin, antiulcer, etc), all affect absorption ■ Other factors influencing intoxication: speed of consumption, individual sensitivity, expectancy ● Alcohol Expectancy Effects ○ Males who expect to get alcohol: ■ Act drunker ■ Show more subjective arousal & sexual disinhibition whether or not they get alcohol ○ Typical Effects on the Body ■ Dilation of blood vessels in skin leading to a warm surface flush (but drop in core body temp) ● If that happens every day, like to an alcoholic, those blood vessels can break ● So, the St. Bernard bringing whiskey to people lost in avalanches, actually probably not a good idea. ■ Decreased Antidiuretic Hormone (ADH) leading to increased urination & dehydration ● Antidiuretic hormone tells your body to save water ● You’ll end up losing more water than you drink ■ In moderate doses, increased HDLs (good) & lowered LDLs (bad) except in smokers ■ Gastric irritation ○ Actions of Alcohol on the Brain (Multiple Actions) ■ Produces most depressant actions by enhancing the inhibitory effects of GABA ● A drug (RO 154513) which keeps alcohol from binding to GABA receptor acts as a “soberup” drug. It actually forced alcohol off the alcohol binding site on the GABA receptor. ● Didn’t get marketed, because it didn’t reverse depression of respiration, & you can’t depend on people to take it appropriately. Full of chances of lawsuits. ■ Alcohol blocks excitatory effect of glutamate (like barbs) so is “extradepressant” in its effects ■ These actions, in turn, lead to the release of 5HT, DA, endorphin & anandamide producing rewarding/mood elevating effects *Some lines of notes copied directly from slides in order to maintain testing accuracy. Most is of the lecture & discussion, not found on slides.
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