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Drugs & Behavior Week Five

by: Sarah Kincaid

Drugs & Behavior Week Five 333

Sarah Kincaid

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Notes covering material on tomorrow's quiz. If you cannot download them immediately send me an email with your studysoup username!
Drugs and Behavior
Class Notes
addiction, tolerance, Withdrawal, dependence, opioids, Neurotransmitters/Receptors, Pharmacodynamics, pharmacokinetics
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This 6 page Class Notes was uploaded by Sarah Kincaid on Tuesday October 4, 2016. The Class Notes belongs to 333 at 1 MDSS-SGSLM-Langley AFB Advanced Education in General Dentistry 12 Months taught by Caine in Fall 2016. Since its upload, it has received 45 views. For similar materials see Drugs and Behavior in Psychology at 1 MDSS-SGSLM-Langley AFB Advanced Education in General Dentistry 12 Months.


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Date Created: 10/04/16
Opioids Quiz 3 Material Opioid system Opioid Neurotransmitters Neurotransmitter Receptors Behavior (Tx) Endorphin mu opioid receptor Analgesia Respiratory suppression Abuse potential Enkephalin Delta opioid receptor nothing Dynorphin Kappa opioid receptor No Tx Drug – Salvia Divinorum A hallucinogen Tx = Therapeutic Effects addiction: tolerance, dependence (stop at nothing to get drug) & withdrawal (physiological symptoms) Tolerance: rightward shift, decrease in potency, “need more to get same effect” In week one, E50= 2 mg. 2.5 mg is given for minor pain Opioid addicts usually people with chronic pain or cancer, athletes, practitioners of martial arts, ice hockey players 2.5 mg is nothing for them ED 50 30 mg. 15 fold rightward shift Due to Δ in brain chemistry.  Spontaneous withdrawal: drug washout (body must metabolize remaining drug in body), takes hours o Betty Ford Center: agree to be captive (lockdown); 24-48 h of withdraw  Precipitated withdrawal: inject with high doses of antagonist; “kicking the habit” (count # of jumps or grams of feces); surmountable antagonism o in humans called rapid detox - 1 day procedure, no physical withdrawal bc under general anesthesia for ~6 hours Opioids  Heroin withdrawal has very clear physiological signs (sweating, vomiting, diarrhea, shaking, Δ body temperature, muscular spasms) o Addicts don’t want to quit heroin because they will get “sick”  On the contrary, cocaine withdrawal is less noticeable, but addicts have dependence (they will not go w/o it) o Addicts will leave their child waiting at school to go get more cocaine  Opioids work on endorphin system and the mu (morphine) receptor o Opioids fit into mu receptor as direct agonists  14% of military take opioids for non-medical purposes  12% of HS seniors take opioids for non-medical purposes o Starts w/ docs Rxing them  ½ well intentioned, treating pain  ½ drug dealers w/ M.D.s o Most addicts started with pain (physical or emotional) o Why they can’t stop – withdrawal (I’ll get sick) Therapeutics Agonists: pain relief (analgesics – pain relief w/o total loss of feeling, anesthetics – block all feeling including pain), cough suppressants, antidiarrhoeals, addiction treatments Rx painkillers #1 prescribed drug, #1 cause of death, most commonly used in surgery. 4 generic pain relievers 1. hydrocodone (Vicodin) -hydrogen and oxygen groups do 2. oxycodone (Oxycontin and Percocet) same stuff 3. hydromorphone -codones are improvements from 4. oxymorphone codeine -morphones are better orally Morphine sulfate  invention of needle morphine; still used for parenteral (injection); wars fentanyl (G)  most commonly used analgesic during surgery & post-op  street name China White – worst disaster in DEA (drug enforcement administration) history loperimide (Immodium)  antidiarrhoeal  lipophilic, easily stored in fat membranes – gets caught in intestines (GI tract) o contract intestines methadone  one of the most controversial drugs (given to opioid addicts in treatment) o as potent/effective/addictive as heroin  not as bad as China White (less potent than fentanyl) but more potent than heroin Opioids  methadone clinics: methadone gets the addicts there every day while behavioral/clinical therapy helps with addiction – resist temptation of high Antagonists: rescue from opioid OD; fertility enhancers (gentle, not highly effective) naloxone (Narcan, also in Suboxone)  inject (not pill – 1 pass metabolism) to counteract OD naltrexone (Vivitrol)  more orally available (pill)  no matter what you do you cannot get high  rightward shift (antagonist)  Problem: compliance (patients aren’t compliant – precipitated withdrawal) Partial agonists: limited maximum effect, lower plateau on y-axis, halve withdrawal, halve respiratory depression and abuse potential, get less high, can become dependent - potency does not matter, what counts is the ceiling on effectiveness - 2 most prescribed partial agonists: buprenorphine (Suboxone) & varenicline (Chantix) Suboxone  most widely used med for treatment of opioid addiction o targeted at addicts at greater risk of dying from their drugs  targets withdrawal not dependence (become dependent on Suboxone)  #1 reason addicts can’t quit: withdrawal o Suboxone works w/o therapy  pD: limited effect  pK: time (1 effect) Tablet on left in image is Suboxone tablet Naloxone: antagonist, mu opioid, 1 pass metabolism (only low doses) Buprenorphine: partial agonist (mu opioid), goes to bloodstream & brain In potency based on the pD graph, fentanyl > buprenorphine > morphine. Effect on mu receptor: Vicodin > endorphin > buprenorphine Difference between fentanyl and morphine is potency (fentanyl is more potent) and respiratory depression Opioids - fentanyl has same Tx effectiveness as analgesics as morphine or hydrocodone All of these drugs (fentanyl, morphine, buprenorphine, hydrocodone) use mu opioid receptor Goal for new opioids: higher TI, lower R.D., = effectiveness Side effects: respiratory depression (R.D.), nausea, sedation, constipation, abuse liability important side effect: R.D. (what kills you); does not discriminate between addicts and EE R.D.: 1 check pulse/heart rate, 2 ndcheck breathing 2 ndmost import side effect: addiction (doesn’t kill you directly, its R.D.) Alternatives (alone or in combinations): NSAIDs (cox inhibitors, OTC analgesics) – aspirin, acetaminophen, ibuprofen, Tylenol, Advil Pharmacokinetics st - partial agonists act on timing of different drugs (absorbed into BBB vs 1 pass) Pharmacodynamics - antagonists cause rightward shift Heroin is 2x or 3x stronger than morphine. However, they are identical in your brain. It’s the morphine that stimulates receptors in brain. Heroin is diacetylmorphine. Acetylate morphine st twice to get heroin, which can be taken orally (1 pass doesn’t effect it like morphine). Heroin passes blood brain barrier (BBB) better than morphine. Heroin deacetylates to morphine. Heroin gives you more morphine in brain than the same mg of morphine. Background  Exogenous = not produced in the body  Opium is extracted from the poppy o Has two major opioids: codeine & morphine  Opioids used as pain (analgesic & anesthetic), antidiarrheal, cough meds o English cultures: drank as laudanum (opium/alcohol mix) o “Mrs. Winslow’s Soothing Syrup for Teething Children” 19 c. th o Opium Wars  Morphine purification & development of syringe needles o Civil War and Franco-Prussian War: injected via i.v. and i.m.  War Disease: morphine addiction o Heinrich Dresser synthesizes heroin (diacetylmorphine) Opioids  Bayer Company (known for Aspirin) marketed heroin as a non- addictive alternative to cough medicines containing “codeine”  Blatant lies – no data Uncolored part is the inactive portion of the tablet, which expands slowly pushing out the oxycodone (1 pill  12 hours) *7 teenagers OD-ed and died bc they crushed these pills and got 12 hours of oxycodone at once th  20 century o 1% of Americans used opioids habitually at beginning of 1900s, now climbing due to increase in Rx opioid abuse o Vicodin is the most prescribed drug in US o Salvia divinorum: kappa agonist and hallucinogen Figure 1. In the past few decades, more people have died of Rx opioids (pills) than street drugs.  Today, the War Disease: PTSD  Another modern opioid: Robitussin  Vicoden is #1 cause of death via accidental overdose (highest in FL) o Import city of illegal substances o “doc-in-box culture”  Need no Rx, ID, medical insurance  Pay cash  Buy Vicoden in mass quantities in cash to resell on the streets  7 people die daily in FL of Rx opioids o Drug abusers are in favor of quality control bc they know what is in the drug and its potency  Perk-30s (sustained release) bring the highest market value in FL bc made for high tolerance after many years  For pain relief, opioids are not given to the elderly because the sedative effect can lead to falls Opioids  Two side effects of opioids that cause people to stop taking them: 1. Nausea 2. Sedation  Note: not most important side effects Review Precursors – chemical ingested that increases natural synthesis of neurotransmitter Ex. L-DOPA, a precursor of dopamine Indirect agonists are a type of reuptake inhibitor. 6 Synaptic Mechanisms: 1. Direct Agonists 2. Reuptake Inhibitors (like indirect agonists) 1-5 are agonists 3. Releasers 2-5 are indirect agonists 4. Enzyme inhibitors (like MAOI) 6 is the only antagonist 5. Precursors 6. Antagonists Neurotransmitter inactivation:  Reuptake into synaptic channel  Enzymatic degradation in synapse


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