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Naturally Naturally-Occurring Opioids Occurring Opioids

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Naturally Naturally-Occurring Opioids Occurring Opioids Drug Groups used for Pain Analgesics 1. Opioid (“opiate”) analgesics 2. NonNon--opioidopioid analgesicanalgesic--antianti--inflammatoryinflammatory Opiates analgesics (NSAIDs) 3. Drugs to increase analgesic effects Psychology 472 – Antidepressants Pharmacology of Psychoactive – Anticonvulsant ––NMDANMDA--antagonistsantagonists (e.g., dextromethorphan) Drugs – Tetrahydrocannabinol (e.g., Sativex) Listen to the audio lecture while viewing these slides 1 Opiates NaturallyNaturally--OccurringOccurring Opioids Two sources: Natural plant product Endogenous transmitters with morphinemorphine-- Opium comes from poppy like actions ((ge.g., endorphins) plant, Opium poppy: morphine and codeine – Not the same variety as the garden plant. All other opioids are eieitherther semi synthetic Difficult to synthesize in or totally synthetic. the lab Opium Poppy 1 TERMINOLOGY Narcotic: Opium: Exeudate of the opium poppy – Contains morphine and codeine as natural From narcos: products. – any sleepsleep--inducinginducing drug Opiate: A drug derived from the opium Today - An illegal drug poppy – (Morphine or codeine) Opioid: Agonist with morphinemorphine--likelike activity ––-- Synthetics 8 Groups of Opiates Antagonists Pure Agonist: Morphine, Heroin, Dilaudid, Numorphan, Demerol, Fentanyl, Oxycodone. Have affinity for receptors but is devoid of morphine action. Partial Agonist: Buprenorphine – Especially Mu receptors (Buprenex, al so i n S ub oxone) Pure Antagonist: Naloxone (Narcan), Mixed AgonistAgonist--AntagonistAntagonist: pentazocine Naltrexone (ReVia, Trexan, Vivitrol), (Talwin), Butorphanol (Stadol), N Nalmefene (Revex) Nalbuphine (Nubain), Dezocine (Dalgan) 10 Background SHORT HISTORY Are derived from the opium poppy or are Is mentioned in recorded history around synthetic copies 3400 B. C. in Mesopotamia Many uses Is beinggygyp,, used by Egyptians, Greeks, – RliRelieve pa in Europeans, Chinese, by 400B.C. – Induce sleep – Primarily used in medicine – Reduce sensation – Pleasure 1500 began to be used for pleasure in India – Becomes very important in commerce 11 12 2 1805 Opium Wars Morphine was first isolated and perfected by March 18, 1839 Friedrich Sertuerner. By Chinese Decree, all traders are Named after the god of Dreams and Sleep, Morpheus required to surrender their opium. – Clldit“MCalled it “Morp hinum ” The British respond with Warships and the First Opium War Follows. It ended in 1842 with the Chinese giving Hong Kong to the British. 18561856--18601860 More History The British renew hostilities with the Chinese over Opium Trade (and During the American Civil War, 400 000 Smuggling) soldiers became addicted to morphine Second Opium War occurs 1874 Wright synthesizes Heroin – French Aid of the British. – Used to treat opium and morphine addiction – Ended with legalization of Opium Trade. 16 Laudanum: Medicinal Opium Commonly opium mixed with Red Wine or Used in all sorts of Port. medicines (OTCS) Potentially dangerous if not properly mixed and products or if too much opium was present. 18 3 Legal Issues arise… Opiate Receptors The Harrison Narcotics Act passes in 1914 in Approximately 17 have been reported attempts to end drug abuse (particularly of Four main groups Heroin) It requires doctors, pharmacists and others who prescribed narcotics to register and ––MuMu (μ), pay a tax. – K(Kappa (κ), This was not the first attempt to legislate drugs ––DeltaDelta (δ) or to tax the use, just the most successful. – Nociceptive Others include – Epsilon (ε), Lota (ι) , Lambda (λ) Zeta (ζ) Includes subgroups (e.g. μ1 , μ2, μ3) 20 Response Depends on the Receptor Activated More Examples Mu 1 Mu and Delta 1 – Supraspinal analgesic properties – Agonists activate mesolimbic dopamine Effects occur above the spinal cord system Mu 2 – Get a rewarding effect, – Respiratory Depression Delta 2 – Dependence – AitAgonists use nonnon--diitdopaminergic system Kappa Receptor Kappa – Sedation – Activation suppresses physical and psychic – Spinal Anesthesia dependence of mu and delta agonists Delta Delta – Site for endogenous opiates – Activation increase the dependence of Mu – Dependence 21 agonists. 22 Opiate Types Many Products Contain Opium Biologically active opiates Opium – Morphine, codeine, thebaine, Morphine SemiSemi--syntheticsynthetic opioids Codeine (Methylmorphine) – Dilaudid, Hydrocodone, Percocet, Heroin, Demerol (Meperidine or Pethidine) oxymorphone, desomorphine,, nicomorphine, Heroin (Diacetylmorphine) dipropanoylmorphine, benzylmorphine and Hydromorphone (Dilaudid) Darvon/Darvocet ethylmorphine and buprenorphine; Fentanyl Fully synthetic Opioids Percocet – fentanyl, pethidine, methadone, tramadol and Others dextropropoxyphene; http://www.opiates.com/opiates/opiatehttp://www.opiates.com/opiates/opiate--library.htmllibrary.html 23 24 4 Other Compounds that bind on Endogenous Opioids Opiate Receptors Are produced naturally in the body Salvinorin A is a KK-- receptor agonist – Endorphins – No real analgesic effects – Enkephalins – Classified as a hallucinogen – Dynorphins DtDextrome thhthorphan – Endomorphins. – Has no analgesic effects – Used in cough medicines 25 26 Actions of Opiates More Actions Analgesia – Usually from opiates acting in the brain and/or Respiratory depression the spinal cord – This is what kills you from an overdose/sedation. – Can also impact other areas as well. – Decreases respiratory center's sensitivity to higher levels of carbon dioxide in blood. Reduce thalamocortical processing and DthhflDepresses the cough reflex higher CNS functions. – Antitussive action can be separated from Inhibits (hyperpolarizes) neurons. other actions Acts presynaptically on glutamate neurons Decreases nausea and vomiting to inhibit glutamate release Causes constipation – Used as a last resort for major diarrhea More Action Overall Effects on the Body Pupil constriction (miosis) Impact all muscles Euphoria – Skeletal, heart – Reduces the inhibitory effect of GABA on Also Impacts lungs, brain, and eyes dopamine neurons Muscles lose their ability to contract over time Cough and nausea centers are suppressed Digestive system slows down 29 30 5 Opium O.P.", "hop", "midnight oil", "tar", "dope", and "Big O Brownish, tartar--likelike substance Usually smoked (Use an opium pipe) – Active alkaloids (morphine) are vaporized – Then inhale the vapors Not used as much today – Other metabolites (morphine, heroin) are more popular 32 Morphine Some Slang Terms Most refined form of Opium M, glad stuff, happy stuff, happy powder, white Taken by injection or orally nurse, red cross, first line, God's Own Medicine, Comes in liquid or pill form Vitamin M, Big M, Emma, Emmy, Miss Emma, Lady M, white lady, cube, cube juice, mo, morf, Commoninthe60Common in the 60’s and 70’s, use decreases since the 80’s morph, morpho, mofo, hard stuff, shit, dope, dry grog, white merchandise, uncle, Uncle Morphy, – Hard to get morphy, coby, cobics, gold dust, monkey dust, – Replaced by synthetic opiates number 13, unkie, mojo, needle candy, others. 33 34 Pharmacokinetics Actions Decreases pain Poorly absorbed when taken orally – Morphine and friends are unbeatable at this time For users Alters mood, reduces anxiety, creates euphoria Cough suppression – Smoked or Injection preferred method Miosis Slowly crosses the bloodblood--brainbrain barrier. Causes sleep Causes decreased gastrointestinal motility Achieves same level in fetus as in – Decreases diarrheal pregnant mother – Used as a last resort (important for cholera) Side effects – Nausea, vomiting – Respiratory depression 36 6 Metabolization Withdrawal Metabolized to an active metabolite: Similar to other opiate withdrawal morphinemorphine--66--glucuronide.glucuronide. – Restlessness, drug craving, sweating, extreme Both have halfhalf--liveslives of about 33––55 hours. anxiety, depression, irritability, fever, chills, With impaired renal function can retching, panting, cramping, insomnia, accumulate the active metabolite and can explilosive dihdiarrhea, itintense ac hes an d pa ins become toxic. Not lifelife--threatening,threatening, but can seem unbearable. Heroin (Diacetylmorphine) Slang Terms for Heroin Comes in different colors Smack, gear, golden brown, brown, dope, Rapidly crosses bloodblood--brainbrain barrier; stuff, crap, shit, horse, white horse, charlie smoked, snorted, or injected. horse, chick, brother, antifreeze, Aries, Slang terms Aunt Hazel, birdie powder, bird shit, bird, – Dragon chasing" (heating of heroin with boy, bomb , Witch Hazel, sweet Jesus, barbital on a piece of foil), scat, blanco, chica, cheva. – Madak and "ack ackack"" (smoking of cigarettes Older terms H, horse, harry containing tobacco mixed with heroin powder) Word “Heroin” usually only by people Metabolized to monoacetylmorphine, working in criminal justice system and morphine, and codeine. pharmacology classes. 40 Pharmacokinetics THE RITUAL IV or smoking are most common methods of ingestion – Intravenous injection = slamming, hooting up"). BLACK TARTAR--MEXICOMEXICO Intravenous injection – Provides the most intense rush ONE TENTH OF A GRAM – Occurs within seven to eight seconds. A HIT Smoking – Is becoming more popular THE WORKS – Purity levels are higher – Decreased risk for BBPs – Reaches peak effects within 10 to 15 minutes. 41 42 7 Withdrawal Hydromorphone (Dilaudid, Palladone) Usually begins in 6 to 24 hours of 10 times as potent as morphine discontinuation of the drug Considered the gem of opiates Similar to other opiates discussed Dilaudid dose = 11––22 mg – StiitdSweating, anxiety, depress ion, genera lflil feeling Effect
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