toxicology of opiates

07/15/14 Gold Coast 1999 1 Toxicology of Opiates Dr. George Braitberg Austin and Repatriation Medical Centre Heidelberg Victoria 07/15/14 Gold Coast 1999 2 Opiates and Opioids • Opiate refers to a substance that originates from opium, and is gained out of the latex of the capsule of the opium plant, Papaver somniferous • Opioid is the term used for substances with an analogue effect to morphine. Opioids are ligands on opioid-receptors and they possess an intrinsic activity. 07/15/14 Gold Coast 1999 3 Opiates and Opioids  Not all opiates bond to opioid- receptors: not all opiates are opioids 07/15/14 Gold Coast 1999 4 Opiates Opiates are the approximately 20 natural substances from the opium-juice of poppy seed capsule 07/15/14 Gold Coast 1999 5 Opiates  Morphine  Codeine (3-ortho-methyl- morphine)  Papaverine  Noscapine 07/15/14 Gold Coast 1999 6 Opioids Opioids are substances with effects similar to morphine: • Natural opioids, opioid opiates • Semi -synthetic opioids • Synthetic opioids • Active metabolic products from Heroin and Morphine • Endogenic, opioid peptides 07/15/14 Gold Coast 1999 7 Opioids with morphine like action  Phenanthrenes: are opium alkaloids that have an effect analogue to that of morphine. They are opioid effective opiates.  Morphine (Morphium): raw opium contains 10- 17% morphine  Codeine: is used mainly as an antitussive. Raw opium contains 1-4% codeine. 07/15/14 Gold Coast 1999 8 Opioids with no morphine like action  Thebaine:starting substance for synthesis of naloxone, naltrexone and buprenorphine; has only a very slight effect on it’s own.  Benzylisochinoline: are opium alkaloids which have no effect analogue to that of morphine.  Papaverine: Phosphodiesterase inhibitor: works mainly spasmolytic.  Noscapine: antitussive without addiction potential. Raw opium contains 2-9% noscapine. 07/15/14 Gold Coast 1999 9 Semisynthetic Opioids  Heroin (DAM, Diamorphine 3,6-O-Diacetylmorphine)  Hydromorphone  Nicomorphine  Dihydrocodeine  Hydrocodone (Dihydrocodeinone)  Buprenorphine 07/15/14 Gold Coast 1999 10 Synthetic Opioids  Methadone  Dextromoramide  Tilidine  Pethidine  Pentazocine [...]... half-life: 4 hours Analgesic Buprenorphine Duration of analgetic effect: 6-8 hours Duration of withdrawal prevention effect in high doses up to 48 hours Elimination half-life: 5 hours Agonist/Antagonist; synthetised out of Thebain 07/15/14 Gold Coast 1999 16 Synthetic Opioids Methadone • Analgesic • Duration of analgetic effect: 8-48 hours • Duration of withdrawal prevention effect in high doses: rarely... physiological and subjective effects of parenterally administered heroin, hydromorphone or morphine for 24, 48 and 72 hours respectively 07/15/14 Gold Coast 1999 24 Naltrexone The lowest effective plasma naltrexone concentration of 2ng/ml provided an average of 86.5% blockade of 25mg IV heroin effects In sustain released therapy for opiate antagonist activity, plasma level of naltrexone should be kept above... Analgesic • Duration of effect: 4-5 hours • Elimination half-life: 2.5 hours 07/15/14 Gold Coast 1999 14 Semisynthetic Opioids Nicomorphine Analgesic Duration of effect: 4-5 hours Elimination half-life: 2-3 hours Dihydrocodeine Antitussive, (Analgesic) Duration of effect: 4-5 hours Elimination half-life: 4 hours 07/15/14 Gold Coast 1999 15 Semisynthetic Opioids Hydrocodone antitussive Duration of effect: 8-10... Dextromoramide •Analgesic Tilidine •Analgesic –Duration of effect: 4-6 hours –Elimination half-life: 3-5 hours Pentazocine •Analgesic –Duration of effect: 3 hours –Elimination half-life: 2-3 hours –Takes effect on κ -Receptoren agonistically and on the µ -Receptoren antagonistially 07/15/14 Gold Coast 1999 18 Pethidine • Analgesic – Duration of effect: 2-4 hours – Elimination half-life: 2.5-3 hours... –Duration of effect: 4-5 hours; in retard form 6-12 hours –Elimination half-life: 3 hours (also in retard form) –Minimal deadly dose: • 25 mg i.v./ 50 mg po 07/15/14 Gold Coast 1999 12 Codeine - opioid and opiate Codeine •Antitussive • (Analgesic) •Duration of effect: 4-6 hours •Elimination half-life 3-4 hours 07/15/14 Gold Coast 1999 13 Semisynthetic Opioids Heroin • Analgesic • Duration of effect:... in the oral form It is a modification of naloxone made by adding a carbonyl group to C-6 Naltrexone competes with the opioid agonists for the mu, delta, and kappa receptor sites in the central nervous system 07/15/14 Gold Coast 1999 26 Naltrexone - Pharmacokinetics Elimination half-life of 3.9-10.3 hours Absorption is rapid and almost complete Bioavailability of only 5-20% (extensive first pass hepatic... 153:851-852, 1989, Loimer N Similar Efficacy of Abrupt and Gradual Opiate Detoxification Am J of Drug and Alcohol Abuse 17 (3):.307-312,1991 07/15/14 Gold Coast 1999 29 Naltrexone in the Literature Resnick RB et alNaloxone-Precipitated Withdrawal: A Method for Rapid Induction Onto Naltrexone Clin Pharm Ther 413(4): 409-413,1977 Lorimer N et al Acute Blocking of NaloxonePrecipitated Opiate Withdrawal Symptoms... Alcohol Dependence 35 (1994) 91-93 Lance L Rapid Opiate Detoxification J of Addictive Diseases.15(2) 1996:117 Gold Coast 1999 30 Naltrexone in the Literature Naltrexone in the Outpatient Treatment of Heroin Withdrawal Kleber HD, Topazian M, Gaspari J, Riordan De, Kosten T Am J Drug Alcohol Abuse 1987; 13:1-17 Clinical Utility of Rapid Clonidine Naltrexone Detoxification for Opiod Abusers Vining E,... Naltrexone In opioid dependence, a 25 mg test dose is given If there are no signs of withdrawal, an additional 25 mg is given, then maintenance naltrexone therapy is set at 50-100 mg per day 07/15/14 Gold Coast 1999 28 Naltrexone in the Literature Presslich O Opiate Detoxification Under General Anesthesia By Large Doses of Naloxone Clin Tox 27 (4&5), 263270 (1989), Loimer N et al Continuous Naloxone... Heroin and morphine produce analgesia by acting on the mu (µ)-type opioid receptors in the brain action of heroin vs morphine are clearly separable 07/15/14 Gold Coast 1999 20 Heroin Addiction In mice (Swiss Webster, SW), heroin acts on delta-type opioid receptors By using specific antagonists, the action of heroin and morphine are clearly separable These studies may provide the basis for relating genetic . activity. 07/15/14 Gold Coast 1999 3 Opiates and Opioids  Not all opiates bond to opioid- receptors: not all opiates are opioids 07/15/14 Gold Coast 1999 4 Opiates Opiates are the approximately. 07/15/14 Gold Coast 1999 1 Toxicology of Opiates Dr. George Braitberg Austin and Repatriation Medical Centre Heidelberg Victoria 07/15/14 Gold Coast 1999 2 Opiates and Opioids • Opiate refers. Opioids • Opiate refers to a substance that originates from opium, and is gained out of the latex of the capsule of the opium plant, Papaver somniferous • Opioid is the term used for substances