Metabolism of opioids

Krondahl E, von Euler-Chelpin H, Qrzechowski A, Ekstrom G, Lennernas H (2001) In vitro metabolism of opioid tetrapeptide agonists in various tissues and subcellular fractions from rats. Peptides 22 613-622. 

C. Ampasavate, G.A. Chandorkar, D.G. Vande Velde, J.F. Stobaugh, and K.L. Audus. Transport and metabolism of opioid peptides across BeWo cells, an in vitro model of the placental barrier. Int I Pharm. 233 85-98 (2002). 

Babies bom to opioid-addicted women also exhibit withdrawal signs, but because of the slower metabolism of opioids in the newborn, the withdrawal signs are more protracted. The babies are often treated with the opium preparation paregoric to reduce withdrawal signs. 

Aminopeptidases are involved in the metabolism of opioid peptides including enkephalins and /3-endorphins. An HPLC method was developed to measure the hydrolysis of these compounds by measuring the formation of tyrosylglycyl-glycine, tyrosylglycine, and tyrosine. 

In practice, the metabolism of opioids appears to be well preserved during periods of acute liver dysfunction, but the drugs are likely to accumulate in prolonged disease. 

MAOIs PETHIDINE, MORPHINE, PHENOPERIDINE, DEXTROMETHORPHAN Two types of reaction are reported 1. Risk of serotonin syndrome with dextromethorphan, pethidine or tramadol and MAOIs 2. Depressive - respiratory depression, hypotension, coma Type 1 reactions are attributed to inhibition of reuptake of serotonin -more common with pethidine, phenoperidine, dextromethorphan. Type II reactions are attributed to MAOI inhibition of metabolism of opioids - more common with morphine Avoid co-administration do not give dextromethorphan, pethidine or tramadol for at least 2 weeks after cessation of MAOI... 

CYP3A4, may contribute to methadone metabolism. Even with adequate methadone plasma levels, some patients continue to abuse drugs, such as sedatives, possibly because they are seeking some form of intoxication rather than relief of opioid hunger (Bell et al. 1990). Relapse to illicit drug use is also common during periods of high stress, even in patients with adequate plasma levels. 

H., Wang, B., Borchardt, R. T., Coumarinic acid based cyclic prodrugs of opioid peptides that exhibit metabolic stability to peptidases and excellent cellular permeability, Pharm. Res. 1999, 36, 7-15. 

Wilcox, R.A. and Owen, H. (2000) Variable cytochrome P450 2D6 expression and metabolism of codeine and other opioid prodrugs implications for the Australian anaesthetist. Anaesthesia and Intensive Care, 28 (6), 611-619. 

The pulmonary absorption and metabolism of an opioid tetrapeptide was investigated in the IPL and in rats in vivo by Tronde and co-workers [68, 140], The lung metabolism, compared after airway and vascular delivery, was consistently showed to be higher after airway delivery indicating some first-pass... 

E. Krondahl, H. von Euler-Chelpin, A. Orzechowski, G. Ekstrom, H. Lennernas, Investigation of the in-vitro Metabolism of Three Opioid Tetrapeptides by Pancreatic and Intestinal Enzymes ,./. Pharm. Pharmacol. 2000, 52, 785 - 795. 

O. S. Gudmundsson, K. Nimkar, S. Gangwar, T. Siahaan, R. T. Borchardt, Phenylpro-pionic Acid-Based Cyclic Prodrugs of Opioid Peptides That Exhibit Metabolic Stability to Peptidases and Excellent Cellular Permeation , Pharm. Res. 1999, 16, 16-23. 

Morphine antagonists and partial agonists. The effects of opioids can be abolished by the antagonists naloxone or naltrexone (A), irrespective of the receptor type involved. Given by itself, neither has any effect in normal subjects however, in opioid-dependent subjects, both precipitate acute withdrawal signs. Because of its rapid presystemic elimination, naloxone is only suitable for parenteral use. Naltrexone is metabolically more stable and is given orally. Naloxone is effective as antidote in the treatment of opioid-induced respiratory paralysis. Since it is more rapidly eliminated than most opioids, repeated doses may be needed. Naltrexone may be used as an adjunct in withdrawal therapy. 

Because of its fast onset (minutes), naloxone (Narcan) administered IV is used most frequently for the reversal of opioid overdose. However, it fails to block some side effects of the opioids that are mediated by the ct-receptor, such as hallucinations. The rapid offset of naloxone makes it necessary to administer the drug repeatedly until the opioid agonist has cleared the system to prevent relapse into overdose. The half-life of naloxone in plasma is 1 hour. It is rapidly metabolized via... 

Mechanism of Action A narcotic antagonist that displaces opioids at opioid-occupied receptor sites in the CNS Therapeutic Effect Blocks physical effects of opioid analgesics decreases craving for alcohol and relapse rate in alcoholism. Pharmacokinetics Well absorbed following oral administration. Metabolized in liver undergoes first-pass metabolism. Excreted primarily in urine partial elimination in feces. Half-life 4 hr... 

Fluoxetine and paroxetine inhibit cytochrome CYP P-450 2D6 and thus may affect metabolism of some opioids, e.g. codeine, 0) codone and tramadol, that are partly metabolised by CYP2D6, many antipsychotic drugs and tricyclic antidepressants. 

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