Metabolism of morphine

Kondo, T., T. Irie, and K. Uekama. 1996. Combination effects of a-cyclodextrin and xanthan gum on rectal absorption and metabolism of morphine from hollow-type suppositories in rabbits. Biol Pharm Bull 19 280. 

The respiratory depression induced by morphine can add to that of alcohol, barbiturates, benzodiazepines (such as Valium), and even with antihistamines taken for allergies. Combined effects of these drugs with morphine can dangerously compromise breathing. Tricyclic antidepressants can hamper the metabolism of morphine. 

The metabolism of morphine and related opiates has been investigated extensively and reviewed/424 426 It tends to be very rapid after parenteral administration but unpredictable after oral dosage. Scheme 2.26 illustrates the major metabolic pathways for morphine (1), codeine (2), and heroin (256). 

OPIOIDS OESTROGENS Effect of morphine may be 1 by combined oral contraceptives Hepatic metabolism of morphine ist Be aware that morphine dose may need to be t. Consider using an alternative opioid such as pethidine... 

UGTs are responsible for the metabolism of many anxiolytics, antidepressants, mood stabilizers and antipsychotics. Inhibition of the metabolism of carbamazepine by valproic acid in part results from an effect on UGTs. Amitriptyline and clomipramine decrease the metabolism of morphine by affecting UGTs. 

The metabolism of morphine is enhanced by rifampicin, resulting in loss of analgesic effects of morphine (56). 

Liras 3 used an OV-17 column for Investigations on the metabolism of morphine and codeine by Arthrobacter species, and gave the gas chromatographic parameters of eight oxidized compounds, found as metabolites (14-hydroxymorphine, 14-hydroxymorphinone, 14-hydroxydihydro-morphinone, dihydromorphinone, codeinone, 14-hydroxycodeine, 14-hydroxycodeionone and 14-hydroxydihydrocodeinone). 

Biological synthesis of the analgesic hydromorphone, an intermediate in the metabolism of morphine, by Pseudomonas putidaMlO... 

Several of the opioids (buprenorphine, hydromorphone, methadone) are metabolised by CYP3A, at least in part, and their metabolism is expected to be reduced by the azoles, which, to varying extents, inhibit CYP3A4. This has been seen when fluconazole and voriconazole are given with methadone, and when ketocona-zole is given with buprenorphine. It has been suggested that keto-conazole inhibits the metabolism of morphine and oxycodone, but evidence for this is sparse. 

Ritonavir decreases pethidine (meperidine) and increases norpethidine levels, which may possibly increase toxicity on long-term use. Similarly, ritonavir and other protease inhibitors increase buprenorphine levels. Ritonavir may increase the metabolism of morphine, and decrease the metabolism of dextropropoxyphene (CYP3A4 substrate) and tramadol or other CYP2D6 substrates (such as codeine). 

Other studies include the pharmacokinetics of codeine and metabolic morphine derived from it, the inhibition of tolerance to morphine by naloxone, a review of the tolerance and dependence mechanism for morphine, studies of plasma ° and brain levels affected by the alkaloids, the teratogenic potency of codeine, and the metabolism of morphine. " Analytical methods for the determination of morphine and related compounds in body fluids, for improved recovery from biological tissues, and methods of radio-immunoassay have been described. 

A Michael addition occurs in the metabolism of morphine. One of the metabolites of morphine is generated via oxidation of the allylic alcohol moiety to produce an a,p-unsaturated ketone ... 

Bmce, N.C., Wilmot, C.J., Jordan, K.N., Trebilcock, A.E., Gray Stephens, L.D., and Lowe, C.R. (1990) Microbial degradation of the morphine alkaloids identification of morphinone as an intermediate in the metabolism of morphine by Pseudomonas putida MIO. Arch. Microbiol., 154, 465-470. 

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