Contraceptive agents metabolism

Important alterations in hepatic drug excretion and metabolism also occur. Estrogens in the amounts seen during pregnancy or used in oral contraceptive agents delay the clearance of sulfobromophthalein and reduce the flow of bile. The proportion of cholic acid in bile acids is increased while the proportion of chenodeoxycholic acid is decreased. These changes may be responsible for the observed increase in cholelithiasis associated with the use of these agents. 

Hormonal Control of Copper Metabolism Recent evidence suggests that metabolism of copper as well as zinc is controlled by the pituitary-adrenal axis (97,98,99). For example, administration of large doses of corticosteroids in humans leads to rapid and sustained drop in serum copper and zinc. Pregnant women and women on oral contraceptive agents show a significant increase in serum copper levels (iOO, 101,102),... 

Chem. Ind. (London) 1969, 1738. Synthesis Edwards, /bid. 80, 3798 (1958) idem, J. Am. Oil Chem. Soc. 47, 441 (1970). Toxic to nonruminant animals by reducing the oxygen-carrying capacity of blood. Metabolism in rats Abou-Donia et ai. Lipids 5, 938 (1970). Poiential use as a male contraceptive agent H. Poso et al. Lancet 1, 885... 

Griseofulvin induces hepatic CYPs and increases metabolism of warfarin, sometimes necessitating dose adjustment it also may reduce the efficacy of low-estrogen oral contraceptive agents. 

The use of oral contraceptive agents (OCAs) is widespread and is being increasingly encouraged in developing countries. Their use has been associated with a number of side effects, in particular, a possible increased risk of thrombotic and embolic vascular disease. There is also evidence that OCAs may affect the metabolism of a number of vitamins. Evidence for deficiency of thiamine, riboflb vin, ascorbic acid, pyridoxine, folic acid, and vitamin B12, and for excess accumulation of vitamin A has been reported. This is of particular concern to populations in which vitamin nutrition may already be suboptimal and has been the subject of recent brief reviews (02, R4, Tl, W13). 

L9. Luhby, A. L., Brin, M., Gordon, M., Davis, P., Murphy, M., and Spiegel, H., Vitamin B metabolism in users of oral contraceptive agents. I. Abnormal urinary xanthurenic acid excretion and its correction by pyridoxine. Amer. J. Clin. Nutr. 24, 684-693 (1971). 

The pretreatment of rats with desipramine resulted in delayed stomach emptying and, hence, slowed absorption of phenylbutazone, oxyphenbutazone, hydrocortisone, and salicylate.On the other hand, desipramine had no apparent effect on the absorption of orally administered amphetamine or phenobarbital. In another study, the interactions of a variety of acutely and chronically administered contraceptive agents and their effect on pentobarbital narcosis in the rat, as well as on certain metabolic transformations in vitro, were examined. Medroxyprogesterone, alone or in combination with ethynylestradiol, stimulated the metabolism of 7nitroanisole, aminopyrine, and aniline in vitro, although these effects cure not as marked as those seen with well-known Inducers such as phenobarbital and pesticides. 

Vitamin B-6 and oral contraceptive agents—Recent studies indicate that the vitamin B-6 requirement for most oral contraceptive users is approximately the same as that for nonusers thus, the current evidence does not appear to justify the routine supplementation of the dietary vitamin B-6 with pyri-doxine. However, some women report that depression occurs when they are taking oral contraceptives, probably as a result of the failure to convert tryptophan to serotonin, a neurotransmitter in the brain. When this problem occurs, the physician may suggest higher levels of vitamin B-6 (about 30 mg daily) in order to normaiize tryptophan metabolism. 

Rifampin Azoles, cyclosporine, methadone propranolol, Pis, oral contraceptives, tacrolimus, warfarin Increased metabolism of other agent Avoid if possible... 

There is an increased risk of craniofacial defects, spina bifida, and developmental delay in children whose mothers received CBZ while pregnant. Thus, women of childbearing age should avoid this agent. If not practical, contraception should be diligently used to avoid pregnancy. In this context, dose adjustment of oral hormonal drugs may be necessary, since CBZ may accelerate their metabolism and compromise contraceptive effectiveness. 

Interactions. Rifampicin is a powerful enzyme inducer and speeds the metabolism of numerous drugs, including warfarin, steroid contraceptives, narcotic analgesics, oral antidiabetic agents, phenytoin and dapsone. Appropriate increase in dosage, and alternative methods of contraception, are required to compensate for increased drug metabolism (see also paracetamol overdose, p. 287). 

Rifampin induces the activity of the hepatic microsomal enzyme, metabolizing numerous drugs including acetaminophen, anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, clofibrate, contraceptives, corticosteroids, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, mexiletine, quinidine, sulfones, sul-fonylureas, theophyllines, tocainide, and verapamil. The plasma levels and effectiveness of these agents may be decreased. 

Sedatives or anticonvulsants (e.g., carbamazepine, oxcarbazepine, phenobarbital, and pheny-toin, but not valproate) that induce CYPs (see Chapter S) can enhance the metabolism of antipsychotic and many other agents (including anticoagulants and oral contraceptives), sometimes with significant clinical consequences. Conversely, selective serotonin (5-HT) reuptake inhibitors including fluvoxamine, fluoxetine, paroxetine, venlafaxine, sertraline, and nefazodone (see Chapter 17) compete for these enzymes and can elevate circulating levels of neuroleptics. 

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