Oral contraceptives toxicity

Optoelectronics Optosil Oraflex Oragrafin Oral care products Oral contraceptives Oral formulations Oral polio virus vaccine Oral toxicity Oramec Orange... 

Oral contraceptives Inhibition of metabolism at CYP2D6 isoenzyme Possible TCA toxicity increased amount of active TCA varies can be up to 30% Lower TCA dose D Arcy, 1986... 

The incidence of serious known toxicities associated with the use of these drugs is low—far lower than the risks associated with pregnancy. There are a number of reversible changes in intermediary metabolism. Minor adverse effects are frequent, but most are mild and many are transient. Continuing problems may respond to simple changes in pill formulation. Although it is not often necessary to discontinue medication for these reasons, as many as one third of all patients started on oral contraception discontinue use for reasons other than a desire to become pregnant. 

Westerholm B. Oral contraceptives and jaundice Swedish experience. In Baker SB de C, Tripot J, editors. Proceedings, European Society for the Study of Drug Toxicity, Oxford, 1968. Amsterdam Excerpta Medica, 1968 158-63. 

Prominent among toxicants that adversely affect both male and female reproductive systems are endocrine disruptors (see Section 9.7). Toxicants that mimic the actions of sex hormones are agonists, and those that prevent hormonal action or bind competitively to hormone receptor sites are antagonists,12 Male patients treated with cimetidine for peptic ulcers have exhibited low sperm counts and abnormal breast enlargement, a condition called gynecomastia. Gynecomastia has also been caused in men working in oral contraceptive production. Ketoconozole inhibits the enzymes required to produce hormones involved in sperm production and can immobilize sperm in seminal fluid. 

PTC rarely may occur secondary to middle-ear disease, minor head injury, childhood systemic lupus erythematosus (SLE), or toxic conditions such as hypervitaminosis A, tetracycline, amiodarone, and oral contraceptive use. 

Fixed dose. The effect that is desired can be obtained at well below the toxic dose (many mydriatics, diuretics, analgesics, oral contraceptives, antimicrobials) and enough drug can be given to render individual variation clinically insignificant. 

Copper intrauterine devices are widely used and highly effective (> 99% at one year) for 5 and some for 10 years. They are especially useful in the over-40s in whom oral contraceptives may become progressively contraindicated and for whom one lUD will last into the menopause. The lUD prevents implantation of the fertilised ovum, and has an additional antifertilisation effect enhanced by the toxic effect of copper ions on the gametes. 

St. John s wort Cyclosporine Digoxin Indinavir, neverapine MAO inhibitors Oral contraceptives Simvastatin SSRIs Warfarin Decreased levels and decreased effect Decreased levels and decreased effect Decreased levels and decreased effect Increased risk of MAO toxicity Decreased levels and decreased effect Decreased levels and decreased effect Increased risk of serotonin syndrome Decreased levels and decreased effect... 

A 39-year-old woman developed idiopathic thrombosis of the posterior tibial vein. Oral contraceptives and resistance to activated protein C were identified as risk factors. After initial treatment with intravenous heparin, she was given phenprocoumon and the oral contraceptive was withdrawn. After 4 months she developed subacute liver failure and phenprocoumon was withdrawn immediately. Autoimmune disease, viral hepatitis, toxic causes, and Budd-Chiari syndrome were excluded. Despite symptomatic treatment, she deteriorated further and orthotopic liver transplantation was performed. Histopathology of the explanted liver further excluded ischemic Uver cell necrosis and Budd-Chiari syndrome. 

Oxcarbazepine has not been associated with hepatotoxi-city or hematological toxicity. It is less likely than carbamazepine to cause hypersensitivity reactions, but may be more often associated with hyponatremia. It is less likely than carbamazepine to induce CYP450 isozymes, but it may significantly increase the clearance of oral contraceptives and significantly induce CYP450 at higher doses. 

Reproductive toxicity Fertility studies are not generally required during early clinical development unless there is good reason. Embryotoxicity/foetal development studies in two species are normally expected if women of childbearing potential are to be included in clinical trials interaction potential with oral contraceptives should be considered in this case. 

Roman, W., and Hecker, R., The toxicity of oral contraceptives. A critical review... 

Public concern has focused on the possible carcinogenic effects of drugs and other chemicals. Long-term chronic toxicity studies in a variety of species have been started in the hope of minimizing potential risk of cancer in man. However, the results of such studies are difficult, sometimes impossible, to interpret. Yet their economic impact can be enormous, as shown by the withdrawal of cyclamates when bladder cancer was observed in a limited number of rodents. Inevitably drugs will be affected too already the safety of certain oral contraceptives has been questioned because of possible carcinogenic effects in the breasts of dogs after extended use. 

Barbiturates and heavy smoking induce nortriptyline metabolism and decrease therapeutic efficacy phenothiazines and haloperidol decrease its metabolism, decreasing therapeutic efficacy methylphenidate, cimetidine, oral contraceptives, propoxyphene, and beta-blockers may inhibit nortriptyline metabolism, increasing plasma levels and toxicity (see Tables 5 through 7). 

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