Ketoconazole hormonal

Endocrine effects Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Small declines in total testosterone with no commensurate elevation in LH have been noted with the use of fluvastatin. Pravastatin showed inconsistent results with regard to possible effects on basal steroid hormone levels atorvastatin, lovastatin, rosuvastatin, and simvastatin did not reduce basal plasma cortisol concentration or basal plasma testosterone concentration or impair adrenal reserve. Appropriately evaluate patients who display clinical evidence of endocrine dysfunction. Exercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels or activity, such as ketoconazole, spironolactone, and cimetidine. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

Itraconazole is usually well tolerated but can be associated with nausea and epigastric distress. Dizziness and headache also have been reported. High doses may cause hypokalemia, hypertension, and edema. Itraconazole, unlike ketoconazole, is not associated with hormonal suppression. Hepatotoxicity occurs in fewer than 5% of cases and is usually manifested by reversible Uver enzyme elevations. 

At high doses, ketoconazole causes a clinically significant reduction in testosterone synthesis and blocks the adrenal response to corticotropin. Gynecomastia, impotence, reduced sperm counts, and dimiiushed libido can occur in men, and prolonged drug use can result in irregular menses in women. These hormonal effects have led to the use of ketoconazole as a potential adjunctive treatment for prostatic carcinoma. 

Ketoconazole has been used for the treatment of patients with Cushing s syndrome due to several causes. Dosages of 200-1200 mg/d have produced a reduction in hormone levels and clinical improvement in some patients. This drug has some hepatotoxicity and should be started at 200 mg/d and slowly increased by 200 mg/d every 2-3 days up to a total daily dose of 1000 mg. 

Ketoconazole Blocks fungal P450 enzymes and interferes with ergosterol synthesis Poorly selective interferes with mammalian P450 function Broad spectrum but toxicity restricts use to topical therapy Oral, topical Toxicity and interactions Interferes with steroid hormone synthesis and phase I drug metabolism... 

Dutasteride (Avodart) [Androgen Hormone Inhibitor/BPH Agent] Uses Symptomatic BPH Action 5a-Reductase inhibitor 4- intracellular androgen levels Dose 0.5 mg PO/d Caution [X, -] Hepatic impair pregnant women should not handle pills Contra Women children Disp Caps SE T Testosterone, T TSH, 4- PSA levels, impotence, 4- libido, gynecomastia Interactions T Effects w/ cimeddine, ciprofloxacin, diltiazem, ketoconazole, ritonavir, verapamil EMS None OD Not expected to produce life-threatening Sxs... 

De Pedrini P, Tommaselli A, Spano G, Montemurro G. Clinical and hormonal effects of ketoconazole on hirsutism in women. Int J Tissue React 1988 10(3) 193-8. 

Ketoconazole (an antifungal agent, see p. 340) strongly inhibits all gonadal and adrenal steroid hormone synthesis. It is used in the treatment of patients with Cushing s syndrome. 

Kovacs L, Somos P, Hamori M. Examination of the potential interaction between ketoconazole (Nizoral) and oral contraceptives with special regard to products of low hormone content (Rigevidon, Anteovin). Ther Hung 1986 34 167. 

Cadmium decreases testosterone production by preventing the synthesis of cholesterol, a precursor of all steroid hormones. Other chemicals that interfere with steroid hormone synthesis include aminoglute-thimide, cyanoketone, and ketoconazole. Copper chelating compounds, such as dithiocarbamates, metam sodium, and carbon disulfide, suppress the conversion of dopamine to norepinephrine and subsequently to epinephrine. 

The most frequent offenders are cytostatic agents and anticoagulants, but hair loss can occur with a variety of common drugs, including hormones, anticonvulsants, amantadine, amiodarone, captopril, cholesterol-lowering drugs, cimetidine, colchicine, etretinate, isotretinoin, ketoconazole, heavy metals, lithium, penicillamine, valproic acid, and propranolol. 

Estrogens, antiandrogens (e.g., luteinizing hormone-releasing hormone superagonists, digoxin, spironolactone, ketoconazole, cimetidine)... 

Some example compounds include aminogluthethimide cyanoketone and ketoconazole (affect hormone synthesis) lithium (interferes with steroidogenic enzymes) endosulphan, lindane, and malathion (affect hormone release and storage) DDT... 

Anticancer drugs etoposide, doxorubicin, vincristine Ca + channel blockers dUtiazem, verapamil HIV protease inhibitors indinavir, ritonavir Antibiotics/antifungals erythromycin, ketoconazole Hormones testosterone, progesterone Immunosuppressants cyclosporine, FK506 (tacrolimus)... 

Some antifungal drugs such as ketoconazole (see Chapter 48) inhibit CYPs and thereby block the synthesis of steroid hormones, including testosterone and cortisol. Because they may induce adrenal insufficiency and are associated with hepatotoxicity, these drugs generally are not used to inhibit androgen synthesis, but sometimes are employed in cases of glucocorticoid excess. 

Four pharmacologic agents are useful inhibitors of adrenocortical secretion. Mitotane (o,p -DDD), an adrenocorticolytic agent, is discussed in Chapter 51. The other inhibitors of steroid hormone biosynthesis are aminoglutethimide, ketoconazole, and trilostane. Aminoglutethimide and ketoconazole are... 

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