Phenytoin with glucocorticoids

In addition to the classical environmental or nutritional cause of these diseases, both osteomalacia and rickets can have a pharmacological origin via chronic treatment with anticonvulsants (phenobarbital and phenytoin) or glucocorticoids. These agents interfere with intestinal absorption of calcium and, thereby, cause pseudohyperparathyroidism. As a result, an increase in bone turnover and a decrease in the formation of appropriately mineralized bone is observed. In these patients, treatment with vitamin D improves calcium absorption, ultimately enhancing mineralization of the bone. 

Several drugs (for example amiodarone, androgens, glucocorticoids, phenytoin, and salicylates) interfere with the transport or metabolism of thyroid hormones and thereby alter thyroid function tests. These have been reviewed (90). In patients taking levothyroxine serum TSH rises after treatment with sertraline (91) and antimalarial prophylaxis with chloroquine and proguanil... 

A systematic review included 18 case reports, two case series, and four analytical studies showing adulteration with various allopathic drugs (142). The adulterants included phenazone (aminopyrine), clobetasol propionate and other glucocorticoids, diazepam, diclofenac, glibenclamide, hydrochlorothiazide, indometacin, mefenamic acid, methylsalicy-late, phenacetin, phenylbutazone, and phenytoin. 

Because of their enzyme-inducing effects, barbiturates can cause increased inactivation of other compounds (anticoagulants, phenytoin, theophylline, digoxin, glucocorticoids, etc.). This may lead to serious problems with drug interactions. 

In most cases the mechanism is not known. Stimulators of vasopressin secretion include vincristine, cyclophosphamide, tricyclic antidepressants, nicotine, epinephrine, and high doses of morphine. Lithium, which inhibits the renal effects of vasopressin, also enhances vasopressin secretion. Inhibitors of vasopressin secretion include ethanol, phenytoin, low doses of morphine, glucocorticoids, fluphenazine, haloperidol, promethazine, oxilorphan, and butorphanol. Carba-mazepine has a renal action to produce antidiuresis in patients with central diabetes insipidus but actually inhibits vasopressin secretion via a central action. 

Patients with hypothyroidism who are taking levothyroxine may become hypothyroid if given drugs that decrease T4 absorption (cholestyramine, iron salts, calcium carbonate, aluminum hydroxide, sucralfate, raloxifene, omeprazole, dietary soy and fiber), increase its clearance (phenytoin, car-bamazepine, phenobarbital, rifampin), or decrease T4 to T3 conversion (amiodarone, glucocorticoids, propranolol). 

The therapeutic effects of dexamethasone, methylprednisolone, prednisolone, prednisone (and probably other glucocorticoids) and fludrocortisone can be markedly reduced by phenytoin. One study su ested that dexamethasone may modestly increase serum phenytoin levels, but another study and two case reports of patients with brain metastases suggest that an important decrease can occur. The results of the dexamethasone adrenal suppression test may prove to be unreliable in those taking phenytoin. 

An adolescent boy with primary adrenal insufficiency developed glucocorticoid deficiency and raised ACTH concentrations after phenytoin treatment 15 days after withdrawal, his serum ACTH concentration was in the reference range... 

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