Endocrine

·         Up to 3 to 4 months may be needed for the full effect TZDs after initiating or changing the dose.

·         Patients taking protamine-containing insulin, vasectomized or infertile males, and those with sensitivity to fish. These patients have a higher risk of developing antiprotamine antibodies and subsequently there is an adverse effect upon protamine administration.

·         Etidronate is used in the treatment of Paget's disease of  bone. It can be administered orally or by injection. The drug affects both normal and abnormal bone resorption and appears to reduce the activity of osteoclasts and osteoblasts. It inhibits the formation, growth, and dissolution of hydroxyapatite crystals, which is probably its main mechanism of action. There occurs a significant reduction in serum Ca following several days of intravenous therapy with etidronate. The drug has a half-life of about 6 h and is excreted unchanged in the urine. Etidronate has also been used to treat patients with hypercalcemia that may be associated with various neoplastic diseases.

·         Glucocorticoids decrease the synthesis of prostaglandins by causing the production of lipocortin, which inhibits the enzyme phospholipase A2. With the inhibition of phospholipase A2, arachidonic acid is not released and, as a consequence, the synthesis of the prostaglandins is decreased or prevented.

·         A variety of drugs that resemble steroid hormones in their structure can traverse cellular membranes and bind to specific cytoplasmic receptors that bind heat shock proteins.

·         Mifepristone is structurally related to norethindrone. This compound is classified as a progesterone antagonist with weak agonistic properties. A single dose can function as an emergency postcoital contraceptive. It also can induce an abortion by causing contraction of the myometrium, which leads to detachment of the embryo. The drug is used in single or multiple doses followed by the administration of a prostaglandin to cause the abortion.

·         Metyrapone, because it decreases serum levels of cortisol by inhibiting the β-hydroxylation of steroids in the adrenal, can be used to assess function of the pituitary-adrenal cortical axis. When metyrapone is given to normal persons, the adenohypophysis secretes more ACTH. This causes a normal adrenal cortex to synthesize increased amounts of 17-hydroxylated steroids, which can be measured in the urine. However, patients who have disease of the hypothalamico-pituitary axis do not produce ACTH in response to metyrapone. As a result, we find no increased levels of the steroids in the urine. Before administering metyrapone, we need to test responsiveness of the adrenal cortex to respond to administration of ACTH.

·         Amiodarone, an iodine-rich drug, has several actions that can lead to clinical hypothyroidism (or, less often and mainly in persons with iodine-deficient diets, hyperthyroidism).

·         Metformin is not metabolized by the liver, but liver dysfunction is one contraindication. That’s mainly because of the risks of the drug’s most important adverse effect, lactic acidosis, which is rare but often fatal when it does occur: impaired liver function impairs lactate elimination and favors its accumulation to toxic levels.