Review of Pharmacology - 9E (2015)

Review of Pharmacology
• Metyrapone inhibits 11 β hydroxylase enzyme (involved in the synthesis of cortisol
and cortisone) and results in the reduced glucocorticoid activity. It was used for
diagnostic purposes and for the treatment of Cushing’s syndrome. It is the only
drug in this group which is safe in pregnancy.
• Aminoglutethimide inhibits the enzyme cholesterol side chain cleavage that helps
in the conversion of cholesterol to pregnenolone. Thus, it inhibits the synthesis
of all corticosteroids. It also inhibits the enzyme aromatase and is useful in breast
carcinoma. Glucocorticoids and mineralocorticoids can be given along with this
agent in the treatment of breast cancer to prevent the precipitation of acute adrenal
insufficiency.
• Mitotane causes atrophy of zona fasciculata and reticularis without affecting zona
glomerulosa. Thus it causes reduction in glucocorticoids and sex steroids. It can
be used for medical adrenalectomy.
• Trilostane inhibits 3 β hydroxysteroid dehydrogenase enzyme, which is involved in the
production of adrenal and gonadal hormones. It is also an aromatase inhibitor.
• Ketoconazole is an antifungal agent that can be used for the treatment of Cushing’s syndrome
due to the inhibitory actions on 17 α hydroxylase and 3β hydroxysteroid dehydrogenase
enzymes.
Corticosteroid Receptor Antagonists
Endocrinology
• Mifepristone is a long acting antagonist at the glucocorticoid and progesterone receptors.
It is used for medical termination of pregnancy, as a post-coital contraceptive and
rarely for inoperable patients of Cushing’s syndrome.
• Spironolactone and epleronone are aldosterone receptor antagonists that are used
as K + sparing diuretics.
• Drospirenone, a progestin in an oral contraceptive, also antagonizes the effects of
aldosterone.
DRUGS AFFECTING BONE MINERAL HOMEOSTASIS
Calcium and phosphate homeostasis is maintained by the action of vitamin D (active form is
calcitriol), parathyroid hormone (PTH) and FGF-23 (Fibroblast growth factor-23). Secondary
regulators of Ca 2+ homeostasis include calcitonin, glucocorticoids and estrogens.
Serum PO 4
3–
Serum Ca 2+ Mechanism
Vitamin D ↑ ↑ ↑ intestinal absorption of both Ca 2+ and PO 4
3-
↓ renal excretion of both
PTH ↓ ↑ ↓ renal excretion of Ca 2+ and ↑ that of PO 4
3-
↑ resorption of Ca 2+ from bone
↑ intestinal absorption of calcium by increasing
calcitriol
FGF-23 ↓ - ↓ Ca 2+ 3-
and PO 4
absorption by intestines
3-
↑ PO 4
excretion by kidneys
Thus vitamin D and calcitonin can be used to treat osteoporosis whereas PTH excess can
result in osteoporosis.
• Plasma Ca 2+ is the major factor regulating PTH secretion. Hypocalcemia stimulates PTH
secretion whereas hypercalcemia inhibits it. Calcium inhibits PTH secretion by
stimulating calcium sensing receptor on parathyroid cells.
• PTH increases circulating calcitriol by two mechanisms; Directly by stimulating 1α
hydroxylase in kidney and indirectly by decreasing serum phosphate.
252
https://kat.cr/user/Blink99/