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DRUGS THAT AFFECT BONE MINERAL HOMEOSTASIS

DRUGS THAT AFFECT BONE MINERAL HOMEOSTASIS. Calcium. Calcium exists in three forms: 50% ionized 40% bound to protein (especially to albumin) 10% complexes to anions.

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DRUGS THAT AFFECT BONE MINERAL HOMEOSTASIS

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  1. DRUGS THAT AFFECT BONE MINERAL HOMEOSTASIS

  2. Calcium • Calcium exists in three forms: • 50% ionized • 40% bound to protein (especially to albumin) • 10% complexes to anions. • Approximately 100-250mg of daily intake is absorbed from the proximal intestine with an equal amount excreted by the kidney. • 98% filtered calcium is reabsorbed.

  3. Calcium metabolism • Control of serum calcium and phosphorus depends on the hormones • Vitamin D • Parathyroid hormone • Calcitonin

  4. Bone remodeling involves dynamic interaction of osteoclast and osteoblast.

  5. Calcium and Phosphateare the two major constituents of the bone. • Normal extra cellular concentrations of calcium is required for proper functioning of nerves, muscles and blood coagulation. • The balance between bone resorption and bone formation is usually maintained up to fourth decade.

  6. Calcium • An adequate intake of Calcium and Vitamin D is essential for: • optimal bone formation in children • prevention of osteoporosis in adults.

  7. Calcium drugs • Calcium carbonate requires stomach acidity for absorption. • Calcium citrate does not requires acidity. • Calcium gluconate is the preferred i.v preparation. • Calcium and Vitamin D are used for: • Prevention and treatment of osteoporosis • Hypocalcemia. • The most common adverse effect of calcium is constipation.

  8. Calcium metabolism • Parathormone (PTH) net effect is to increase plasma calcium and decrease phosphate concentration. Kidney : • PTH stimulates reabsorption of calcium by the renal tubules. • PTH decrease the reabsorption of phosphate from renal tubules – this ↓ plasma phosphate concentration, which in turn ↑ plasma calcium.

  9. Calcium metabolism PTH :Bone : • PTH increase bone resorption by stimulating osteoclast activity which enables the bone calcium to enter the extra cellular pool (High dose). PTH : GIT : • It increase calcium and phosphate absorption by activating the synthesis of 1,25 dihydroxyvitamin D-3 (Calcitriol).

  10. Calcium metabolism PTH : • In low and intermittent doses, PTH increase bone formation without stimulating bone resorption. • TERIPARATIDE – recombinant PTH approved for the treatment of osteoporosis.

  11. Calcium metabolism • Vitamin D :It is a prohormone. • Vitamin D-3 (cholecalciferol) and Vitamin D-2 (ergocalciferol) are the major forms of vitamin D. • Vitamin D-3 is produced in the skin from 7-dehydrocholesterol under the influence of ultra-violet light. • Vit-D-3 is an inactive precursor of active 1,25 dihydroxyvitamin D-3 (Calcitriol).

  12. Calcium metabolism Vitamin D : Net effect is to increase plasma calcium and phosphate concentration. • The hydroxylation of Vitamin D-3 at the 25 position in the liver results in 25 Hydroxyvitamin-D3 (Calcifediol). • PTH stimulates the renal hydroxylation at position 1 resulting in 1, 25 Dihydroxyvitamin D-3 (Calcitriol).

  13. Calcium metabolism Vitamin D : • Calcitriol’s primary effect is on the small intestine where it increase dietary calcium and phosphate absorption. • Vitamin D promotes mineralization bone formation. • Calcium and phosphate excretion may be decreased by renal tubules.

  14. Calcium metabolism Vitamin D : • It inhibits parathyroid hormone secretion from the parathyroid gland. • Vitamin D affects the immune system by promoting phagocytosis, anti-tumor activity, and immunomodulatory functions.

  15. Vitamin D is used to prevent and treat: • osteoporosis • Rickets: vit. D deficiency in children • osteomalacia • In renal failure, it is advisable to use the active form, calcitriol as they cannot synthesize it. • Calcipotriol, synthetic derivative of vitamin D, is used in psoriasis.

  16. Calcitonin :Itis released in response to increased plasma calcium and it decrease plasma calcium. • It is secreted by the parafollicular cells of the thyroid gland. • It is administered parenterally or nasal inhalation. • Salmon calcitonin is 100 times more potent than human calcitonin.

  17. Calcitonin :Principal effects are to lower serum calcium and phosphate • It inhibits osteoclast activity, decrease bone resorption thus lowers serum calcium and phosphate and reduce bone pain. • It decrease the reabsorption of calcium and phosphate from the renal tubules.

  18. Calcitonin: It increase BMD in spine • Used in paget’s disease of bone(enlarged and deformed bones) • Osteoporosis • Hypercalcemia • Usually reserved for post menopausal women (who cannot take estrogen).

  19. Phosphate • Phosphate helps maintain acid-base equilibrium. • Buffers and allows for renal H+ excretion. • Helps regulate calcium metabolism, and is an active intermediate of energy metabolism (ATP). • Approximately 67% of an oral dose is absorbed from the intestine. • Excretion is via the kidney.

  20. Biphosphonates : • Alendronate (Fosamax) • Risedronate (Actonel) • Ibandronate (Boniva) • Zoledronate(Zometa) • These compounds have P-C-P which is nonhydrolyzable compared with Pyrophosphate P-O-P found in bone hydroxyapatite.

  21. Calcium metabolism Biphosphonates : • It adsorbs to hydroxyapatite and become a part of the bone structure. • They are slowly released from the bone during the bone remodeling. • Biphosphonates prevent bone resorption by inhibiting osteoclast activity • Prevent attachment of osteoclast to bone. • Decrease the activity of osteoclast .

  22. Biphosphonates : • Used in steroid inducedosteoporosis, paget’s disease and hypercalcemia of malignancy • Biphosphonate result in esophagitis and GIT distress.

  23. Miscellaneous agents : • Estrogensare considered as first line of therapy for prevention of osteoporosis in postmenopausal women. • Estrogens decrease bone resorption by: • inhibiting IL-1, TNF and CSF from monocytes • decrease osteoclast differentiation / activation which slows bone loss in women. • Raloxifene, selective estrogen receptor modulator, can be used for prevention of osteoporosis in women with breast / endometrial cancer.

  24. Fluoride : • It is well established for the prophylaxis of dental caries. • It stimulates new bone formation. • It increase the bone crystal size and render the bone more resistant to resorption.

  25. Bone Plicamycin : • A cytotoxic antibiotic is an inhibitor of osteoclast and block the action of PTH. • Used to treat Paget’s disease. Glucocorticoids : • It decrease osteoblast activity and cause osteoporosis.

  26. Thiazides • Treatment of bone mineral disorders. • Reduce Renal Ca excretion. • Increases effectiveness of PTH. • Block Na reabsorption, increasing Ca exchange (distal tubule). • Reduce incidence of stone formation.

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