Parathyroid Pharmacology PDF

Parathyr By oid Dr. Dalia Ahmed pharmac El Bahy ology ILOS After the lecture, students should be able to: Identify pharmacological effects of parathyroid hormon on bones. Identify agent that affect calcium homeostasis, therapeutic uses and their adverse reaction.  Drugs...

Parathyr By oid Dr. Dalia Ahmed pharmac El Bahy ology ILOS After the lecture, students should be able to: Identify pharmacological effects of parathyroid hormon on bones. Identify agent that affect calcium homeostasis, therapeutic uses and their adverse reaction.  Drugs Affecting Ca+2 Homeostasis Classification Agents that promote Ca+2and bone resorption: Parathyroid hormone (PTH) and analogs.  Vitamin D, metabolites, and analogs. Agents that inhibit Ca+2and bone resorption:  Bisphosphonates.  RANK ligand (RANKL) inhibitors.  Calcitonin.  Estrogens and SERMs. 4 5  1-Parathyroid hormone (PTH) Actions: In the kidney: PTH increases the reabsorption of Ca+2and Mg+2 increases the production of 1,25-(OH)2 D3 PTH also decreases reabsorption of phosphate, bicarbonate, sodium, and chloride. In bone: PTH can increase both the rate of bone formation and bone resorption. This is mediated by cytokines such as RANKL (Receptor activator of nuclear factor-k B ligand) produced by osteoblasts that regulate the number and activity of osteoclasts. 6 (a) Continuous exposure to PTH results in net bone resorption (b) Pulsatile exposure results in net bone formation. In GIT: PTH increases intestinal absorption of Ca+2 and phosphate indirectly by ↑1, 25-(OH)2D3. 7 N.B. Teriparatide Teriparatide is recombinant human PTH which behaves as a full PTH agonist. Teriparatide is administered parenterally once a day, and this intermittent exposure results in net bone formation. Teriparatide is used in the treatment of osteoporosis. Major adverse effects are hypercalcemia and hypercalciurea. 9  Calcium sensor sensitizers (calcimimetics) The parathyroid gland senses Ca+2 via the action of the protein calcium- sensing receptor (CaSR). Activation of CaSR reduces the amount of PTH synthesized and released by the gland. Cinacalcet (Sensipar) is an oral agent that acts similar to Ca+2 on the CaSR; this reduces serum PTH. Cinacalcet is approved for use in patients with hyperparathyroidism 2ry to renal disease. Hypocalcemia is the major adverse effect of cinacalcet. 10  2-Vitamin D and vitamin D metabolites Actions: (1) Calcitriol increases plasma levels of both Ca+2 and phosphate by acting on several organ systems: Intestine: Increases Ca+2absorption from the GIT. Bone: Mobilizes Ca+2and phosphate, probably by stimulation of calcium flux out of osteoblasts. Kidney: Increases reabsorption of both Ca+2 and phosphate (2) All vitamin D metabolites bind to a specific plasma-binding protein, vitamin D-binding protein. (3) Vitamin D, calcifediol, and calcitriol are all administered orally; calcitriol may be administered parenterally. Therapeutic uses: -To elevate serum Ca+2 in hypocalcaemia caused by a number of diseases, including vitamin D deficiency (nutritional rickets), hypoparathyroidism, renal disease, malabsorption and osteoporosis. -Topical calcipotriene has been approved for the treatment of psoriasis; it reduces fibroblast proliferation and induces differentiation of epidermal keratinocytes. 12  3-Bisphosphonates Mechanism of action: These drug impairs various functions and induces apoptosis of osteoclasts. First generation: Etidronate Second generation:Alendronate, Pamidronate, they are at least 10 times more potent than 1st generation. Third generation: Risedronate, Zoledronate and are 10,000 times more potent than1st generation. Pharmacokinetics: Poorly absorbed orally (