Drugs for osteoporosis (download the lecture from www.skilltest.co.in) Dr. Sarvesh Singh Associate Professor Dept. of Pharmacology KGMU, Lucknow E-mail-drsarveshsingh@gmail.com d

PLASMA CALCIUM LEVEL Regulated by 3 hormones: Parathormone (PTH) Calcitonin Calcitriol (active form of vit D) d

PARATHORMONE (PTH) Stimulus for secretion of PTH: Fall in plasma Ca2+ Calcium-sensing receptors (CaSR) present on the surface of parathyroid cells. d

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ACTIONS OF PTH PTH increases plasma calcium levels by: Bone: Bone resorption: increases 2. Kidney: Calcium reabsorption in the distal tubule: increases 3. Intestines: Calcium absorption increases indirectly Enhance the formation of calcitriol (active form of vit D) Calcitriol promotes intestinal absorption of calcium d

MECHANISM OF ACTION OF PTH Mainly on bone: Bone resorption: Activation of osteoclast: Expression of PTH receptors: PTH receptor is a G protein coupled receptor Expressed on osteoblasts Absent on osteoclasts   d

PTH ACTION ON OSTEOBLAST PTH receptor located on osteoblast membrane PTH induces a factor 'Receptor for activation of nuclear factor-KB-ligand' (RANKL) RANKL diffuses and combines with RANK on osteoclast precursors PRECURSORS TRANSFORM INTO OSTEOCLASTS d

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TERIPARATIDE RECOMBINANT HUMAN PARATHYROID HORMONE Approved for the treatment of: Severe osteoporosis PTH at high concentration: Bone resorption predominates PTH at low concentration with intermittent exposure: Bone formation predominates Only agent which stimulates bone formation Equally or more effective than estrogens and BPNs: In reducing risk of vertebral as well as non-vertebral fractures d

TERIPARATIDE Injected s.c. once daily Given once daily produces intermittent action LIMITATIONS: High cost Need for daily s.c. injection d

Drugs for Osteoporosis Calcium and Vitamin D3 Bisphosphonates HRT Raloxifene- selective oestrogen receptor modulator (SERM) which selectively binds to oestrogen receptors on bone. Teriparatide- a fragment of recombinant human parathyroid hormone Calcitonin- Given as a nasal spray of synthetic calcitonin d

Bisphosphonates d

Bisphosphonates First line treatment for primary and secondary prevention of osteoporotic fractures Reduce bone resorption by inhibiting action of osteoclasts Accelerate apoptosis of osteoclasts Disruption of cytoskeleton and ruffled border Most effective antiresorptive drugs Available orally as daily or weekly tablet, or as a yearly injection Daily and weekly- alendronate, risedronate Yearly IV- zoledronate infusion d

Side Effect Oesophageal irritation/ ulceration if insufficient water taken with tablet or lie down after taking d

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