PthD in Paleontology Teriparatide, Vitamin D, Cinacalcet, Sevelamer

3.3 - "PthD in Paleontol Paleontology": ogy": Teriparatide, Vita Vitamin min D, Cinacalcet Cinacalcet,, Sevelamer • Treat osteoporosis by increasing bone formation & bone mineral density for the duration of treatment. • Parathyroid hormone (PTH) (PthD) o Regulates bone formation & resorption. Effects: ▪ Stimulates preosteoblast maturation to osteoblasts (osteo-builders = osteoblasts; PthD teaching builders). ▪ Stimulates osteoblasts to express RANKL (receptor activator of nuclear factor κ-Β ligand) (RANKL = crank-drill; builder giving drill to kids, and kids drilling away bones). RANKL binds to RANK on osteoclasts, increasing osteoclast proliferation & differentiation. Appropriately activated, osteoclasts increase bone resorption & turnover and release phosphate & calcium from bone, allowing bone development & systemic metabolic function (destructive class kids = osteoclasts; kids releasing both Ⓟ shaped shell fossils and calcified bones). Note that this activation is indirect. ▪ Net effect of endogenous PTH: ↑bone resorption o PTH increases kidney calcium resorption and phosphate excretion (PthD is gathering calcified bones and dropping P-shaped fossils at kidney-shaped pit). Net effect: ↑calcium levels & ↓phosphate levels o PTH increases activity of 1-α-hydroxylase in the kidney →↑production of 1,25-dihydroxy-vitamin D (calcitriol) (Calci-TRON robot = calcitriol; robot head with 1 antenna = 1-α-hydroxylase; PthD is activating robot) o High serum Ca feeds back to parathyroids, inhibiting PTH production and release via calcium-sensitive receptors (calcium backup on conveyer belt blocking the PthD from the field). • Vitamin D o Two forms: D2 (ergocalciferol) from plants (earth friendly battery under tree). D3 (cholecalciferol) is obtained from sun or dairy products (solar calciferol cart being pulled by dairy cow). Either form can be administered therapeutically. o Activated by: ▪ 1) Liver hydroxylates vitamin D to 25-hydroxy-vitamin D (robot body added to D battery in liver-barrow) ▪ 2) In kidney, 1-α-hydroxylase converts to 1,25-dihydroxy-vitamin D (calcitriol) (#1 on head to remind that’s the last step). o Activated vitamin D functionally acts as a steroid (lipophilic, intracellular receptor). Has a number of downstream effects: ▪ Calcitriol increases phosphate & calcium resorption in the kidney (robot picking up bones & phosphate shells at kidney pit) ▪ Potent stimulant of intestinal calcium & phosphate absorption (robot picking up bones & phosphate shells at colonic truck) ▪ Stimulates maturation of osteoblasts → ↑bone formation (robot teaching osteo-builders), and stimulates osteoblast production of RANKL → activation of osteoclasts. Potent stimulator of both; net effect is bone turnover (robot delivering crank drills to class). ▪ Inhibits PTH production (rolling over tent, trapping PTH) o Indications for exogenous administration ▪ Osteoporosis ▪ Topical treatment can be given for psoriasis (kidney worker with pads) ▪ Can be used for long-term management of hypocalcemia (robot stabilizing seizing scientist) • Hypocalcemia can cause seizures, paresthesias, muscle cramps, trismus, tetany (shaking structure, clenched fist) • Commonly caused by hypoparathyroidism (falling PhD badge; undone bowtie for thyroid surgery damage to PTH glands). Vitamin D will be less effective d/t decreased activation of kidneys o Note that inactivated vitamin D will be ineffective in kidney failure d/t inability to activate (cracked kidney tower). In this case, give as calcitriol (robot stabilizing kidney shaped water tower). o Deficiency ▪ Osteomalacia in adults, rickets in children (robot stabilizing rickety tower) ▪ May see in chronic renal failure, dietary deficiency, ↓sunlight exposure. o Adverse effects ▪ Teriparatide & Vitamin D therapy can both cause hypercalcemia (raised calci-yum ice cream) • Teriparatide (TA) o Recombinant PTH. Effects include: ▪ Net effect when given in low-intermittent doses increases bone formation (in contrast with the effects of endogenous PTH). • Stimulations maturation & increases anabolic function of osteoblasts (TA teaching osteo-builders). • Does not activate osteoclasts (TA not dealing with classmates) ▪ Increases kidney resorption of calcium, dumping phosphate (TA is gathering calcified bones and dropping P-shaped fossils at kidney-shaped pit). ▪ Increases calcitriol production (TA helping build robot o Used in treatment of osteoporosis (fresh piece of calcified chalk) o Adverse effects: ▪ Teriparatide & Vitamin D therapy can both cause hypercalcemia (raised calci-yum ice cream) • Cinacalcet (worker calculating calcium) o Calcimimetic; activates calcium sensing receptor in parathyroid gland → ↓PTH production. Useful to treat hypercalcemia d/t primary or secondary hyperparathyroidism (cinacalcet worker calculating the bone buildup going into the parathyroid tent). • Sevelamer (shoveler) o Non-absorbable phosphate binding polymer that binds Ⓟ in the GI tract, decreasing phosphate absorption (shoveler in truck) o Used to treat hyperphosphatemia d/t CKD