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48 Cards in this Set
- Front
- Back
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What peptide hormone acts on G coupled receptors to increase cAMP in bone and renal tubular cells?
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Parathyroid hormone
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What specific actions Does Parathyroid hormone have in the Kidney?
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In renal cells, inhibits Ca secretions, promotes Phosphate secretion, and stimulates production of 1,25 dihydroxycholecalciferol (aka) dihydroxyvitamin D.
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What specific actions does parathyroid hormone cause in bone?
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promotes bone turnover by stimulating both osteoblast and osteoclast activity.
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Actual mechanism by which Parathyroid hormone increases osteoclast activity
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acts on osteoblasts to stimulate their production of RANK ligands (RANKL), a member of the TNF cytokine family, which binds to the RANK receptors on osteoclasts, increasing their activity and differentiation of their precursurs
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Based on dose, what two effects can parathyroid have on bone?
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at continuous high levels, the effect is increased bone resorption, hypercalcemia and hyperphosphatemia. at low intermittent doses, causes a net increase in bone formation
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What is teriparatide, and what is it used for?
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a recombinant, truncated form of PTH, used for osteoporosis
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How does the body regulate the synthesis and secretion of PTH by the parathyroid?
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mostly by the serum levels of free ionized Ca++, however levels of active Vit D metabolites also play a role
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What are the ways the body can get vitamin D?
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synthesized in the skin from 7-dehydrocholesteral with UV light, in the diet from D3 cholecalciferol, or in the plant form D2 ergocalciferol.
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What are the two active metabolites? where are they formed? which one is most active?
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25 hydroxyvitamin D (calcifediol) formed in Liver, and 1,25 Dihydroxyvitamin D (calcitriol) formed in the kidney. the 1,25 metabolite is hormonally active variant
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Renal synthesis of Vit D is stimulated by what?
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increased PTH and fibroblast growth factor 23 (FGF23) which is produced by osteoblasts and osteoclasts.
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Role of vitamin D metabolites in the regulation of Ca and phosphate?
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causes net increases in serum Ca levels by: stimulating intestinal calcium absorption and bone resorption, and by decreasing renal excretion. They also increase urinary calcium.
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Name two diseases caused by vitamin D deficiency
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Decreased bone mineralization causing: Rickets in kids, and osteomalacia in adults
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What effect do vitamin D metabolites have on parathyroid hormone?
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they inhibit its release both directly, and indirectly by increasing serum calcium
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What are some clinical uses for Vit D supplementation?
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nutritional deficiencies, intestinal osteodystrophy, chronic kidney or liver disease, hypoparathyroidism, and nephrotic syndrome. also used with Ca in the prevention and treatment of osteoporosis
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2 types of oral Vit D supplements
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cholecalciferol and ergocalciferol
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For patients with liver or kidney disease that cannot convert Vit D to active metabolites, which drug is used?
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Calcitrol
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Clinical uses for Calcitrol
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treatment of secondary hyperparathyroidism due to kidney disease. reduces PTH, corrects hypocalcemia, and improves bone disease hypercalcemia,
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Side effects of Calcitrol
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can cause hypercalcemia and hypercalciurea
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What is a prodrug converted in the liver that has the same clinical use as Calcitrol with less side effects?
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(Doxercalciferol) 1A hydroxyvitamin D2, gets converted in liver into the active metabolite 1,25 (OH)2 D
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What are two drugs that are analogues of Calcitrol that have less side effects?
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pareicalcitrol (19-nor-1,25-dihydroxyvitamin D2) and calcipotriene. cause less hypercalcemia
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Primary toxicities seen with chronic overdose of Vit D or its metabolites.
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hypercalcemia, hyperphosphatemia, and hypercalciurea
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Which drug is approved for topical use in psoriasis?
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Calcipotriene (calcipotriol)
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Thyroid hormone that decreases serum Ca and Phosphate by inhibiting bone resorption and inhibiting renal excretion of these minerals
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Calcitonin
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Calcitonin's effect on Bone formation
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initially is not impaired, but ultimately it is reduced
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Clinical use for Calcitonin
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conditions when an acute reduction in serum Calcium is needed. (Paget's disease, and hypercalcemia)
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Calcitonin's role in treatment of Osteoporosis.
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Has been shown to increase bone mass, and reduce fractures. Salmon calcitonin is used clinically due to its longer half-life and potenty
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Modes of administration of Calcitonin
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can be injected or inhaled via nasal spray
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Selective Estrogen Receptor Modulator that can prevent or delay bone loss in post menopausal women.
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Raloxifine. works by inhibiting PTH stimulation of bone resorption
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Chronic use of which class of drugs causes Osteoporosis in adults
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Corticosteroids. (they inhibit bone maintenance)
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What are a class of drugs that reduce both the resorption and formation of bone, by an action on the basic hydroxyapatite structure?
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Biphosphonates
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Biphosphonate action on osteoclasts directly
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they inhibit Farnesyl pyrophosphate synthase, an enzyme that plays a critical role in osteoclast survival
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Clinical use for Biphosphonates:
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used in the management of hypercalcemia associated with some malignancies, and to treat Paget's disease
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Chronic Biphosphonate therapy has also been used to treat what condition
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all forms of osteoporosis. It has been shown to increase bone density and reduce fractures
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Biphosphonates available for parenternal treatment of hypercalcemia
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Pamidronate, etidronate, and zoledronic acid. they are also available as oral medications
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Problem with the oral use of biphosphonates
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their oral absorption is very low, <10%, and food inhibits their absorption
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Biphosphonates used in daily oral dose for osteoporosis
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alendronate, risendronate, and ibandronate
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Biphosphonates used in Weekly oral dose for osteoporosis
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alendronate and risendronate
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Biphosphonate used in monthly oral dose, or quarterly injected dose, for osteoporosis
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ibandronate
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Biphosphonate used in annual infusion for osteoporosis
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zoledronate
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Toxicities of oral Biphosphonates
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gastric and esophageal irritation, patients are advised to take with lots of water, and not take prior to laying down (reflux)
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Higher doses of Biphosphonates have been associated with what toxicities?
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renal impairment and osteonecrosis of the jaw
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Which drug lowers PTH secretion by altering the Ca sensing receptor in the parathyroid gland
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Cinacalcet
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Clinical use for Cinacalcet
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treatment of 2ndry hyperparathyroidism due to chronic kidney disease, and for patients with hypercalcemia in patients with parathyroid carcinoma.
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Toxicities of Cinacalcet
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hypocalcemia and adynamic bone disease, due to profoundly decreased bone cell activity
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Drug used in Europe for Osteoporosis, promotes osteoclast apoptosis, and increases concentrations of bone formation markers
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Strontium Ranelate
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Drug that inhibits bone resorption, used to manage hypercalcemia seen in some malignancies and in Paget's disease,
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Gallium Nitrate
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Drug used to reduce serum calcium and bone resorption in Paget's disease, but due to risk of serious toxicity is only used in short term acute treatment
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Plicamycin (mithramycin) can cause: thrombocytopenia, hemorrhage, hepatic, and renal damage
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Diuretics that have an effect on serum and urinary Ca levels
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Furosemide (loop diuretic), and the Thiazides
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