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50 Cards in this Set
- Front
- Back
What drugs can induce osteoporosis?
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• Heparin
• Glucocorticoids • Antiepileptics (phenytoin & carbamazepine) • Progestins (contraceptives) |
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What bone mineral homeostasis disorder is a malabsorptive GI disorder (inherited or acquired) which often resultsin the formation of Ca++oxalate stones?
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Enteric Oxaluria
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Bone is comprised primarily (70%) of?
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Hydroxyapatite
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What hormone causes ↑ bone resorption, ↑ absorption of Ca++ from the intestine, ↓ Ca++ loss in urine, and ↑ loss of phosphate in urine?
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Parathyroid hormone
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Naturally occuring form of Vitamin D; made by the skin upon sun exposure; found in foods & most supplements
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Cholecalciferol (Vitamin D3)
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Prehormone made directly from cholecalciferol in the liver; low biologic activity, but major form circulating in the blood stream.
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Calcidiol (25-hydroxyvitamin D3)
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Concetrations of this are measured by typical blood test for vitamin D deficiency?
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Calcidiol (25-hydroxyvitamin D3)
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Activated from made from calcidiol in the kidneys and tissues; the most potent steroid hormone in the body
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Calcitriol (1, 25-dihydroxyvitamin D3)
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Made in the laboratory by raidating fungus; not naturally occuring in the body; used in prescription vitamin D
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Ergocalciferol (Vitamin D2)
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What hormone is lipophilic, binds to receptors located throughout the body, regulates Ca++ & phosphorus levels in the blood, ↑ Ca++ & P absorption from GI, ↑ Ca++ in the kidneys, ↑ bone formation, ⊣ parathyroid secretion, promotes immunosuppression, phagocytosis & anti-tumor activity
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Vitamin D
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How does Vitamin D affect the kidneys?
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↑ reabsorption of Ca++ (does not promote Phosphorus wasting like PTH)
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How does Vitamin D affect PTH secretion?
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Inhibits PTH secretion from the parathyroid gland
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How does Vitamin D affect the immune system?
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Causes immunosuppression, phagocytosis, & anti-tumor activity
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What is the mechanism by which Vitamin D modulates Ca++ homeostasis?
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Lipophilic steroid hormone so it mediates gene expression
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Where is vitamin D first hydroxylated? Where does the second hydroxylation (to active form) occur?
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Liver, then Kidney to Calcitriol (active form)
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What drugs can decrease vitamin D absorption?
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• Statins & cholestyramine (because Vitamin D is lipophilic)
• Corticosteroids |
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What drugs increase Vitamin D metabolism in the liver to an inactive product?
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• p450 inducers, phenytoin & phenobarbital
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What cells secrete calcitonin? What stimulates its release?
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• Parafollicular cells of the thyroid gland
• Release stimulated by hypercalcemia |
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What hormone ↓ serum Ca++ and phosphate
• ↓ Osteoclastic bone resorption, ↓ reabsorption of Ca++ & phosphate in kidney? |
Calcitonin
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What hormone is useful in treating Paget's disease, hypercalcemia, & osteoporosis?
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Calcitonin
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What are the side effects of calcitonin?
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GI symptoms, nausea, flush
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What are the effects of glucocorticoids on Ca++ homeostasis?
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• ↓ Vitamin D- mediated Ca++ absorption, ↑ renal Ca++ excretion (overall ↓ serum Ca++)
• ↓ bone formation & ↑ osteoclast differentiation (overall causes osteoporosis) |
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How are prednisone & dexamethasone used w/r/t Ca++ homeostasis?
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• Used to Tx hypercalcemia associated w/ malignancy & granulomatous disease
• Useful in Vitamin D intoxication |
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What hormone acts as a 2º regulator of Ca++ by ↓ PTH mediated bone-resorption?
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Estradiol (other estrogens)
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Why is the use of estrogents to prevent post-menopausal osteoporosis discouraged?
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Side effx on breast, uterus, & CVS
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What drug can be used as an alternative to estrogen replacement therapy? What class of drugs is it in?
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Raloxifen (Estrogen receptor agonist)
A SERMs, selective estrogen receptor modifier |
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What class of drugs, that are analogues of pyrophosphate are used to impact bone mineral homeostasis?
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Bisphosphonates
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List the potency of the bisphosphonates
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Most potent: Zoledronate
Risedronate Ibandronae Alendronate Pamidronate Tiludronate Least potent: Etidronate |
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How do bisphosphanates fxn in bone mineral homeostasis?
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• Analogues of pyrophosphate Ppi, but the BP's core (P-C-P core) is less degradable than pyrophosphate (P-O-P core)
• The BPs bind to hydroxyapatite and ⊣ bone resorption by osteoclasts (cause a modest ↑ in bone mineral density) |
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Which bisphosphonates are NOT aminobisphosphonates (N-BPs)? Which type is more potent?
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• Etidronate & Tiludronate are NOT N-BPs
• N-BPs are more potent |
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What is the MOA of N-BPs?
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B• Block farnesyl pyrophosphate (FPP) synthesis in the HMG-CoA reductase pathway (mevalonate pathway) which leads to osteoclast apoptosis
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How are Bisphosphonates metabolized?
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• Poor GI absorption • Only 50% of absorbed drugs are taken up in bones • Eliminated in urine unaltered • Absorbed drugs accumulate in bones for months |
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What are the side effx of Bisphosphonates?
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• Gastric & esophageal irritation (most pronouced in Pamidronate) **Ask ptst o take w/ water and remain upright for 30 mins
• ↑ risk for atypical subtrochanteric femoral fractures |
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What bisphosphanate causes the least amount of gastric & esophageal irritation? Which has the most pronounced affect?
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• Least Etidronate
• Most irritation: Pamidronate |
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What drug affecting bone mineral homeostasis is a calcimimetic? What is its MOA?
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• Cinacalcet
• Acts on Ca++ sensing receptor, ↓ its sensitivity and subsequently blocks PTH secretion. |
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What is Cinacalcet indicated for?
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• Parathyroid carcinomas & 2º hyperparathyroidism in chronic kidney disease
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What drug fxns to ↓ renal calcium excretion by blocking Na++ reabsorption in the proximal tubule?
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Thiazides
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What is the MOA of thiazide diuretics?
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• ↓ renal calcium excretion by blocking Na++ reabsorption in the proximal tubule
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What are Thiazide diuretics indicated for (for Ca++ homeostasis)? What are potential side effx?
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• ↓ Hypercalciuria and stone formation
• Side effect is hypercalcemia |
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What drug stabilizes the hydroxyapatite crystal?
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Fluroide
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What drug, a recombinant PTH 1-34, is used to stimulate noew bone formation?
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Teriparatide
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What drug is used to ↑ bone ass and reduce spine fractures?
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Calcitonin
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What class of drugs are used to ↑ bone density?
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Bisphosphonates
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What hormone ↓ bone resorption and ↑ renal Ca++ excretion?
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Calcitonin
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What hormone ↓ PTH effect on bone resorption?
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Estrogen
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What drug binds to hydroxyapatite and retard the formation and dissolution of hydroxyapatite crystals (slows bone resroption)
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Bisphosphonates
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What is gallium nitrate used for in Ca++ homeostasis?
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Tx hypercalcemia of malignancy
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2. Which of the following agents promotes bone resorption and is useful for treatment of hypocalcemia?
A. Calcitonin B. Calcitriol C. Estrogen D. Hydrochlorothiazide E. Prednisone |
B. Calcitriol
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5. Renal failure is most likely to disrupt the synthesis of:
A. Calcitonin B. Vit D3 C. Vit D2 D. 25(OH)2D3 E. 1,25 (OH)2D3 |
E. 1,25 (OH) 2D3
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8. Vit D is useful for treatment of rickets caused by
A. Deficiency in 25(OH)D-1α-hydroxylase B. Mutation in Vit D receptor C. Mutations in PHEX and FGF23 |
C. Mutations in PHEX and FGF-23
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