Hypercalcemia and Hypocalcemia Drugs 2-12 – Flashcards
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Explain the regulation of parathyroid hormone release
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Ca binds to Ca sensing receptor (CaSR) on PT gland which inhibits secretion of PTH
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Explain the role of the following in calcium and phosphate homeostasis: 1. parathyroid hormone
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1. increases bone resorption, kidney reabsorption *causing increased Ca, decreased P*
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Explain the role of the following in calcium and phosphate homeostasis: 1. Vitamin D
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1. increases intestinal absorption of Ca *increasing Ca*
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Explain the role of the following in calcium and phosphate homeostasis: 1. Calcitonin
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1. inhibits osteoclasts *decreasing serum Ca, P*
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Explain the control of osteoclast and osteoblast activity: 1. osteoclast 2. osteoblast
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1. PTH stimulates it, calcitonin inhibits it 2. exogenous PTH stimulates it
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Differentiate between Vitamin D3 (cholecalciferol) and 1,25(OH)2D3 (calcitriol) and where activation occurs: 1. Vit D3
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1. stored form (made from UV exposure to skin or obtained from diet)
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Differentiate between Vitamin D3 (cholecalciferol) and 1,25(OH)2D3 (calcitriol) and where activation occurs: 1. 1,25-OH-D3
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1. made in the kidney from action of 1a hydroxylase which activates it
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Identify the main causes and symptoms of hypercalcemia
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PT gland tumor makes too much PTH Malignant tumor produces PTH-related protein (PTHrP) Too much vitamin D Cancer that metastasizes to bone, stimulates osteoclast formation and activation, and causes bone resorption
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Identify the main causes and symptoms of hypocalcemia
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hypoparathyroidism vit D deficiency pseudohypoparathyroidism
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Explain the main causes of vitamin D deficiency
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-chronic kidney disease b/c there is a lack of 1a hydroxylase which can cause increased PTH (b/c low calcitriol) which will cause high Phosphate levels and possibly normal Ca levels if enough PTH -nutritional deficiency -lack of sunlight exposure -malabsorption
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Differentiate between osteoporosis and osteomalacia: 1. osteoporosis
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1. excessive bone remodeling leading to porous bone b/c of excessive osteoclast activity
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Differentiate between osteoporosis and osteomalacia: 1. osteomalacia
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1. decreased bone mineralization (loss of hydroxyapatate crystals - soft bone)
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List the different agents used to treat: the following from either primary hyperparathyroidism or hypercalcemia of malignancy. 1. acute, symptomatic/severe hypercalcemia how soon they are effective and how long they last
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1. volume expansion with isotonic saline - only acute setting add loop diuretic if pt has renal or heart failure - long time calcitonin- 48hrs bisphosphonate (pamidronate)- w/in 48hrs and then long time
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Explain the rationale for using IV saline to treat acute, severe and/or symptomatic hypercalcemia
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this will dilute Ca in the blood and facilitate urinary Ca excretion via increased diuresis
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Explain the advantages/disadvantages of using a loop diuretic in treating acute, severe and/or symptomatic hypercalcemia
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advantages - inhibits NKCC in TAL, blocking K secretion into tubule diminishing (+) lumen voltage leading to less driving force to push Ca across tight junction into interstitium.. useful for pt w/edema, renal failure, heart failure & hypercalcemia DON'T give if pt has normal hydration status/dehydrated, b/c increases diuresis
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Compare the mechanism of the bisphosphonates and calcitonin in treating hypercalcemia (acute or chronic therapy), osteoporosis, and Paget's disease: 1. calcitonin 2. bisphosphonate
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1. directly binds to osteoclasts and inhibits them 2. binds to remodeling site and prevents attachment of osteoclasts to bone and taken up by osteoclasts, inhibiting its activity and can cause apoptosis .. prevents breakdown of bone, increased bone mineral density but do not form new bone ..
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Compare and explain the ability of the first and second generation bisphosphonates to cause osteomalacia, esophagitis, bone/muscle pain, atypical femur fracture and osteonecrosis of the jaw 1. Etidronate, Tiludronate 2. Pamidronate, Alendronate, Risedronate 3. 1st & 2nd gen
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1. osteomalacia - b/c it inhibits bone mineralization (decreased osteoblast activity b/c it inhibits osteoclasts .. osteoblasts fill in what clasts tear up), 2. atypical femur fracture, esophagitis, bone/muscle pain, osteonecrosis of jaw 3. both types can cause esophagitis b/c pill can stick to esophagus, bone, muscle pain, atypical femur fracture (b/c less remodeling), osteonecrosis of the jaw (b/c of trauma to bone along w/continual stress from chewing)
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Explain the mechanism of action of cinacalcet in treating hypercalcemia associated with parathyroid carcinoma, and primary hyperparathyroidism, and why it is not useful in hypercalcemia of malignancy or vitamin D intoxication
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it enhances sensitivity of Ca sensing receptors in parathyroid to Ca, lowering the [Ca] at which PTH is suppressed, decreases PTH, decreasing serum Ca.. but not useful w/malignancy or Vit. D intoxification b/c they are not related to hyperparathyroidism
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Identify and explain the main side effect of cinacalcet
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hypocalcemia
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Compare and explain the use of calcium, Vitamin D (cholecalciferol) and calcitriol in the treatment of Rickets, osteomalacia, & hypoparathyroidism: 1. Rickets/osteomalacia 2. Hypoparathyroidism
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1. there is a deficiency in vit. D thus administering it will correct the pathology.. 2. with hypoparathyroidism, there are low levels of serum Ca, thus giving Ca and vit D will increase serum Ca (vit D will increase reabsorption of Ca from gut) .. calcitriol is better choice than cholecalciferol b/c of the decreased PTH there will be less 1a hydroxylase activity
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Explain the mechanism of action of teriparatide in the treatment of osteoporosis
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the exogenous PTH stimulates osteoblasts thru a different receptor than endogenous PTH which increases osteoblast activity
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What are some causes of hypercalcemia?
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-PT gland tumor makes too much PTH -Malignant tumor produces PTH-related protein (PTHrP) -Too much vitamin D -Cancer that metastasizes to bone, stimulates osteoclast formation and activation, and causes bone resorption
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Is hypercalcemia always symptomatic?
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no, depends on degree of hypercalcemia and rate of rise of serum [Ca]
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How can you approach treating severe and/or symptomatic hypercalcemia?
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increase urinary Ca excretion inhibit bone resorption decrease Ca absorption
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A 63-year-old female has lost her appetite with weight loss, and is constipated. She has been urinating alot and complains of thirst. Her blood pressure is 110/70 mm Hg, heart rate is 80 bpm. Her mucus membranes are somewhat dry and sticky. Serum creatinine is 2.1 mg/dL (normal 0.6-1.2 mg/dL), with normal electrolytes and glucose levels, but serum calcium is 14.1 mg/dL (normal 9.0-11.0 mg/dL). What would be the best treatment?
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IV normal saline
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The patient has symptomatic hypercalcemia and is dehydrated with presumed prerenal azotemia. What would be the best treatment?
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IV normal saline (restores volume status, dilutes Ca in blood, facilitates urinary Ca excretion)
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What diuretic will increase Ca excretion by the kidney?
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loop diuretic
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when might you use a loop diuretic to treat hypercalcemia?
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-if they develop edema after IV saline -in a pt with symptomatic hypercalcemia and heart failure
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What happens to bone with primary hyperparathyroidism and hypercalcemia of malignancy?
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bone resorption (releases Ca2+ into blood)
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What hormone decreases osteoclast activity?
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calcitonin
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How does calcitonin lower serum Ca levels in a patient with primary hyperparathyroidism?
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decrease bone resorption (b/c it inhibits osteoclasts)
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What will produce a more sustained lowering of serum Ca than calcitonin?
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bisphosphonates
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what will pamidronate do to bone resorption?
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decrease it
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Which agent would be most useful in preventing hypercalcemia and adverse skeletal events in a patient with metastatic cancer to bone.
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bisphosphonate
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what is a side effect of the 1st gen bisphosphonates (Etidronate, Tiludronate)?
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osteomalacia
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how do bisphosphonates cause osteonecrosis of the jaw?
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trauma to bone along w/continual stress from chewing. Bone has a limited capacity for healing due to the effects of bisphosphonate therapy (no bone remodeling)
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how can PTH secretion be reduced?
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raise serum levels of Ca sensitize CaSR to Ca
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Why would you not use Cinacalcet to treat hypercalcemia of malignancy (not referring to parathyroid carcinoma)?
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there is low PTH, thus not helpful b/c PTH-independent
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What can contribute to a vitamin D deficiency?
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nutritional deficiency lack of sunlight exposure malabsorption chronic kidney disease
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what does Vit D deficiency cause in: 1. children 2. adults
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1. rickets 2. osteomalacia
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What is the primary cause of hypocalcemia from a vitamin D deficiency?
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decreased intestinal absorption of Ca
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An elderly black female was admitted to the hospital from a nursing home because of progressive weakness. Her labs revealed a serum total calcium level of 8.2 mg/dL (normal 9.0-11.0 mg/dL), serum phosphorus of 2.6 mg/dL (normal 3.0-4.5 mg/dL) 25-hydroxyvitamin D level was 4 pg/dL (normal: 10-55 pg/dL), and her iPTH level was 161 pg/dL (normal: 14-72 pg/dL). What will you use to treat her?
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calcium & Vit D
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What usually happens to phosphorus and PTH with chronic kidney disease?
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phosphorus is elevated PTH is elevated
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What can happen to Ca levels if a patient with either a vitamin D deficiency or chronic kidney disease has high enough PTH levels?
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normal serum Ca
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What contributes to hypocalcemia from hypoparathyroidism?
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decreased PTH
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what happens to Ca in hypoparathyroidism?
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hypocalcemia occurs
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what happens to P in hypoparathyroidism?
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possibly normal or hyperphosphatation (b/c low PTH, thus not action on kidney to excrete P)
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What would you use to treat hypoparathyroidism?
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vitamin D calcitriol Calcium supplement
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How can you treat osteoporosis?
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inhibit osteoclasts enhance osteoblast activity
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Which agents will work on bone to inhibit osteoclast activity?
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bisphosphonates calcitonin
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What agent will work on bone to selectively increase osteoblast activity?
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exogenous PTH
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what is Paget's disease?
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Disorder of increased skeletal remodeling Uncontrolled osteoclastic bone resorption with secondary increases in bone formation New bone is poorly organized
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what would you use to treat Paget's disease?
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inhibit osteoclasts (calcitonin, bisphosphonates, plicamycin [last resort])
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Predict the effect of the following on serum calcium, phosphorus and PTH levels: 1. primary hyperparathyroidism
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1. high PTH causing high Ca, low P
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Predict the effect of the following on serum calcium, phosphorus and PTH levels: 1. secondary hyperparathyroidism due to vit D deficiency 2. secondary hyperparathyroidism due to chronic kidney disease
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1. increased PTH, possibly normal Ca, low phosphate 2. increased PTH, possibly normal Ca, high phosphate (can't excrete P)
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Predict the effect of the following on serum calcium, phosphorus and PTH levels: 1. hypercalcemia of malignancy
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1. high Ca, high P, low PTH
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Predict the effect of the following on serum calcium, phosphorus and PTH levels: 1. vit D intoxification
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1. high Ca, normal to high P, low PTH
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Predict the effect of the following on serum calcium, phosphorus and PTH levels: 1. hypoparathyroidism
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reduced serum Ca and PTH Possibly normal or elevated b/c PTH is not acting on kidney to excrete P
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Predict the effect of the following on serum calcium, phosphorus and PTH levels: 1. secondary hypoparathyroidism
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1. low Ca, normal to high P, low PTH .. due to surgical misadventure?
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What is the underlying factor in all high altitude diseases?
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hypoxia
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What effect will a decrease in arterial PO2 have on ventilation
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increase it
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What effect will hyperventilation have on blood pH?
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respiratory alkalosis
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What effect does high blood pH have on the hyperventilatory response to a reduced PO2?
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decrease
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What effect will acetazolamide have on blood pH?
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more acidic
