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Endo II: Test 2 > Pharm: Agents that affect bone mineral homeostasis > Flashcards

Pharm: Agents that affect bone mineral homeostasis Flashcards

1
Q

calcium

A
  • 98% of filtered Ca2+ reabsorbed by kidney
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2
Q

phosphate

A
  • 85% of filtered phosphate is reabsorbed by the kidney
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3
Q

teriparatide

A
  • synthetic PTH hormone

MOA: continuous administration of PTH osteopenia; but intermittent PTH promotes bone growth

Use: osteoporosis

ADR’s: orthostatic hypotension, hypercalcemia, dizziness, nausea, hyperuricemia, angina

CI: not advised for patients who have increased risk of osteosarcoma! (Paget’s disease, high alk phos levels)

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4
Q

calcitonin

A
  • hormone excreted by parafollicular cells of thyroid

MOA:

  • decreases serum calcium and phosphate actions
  • Bone: inhibits osteoclast bone resorption and formation over time
  • Renal: decreases calcium and phosphate reabsorption and other ions like sodium, potassium, Mg+ in the kidney

Use:
- disorders of increased skeletal remodeling (Paget’s disease, osteoporosis)

ADR’s: nausea, hand swelling, urticaria, intestinal cramping

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5
Q

cholecalciferol

A
  • vitamin D3 (natural)

MOA:
- increases intestinal absorption of Ca2+ and PO- as well as bone turnover

Use:

  • cure of nutritional rickets
  • tx for metabolic rickets/osteomalcia (no liver failure or kidney disease)
  • tx of hypoparathyroidism
  • prevention/tx of osteoporosis

ADR’s:

  • hypercalcemia, nausea, vomiting, constipation
  • ** arrhythmias and pancreatitis ***
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6
Q

Ergocalciferol

A
  • vitamin D2 (plant-based)

MOA:
- increases intestinal absorption of Ca2+ and PO- as well as bone turnover

Use:

  • cure of nutritional rickets
  • tx for metabolic rickets/osteomalcia (no liver failure or kidney disease)
  • tx of hypoparathyroidism
  • prevention/tx of osteoporosis

ADR’s:

  • hypercalcemia, nausea, vomiting, constipation
  • ** arrhythmias and pancreatitis ***
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7
Q

calcitriol

A
  • the potent vitamin D metabolite (1,25 dihydroxyvitamin D)

MOA:
- increases intestinal absorption of Ca2+ and PO- as well as bone turnover

Use: *** used for RENAL and LIVER failure **

  • cure of nutritional rickets
  • tx for metabolic rickets/osteomalcia
  • tx of hypoparathyroidism
  • prevention/tx of osteoporosis

ADR’s:

  • hypercalcemia, nausea, vomiting, constipation
  • ** arrhythmias and pancreatitis ***
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8
Q

raloxifene

A
  • selective serotonin (estrogen) receptor modulator: SERM

MOA: serves as an agonist in bone of estrogen, but doesn’t stimulate the endometrium, cause problems in breasts or CV system

USE: tx and prevention of post-menopausal osteoporosis

ADR’s: hot flashes, leg cramps, thromboembolism ** (3x risk of DVT and PE!!!)

CI: hx of DVT or coronary heart disease, or risk factors of stroke

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9
Q

alendronate

A
  • biphosphonate

MOA: analog of pyrophosphate in which P-O-P is replaced by P-C-P bond (incorporates itself into the bone and inhibits osteoclasts)

  • Ca2+ chelation in sites of active bone remodeling
  • inhibits osteoclasts
  • increased bone mineral density

USE:

  • osteoporosis
  • hypercalcemia assoc. w/ malignancy
  • Paget’s disease

ADR’s:

  • esophageal/gastric irritation in oral formations
  • osteonecrosis of jaw
  • subtrochanteric femur fractures (d/t oversupression of bone formation)
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10
Q

denosumab

A

MOA: monoclonal antibody that binds and prevents action of RANKL

  • mimics osteoprotegerin by reducing binding of RANKL to RANK and blocking osteoclast formation and activation (prevents osteoclastogenesis)

USE: post-menopausal osteoporosis
- some breast/prostate cancers

PK: subcutaneous every 6 mos

ADR’s: well tolerated but…

  • can increase risk of infection d/t interference w/ immune system RANKL expression
  • risk of osteonecrosis of jaw/subtrochanter
  • can lead to transient hypocalcemia
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11
Q

normal extracellular calcium levels?

A

8.5-10.4 mg/dL

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12
Q

normal extracellular phosphate levels?

A

2.5-4.5 mg/dL

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13
Q

glucocorticoids?

A
  • antagonize vit D stimulated intestinal Ca2+ transport
  • stimulate renal calcium excretion
  • block bone formation

= decreased total body calcium stores

USE: reversing hypercalcemia assoc. w/ lymphomas/granulomatous sarcoidosis or Vit D intoxication

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14
Q

estrogens?

A

prevent accelerated bone loss by reducing action of PTH

MOA: prevent maturation of osteoclast precursors to mature osteoclasts

Use:

  • primary hypogonadism
  • post-menopausal hormone replacement
  • hirsutism and amenorrhea

ADR’s: increased risk of cardiovascular risks and breast cancer (only used in pts. that are postemenopausal w/ significant hotflashes, and already have osteoporosis)

CI:
- liver disease, undiagnosed genital bleeding, hx of thromboembolizm, heavy smokers

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15
Q

fibrobastic growth factor 23?

A
  • single chain protein that inhibits 1,25 (OH)2 D production and inhibits phosphate reabsorption in kidney
  • intestine: decreases calcium and phosphate absorption by inhibiting production of Vit D
  • kidney:: increased phosphate excretion
  • bone: decreased mineralization due to hypophosphatemia

can cause hypophosphatemia and inappropriate low levels of Vit D

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16
Q

effects of hypercalcemia?

A

CNS depression, coma, potentially lethal

17
Q

causes of hyperCa?

A

thiazide therapy, hyperparathyroidism, cancer, hypervitaminosis D, sarcoidosis, thyrotoxicosis, milk-alkali syndrome, adrenal insufficiency

  • calcium level up to 12 is considered mild
  • calcium 12-14 = moderate level
  • calcium >14 = severe:
18
Q

tx of hyperCa?

A

this is treatment of severe calcium

  1. saline diuresis +/- furosemide
  2. bisphosphonates - seen effects in several days
  3. calcitonin - effects seen in 4-6 hours
  4. phosphate: fastest and surest way to decrease calcium - but has risks of servere hypocalcemia, ARF, hypotension
  5. glucocorticoids
19
Q

effects of hypocalcemia?

A

neuromuscular tetany, paresthesias, laryngospasm, mm. cramps, seizures

20
Q

causes of hypoCa?

A

hypoparathyroidism, Vit D deficiency, CKD, malabsorption

21
Q

tx of hypoCa?

A
  1. Calcium IV along w/ Vit D calcitrol
22
Q

hyperphosphatemia?

A
  • common complication of renal failure

- tx: dietary phosphate restriction, phosphate binding gels, calcium supplements

23
Q

tx of hypoparathyroidism?

A

calcium and vit D supplementation

24
Q

osteoporosis

A
  • abnormal loss of bone predisposing pts. to bone fractures
  • most common in post-menopausal women
  • may be d/t prolonged glucocorticoid use, endocrine disease, malabosprtion syndrome, alcohol or cigarette smoking

tx options:
- bisphosphonates (alendronate), SERM’s (raloxifene), Ca2+ and Vit D supplements, teriparatide, calcitonin, denosumab

25
Q

Paget’s disease tx?

A

calcitonin and bisphosphates (should not exceed 6 mos, but can be repeated after 6 mos) are first line tx

26
Q

basic bone phys?

A

PTH and 1,25 (OH)2 D – stimulate osteoblast and osteoclast formation

  • osteoblasts stimulate osteoclast formation through RANKL and MCSF
  • (Osteoprotegerin) OPG inhibits osteoclast formation by acting as decoy ligand for RANKL
  • estrogen, bisphosphonates and calcitonin inhibit osteoclast breaking down calcified bones
27
Q

PTH

A
  • increased serum calcium
  • decreased serum phsophate

Actions on bone:

  • Indirectly increases activity and number of osteoclasts
  • Acts on osteoblasts –> induces RANKL
  • RANKL increases osteoclast activity and number
  • Increases bone remodeling
  • Net effect = bone resorption (but low, intermittent doses increase bone formation)

Actions in kidney:

  • Increases reabsorption of calcium; inhibits reabsorption of phosphate
  • Stimulates 1,25(OH)2D (calcitriol) production
28
Q

Vitamin D

A
  • Applied to natural cholecalciferol (vitamin D3) and plant-derived ergocalciferol (vitamin D2)
  • Activity results:
  • Increased calcium and phosphate
  • Increased bone turnover

Actions in intestine:
- Augmented absorption of calcium and phosphate

Actions on bone:

  • Promotes recruitment of osteoclast precursors
  • Induces RANKL

Requires three steps of biotransformation:

  1. UV light
  2. livery hydroxylation
  3. kidney hydroxylation
29
Q

case 1: 60 y/o male w/ severe IBD. lab values: Ca2+ is 7, physician suspects malnutrition/malabsorption. they have albumin of 2.7 and Scr of 1.1

A

corrected calcium: (4-albumin)*.8 + serum calcium = 8 mg/dL

For calcium deficiency:

  • initiate oral calcium carbonate first (preffered)
  • or initiate calcium gluconate IV
30
Q

65 y/o female w/ hx of HTN, BMD T-score is -2.4 at hip and -2.6 at spine. should patient receive calcium and vit D supplementation?

A

yes she should if she is depleted

  • recommend weight bearing exercise
  • mm. strengthening
  • avoid smoking and consume only moderate amounts of alcohol

When is drug therapy indicated?

  • if pt. has hip/spine fracture
  • if patient has -2.5 T score
  • if patient has T score greater than -1 and have increased risk of osteoporosis fracture
31
Q

T score rating

A

+1 to -1 = normal

T-score between −1 and −2.5 indicates that you have low bone mass, although not low enough to be diagnosed with osteoporosis.

T-score of −2.5 or lower indicates that you have osteoporosis.

32
Q

AE of constipation, intestinal bloating excess gas

A

Calcium

33
Q

AE of hypotension, hypercalcemia and dizziness

A

synthetic PTH - teriparatide

34
Q

AE of nausea and hand swelling

A

calcitonin - inhibits osteoclastic bone resoprtion

35
Q

AE of hot flash, leg cramps, thromboembolism

A

raloxifene = estrogen receptor agonist in bone

36
Q

AE of esophageal and gastric irritation

A

alendronate: inhibits osteoclasts and inhibits dissoolution of hydroxyapatite

37
Q

AE hypocalcemia, potential increased risk of infection and osteonecrosis

A

Denosumab - binds and prevents action of Rank L

Endo II: Test 2 (10 decks)

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