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Endocrine Block 3 > Calcium and Bone Pharmacology > Flashcards

Calcium and Bone Pharmacology Flashcards

1
Q

What conditions are responsible for 90% of hypercalcemia?

A

1) Hyperparathyroidism – mild and prolonged
2) Malignancy – more severe, ≈20% of cancer patients (lung, breast, hematologic); most commonly caused by increased production of PTHrP

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2
Q

What are the 3 goals of hypercalcemia therapy?

A

1) Increase urinary calcium excretion
2) Diminish intestinal absorption of calcium
3) Inhibit accelerated bone resorption

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3
Q

What is the treatment of hypercalcemia?

A
  • Treat underlying disease
  • Avoid certain meds – Thiazides, vitamin D
  • Curtail dietary intake Ca++ and Vitamin D
  • ↑ Salt and water intake
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4
Q

What is the first line therapy for hypercalcemia?

A
  • Bisphosphonates
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5
Q

What is the effect of bisphosphonates?

A
  • Inhibition of accelerated bone resorption

- Nonhydrolyzable analogue of pyrophosphate that is resistant to phosphatases

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6
Q

How long is the effect of bisphosphonate?

A

Zoledronate (highly potent newer drug), and others – effect may last for months

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7
Q

What is the mechanism of action of bisphosphonates?

A
  • Binds to bone matrix and undergoes endocytosis by osteoclasts (is absorbed into the bone)
  • Intracellular release into the cytosol
  • Inhibition of cell function; induction of apoptosis
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8
Q

What are the adverse effects of bisphosphonates?

A
  • Hypocalcemia
  • Acute phase reaction - transient flu-like syndrome (common)
  • Potential nephrotoxicity
    • Precipitation of calcium bisphosphonate
  • Jaw necrosis (rare)
    • mostly in oncology patients
    • after oral surgery or infection (dental consult before beginning therapy)
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9
Q

What is the second line treatment for severe hypercalcemia?

A

Calcitonin

- endogenous peptide hormone , C cells of thyroid gland secrete in response to high calcium

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10
Q

How is calcitonin administered?

A
  • Subcutaneous or intramuscular injection

- Salmon calcitonin is used due to potency

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11
Q

What is the mechanism of action of calcitonin?

A
  • cell surface G-protein-coupled receptor on osteoclasts, ↓ bone resorption
  • ↑ urinary calcium excretion
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12
Q

What is another use for calcitonin?

A
  • Bone analgesic
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13
Q

How does resistance to calcitonin develop?

A
  • Resistance from down regulation of receptors, and from antibody formation
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14
Q

In what population is hypocalcemia often seen?

A
  • Hospitalized patients

- due to chronic/acute renal failure, vitamin D deficiency, Mg++ deficiency, acute pancreatitis, hypoparathyroidism

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15
Q

What is the treatment for mild/asymptomatic hypocalcemia?

A
  • Oral calcium supplements (calcium carbonate)
    • Goal is to increase intestinal calcium absorption
    • Can use vitamin D to enhance absorption, active form (calcitriol) may be used
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16
Q

What is the treatment of severe hypocalcemia? (i.e. seizures, tetany)

A
  • IV calcium

- Calcium gluconate (best), calcium chloride (more Ca+, more rapid but more irritating to veins)

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17
Q

What is the most common cause of hypercalcemia?

A

Hyperparathyroidsm

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18
Q

What are the common causes of hyperparathyroidism?

A
  • Primary – parathyroid adenoma or hyperplasia, carcinoma (rare) – treat with parathyroidectomy
  • Secondary – chronic renal failure, malabsorption syndromes (activation of parathyroids to low calcium)
  • Tertiary – progression into autonomous hypersecretion of PTH associated with hypercalcemia (not significant)
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19
Q

What drug is used in secondary hyperparathyroidism in chronic kidney disease?

A

Calcimimetics => Cinacalcet Hydrochloride

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20
Q

What are the other indications of cinacalcet hydrochloride?

A
  • Hypercalcemia in parathyroid carcinoma

- Primary hyperparathyroidism

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21
Q

What are the major side effects of cinacalcet?

A

hypocalcemia, nausea, vomiting

22
Q

What is the mechanism of action of cinacalcet?

A
  • Allosteric regulator of CaSR

- which decreases serum PTH

23
Q

What are the major preventative measures against osteoporosis?

A

1) Optimize calcium and vitamin D intakes throughout life
2) Weigh bearing exercise
- increases bone mass (anabolic effect)
- Decreases falls (strength and balance)
3) Falls Prevention

24
Q

What types of calcium supplements are available?

A
  • Calcium carbonate (Tums) – highest Ca++ content (40%), absorption impaired with achlorhydria
  • Calcium citrate (Citracal)– more bioavailable, lower Ca++ content (21%)
25
Q

What are the side effects of calcium supplements?

A
  • GI effects
  • Decreased absorption of other minerals, drugs
  • Milk-alkali syndrome
26
Q

Adequate absorption of calcium requires what other supplement?

A

Vitamin D

27
Q

What is the primary function of vitamin D?

A

↑ GI absorption of calcium via increased intestinal calcium transport

28
Q

What occurs when there is inadequate vitamin D?

A

When vitamin D is inadequate => secondary hyperparathyroidsm

29
Q

What are the primary vitamin D supplements?

A
  • vitamin D2 (ergocalciferol) and D3 (cholecalciferal) - oral
  • 1,25(OH)2D - calcitriol - fully active, more
30
Q

What other patients should take vitamin D supplements?

A
  • fat malabsorption

- fat soluble, toxicity (hypervitaminosis D)

31
Q

What is the approach to osteoporosis therapy?

A
  • Vitamin D
  • Calcium
  • Anti-resportive agents (i.e. *bisphosphonates, SERMS, Danosumab, calcitonin) block bone respiration
  • Bone forming (anabolic) agents (i.e. PTH) increase bone formation
32
Q

What is the first lien therapy for osteoporosis?

A

Bisphosphonates (Fosamax and other oral analogs)

33
Q

What is the action of bisphosphonates?

A
  • Antiresportive, inhibits osteoclasts
  • Increases bone mineral density
  • Decreases fractures
34
Q

How can bisphosphonates administered?

A
  • Orally => empty stomach and lots of water

- Injection => every 3 months (ibandronate) or yearly (zoledronate)

35
Q

What are the adverse effects of bisphosphonates?

A
  • GI irritation ( esophagus, stomach)
36
Q

What drug is used in postmenopausal osteoporosis?

A
  • Estrogen
37
Q

What is the action of estrogen in osteoporosis?

A
  • Antiresorptive, inhibits osteoclasts, reduced turnover, nuclear ER complex regulates OB gene expression
  • ↑ BMD and ↓ fractures
  • Used to treat menopausal symptoms
38
Q

What risk is associated with estrogen use?

A

May ↑ risk of heart attacks, strokes, breast cancer, migraines, blood clots (WHI study)

39
Q

What SERM (selective estrogen receptor modulator) is used for post menopausal osteoporosis?

A

Raloxifene

  • Less effective for osteoporosis than other agents
  • Does not help with menopausal symptoms
40
Q

What is the action of Raloxifene?

A

Agonist (estrogenic) effects in bone, antagonist in breast and uterus

41
Q

How is Raloxifene administered?

A

Easy to take orally

42
Q

What is the action of calcitonin?

A
  • Antiresorptive agent, inhibits osteoclasts (cell surface receptor on OC)
  • Analgesic effect (helpful for bone pain)
43
Q

What is the homeostatic role of PTH?

A

Homeostatic role – maintains blood calcium by withdrawal from bone stores, reduces bone mass

44
Q

What is the THERAPEUTIC role of PTH?

A

Therapeutic role – intermittent PTH treatment BUILDS bone mass

45
Q

What is teriparatide?

A
  • PTH analog => first 34 amino acid of active PTH
46
Q

What is the action of Teriparatide?

A
  • Stimulates osteoblasts and new bone growth
  • ↑ turnover, improves micro-architecture
  • ↑ BMD and ↓ fractures
  • Very effective, but very expensive
47
Q

How is Teriparatide administered?

A

Daily subcutaneous injection (intermittent), short half life

48
Q

What adverse side effects associated with Teriparatide?

A
  • hypercalcemia

- hypercalciuria,

49
Q

What is the indication of Teriparatide?

A

Use in patients with high risk of fracture

50
Q

Should Terparatide be used with bisphosphonates?

A

Use with Bisphosphonates is controversial => likely should not use

Endocrine Block 3 (5 decks)

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