Calcium and Bone Pharmacology Flashcards Preview

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Flashcards in Calcium and Bone Pharmacology Deck (50)
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1

What conditions are responsible for 90% of hypercalcemia?

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

2

What are the 3 goals of hypercalcemia therapy?

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

3

What is the treatment of hypercalcemia?

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

4

What is the first line therapy for hypercalcemia?

- Bisphosphonates

5

What is the effect of bisphosphonates?

- Inhibition of accelerated bone resorption
- Nonhydrolyzable analogue of pyrophosphate that is resistant to phosphatases

6

How long is the effect of bisphosphonate?

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

7

What is the mechanism of action of bisphosphonates?

- 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

8

What are the adverse effects of bisphosphonates?

- 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)

9

What is the second line treatment for severe hypercalcemia?

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

10

How is calcitonin administered?

- Subcutaneous or intramuscular injection
- Salmon calcitonin is used due to potency

11

What is the mechanism of action of calcitonin?

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

12

What is another use for calcitonin?

- Bone analgesic

13

How does resistance to calcitonin develop?

- Resistance from down regulation of receptors, and from antibody formation

14

In what population is hypocalcemia often seen?

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

15

What is the treatment for mild/asymptomatic hypocalcemia?

- 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

16

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

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

17

What is the most common cause of hypercalcemia?

Hyperparathyroidsm

18

What are the common causes of hyperparathyroidism?

- 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)

19

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

Calcimimetics => Cinacalcet Hydrochloride

20

What are the other indications of cinacalcet hydrochloride?

- Hypercalcemia in parathyroid carcinoma
- Primary hyperparathyroidism

21

What are the major side effects of cinacalcet?

hypocalcemia, nausea, vomiting

22

What is the mechanism of action of cinacalcet?

- Allosteric regulator of CaSR
- which decreases serum PTH

23

What are the major preventative measures against osteoporosis?

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

What types of calcium supplements are available?

- Calcium carbonate (Tums) – highest Ca++ content (40%), absorption impaired with achlorhydria

- Calcium citrate (Citracal)– more bioavailable, lower Ca++ content (21%)

25

What are the side effects of calcium supplements?

- GI effects
- Decreased absorption of other minerals, drugs
- Milk-alkali syndrome

26

Adequate absorption of calcium requires what other supplement?

Vitamin D

27

What is the primary function of vitamin D?

↑ GI absorption of calcium via increased intestinal calcium transport

28

What occurs when there is inadequate vitamin D?

When vitamin D is inadequate => secondary hyperparathyroidsm

29

What are the primary vitamin D supplements?

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

30

What other patients should take vitamin D supplements?

- fat malabsorption
- fat soluble, toxicity (hypervitaminosis D)