Flashcards in Calcium and Bone Pharmacology Deck (50)
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
What are the 3 goals of hypercalcemia therapy?
1) Increase urinary calcium excretion
2) Diminish intestinal absorption of calcium
3) Inhibit accelerated bone resorption
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
What is the first line therapy for hypercalcemia?
What is the effect of bisphosphonates?
- Inhibition of accelerated bone resorption
- Nonhydrolyzable analogue of pyrophosphate that is resistant to phosphatases
How long is the effect of bisphosphonate?
Zoledronate (highly potent newer drug), and others – effect may last for months
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
What are the adverse effects of bisphosphonates?
- 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)
What is the second line treatment for severe hypercalcemia?
- endogenous peptide hormone , C cells of thyroid gland secrete in response to high calcium
How is calcitonin administered?
- Subcutaneous or intramuscular injection
- Salmon calcitonin is used due to potency
What is the mechanism of action of calcitonin?
- cell surface G-protein-coupled receptor on osteoclasts, ↓ bone resorption
- ↑ urinary calcium excretion
What is another use for calcitonin?
- Bone analgesic
How does resistance to calcitonin develop?
- Resistance from down regulation of receptors, and from antibody formation
In what population is hypocalcemia often seen?
- Hospitalized patients
- due to chronic/acute renal failure, vitamin D deficiency, Mg++ deficiency, acute pancreatitis, hypoparathyroidism
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
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)
What is the most common cause of hypercalcemia?
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)
What drug is used in secondary hyperparathyroidism in chronic kidney disease?
Calcimimetics => Cinacalcet Hydrochloride
What are the other indications of cinacalcet hydrochloride?
- Hypercalcemia in parathyroid carcinoma
- Primary hyperparathyroidism
What are the major side effects of cinacalcet?
hypocalcemia, nausea, vomiting
What is the mechanism of action of cinacalcet?
- Allosteric regulator of CaSR
- which decreases serum PTH
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
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%)
What are the side effects of calcium supplements?
- GI effects
- Decreased absorption of other minerals, drugs
- Milk-alkali syndrome
Adequate absorption of calcium requires what other supplement?
What is the primary function of vitamin D?
↑ GI absorption of calcium via increased intestinal calcium transport
What occurs when there is inadequate vitamin D?
When vitamin D is inadequate => secondary hyperparathyroidsm
What are the primary vitamin D supplements?
- vitamin D2 (ergocalciferol) and D3 (cholecalciferal) - oral
- 1,25(OH)2D - calcitriol - fully active, more