Calcium Homeostasis Flashcards
How does PTH affect calcium homeostasis?
- initiates conversion activation of D3 in the kidneys
- promotes phosphorous excretion and calcium reabsorption in the kidney
- promotes bone recycling (osteoclast and osteoblast activity)
What is the effect of activated vitamin D on calcium homeostasis?
- promotes bone recycling (osteoclast and osteoblast activity)
- promotes absorption of calcium and phosphorous from the gut
- promotes reabsorption of calcium and phosphorus from the renal tubules
Through what mechanism do PTH and activated VitD affect bone mineral homeostasis?
- promote differentiation of preosteoclasts
- promote differentiation of preosteoblasts
- promote activation of osteoblasts, which release RANK-L and activate osteoclasts as well
What are four important biologic actions of calcium?
- clotting of blood
- ossification of bone
- muscle contraction
- release of endocrine hormones and neurotransmitters
How does hypercalcemia present?
generalized weakness and smooth muscle dysfunction
- stones, bones, groans, thrones, and psych overtones
- renal stones, bone pain, abdominal pain, urinary frequency, anxiety and altered mental status
How does hypocalcemia present?
- tetany
- QT prolongation
- seizures
- Chvostek and Trousseau sign
What are the two primary pharmacological uses of calcium supplements?
- treat hypocalcemia due to dietary insufficiency, malabsorption, renal disease, or hypoparathyroidism
- prophylaxis and treatment of osteoporosis
What are the dietary recommendations for calcium intake?
- 1000 mg/day for most adults
- 1200 mg/day for women over 50 and men over 70
Calcium Carbonate
- an oral calcium supplement
- commonly used because it is cheap and the pills are small
- but is more likely to cause gas, bloating, and constipation
- also neutralizes gastric acid and can cause rebound acid secretion
- need to take with food
How does calcium citrate compare to calcium carbonate?
- both are oral preparations of calcium
- carbonate is cheaper and more concentrated so pills are smaller
- citrate has fewer GI problems, does not affect gastric pH, and can be taken without food
What are the downsides of calcium gluconate?
- it can be irritating to the veins (but is least likely of the IV preparations)
- rapid infusion can cause arrhythmias
Rapid infusion of calcium can cause what adverse effect?
arrhythmias
By what mechanism do bisphosphonates impact calcium homeostasis?
- they are pyrophosphate analogs in which the P-O-P bond has been replaced with a non-hydrolyzable P-C-P bond
- they suppress the activity of osteoclasts by inhibiting formation and dissolution of hydroxyapatite crystals
- they also inhibit farsenyl pyrophosphate synthase, which also impairs osteoclast activity
BIsphosphonates
- pyrophosphate analogs used to promote bone formation and inhibit resorption
- they suppress the activity of osteoclasts by impairing formation and dissolution of hydroxyapatite crystals and by inhibiting farsenyl pyrophosphate synthase
- used for osteoporosis, bone metastases, Paget’s disease of bone, and hypercalcemia
- poor oral absorption, so taken with a full glass of water without food, and remain standing for 30 minutes
- may cause esophageal and gastric irritation, adynamic bone (“bad bone”), osteonecrosis of the jaw, or renal failure
- adynamic bone and osteonecrosis are why continuous use for more than five years is not recommended; should take a “drug holiday”
What are the primary uses of bisphosphonates?
- osteoporosis
- bone metastases
- Paget’s disease
- hypercalcemia
How do etidronate, alendronate, and risedronate compare?
- all are oral bisphosphonates
- etidronate < alendronate < risedronate half life
- etidronate is limited to those with Paget’s disease
What is unique about etidronate?
it is a bisphosphonate with a relatively short half life (1x daily dosing) that is only used for those with Paget’s disease
What is unique about pamidronate?
it is a bisphosphonate used only in those with Paget’s disease or a malignancy
How do glucocorticoids affect calcium homeostasis?
- they decrease calcium absorption and increase excretion
- may lead to osteoporosis
How do thiazide diuretics impact calcium homeostasis?
- decrease renal calcium excretion, augmenting the effects of PTH
- used for those with hypercalciura and calcium-based nephrolithiasis
What use does raloxifene have in calcium homeostasis? What class of drug is it?
a SERM used for the treatment of osteoporosis
Teriparatide
- a recombinant form of PTH
- stimulates new bone that is structurally normal
- not recommended for more than 2 years because of a black box warning for osteosarcoma
- administered subcutaneously
How does calcitonin affect calcium homeostasis?
it tends to counteract PTH
- it impairs bone resorption without impacting deposition
- it promotes renal excretion of calcium and phosphate
How is calcitonin used pharmacologically?
- it is used to increase bone mass because it inhibits resorption much like bisphosphonate
- it is not as effective as bisphosphonates or teriparatide
Denosumab?
- a monoclonal antibody that inhibits RANKL
- suppresses bone resorption
- may have immunosuppressive side effects
- administered subcutaneously on a biannual basis
How are androgens and estrogens used for treatment of calcium homeostasis?
- they reduce the bone-resorbing effects of PTH
- used in the treatment of osteoporosis
- but not recommended for postmenopausal women because of their effects on breast, uterus, and CV system
- testosterone is first converted to estrogen
How does fluoride improve calcium homeostasis?
- it stabilizes hydroxyapatite crystals in bone and teeth
- used to prevent dental caries
- experimental use for osteoporosis
- toxicity occurs well beyond the level found in drinking water but presents with GI pain, n/v, and headaches
Cinacalcet
- a drug affecting calcium homeostasis
- activates the calcium-sensing receptor on the parathyroid gland and suppresses PTH release
- used for secondary hyperparathyroidism: renal disease and parathyroid carcinoma
Where do we get vitamin D naturally?
- D3 is formed in the skin by UV irradiation
- D2 and D3 can also be found in the diet
What is the most active form of vitamin D?
1,25(OH2)D3, also known as calcitriol
What is calcitriol?
1,25(OH2)D3, the most active form of vitamin D
What is the recommended serum level for Vitamin D?
30-70 ng/mL
Vitamin D deficiency in children causes what disease?
Rickets with abnormal and retarded bone growth
How does Vitamin D toxicity manifest?
very difficult to achieve but presents with hypercalcemia, hypercalciuria, n/v, decreased appetite, frequent urination, and renal failure
What are the following also known as:
- cholecalciferol
- ergocalciferol
- calcitriol
- calcipotriene
- doxercalciferol
- paracalcitrol
- cholecalciferol: D3
- ergocalciferol: D2
- calcitriol: 1,25(OH)2D3
- calcipotriene: no aka
- doxercalciferol: 1a-(OH)D2
- paracalcitrol: 19-nor-1,25(OH)D2
Under what circumstances wouldn’t you use D3 to supplement a vitamin D3 deficient patient?
if they can’t convert it to calcitriol on their own
What are the most common causes of vitamin D deficiency?
- inadequate intake
- inadequate exposure to sunlight
- renal dysfunction
- administration of anticonvulsants that increase metabolic of 25(OH)D
What are the clinical uses of Vitamin D?
- treatment and prophylaxis of nutritional rickets
- treatment of metabolic rickets secondary to renal hydroxylase deficiency or chronic renal failure (prevents calcitriol formation)
- osteoporosis and osteomalacia in combination with calcium supplementation
- psoriasis
- hypoparathyroidism
- secondary hyperparathyroidism in renal disease
What form of vitamin D supplement is used to treat psoriasis?
topical calcipotriene
What is metabolic rickets?
a genetic defect in renal hydroxylase or chronic renal failure, which prevent endogenous production of calcitriol from D2/D3
How is vitamin D supplementation used in the treatment secondary hyperparathyroidism in renal disease?
- these patients have low 1,25(OH)2D
- treat with doxercalciferol or paracalcitrol
What are doxercalciferol and paracalcitrol used to treat?
secondary hyperparathyroidism due to renal disease
What are the advantages/disadvantages of supplementing with D2 versus D3?
- D3 is more effective at increasing plasma D concentrations
- has a longer half life and higher affinity for receptors in human tissue
- however, it is over the counter
- as a result, D2, which is a prescription, is used more frequently because the formulation is more regulated and reliable despite being less effective
- additionally D3 is derived from animal sources and may be objectionable to vegans
