Bone Mineralization Drugs Flashcards
Discuss the regulatory actions of calcium.
High calcium levels result in the conversion of vitamin D to its inactive form D3 instead of the active 1,25 and inhibits PTH secretion.
Describe the clinical uses of calcium.
Calcium salts are used to tx hypocalcemia. IV calcium salts (usually Ca++ chloride and Ca++ gluconate) for severe cases.
What can you give with calcium for rapid rise of serum Ca++ levels in severe hypocalcemia?
Calcitriol. Raises levels within 24-48h.
What are the daily recommendations for calcium intake?
19-50 y.o.: 1000mg
>50 y.o.: 1200mg
Describe the mechanism of action and clinical use of Teriparatide.
It is thought to preferentially activate osteoblasts for the treatment of osteoporosis. It increases serum Ca++ (like PTH). Available as injection.
What adverse effect is associated with Teriparatide?
Increased risk of osteosarcoma
Describe the effects of PTH at low/intermittent levels.
Builds up bone- stimulates conversion of osteoblast precursors to active osteoblasts for bone formation
Describe the action of PTH at high levels.
Breaks down bone- kidneys decrease Ca++ excretion and bones resorb Ca++, and enhances vitamin D production in the kidney. Ultimate goal of increasing serum Ca++ levels.
What is the net result of excess PTH?
To raise serum Ca++ and reduce phosphate.
Describe the metabolism of Vitamin D.
It circulates bound to plasma protein and is converted via skin, liver, and finally kidneys to reach active form calcitriol.
Describe the actions of calcitriol (active vitamin D).
It acts as a hormone, binding receptors in many tissues and inducing Ca++-binding proteins in the intestine and modulates Ca++ flux across brush border and basolateral membranes. Also stimulates osteoblast synthesis and this induces increases osteoclast activity. Regulates PTH secretion.
What is the result of Vitamin D toxicity?
hypercalcemia
What is the net effect of active Vitamin D?
Raises both serum Ca++ and phosphate.
What are the clinical uses of Vitamin D?
Prophylaxis for deficiency and hypoparathyroidism
What special consideration effects Vitamin D administration?
Renal failure. These patients can’t convert inactive vitamin D to calcitriol very well, so you need to give them calcitriol.
Discuss the general purpose of bisphosphonate use.
These drugs are non-hormonal agents affecting bone mineral homeostasis, concentrating at sites of active remodeling in bone. They are used to treat osteoporosis and Paget’s disease
Name the three bisphosphonates discussed in lecture and their mechanism of action.
“AIR”: alendronate, ibandronate, risedronate
They interfere with cholesterol synthesis thus inhibiting activation of osteoclasts
Which of the three bisphosphonates discussed in lecture is 3rd generation and thus more potent?
Risedronate
Discuss longterm use of bisphosphonates.
Longterm use may lessen their benefits because they suppress bone turnover, preventing remodeling/healing of cracks.
Describe the pharmacokinetics of bisphosphonates.
They are poorly absorbed and should be taken on an empty stomach with water, sitting upright to prevent esophagitis.
How often are bisphosphonates taken?
Alendronate is taken once weekly, Ibandronate and Risedronate are taken once monthly.
Describe the actions of calcitonin.
It regulates circulating Ca++ levels by reducing Ca++ retention and opposing osteoclast action. It also lowers phosphate levels via bone and kidney action.
Describe the clinical use for calcitonin.
It is used to treat Paget’s disease
In what forms is calcitonin available for administration?
Nasal spray and parenteral injection
