Calcium and Phosphate Balance Pharmacology Flashcards
When lab values are obtained for "vitamin D," what compound is being measured? A. ergocalciferol B. calcitriol C. calcidiol D. cholecalciferol E. cinacalcet
C
The semantics in the vitamin D field are confusing and technically not very accurate. “Vitamin D” is either cholecalciferol (D3) or ergocalciferol (D2). Calcitriol, 1,25(OH)2D, is the active metabolite of vitamin D3 that interacts with the vitamin D receptor, but it is calcidiol, 25(OH)D, that is measured as “vitamin D” in clinical laboratory determinations.
There is currently only one drug available that stimulates new bone formation. What is it? A. Calcitonin B. Teriparatide C. Calcitriol D. Cinacalcet E. Ergocalciferol
B
Teriparatide, a synthetically produced version of the amino terminal 1-34 amino acids of human PTH, is
the only drug currently available that actually stimulates osteoblasts to increase new bone formation (mineral + matrix). Calcitonin prevents bone resorption by acting directly to inhibit osteoclast activity, calcitriol can contribute to bone formation by ensuring that adequate calcium is available to mineralize the bone, but it does not stimulate new bone formation. Other drugs you will learn about in Endo 2 can increase bone mineral in osteoporosis, but do not increase new bone formation (mineral plus matrix).
True or false: Calcidiol is the high affinity ligand for vitamin D receptor activation.
FALSE Although calcidiol (25-OHD) can bind the vitamin D receptor with very low affinity, this only results in biological response when the levels of calcidiol are exceedingly (nonphysiologically) high. The high affinity ligand for vitamin D receptor activation is calcitriol.
Which of the following compounds is the most appropriate to use for vitamin D supplementation in a normal, healthy person? A) Cholecalciferol B) Cinacalcet C) Calcitriol D) Calcitonin E) Teriparatide
A
Vitamin D itself (cholecalciferol or ergocalciferol), which has no known biological activity, isvthe most appropriate compound to use for vitamin D supplementation in normal people.vAdequate production and/or intake of vitamin D assures that there will be optimal substrate available for normal physiological regulatory processes to produce appropriate concentrations of calcitriol.
Which of the following conditions is the most high risk adverse effect of calcitriol administration? A) Hypophosphatemia B) Hyperparathyroidism C) Osteoporosis D) Hypocalcemia E) Hypercalcemia
E
Calcitriol leads to increased intestinal Ca absorption, which may eventually cause an increase in serum Ca. When Ca goes up, production of PTH declines and production of calcitriol will decline. Normally, this would lead to a decrease in intestinal Ca absorption. However, if the calcitriol is being given as a drug, the circulating level will not decline, in spite of decreased endogenous production, and so intestinal Ca absorption will continue to be stimulated. In addition, if calcitriol levels remain elevated long enough, bone resorption may also be
induced, further contributing to hypercalcemia.
Which of the following pathological conditions is most likely to require treatment with calcitriol? A) Renal failure B) Bone cancer C) Primary hyperparathyroidism D) Primary vitamin D deficiency
A
As renal failure advances, the loss of renal tubules leads to a situation in which the kidney can
no longer provide adequate 1-hyroxylation of 25-OH-D to produce calcitriol. When this happens, administration of calcitriol can help promote intestinal Ca absorption. Primary Vitamin D deficiency should be treated with the parent compound, vitamin D (chole- or ergocalciferol). Bone cancer and hyperparathyroidism may cause hypercalcemia, for which there would be no reason to give calcitriol.
Which of the following statements is most accurate regarding the mechanism of action of
A) It stimulates cAMP formation to increase PTH secretion
B) It is a competitive antagonist of the calcium-sensing receptor
C) It is an allosteric modulator of the calcium-sensing receptor
D) It regulates the synthesis of PTH via an intracellular receptor
E) It is a co-modulator of the vitamin D receptor
F) It is a direct agonist of the Ca-sensing receptor
C
Cinacalcet is an allosteric modulator of the Ca-sensing receptor. It does not bind to the same site in the receptor as Ca does. In the presence of cinacalcet, the receptor has an enhanced effect to decrease PTH relative to the effect of the same level of serum Ca in the absence of cinacalcet.
Which of the following conditions is most likely to be effectively treated with cinacalcet?
A) Vitamin D deficiency
B) Secondary hyperparathyroidism in renal failure
C) Hypocalcemia
D) Primary hyperthyroidism
E) Osteoporosis
B
The effect of cinacalcet is to reduce PTH secretion. It is primarily used to treat hyperparathyroidism secondary to renal failure, but can also be useful in primary
hyperparathyroidism. In vitamin D deficiency per se (lack of the parent compound), as well as hypocalcemia, there may be physiologically appropriate hyperparathyroidism. There is no known major effect of cinacalcet in hyperthyroidism or osteoporosis.
Which type of bone cell is the primary target of calcitonin in the treatment of
A) Osteocyte
B) Osteoclast
C) Osteoblast
B
The direct action of calcitonin to inhibit osteoclast activity makes it a rapidly-active agent to decrease bone resorption in the short term. It is not an effective overall monotherapy for osteoporosis.
Which type of bone cell is the primary target of teriparatide in the treatment of osteoporosis? A) Osteocyte B) Osteoclast C) Osteoblast
C
Normal physiological levels of PTH stimulate osteoblastic bone formation. The goal of teriparatide administration is to mimic this effect. Exposure to higher levels of PTH can begin to recruit osteoclasts.
