OSTEOPOROSIS DRUGS

REQUIRED READING: AGENTS THAT AFFECT BONE MINERAL HOMEOSTASIS
Katzung’s Basic and Clinical Pharmacology
13th edition
Chapter 42

After attending the lecture and reading the textbook, you should be able to answer these questions.

1. Is osteoporosis a condition that disturbs the structural support of the body? What are the three major body organs involved in calcium and phosphate homeostasis? What is the normal range of calcium in the blood?

2. What is parathyroid hormone (PTH)? Which glands of the body secrete PTH? What is the physiological effect of PTH? How many amino acids are in PTH? Is the secretion of PTH inversely related to plasma Ca++ levels? What hormone in the body has the opposite effect of PTH? What physiological effect is achieved with prolonged, chronic, exposure to PTH? How does that differ from intermittent exposures to PTH?

3. Describe the PTH receptor. Is it a nuclear receptor? What 2nd messenger accumulates within the cell following activation of the receptor? Does PTH stimulate the activity of many proteins? Does it inhibit the activity of other proteins? Pretty cool, eh? (PS. No need to memorize that list. But one should realize that PTH can both stimulate and inhibit the functions of unique gene products.)

4. What vitamin is required for PTH to exhibit its full spectrum of action? Describe the relevant steps in the conversion of 7-dehydrocholesterol to vitamin D3 and metabolism of D3 to 1,25(OH)2D3 (calcitriol). What do you suspect could happen to calcitriol biosynthesis in a patient with renal failure?

5. What is hypocalcemia? What are the pharmacotherapeutic options available to treat HYPOcalcemia?

6. What is osteoporosis? What pharmacologic options are available to treat this disease? Which of these agents are hormonal? Which of them are non hormonal?

7. Draw the general structure of the nitrogen-containing bisphosphonates. What is FPPS? What is the therapeutic mechanism of action of the bisphosphonates? Are these agents well-absorbed after oral administration? Are there dietary factors that can influence the absorption of these agents?

8. What are the FDA-labeled indications for alendronate? What is the mechanism of action of alendronate? Does the bioavailability of this drug? Describe the Phase I and Phase II metabolism of alendronate. What are the common adverse effects associated with this drug? What are some rare but serious adverse effects associated with this drug? Is alendronate given as an oral administration? As an intramuscular administration? As an inhalational administration?

9. What are the clinical indications for risedronate? Is it given orally? Intramuscularly? Intravenously? What are its chief adverse effects?

10. What are the clinical indications for ibandronate? Is it given orally? Intramuscularly? Intravenously? What are its chief adverse effects? Daily? Yearly? Monthly? Weekly?

11. What are some contraindications to the bisphosphonates?

12. Any relevant drug drug interactions with bisphosphonates?

13. What are the clinical indications for zoledronic acid? Is it given orally? Intramuscularly? Intravenously? What are its chief adverse effects? Why do you think that esophageal toxicity not on this list?

14. Why is salmon calcitonin the preferred agent to human calcitonin? How does the drug work? What is it used for? Is the preferred route of administration oral dosing? Why or why not? What are the common adverse effects of calcitonin?

15. Raloxifene is important in osteoporosis. Why? How does it work? In breast and uterus, how does raloxifene work? What about in the bone? Is it an agonist or an antagonist of estrogen receptors? Is it well absorbed after oral administration? What is its bioavailability? Why the big difference in absorption vs. bioavailabilty? What is the predominant Phase II conjugate of raloxifene? What is its elimination half-life? What are some precautions and adverse effects associated with this drug?

16. What are the clinical uses of calcitriol? What are some of its proposed mechanisms of action in the relief of osteoporosis? Is calcitriol absorbed well via oral administration? Compare and contrast the physiological actions of PTH and calcitriol.

17. What is teriparatide? What are its FDA-labeled indications? What is one of the rare but serious adverse effects associated with this drug? Will it be administered orally? Why or why not?

HRT and menopause

1. What is menopause? What are the symptoms associated with menopause that have found to be alleviated by estrogen?


2. Aside from increased chance of postmenopausal bleeding, what other adverse effects can occur in patients taking estrogen replacement therapy? How can adverse effects like nausea and breast tenderness be managed? Does E+P HRT increase the risk of certain adverse effects? What are those adverse effects? Do these adverse effects occur in all women taking estrogen? Is the endometrium particularly sensitive to unopposed estrogen toxicity? What happens to the risk of endometrial cancer in patients taking estrogen and progesterone combination therapy?