ESTROGENS SERMs PROGESTINS and ANDROGENS

REVIEW QUESTIONS: ESTROGENS SERMs PROGESTINS ANDROGENS

REQUIRED READING:
Katzung’s Basic and Clinical Pharmacology
13th edition
Chapter 40

Infertility- know the mechanism of action, route of administration, most common adverse effects, any rare but serious adverse effects, efficacy rates (in other words, are these drugs effective?), incidence of multiple gestation, risks to the developing baby (if any), risk of ovarian hyperstimulation syndrome, etc… pertaining to clomiphene, metformin and bromocriptine.


Hormonal Contraception (the answers are in your lecture notes, lecture slides, the narrations of slides not presented in class-- see DropBox-- or in the book chapter).

1. What happens to the release of LH and FSH by the pituitary when plasma levels of both estrogen and progesterone are high?

2. What two types of agents do combination oral contraceptives (OCs) contain? For most OCs, what is the standard dosing regimen? Of 28 tablets, how many are “active” and how many are “inert?” What happens during the seven days of “inert” tablets? Is the choice of combo OC universal? Or is it patient-specific? How should the doses be decided?

3. What are the proposed mechanisms of action for the combination oral contraceptives? How about for the progestin-only OCs? What types of products are available? What is emergency contraception? What types of emergency contraceptive products are available? What is extended regimen contraception?

4. Comment on some of the interesting adverse effects relating to transdermal administration or administration via vaginal ring (see narrated slides for best information).

5. Compared to estradiol, what are the chief pharmacokinetic parameters (half-life, bioavailability, protein binding) for ethinyl estradiol? How is the compound eliminated from the body?

6. What is the major metabolite of the synthetic progestins? Is that metabolite active or inactive? How are progestins eliminated from the body? Compared to progesterone, what are the chief pharmacokinetic parameters (half-life, bioavailability, protein binding) for norethindrone?

7. With respect to the combination OCs, does either drug alter the pharmacokinetics of the other?

8. What is the difference between monophasic, biphasic, and triphasic OCs? Why are withdrawal- bleeding periods, on average, shorter for products such as loestrin 24 Fe than with other combo OCs?

9. Long-duration contraception with progesterone-only agents can be achieved using parenteral routes of administration such as implantable or intramuscular preps. Which progestin is available as a subcutaneous implant? As an i.m. injection? Why are progestin-only contraceptive tablets a possible option for nursing mothers? Are menstrual irregularities commonly observed in women taking progesterone-only OCs? Do women on oral progestin-only tablets need to take them every day? Or do they take 21 active pills and 7 inactive pills each month?

10. Estrogens and clotting factors. Estrogens increase the synthesis by the liver of of clotting factors VII, VIII, IX and X and decrease the synthesis of antithrombin III. Why is that not good? (SEE slides) What are the pharmacological effects of the combination oral contraceptives on: the ovaries, the skin (chloasma, what is that?) and the cardiovascular system?

11. In which patients are the oral contraceptives contraindicated. Why? What are some of the common and rare but serious adverse effects associated with the OCs?

12. What possible drug-drug interactions can be predicted in patients taking oral contraceptives and certain antibiotics? In patients taking oral contraceptives and inducers of CYP450s (eg. Rifampin, griseofulvin)? How about gabapentin and OCs?

13. What is so unique about drospirenone? Does is have antiandrogenic activity? Does it have antimineralocorticoid activity? Should women with renal failure take an oral contraceptive that contains drospirenone?

14. You will need to look this up (beyond the slides)... is there a relationship between the use of depot leuprolide and depot medroxyprogesterone with regard to adverse effects on bone mineral density?

15. See slides on Androgens (not narrated, sorry).. List the pharmacological effects associated with testosterone replacement therapy in men.

16. What is gynecomastia and how is it related to testosterone replacement therapy?

17. Describe the androgen receptor in detail.

18. List the name and routes of administration for the most common androgens used in testosterone replacement therapy.