Pharm: hormonal contraceptives and androgens Flashcards
1
Q
Combination contraceptives mechanism of action 1
A
- Contain a synthetic estrogen (ethinyl estradiol) and a progestin, can be in form of pill (COC), patch, or vaginal ring
- Synthetic progestins and estrogens are resistant to hepatic metabolism and lead to high plasma concentration for sustained periods of time
- Progestin action is responsible for contraception, estrogen action responsible for stabilizing endometrium and minimizing bleeding
- Progestin actions (alone or in COC): are anovulatory by decreasing GnRH, LH and FSH via negative feedback (prevent follicular maturation and ovulation) and prevent LH surge
2
Q
Combination contraceptives mechanism of action 2
A
- Additional mechanisms: produce thick cervical mucus to reduce sperm penetration, prevent fertilization by altering transport of ovum and sperm in fallopian tube
- Drawbacks to COC: estrogen in COCs can cause N/V, chloasma (skin pigmentation enhancement when exposed to sunlight), increased risk of MI in pts that are >35 and smoking
- Synthetic estrogens accumulate in liver (not rapidly inactivated) and cause hepatic effect: HTN, thromboembolism, gallstone formation
- Low dose estrogen (COC) is not teratogenic (only high doses)
3
Q
Progesterone-only contraceptives 1
A
- POP, DMPA shot, skin implant
- POP not very effective in inhibiting ovulation, but work by additional mechanisms of progesterone (thickened cervical mucus, decreasing fallopian tube transport)
- DMPA inhibits ovulation
- Implants use the same progestin as vaginal ring and patches, a form of progestin that is a prodrug and activated by hepatic metabolism (implant efficacy is comparable to COC)
4
Q
Progesterone-only contraceptives 2
A
- Drawbacks of progestin-only contraceptives: irregular uterine bleeding due to progestin causing thinning and atrophic-like changes in endometrium
- POPs must be taken at same time each day (w/in 3 hrs) or are ineffective
- Indications for progestin-only contraceptives: >35yo smokers, lactating mother (estrogens can block prolactin receptor and reduce milk production)
5
Q
Emergency contraceptives
A
-Progestin pill that delays LH surge and thus delays ovulation
6
Q
Drug interactions w/ COCs
A
- Some drugs such as anti epileptics (phenytoin, barbiturates, carbamazepine), rifampin, and st. john’s wort increase expression of CYP (CYP inducers)
- Since both E and P are metabolized by CYP these drugs can lower the conc of E/P
- This can result in contraceptive failure or BTB
- Adjustment: if pt is on AEDs then use non-hormonal contraceptives
7
Q
Contraindications for COC
A
- CVD, uncontrolled HTN
- Smokers >35 (use progestin-only)
- Breast or endometrial CA CA
- Hepatic disease
- Lactating mother (use progestin-only)
- Undiagnosed genital bleeding
- Thromboembolic disease (obesity will increase risk)
8
Q
Non-contraceptive uses for COC
A
- Decrease ovarian and endometrial CA by 50%
- Reduces acne, hirsutism and allopecia
- Ethinyl estradiol inhibits 5a reductase and thus lowers DHT amount
- On sebaceous glands low DHT leads to decreased sebum and less acne
- On face/chest hair follicles low DHT leads to decreased hair growth
- On scalp hair follicles low DHT leads to increased hair growth
- COCs can be used to Rx dysmenorrhea, endometriosis, and fibrocystic breast disease (progestin is responsible)
9
Q
Clinical uses of androgen replacement therapy 1
A
- Testosterone esters (IM injection): natural T that is inactivated by liver and thus doesn’t accumulate and no hepatic effect
- Used for induction of secondary sex characteristics, somatic development, libido and potency (used to induce puberty in hypogonadism pts)
- Native T (patches/gel): used for maintenance in secondary sex characteristics, libido, potency in primary hypogonadism (klinefelter) and secondary hypogonadism (kallman syndrome) as well as older men
10
Q
Clinical uses of androgen replacement therapy 2
A
- Since exogenous T is not concentrated in testes, and they do decrease FSH/LH levels via negative feed back, there is decreased T production in testes (pts remain infertile and testes are atrophic)
- Other side effects: acne due to increased stimulation of sebaceous gland by DHT, polycythemia (androgens increase erythropoiesis), gynecomastia due to increase in T->E via aromatase (T receptors on breast get saturated, higher amounts of E from aromatase conversion stimulate breast growth: increased E/T ratio)
- Give aromatase inh to prevent gynecomastia
11
Q
Anabolic steroids and Danazol 1
A
- Anabolic steroids (17a alkylated): not used in androgen replacement Rx, used to stimulate appetite and muscle mass in chronically ill (incl AIDS) pts
- Mech is blocking GCC-induced protein catabolism
- Since 17a alkylated androgens are not inactivated quickly in liver they cause hepatic effect: increase protein synthesis, increase LDL, cholestatic jaundice, increase risk for liver tumors
- Also render pts infertile due to decreased FSH/LH and thus decreased T production in testes
12
Q
Anabolic steroids and Danazol 2
A
- Beneficial effect of hepatic effect from anabolic steroids: increase synthesis of C1 esterase inhibitor (Rxs hereditary angioneurotic edema)
- Danazol is a 17a alkylated steroid that is weakly androgenic and thus is used in both men and women to Rx hereditary angioneurotic edema
- By inducing synthesis of C1 esterase inhibitor there is proper inhibition of complement cascade
- Can also be used to Rx fibrocystic breast disease
13
Q
Drugs to suppress androgen synthesis and action
A
- Can suppress androgens at various points in the HPG axis
- Can use GnRH/LHRH agonists to cause decreased LH/FSH release (effectively castration)
- Can use 5a reductase inh (finasteride) to prevent conversion of T to DHT
- Can use spironolactone to prevent T and DHT from binding to receptor (not used in men)
14
Q
GnRH agonists
A
- Leuprolide binds to GnRH receptor in pit in a non-pulsatile manner and causes down-regulation of the receptor-> decreased secretion of LH/FSH (pharmacological castration/oophorectomy)
- Used in prostate and breast CAs, endometriosis, and central precocious puberty
- Prostate growth is sensitive to T production, thus lowering T production from testes decreases prostate growth
- Prostate CA can start making its own T synthesis, at which point you must use Abiraterone which inhibits T production in prostate in testis (used in castration-resistant prostate CA)
15
Q
Finasteride
A
- Selectively inhibits 5a reductase type 2 (type 2 in men, type 1 in women)
- Used to Rx BPH in pts w/ large prostates, since BPH is due to DHT production causing proliferation of SmM in prostate
- There is no decrease in libido or impotence, also helps to prevent alopecia (DHT causes loss of head hair) and it reduces chest hair (DHT increases chest/facial hair)
- Finasteride is not used in women (they don’t have type 2 5a reductase)
- Usually used in conjunction w/ a1 adrenergic antagonists
