Reproduction Pharmacology

Front 1

Describe the normal physiology of BPH

Back 1

1. Testosterone, made by the Leydig cells of the testes, crosses the prostatic cell membrane to enter the cytoplasm.
2. In the cytoplasm, 5-alpha reductase converts testosterone into dihydrotestosterone (DHT).
3. DHT enters the cell nucleus where it stimulates cellular function,
glandular proliferation, and prostatic hypertrophy
4. DHT is the physiologically active androgen in the prostate.

Front 2

Name commonly prescribed 5-alpha reductase inhibitors

(name 2)

Back 2

1. Finasteride (Proscar)
2. Dutasteride (Avodart)

Front 3

5-alpha reductase inhibitors

(Use, MOA, AEs)

Back 3

1. BPH, prostate size decrease by 25% (TAKES 6 MONTHS THOUGH)
2. Blocks T --> DHT locally (in prostate)
3. Decrease of PSA by 50%, be aware of this. (low chances of decreased libido, ED, etc...)

Front 4

Describe the normal physiology of alpha-1 inhibitors in regard to BPH

Back 4

1. Alpha-1 and alpha-2 adrenergic receptors are found throughout the human body and when stimulated cause smooth muscle contraction.
2. Smooth muscle cells in prostatic stroma and capsule have generous supply of alpha-1 receptors.
3. Stimulation of these receptors causes smooth muscle contraction with resultant increased resistance to urine flow.
4. Alpha-1 receptors also found in blood vessels, CNS, other sites.
5. Subtypes of alpha-1 receptors include: A, B, C.
It is the alpha-1A receptor that predominates in the prostatic smooth muscle cells.

Front 5

Name commonly prescribed alpha-1 antagonists used in BPH

(2 classes, name 3 in each class)

Back 5

Selective
1. Tamsulosin (Flomax)
2. Alfuzosin
3. Silodosin

Non-Selective
1. Prazosin
2. Tetrazosin
3. Doxazosin

Front 6

Alpha-1 antagonists

(Use, MOA, AEs)

Back 6

1. BPH, HTN
2. Causes relaxation of prostatic sm muscle, decreases resistance to flow, alleviates sx (affects systemic vessels with nonselectives to treat HTN)
3. ORTHOSTATIC HYPOTENSION (less with selectives), ED, Retrograde ejaculation

Front 7

Describe the normal physiology in the development of prostate cancer

Back 7

1. Hypothalamus produces gonadotropin releasing hormone (GnRH).
2. GnRH stimulates anterior pituitary to release follicle stimulating hormone (FSH) and leutinizing hormone (LH).
3. LH stimulates Leydig cells of testes to secrete testosterone (T).
4. T has many end organ targets, one of which is the prostate gland.
5. Testes responsible for 95% of T production. Adrenal glands produce remaining 5%. These adrenal androgens are not under GnRH control.
6. Prostate cancer is T dependent

Front 8

GnRH agonists

(common Rx - 3)

Back 8

1. Leuprolide
2. Goserelin
3. Triptorelin

Front 9

GnRH agonists

(Use, MOA, AEs)

Back 9

1. Prostate cancer
2. GnRH analogue initially stimulates anterior pituitary to secrete LH and FSH, T levels initially rise (flare), but then receptors down regulate at the level of the hypothalamus and LH and FSH eventually drop to castrate levels. Adrenals make some T though
3. Flares (use with flutamide), hot flashes, loss of libido, ED, osteopososis, weight gain

Front 10

Name the GnRH agonist that is implantable.

Back 10

1. Viadur (a form of Leuprolide)

Front 11

Antiandrogens

(common Rx - 3)

Back 11

1. Flutamide
2. Ficalutamide
3. Nilandron

Front 12

Describe the normal physiology of the antiandrogens in castration therapy.

Back 12

1. Andrenal steroidogenesis produces a small amount of androgen, contributing 5% of total androgen production. These adrenal androgens can be a significant source of continued androgen stimulation of prostate cancer cells despite androgen ablation with GnRH agonists, or, surgical castration. The use of antiandrogens is generally to block the action of these adrenal androgens within prostate cells and promote a state of “total androgen blockade.”
2. It is useful to note that antiandrogens, used alone, block receptors at many sites including the pituitary and perhaps hypothalamic levels. Feedback inhibition is thus lost and is sensed as a deficiency of testosterone by these centers. LH levels can thus rise, resulting in increased T levels. Therefore, antiandrogen monotherapy has not proven reliable in inducing castrate levels of testosterone.

Front 13

Antiandrogens

(Use, MOA, AEs)

Back 13

1. Used with GnRH agonists in prostate cancer to prolong survival and symptom free interval
2. HEPATOTOXICITY, gynecomastia, visual disturbances. They block androgen receptors at many sites (including pituitary and hthal)
3. Not indicated for monotherapy (will rise LH --> T),

Front 14

What drugs could you use to treat N/V in pregnancy?

Back 14

1. Doxylamine (antihistamine)
2. Phenothiazine (DA receptor agonist)
3. Ondansetron (5-HT3 antagonist)

Front 15

What drugs could you use to treat heartburn in pregnancy?

Back 15

1. Antacids (MgOH, AlOH, CaCO3) - CaCO3 has short t1/2, used commonly b/c pregnant women need Ca anayway

Front 16

What drugs could you use to treat constipation in pregnancy?

Back 16

1. Fluids and exercise
2. Bulk forming agents (Rx of choice)
3. Lactulose and MgSO4
**avoid mineral oil (vit K absorption) and castor oil (causes uterine contractions)

Front 17

What drugs could you use to treat coagulation disorders in pregnancy?

Back 17

*** no warfarin, cat X***
1. LMWH (Rx of choice - doesn't cross placenta) **dose adjustments must be made (factor Xa assay due to changes in drug metabolism in diff trimesters)**

Front 18

What class of drugs are provven efficacious to prevent preterm birth?

What is the best outcome with use of these agents?

Back 18

1. Tocolytics (Ritodrine, terbutaline, MgSO4)
2. delay for 48 hrs to make time to give corticosteroids for lung development

Front 19

Ritodrine, Terbutaline

(Use, MOA, AEs)

Back 19

1. Tocolysis
2. Relax uterus
3. HTN, high HR, palpitations, hyperglycemia

Front 20

Magnesium Sulfate

(Use, MOA, AE, Tox)

Back 20

1. Tocolysis
2. Antagonizes Ca to prevent actin/myosin interaction suppressing contractions
3. Flushing, burning at site, nasal congestion, N/V, SOB, Pulmonary edema
4. Flushing, sweating, hypotension, DEPRESSED REFLEXES, circulatory collapse
**also given to prevent seizures in pre-eclamptic women likely to progress to eclampsia**

Front 21

Uses in Labor...

Nifedipine

(MOA, AEs)

Back 21

1. CCB
2. Flushing, headaches, decreased BP

Front 22

Use in pregnancy...

Indomethacin

(MOA, AEs, Fetal AEs)

Back 22

1. Unknown in labor
2. GI upset, hypotension, masks fever
3. OLIGOHYDRAMNIOS, premature closure of PDA, hyperbilirubinemia, low urinary output, decreased GFR

Front 23

Use in pregnancy...

Betamethasone, dexamethasone

(Use, AE)

Back 23

1. Hastens fetal lung maturation, decreases incidence of NRDS
2. Temporary hyperglycemia

Front 24

What drug is used to facilitate lactation in pregnant women?

Back 24

1. Metachlopramide

Front 25

Metachlopramide

(Use, MOA, AEs)

Back 25

1. Facilitate lactation in pregnant women
2. DA receptor antagonist action stimulates prolactin release
3. Sedation, EPS - TARDIVE DYSKINESIA

**DA is an NT and a hormone... it acts to decrease prolactin. If you block those DA receptors you block the inhibition of prolactin and stimulate lactation. Metachlopramide antagonizes D2 receptors and induces lactation***

Front 26

Methylsergide

(Class, Use, AEs)

Back 26

1. Ergot alkaloids
2. Lactation inhibition (not to be used in BREAST FEEDING! Enters breast milk). Also used to prevent post-partum hemorrhage.
3. Edema, CNS effects, vasoconstriction, paresthesias

Front 27

What drugs would you prescribe to induce labor?

(2 common Rx)

Back 27

1. Prostaglandins (Dinoprostone, Misoprostol)
2. Oxytocin

Front 28

Oxytocin

(Use, AEs, Special considerations)

Back 28

1. Induces labor
2. Uterine rupture, uteroplacental hypoperfusion, fetal distress from hypoxia, Mom - Fluid retention
3. MUST MONITOR MOM/FETAL HR AND BP

Front 29

What drugs require the mother to "pump and dump" because they appear in high concentrations in the breast milk and may affect the child?

Back 29

1. Sulfonamides

Front 30

Define a "pregnancy category X" drug:

Back 30

1. Definite fetal risk based upon animal or human studies or human experience, the risk clearly outweighs the benefits or there is no indication for the use in a pregnant woman (isotrentinoin, OCP, warfarin)

Front 31

Define a "pregnancy category D" drug:

Back 31

1. There is positive evidence of fetal risk but there may be a situation where benefits might outweigh the risk (Doxycycline, lithium, valproic acid)

Front 32

In general, define "pregnancy categories A, B, and C:

Back 32

1. A - its OK
2. B and C are very nebulous, we just don't know...

Front 33

Folic Acid in Pregnancy

(how much needs to be supplimented, decrease in folate by what % in pregnancy, should be started when, what drugs increase folate metabolism)

Back 33

1. at least 600 ug/day
2. 25% decrease
3. Before CONCEPTION
4. !Trimethoprim, carbamazepine, phenytoin, phenobarbital, primidone, valproic acid

Front 34

Iron In pregnancy

(how much elemental Fe do they need, AEs, special consideration)

Back 34

1. 27 mg elemental Fe
2. constipation heart burn, stomach upset, Overdose (chelate with deferoxamine)
3. need acid environment to absorb, take with OJ

Front 35

Calcium in Pregnancy

(how much is needed, how much do most prenatal vitamins give)

Back 35

1. 1200 mg/day
2. 200-300 mg

Front 36

This drug prevents activation of testosterone to a more active form and interferes with masculinization of the fetus and is very lipophilic:

Back 36

1. Finasteride/dudasteride

Front 37

This drug crosses the placenta, is category X, and is used as an anticoagulant:

Back 37

1. Warfarin

Front 38

What type of drug is the number 1 cause of nongenetic mental retardation:

Back 38

1. Iodides (all drugs that lower thyroid levels)

Front 39

These drugs can cause masculinization of the female fetus

Back 39

1. Androgens (hormones)

Front 40

This drug is an antiepileptic and is associated with cleft lip/palate:

Back 40

1. Topiramate

Front 41

This class of drugs may cause pulmonary HTN after babies are born and they do through w/draw syndrome:

Back 41

1. SSRI, Paroxitene is category D

Front 42

These 2 drug classes cause renal agenesis and oligohydramnios:

Back 42

1. ACEs/ARBS

Front 43

Nonoxynol-9

(Class, MOA, Efficacy, Risks/Benefits)

Back 43

1. Spermicide
2. Kills sperm on contact
3. Failure rate ~20-25%
4. Benefits: no increased risk of teratogenicity, lower HPV rates // Risk: do not protect vs STDs, irritation to vaginal mucosa may actually increase viral infection rates

Front 44

Cervical Mucus Method

(Basics, Method Failure Rate, D/C Rate)

Back 44

1. Abstain during menses and every other day until mucus change (no coitus from mucus change until four days after return to normal)
2. 3%
3. 73%

Front 45

Failure Rates:

Male Condoms
Female Condoms
Diaphragm
Vaginal Sponge

Back 45

1. 2-20%
2. 21-26%
3. 16-18%
4. 15-20%

Front 46

Yuzpe Method (emergency contraception)

(Components, MOA, Efficacy, AEs)

Back 46

1. 0.05mg Ethinyl Estradiol, 0.5mg Norgestrel (Estrogen + Progesterone)
2. MANY (prevent ovulation, alter sperm transport/tubal motility, loss of sperm and pre-embryo viability, asynchrony of endometrium, alter uterine pH)
3. 75% effectiveness
4. N/V most common, irregular bleeding, mastalgia

Front 47

Plan B


(Components, MOA, Efficacy, AEs)

Back 47

1. Levonorgestrel 0.75 (Progesterone)
2. Alters tubal transport of ova and/or sperm, preventing ovulation or fertilization; alters endometrium preventing implantation
3. 75% effective
4. Less frequent/severe than Yuzpe Method, menstrual irregularities
**OTC for >/= 17yo