Pharm during pregnancy

Question 1

which drugs will cross placenta lamost immediately?

Answer 1

lipophilic drugs with low molecular weight (highly ioniezed/polar compounds cross much more slowly, esp. if have high molecular weight)

Question 2

teratogen

Answer 2

(a) The drug results in a characteristic set of malformations, indicating selectivity for certain target organs
(b) The drug exerts its effects at a particular stage of fetal development (see figure below)
(c) The drug shows a dose-dependent incidence

morphologic abnormalities: weeks 3-8

phsiologic defects/minor morphologic abnormalities = weeks 9-term

Question 3

pyridoxine

Answer 3

antiemetic drug

i) Pyridoxine (vitamin B6)
(1) MOA: Precursor to pyridoxal, which functions in the metabolism of proteins, carbohydrates, and fats; pyridoxal also aids in the release of liver and muscle-stored glycogen and in the synthesis of GABA (within the central nervous system) and heme
(2) Also used for treatment and prophylaxis of neurological toxicities associated with isoniazid

Question 4

Doxylamine

Answer 4

antiemetic drug

ii) Antihistamines (H1 antagonists) (doxylamine, diphenhydramine, dimenhydrinate, meclizine)
(1) MOA: antagonists at H1 receptors
(2) Anticholinergic activity thought to help with nausea and vomiting
(3) Doxylamine most commonly used in combination with pyroxidine

Question 5

diphenyhdramine

Answer 5

antiemetic drug`

ii) Antihistamines (H1 antagonists) (doxylamine, diphenhydramine, dimenhydrinate, meclizine)
(1) MOA: antagonists at H1 receptors
(2) Anticholinergic activity thought to help with nausea and vomiting
(3) Doxylamine most commonly used in combination with pyroxidine

Question 6

dimenhydrinate

Answer 6

antiemetic drug

ii) Antihistamines (H1 antagonists) (doxylamine, diphenhydramine, dimenhydrinate, meclizine)
(1) MOA: antagonists at H1 receptors
(2) Anticholinergic activity thought to help with nausea and vomiting
(3) Doxylamine most commonly used in combination with pyroxidine

Question 7

meclizine

Answer 7

antiemetic drug

ii) Antihistamines (H1 antagonists) (doxylamine, diphenhydramine, dimenhydrinate, meclizine)
(1) MOA: antagonists at H1 receptors
(2) Anticholinergic activity thought to help with nausea and vomiting
(3) Doxylamine most commonly used in combination with pyroxidine

Question 8

promethazine

Answer 8

antiemetic drug

iii) Dopamine antagonists (promethazine, prochlorperazine, droperidol)
(1) MOA: antagonists at dopamine receptors
(2) Muscarinic-blocking effect and/or inhibition of dopamine signaling in the chemoreceptor zone may be responsible for antiemetic activity; dopamine receptors in the stomach mediate the inhibition of gastric motility

Question 9

prochlorperazine

Answer 9

antiemetic drug

iii) Dopamine antagonists (promethazine, prochlorperazine, droperidol)
(1) MOA: antagonists at dopamine receptors
(2) Muscarinic-blocking effect and/or inhibition of dopamine signaling in the chemoreceptor zone may be responsible for antiemetic activity; dopamine receptors in the stomach mediate the inhibition of gastric motility

Question 10

droperidol

Answer 10

antiemetic drug

iii) Dopamine antagonists (promethazine, prochlorperazine, droperidol)
(1) MOA: antagonists at dopamine receptors
(2) Muscarinic-blocking effect and/or inhibition of dopamine signaling in the chemoreceptor zone may be responsible for antiemetic activity; dopamine receptors in the stomach mediate the inhibition of gastric motility

Question 11

ondansetron

Answer 11

antiemetic drug

iv) Serotonin antagonists (ondansetron)
(1) MOA: selective 5-HT3-receptor antagonist, which blocks serotonin both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone
(2) Common uses include prevention of nausea and vomiting associated with moderately- to highly-emetogenic cancer chemotherapy; radiotherapy; prevention of postoperative nausea and vomiting

Question 12

when to tx HTN?

Answer 12

above 150/100

Question 13

acute HTN managemetn?

Answer 13

(1) Labetalol
(a) MOA: acts as an antagonist of alpha-, beta1-, and beta2-adrenergic receptors
(b) Used to treat moderate to severe hypertension

(2) Hydralazine
(a) MOA: dilates arterioles but not veins
(b) Used to treat moderate to severe hypertension

(3) Nifedipine and nicardipine
(a) MOA: inhibits cardiac and smooth muscle L-type calcium channels, producing a relaxation of coronary vascular smooth muscle (vasodilation); increases myocardial oxygen delivery in patients with vasospastic angina; reduces peripheral vascular resistance, producing a reduction in arterial blood pressure
(b) Used to treat hypertension, angina, arrhythmias

Question 14

tx of preexisting HTN?

Answer 14

i) ACE inhibitors, angiotensin receptor antagonists and direct renin inhibitors should NOT be administered in pregnancy!!!
ii) Labetalol (see above)

iii) Methyldopa
(1) MOA: reduces blood pressure by stimulating central alpha-adrenergic receptors, which results in a decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature
(2) Reduces peripheral vascular resistance with a variable reduction in heart rate and cardiac output
(3) Most common undesired effect is sedation, especially at the onset of treatment
(4) Widely used in the past but now used primarily to treat moderate to severe hypertension during pregnancy

iv) Nifedipine (see above)

v) Thiazide diuretics
(1) MOA: inhibits the Na+/Cl- cotransporter (NCC), inhibiting NaCl reabsorption from the luminal side of epithelial cells in the distal convoluted tubule
(2) Toxicities include hypokalemic metabolic alkalosis, impaired carbohydrate tolerance (manifests as hyperglycemia), hyperlipidemia, and hyponatremia among others

Question 15

tocolytics

Answer 15

drugs utilized to suppress preterm labor and include beta-adrenergic receptor agonists, magnesium sulfate, calcium channel blockers, and cyclooxygenase (COX) inhibitors

Question 16

Beta-adrenergic receptor agonists

Answer 16

tocolytic

i) MOA: bind to beta¬2-adrenergic receptors and increase intracellular adenylyl cyclase, which increases cAMP and ultimately decreases myometrial contractility
ii) Target cells eventually become desensitized, thereby limiting efficacy (tachyphylaxis)
iii) Ritodrine is the most evaluated beta agonist used in the inhibition of preterm labor, but is currently unavailable in the US
iv) Many adverse maternal effects result from activation of beta1- and beta2-receptors, which results in tachycardia, lower blood pressure, and bronchial relaxation
v) Cardiovascular fetal adverse effects are analogous to the maternal effects

Question 17

Magnesium sulfate

Answer 17

tocolytic

MOA unknown

iii) Few maternal adverse effects (diaphoresis and flushing are the most common; monitor for hypermagnesmia)
iv) Maternal therapy causes a slight decrease in baseline fetal heart rate and fetal heart rate variability, which are not clinically significant
v) Parenteral administration
vi) Contraindicated in pregnant women with myasthenia gravis because it decreases acetylcholine in motor nerve terminals
vii) Use with caution in women with known myocardial compromise or cardiac conduction defects because of its antiinotropic effects (high doses can cause PR and QT elongation and/or heart block) and in women with compromised renal function (magnesium sulfate is eliminated renally)

Question 18

CCBs

Answer 18

tocolytic

i) Use is questionable due to lack of large-scale trials evaluating efficacy of CCBs in comparison to placebo for treating preterm labor (may also be no more effective than beta agonists)
ii) The primary fetal concern is the potential for reducing uterine and umbilical blood flow

Question 19

indomethacin

Answer 19

tocolytic

f) COX inhibitors
i) Indomethacin (nonspecific COX inhibitor) is the most commonly used tocolytic of this class
ii) Inhibition of COX reduces the formation of prostaglandins and reduces uterine contractions (prostaglandins augment uterine contraction)
iii) The primary fetal concerns with the use of indomethacin and other COX inhibitors are constriction of the ductus arteriosus (may lead to pulmonary hypertension) and oligohydramnios (reduction in amniotic fluid volume)

Question 20

oxytocin

Answer 20

induction of labor

i) Endogenous posterior pituitary hormone that is synthesized in neuronal cell bodies in the hypothalamus and transported via axons to the posterior pituitary, where it is stored and released into circulation
ii) MOA: stimulates uterine muscle contraction after activating oxytocin receptors (G-protein coupled receptors linked to Gq, phosphoinositide-calcium second-messenger system)
iii) Stimulates the release of prostaglandins and leukotrienes that augment uterine contraction
iv) Causes contraction of myoepithelial cells surrounding mammary alveoli, which leads to milk ejection
v) Indications include induction of labor at term; control of postpartum bleeding; adjunctive therapy in management of abortion
vi) Toxicity is rare (toxicity that does occur is due either to excessive stimulation of uterine contractions or to inadvertent activation of vasopressin receptors at high concentrations of oxytocin)

Question 21

misopristol

Answer 21

b) Intravaginal prostaglandin E2 or E1 (e.g., misoprostol) can be used to ripen the cervix and induce labor (off-label use)

Question 22

teratogenic risk category A

Answer 22

Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in late trimesters) and the possibility of fetal harm appears remote.

Question 23

teratogenic risk category B

Answer 23

Either animal-reproduction studies have not demonstrated a fetal risk, but there are no controlled studies in pregnant women, or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).

Question 24

teratogenic risk category C

Answer 24

Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Question 25

teratogenic risk category D

Answer 25

There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Question 26

teratogenic risk category X

Answer 26

Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.