Drugs During Pregnancy (Linger) Flashcards
what are a couple drugs used in C-sections
(i) Thiopental (barbiturate) is very lipophilic and crosses the placenta almost immediately, causing sedation or apnea in the newborn
(ii) Succinylcholine and tubocurarine (neuromuscular blocking drugs) are highly charged, cross the placenta slowly, and achieve minimal concentrations in the fetus
what if a mother is pregnant and needs anticoagulation drugs…. what should be used and what should be avoided?
for pregnant women who need anticoagulation agents, heparin may be given safely (high molecular weight and polar, thus does not cross the placenta) while warfarin is teratogenic, crosses the placenta, and should be avoided during all stages of pregnancy
what types of drugs cross the placenta more readily
lipophilic drugs
low molecular weights
non-polar
unbound proteins (compared to drugs with high protein binding)
viral protease inhibitors and pregnancy
these are P-glycoprotein substrates and achieve low fetal concentrations , which may increase the risk of HIV infection transfer from mother to fetus
how does the fetus metabolize compounds in terms of speed of metabolism compared to children or adults
(f) Of note, the fetus metabolizes compounds at a slower rate than children or adults due to a lack of enzyme expression, a reduced activity of metabolic enzymes, or reduced availability of essential endogenous cofactors due to the stage of gestational development
Zidovudine
shown to decrease HIV transmission from the mother to the fetus by roughly 60%
female fetus exposure to DES causes increased risk for what?
(2) An increased risk for adenocarcinoma of the vagina (with onset after puberty)
what are the teratogenic mechanisms of drugs
(a) Drugs may have a direct effect on maternal tissues with indirect effects on fetal tissues
(b) Drugs may interfere with the passage of oxygen or nutrients through the placenta, affecting the most rapidly metabolizing tissues of the fetus
(c) Drugs may have direct actions on the processes of differentiation in developing tissues
(d) Deficiency of critical substances may play a role in the development of fetal abnormalities (e.g., folic acid deficiency)
(e) Cumulative effects on multiple organs may result from continued exposure to a teratogen
a teratogen has what 3 characteristics
(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
what 5 drug classes are used in the treatment of hyperemesis gravidum
Pyridoxine (vitamin B6)
Antihistamines (H1 antagonists)
- doxylamine
- diphenhydramine
- dimenhydrinate
- meclizine
Dopamine Antagonists
- promethazine
- prochlorperazine
- droperidol
Serotonin Antagonists
-ondansetron
Glucocorticoids
MOA of pyridoxine
(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
MOA of antihistamines
H1 antagonists
anticholinergic activity thought to help with nausea and vomiting
(3) Doxylamine most commonly used in combination with pyroxidine
dopamine antagonists MOA
(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
Serotonin Antagonists MOA
(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
above what level of BP should you treat
above 150/100 consistently
what agents can be used for treatment of preeclampsia
Labetalol
Hydralazine
Nifedipine and Nicardipine
labetalol MOA
(a) MOA: acts as an antagonist of alpha-, beta1-, and beta2-adrenergic receptors
(b) Used to treat moderate to severe hypertension
hydralazine MOA
(a) MOA: dilates arterioles but not veins
nifedipine and nicardipine MOA
(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
used to treat HTN, angina, arrhythmias
if the pt has HTN prior to pregnancy, what medications should be stopped during pregnancy
ACE inhibitors
ARB’s
direct renin inhibitors
Methyldopa MOA
(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
used in pt’s who had pre-existing HTN and now are pregnant
toxicities of thiazide diuretics (which are used in pt’s who are pregnant with pre-existing HTN)
(2) Toxicities include hypokalemic metabolic alkalosis, impaired carbohydrate tolerance (manifests as hyperglycemia), hyperlipidemia, and hyponatremia among others
how do you manage gestational diabetes mellitus
Exercise
-increases tissue sensitivity to insulin
Insulin
- lispro and aspart (fast)
- improve postprandial excursions compared to human regular insulin and are associated with lower risk of delayed postprandial hypoglycemia
what is the leading cause of infant mortality in the US
preterm birth
what are tocolytics
drugs utilized to suppress preterm labor and include beta-adrenergic receptor agonists, magnesium sulfate, calcium channel blockers, and cyclooxygenase (COX) inhibitors
MOA of b-adrenergic receptor agonists
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
What are the adverse effects of Beta agonists in pregnancy
tachycardia, low blood pressure, bronchial relaxation
v) Cardiovascular fetal adverse effects are analogous to the maternal effects
what is the proposed action of magnesium sulfate in pregnancy
(1) Magnesium competes with calcium at the level of plasma membrane voltage-gated calcium channels
(2) Magnesium hyperpolarizes the plasma membrane and inhibits myosin light-chain kinase activity by competing with intracellular calcium at this site
(3) Interference with the activity of myosin light-chain kinase reduces myometrial contractility
what re the adverse maternal and fetal effects of using mag sulfate
few!! - diaphoresis, flushing
iv) Maternal therapy causes a slight decrease in baseline fetal heart rate and fetal heart rate variability, which are not clinically significant
what are the contraindications for using mag sulfate
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)
what is the concern in using Calcium Channel blockers for inhibition of preterm labor
ii) The primary fetal concern is the potential for reducing uterine and umbilical blood flow
most commonly used COX inhibitor used for inhibiting preterm labor
indomethacin
COX inhibitor MOA in inhibiting preterm labor?
ii) Inhibition of COX reduces the formation of prostaglandins and reduces uterine contractions (prostaglandins augment uterine contraction)
primary fetal concerns in using COX inhibitors for inhibition of preterm labor
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)
what two therapies are used for the induction of labor?
Oxytocin
Intravaginal prostaglandins E2 or E1 (e.g. misoprostol)
MOA of oxytocin
ii) MOA: stimulates uterine muscle contraction after activating oxytocin receptors (G-protein coupled receptors linked to Gq, phosphoinositide-calcium second-messenger system)
stimulates the release of prostaglandins and leukotrienes that augment uterine contraction
causes contraction of myoepithelial cells surrounding mammary alveoli which leads to milk ejection
what are the indications for oxytocin
-induction of labor at term
control of post-partum bleeding
adjunctive therapy in management of abortion
what are the most popular systemic agents used in management of pain during labor and delivery
opioids
- morphine
- fentanyl
- meperidine
or mixed opioid agonists-antagonists
- nalbuphine
- butorphanol
what are the effects of opioids on the mother and fetus
ii) Opioids exert their effects in the maternal brain, although a portion of the dose also crosses the placenta and affects the fetus, which decreases fetal heart rate variability and results in respiratory depression in the neonate
what are the most commonly used non-opioid agents used in controlling pain during labor and delivery
promethazine (phenothiazine)
hydroxyzine (antihistamine)
used in conjunction with opioids to potentiate analgesia and decrease side effects such as nausea and vomiting
nueraxial analgesics
which agents are used?
ii) Provide unparalleled pain relief for labor and delivery
iii) Local anesthetics (bupivacaine, ropivacaine), with or without opiates, are typically used in spinal and epidural techniques
Class A
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.
Class B
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).
Class C
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.
Class D
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).
Class X
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.
look at the table regarding drugs which effects on the fetus
do it
first trimester defects of fetus with warfarin use
Hypoplastic nasal bridge, chondrodysplasia
second tri defects of fetus with warfarin use
CNS malformation
third tri defects of fetus with warfarin use
Risk of bleeding (discontinue use 1 month before delivery)
