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Flashcards in CNM Varney's Pharmacology Review Deck (90):

in pregnancy, decreased gastric emptying is probably associated with

increased levels of progesterone


decreased gastric emptying results in drugs remaining in the stomach for approximately ? as long as in non-pregnant women

twice as long


decreased gastric motility may affect drug absorption how?

possibly increase in absorption of drugs in the small intestine and may increase absorption of hydrophilic drugs that tend to cross the GI epithelia slowly


pH of stomach does what in pregnancy?

increased pH = more alkaline
So...drugs that are weak bases have increased absorption because less of the drug is ionized and more of the agent passively diffuses out of the stomach.
Weak ACIDS = more drug ionized in the stomach and less is passively diffused
However, therapeutic windows of most agents is wide enough that modifications in drug dosing are not needed


respiratory changes in pregnancy =?

changes esp in aslveolar ventilation lead to increased particle uptake and diffusion of aerosols and bronchodilators. Less drug may be needed to obtain same therapeutic effect found in a nonpregnant woman


During pregnancy, increased cardiac output does what to skin perfusion?

Significantly increases skin perfusion.
Thus, enhanced absorption of most transdermal and subcutaneous drugs, especially water-soluble ones


Why do drugs that are highly bound to protein have a change in effect near the end of pregnancy?

Because intravascular volume expansion results in a lower serum albumin [ ]. More free drug is available at lower plasma [ ] since less albumin binding of drug exists.
Drugs that are generally highly bound to albumin, such as SSRIs or antiepileptic drugs, tend to demonstrate an INCREASED effect.


most transplacental movement of drugs from mother to fetus occurs by...

simple diffusion


in general, increased drug distribution in preg is assoc with

the 50% incr in blood volume


estrogen and progesterone have been found to inhibit some enzyme activity in the liver, resulting in...

increased drug accumulation or decreased elimination of agents like caffeine


placenta can/cannot accomplish metabolism of drugs

It CAN. the placenta has Cyp450 pathways. It has been found that the placenta contains approx half the amount of liver enzyes as the aternal liver, though the effect of these enzymes remains poorly understood


drug clearance in the urinary system

protein-bound drugs not easily absorbed, while lipophilic drugs usually reabsorbed


glomerular filtration rate increases by 50% during pregnancy, allowing

water soluble drugs to be cleared more rapidly


creatinine clearance in pregnancy

tends to mimic glomerular filtration rate and reaches a maximum at 34 weeks. Thus, renally excreted drugs like beta-lactam penicillins and aminoglycosides like gentamicin are cleared more rapidly during pregnancy


Therapeutic effects to monitor in pregnancy

aminoglycosides like gentamicin or other agents such as ampicillin or cefazolin, since serum [ ] appear to be decreased in pregnancy


Monitor in pregnancy - may have to change doses

theophylline for asthmatic bc its serum [ ] rise in pregnancy


period of organogenesis

3-8 wks postfertilization, or 5-10 gestational weeks


Category A

controlled studies in women fail to demonstrate a risk to the fetus in the 1st trimester (and no evidence of risk in later trimesters); the possibility of fetal harm appears remote


Category B

Either animal reproduction studies have not demonstrated a fetal risk but there are o 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 1st trimester (and no evidence of risk in later trimesters)


Category C

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


Category D

There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (eg,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)


Category 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.





phenobarbital and cocaine have been associated with what affect on fetus?

decreased intelligence, though not necessarily mental retardation


All or none effect

in women who are exposed to agents prior to tissue differentiation (usually <20 days postfertilization or up to approximately 4-5 gestational weeks) the teratogenic agents tend to result in either a SAB or no effect at all


ACE inhibitors linked to infants

low birth weight


NSAID teratogenic effects

theorized premature closure of the ductus arteriosus; necrotizing enterocolitis;
also assoc with postterm pregnancy


tetracycline teratogenic effect

abnormalities of teeth.
no known effect unless exposure occurs in 2nd or 3rd trimester


valproic acid teratogenic effect

neural tube defects, minor facial defects.
incidence approx 1%. exposure must be in 1st trimester, before closure of neural tube


cephalosporin teratogenic effects

(cefaclor/Ceclor, cefixime/Suprax, ceftriaxone/Rocephine)
Few studies of cephalosporins have been conducted in 1st trimester, but no adverse effects have been reported, and they, like penicillins, belong to the beta-lactam classification of antimicrobial agents.
Since penicillins and erythromycin (e-base, azithromycin, clarithromycin) have been studied extensively and not found to be assoc with teratogenic effects, many scientists advocate using them as first-line therapies whenever possible.


Sulfonamides teratogenic effect

Not teratogenic, but timing must be observed!
Highly protein-bound and can displace bilirubin from binding sites. Most common agents are combination of sulfamethoxazole and trimethoprim (Bactrim, Septra). sinc e the placenta clears bilirubin, admin of sulfas becomes problematic when admin near delivery and the free bilirubin is in the newborn's system where immature liver is unable to compensate.
Sulfonamides should be avoided in 3rd trimester!


Metronidazole teratogenic effect

Flagyl is well-established antiprotozoal agent and is tx of choice for trich/BV. No teratogenic effect has been found with metronidazole, even though its MoA involves bacterial mutation. Category B.
No evidence that should be withheld in first trimester, but sometimes is for fear of it becoming a litogen.


Why was DES used?

to prevent SAB, PTL, and Pre-E. It was found NOT to be efficacious for those indications.
It is capable of transplacental carcinogenesis in humans.


estrogen/progesterone teratogenic effects

No evidence exists linking any hormonal contraceptives to teratogenic effects


Vitamin A supplementation threshold

should not exceed 5,000 IU daily


vitamin B9

folic acid


NSAIDs teratogenic effect

strictly speaking include acetylsalicylic acid or aspirin.
All have been implicated in the disruption of the prostaglandin cascade involved in initiation of labor and are thus linked to post-term pregnancy.
Theoretically may also be linked with premature closure of ductus arteriosus.
Aspirin has been associated with some bleeding issues throughout pregnancy as well as competition with bilirubin for albumin binding sites.
An alternative agent without anti-inflammatory action (acetaminophen) is Category B, and is preferred choice of analgesic for minor pain during pregnancy.


Opiate analgesic teratogenic effect

have not been implicated with teratogenicity. Caution for use in preg is based on fear of addiction, not teratogenicity.


nicotine teratogenic effects

not a known teratogen, but is fetotoxic.
Linked to LBW, reduced uteroplaental blood flow, placental abruption, possibly PTB.
Postnatally, child of smoker more likely than child of nonsmoker to die of SIDS.


Caffeine teratogenic effects

the half-life is tripled in pregnancy.
High levels of caffeine assoc with SAB and sleketal anomalies.
One cup/day failed to demonstrate any association.
Theoretically, decaf has little/no effects on embryo/fetus.


aspartame contraindicated in what condition?



cocaine teratogenic effects

abruptio placentae, PTL, long-term deficits in mental skills


Newborns exposed to phenytoin, carbamazepine, or pheobarbital are at risk of...

coagulation problems secondary to drug-induced vit K deficiency, and need prompt supplemental vitamin K.


if on antiepileptic drugs, how much extra folic acid should a woman take?

4 mg of folic acid preconceptually and in early pregnancy





benzodiazepine teratogenic effect

controversy about whether or not assoc with cleft palate.
When admin late in preg or during labor, significant doses of diazepam may result in neonatal irritability, tremors, hyperreflexia


tricyclic antidepressants (TCAs) and SSRI teratogenic effects

TCAs: amitriptyline/Elavil, imipramine/Tofranil, protriptyline/Vivactil (Category D)
SSRIs: fluoxetine/Prozac, paroxetine/Paxil, sertraline/Zoloft
have NOT been found to be teratogens


MAOIs teratogenic effects

phenelzine/Nardil, tranylcypromide/Parnate, St. John's wort
NOT recommended for use in pregnancy


Mood stabilizer teratogenic effects

lithium/Eskalith/Lithobid/Lithonate appears to be linked with cardiovascular anomalies, including Ebstein's anomaly (malattachment of tricuspid valve leaves). Also assoc with polyhydramnios
usually used to tx bipolar dz
Alternatives in preg include inticonvulsant agents like carbamazepine/Tegretol


untreated hyperthyroidism in preg linked with



tx with radioactive iodine in preg



the drug of choice for hyperthyroidism in pregnancy

propylthioruacil (PTU)
May result in fetal hypothyroidism when drug used in high doses, so monitor closely
Methimiazole/Tapazole has been linked to aplasia cutis in newborn, but this assoc has been called into question.


meds to avoid in woman with chronic hypertension

ACE inhibitors: captopril/Capoten, enalapril/Vasotec
Use in 2nd/3rd trimesters axxoc with LBBW, oligohydramnios, hypoplastic fetal lung development


affects of beta-adrenergic antagonists in preg

atenolol/Tenormin has been assoc with IUGR


Propanolol/Inderal use in preg assoc with

neonatal hypoglycemia, IUGR, fetal and neonatal bradycardia, although unknown whether fetal effects are due to dz process, drug, or interaction bt the two


alpha-adrenergic antatgonists in pregnancy

prazosin/Minipress have not been linked with fetal growth restriction. Commonly used in pregnancy since they effectively can control HTN


calcium channel blockers in pregnancy

has not demonstrated harmful fetal effects


nifedipine/Adalat, Procardia in pregnancy

as tocolytic and agent for tx of pre-E and chronic HTN ....???


nicardipine in pregnancy

more effective and fewer s/e for tx HTN than metoprolol


anticoagulant of choice in pregnancy

heparin, either regular or low molecular weight


Anticoagulants NOT to use in pregnancy

coumarins, including warfarin (Coumarin), wesily crosses placenta. Approx 1/4 embryos are born with fetal warfarin syndrome (nasal hypoplasia, optic atrophy, mental retardation). When fetus exposed, results may include cataracts, microcephaly, microphthalmia, as well as fetal and maternal hemorrhage


tocolytics in pregnancy

use in 2nd and 3rd trimester; avoid classic teratogenic period.
use of magnesium sulfate as tocolytic/tx for pre-E may result in infant who is lethargic and hypotonic at birth


common side effect of beta-adrenergic tocolytics

ex: terbutaline/Brething, ritodrine/Yutopar
None have been identified as teratogenic


hypoglycemic agents in pregnancy

oral hypoglycemics have been implicated with profound neonatal hypoglycemia since placental transfer is relatively easy.
IUFD has also been reported.
In contrast, insulin is a large molecule and has been the drug of choice for mgmt of DM during pregnancy.
Glyburide: has neither beeen found in cord blood nor assoc with neonatal effects.


anticancer drugs in pregnancy

may target rapidly-growing trophblastic and embryonic tissue as well as cancerous cells
Depending on when admin, chemotherapeutic agents can cause SAB or major teratogenic manifestations


for the majority of drugs, how much gets into breastmilk?

less than 1 percent of the maternal plasma level of the drug crosses into the breastmilk


Factors that increase the likelihood of drug transfer into breastmilk

lipid solubility, low molecular weight, long half-life, capacity to remain unbound and nonionized in the maternal plasma


excretion of drugs into breastmilk primarily involves

passive diffusion


drugs may pass by secretory methods through capillary walls into

alveolar cell lining of the milk buds and through both walls to the alveolar cells to penetrate milk


re: drug transfer in first 1-2 weeks postpartum

large gaps exist between alveolar cells, facilitating easy transfer of various agents including immunoglobulins. As mlk production is established and the alveolar cells expand, the intracellular gaps tend to close, making drug transfer more difficult.


Since the majority of milk is produced at the time of feeding and blood flow to the breast is maximized at this time...

women should be educated about time for peak plasma levels of a drug and counseled to avoid breastfeeding during these times.


the majority of drugs have an MPR of 1 or less, indicating...

that the level of drug in breastmilk is the same or less as in maternal plasma.
However, other factors to consider include rate of clearance in neonate, length of half-life


antimicrobials considered compatible for the breastfeeding dyad

Penicillins: ampicillin/Omnipen/amoxicillin/Amoxil
related cephalosporins: cefaclor/Ceclor, cefixime/Suprax, ceftriaxone/Rocephin


anitimicrobials to be avoided in breastfeeding

sulfa drugs (Bactrim, Septa) should be avoided during first month of life because of the issue of competing for albumin-binding sites with bilirubin


Tetracyclines and breastfeeding

tend to bind with breastmilk, causing only a small amount oto be ransferred to the infant. Studies of dosing regimens lasting 10 days or less have failed to demonstrate any adverse neonatal effects. However, long-term use may have bone or dental impact; use antimicrobials instead.


Quinolones and breastfeeding

generally discouraged due to theoretical risk of arthropathies, though AAP states that it is compatible with the lactating mother.
ofloxacine/Folxin, levoofloxacin/Levaquin, ciprofloxacin/Cipro/Baycip/Ciflox/Ciplox


Erythromycin and breastfeeding

one of the agents that is more highly [ ] in breastmilk than in maternal plasma (MPR >1.0)
Most common problem with this macrolide is drug-to-drug interactions with other agents, like some nonsedating antihistamines.


Metronidazole (Flagyl) and breastfeeding

AAP recommends when 2gm dose used, that pump/dump for 24 hours. Use metraGEL for BV during this time.
S/E is reason for advising against bf: neonatal vomiting and potential blood dyscrasias


Aminoglycosides (kanamycin/Kantrex)

compatible with bf


Codeine and meperidine (Demerol) and breastfeeding

appear in low levels in breastmilk and generally do not warrant cessation of either the drug or bf for the couplet


NSAIDs and bf

considered reasonable choices while bf bc negligible amounts have been found in breastmilk.


antihistamines and breastfeeding

should be used with caution or avoided during breastfeeding (regardless if indicated for respiratory or GI reasons) because of concerns regarding anticholinergic side effects and possible diminished milk supply rather than any direct effects on the newborn


heartburn (pyrosis) and breastfeeding

Cimetidine/Tagamet is an antisecretory antihistamine, has antiandrogenic effects and possesses MPR >1, whereas antacids can also be used for heartburn and are compatible with breastfeeding


anticoagulant therapy and breastfeeding

heparin, low molecular weight heparin, and warfarin ARE compatible with bf


hypERthyroidism and bf

propylthiouracil (PRU) is drug of choice
AVOID methimazole/Tapazole


Smoking and bf

bf ameliorates the risk of SIDS as well as decreases the incidence of respiratory infections in children of smoking mothers compared to bottle-fed babies of smoking mothers


Caffeine and bf

caffeine accumulates in infant



metoclopramide/Reglan (dopamine antagonist)
S/E: fatigue, mental exhaustion, extrapyramidal generally used for only a short period


Herbal galactagogues



Radioactive compounds that require temporary cessation of bf

copper 64, gallium 67, indium 111, iodine 123, iodine 125, iodine 131