CNM Varney's Pharmacology Review Flashcards
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.
isotretinoin
Accutane
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 …in 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
