✓ 29- Drugs During Pregnancy, Labor and Lactation Flashcards
What drugs are capable of crossing the placental barrier?
Drugs that are:
- Low M.W [< 500 Da]
- Non-polar
- Non-protein binding
What effect does heparin administration have on the growing fetus?
No effect as it doesn’t cross the placental barrier
What effect does insulin administration have on the growing fetus?
No effect as it doesn’t cross the placental barrier
T/F: concentrations of drugs is much lower in fetal circulation as compared to maternal.
False, majority of drugs reach concentration in the fetus like those in maternal blood
T/F: Paracetamol is contraindicated throughout the pregnancy and is not used in pregnancy under any circumstances.
False, it’s a category B drug that can be used for fever to prevent any harm it may cause the fetus
What drugs is used for gestational DM?
Insulin
Are drugs a common cause of fetal congenital abnormalities?
No, only causes 2-3% of cases
How can drugs affect the growing fetus?
- Directly interacts with fetal tissue
- Contracting uterine muscle
- Reduced fetal BF ( placental ischemia)
How can drugs reduce fetal blood glow?
→ Placental vasoconstriction→ Lowers Systemic BP in mother → decreasing fetal BF [indirectly]
What is the “ All or None” period?
1st week of fertilization/pre-implantation period
What is the “teratogenesis” period?
Organogenesis period [2-8 week]
What is the “Organ Dysfunction” period?
Fetal development period [3-9 months]
What drugs may effect the fetus during the pre-implantation period?
- Alchohol
- Methotrexate
What drugs may effect the fetus during the organogenesis period?
- Thalidomide
- Warfarin
- Valproate
- Vitamin A derivatives
What structural deformity is caused by Valproate?
- Tall forehead
- Cleft lip
What structural deformity is caused by Thalidomide?
- Amelia
- Phocomelia
What structural deformity is caused by Warfarin?
- Nasal hypoplasia
What structural deformity is caused by Vitamin A derivates?
- Skeletal deformities
What drugs may effect the fetus during the fetal development period?
- Antithyroid drugs
- ACEI
- Aminoglycosides
- Tetracyclines
What structural deformity is caused by Antithyroid drugs?
Neonatal hypothyroidism [Goiter]
What structural deformity is caused by ACEI?
Fetal renal failure
What structural deformity is caused by Aminoglycosides?
Kidney damage and hearing problem
What structural deformity is caused by tetracycline
Bone and teeth formation
What drugs given around labor effects the fetus?
- Aspirin
- NSAIDs
- Opiates
- Sulfonamides
- Benzodiazepines
What effects are seen when Sulfonamides is administered around labor?
- Neonatal Jaundice
- Hemolytic anemia
What effects are seen when large doses of Aspirin and NSAIDs are administered around labor?
- Delayed labor
- Bleeding
- Premature closure of Ductus Arteriosus
What effects are seen when Opiates and Benzodiazepines are administered around labor?
- Respiratory depression
- Feeding difficulties
- Hypotension
Define Category A drugs
- Remote possibility of fetal harm
- Studies show no fetal risk during pregnancy
List examples of Category A drugs
- Vitamin B6
- Thyroid Hormone
Define Category B drugs
No studies on human, but animal studies show no risk
List examples of Category B drugs
- Paracetamol
- Penicillins
Define Category C drugs
No studies in humans, and animal studies show some risks. But drugs benefits outweigh potential risk
List some examples of Category C drugs
- Quinolone antibiotics [Ciprofloxacin]
- Corticosteroids
- Fluconazole
Define Category D drugs
Evidence of human fetal risks, so it shouldn’t be used during pregnancy except if needed for serious disease and no effective alternative
List some examples of Category D drugs
- Phenytoin
- Valproic acid
- Tetracycline
- Aminoglycosides
Define Category X drugs
Studies or experience show fetal abnormalities in both humans and animals, and risks clearly exceed benefits
List some examples of Category X drugs
- Thalidomide
- Warfarin
- Retinoids
Who cannot use Category X drugs?
Pregnant women or those trying to get pregnant
How does pregnancy affect drug absorption?
Reduced gastric acid secretion and intestinal motility due to increased female hormones
Frequent vomiting in early pregnancy
What is the fetal development period?
From 3rd-9th months, at this point drugs modify the function of fetal organs, not their gross appearance
What is the organogenesis period?
A period of teratogenesis, where drugs cause structural deformities. This is from Week 2-8
What is the pre-implantation period?
Fetus may recover or die from the effects of the drug. This period is up until a week of fertilization
How does pregnancy affect drug’s volume of distribution?
- Increase of intravascular and extravascular water content → increased VD for hypophilic drugs
- Increase in fat deposition and body weight → increase of VD for fat soluble drugs
- But there’s a decreased serum albumin
How does pregnancy affect the metabolism of metoprolol?
CYP2D6 is induced during pregnancy → increased metabolism → decreased efficacy
How does pregnancy affect the metabolism of imipramine?
Estrogen decreases oxidation → increases efficacy
How does pregnancy affect the renal clearance of drugs?
Increases clearances due to increased maternal CO [30%], RBF, and GFR
How does pregnancy affect the clearance of penicillins?
Penicillins, such as amoxicillin, are cleared through renal elimination, and it’s clearance is increased during pregnancy
How does pregnancy affect the hepatic metabolism of drugs?
Hepatic clearance increases due to induction of hepatic enzymes and increased hepatic blood flow
How does pregnancy affect the bile dependent elimination of drugs?
Elevated estrogen causes cholestasis, reducing thus route of elimination and increased efficacy of drugs eliminated through this route
What drugs are used in higher doses in the second and third trimesters and why?
Phenytoin and Valproic acid, as their clearance is increased during pregnancy
What drugs should be avoided in breast feeding?
- Benzodiazepines
- Narcotic analgesics
- Anti thyroid drugs
- Sulfonylureas
- Anti cancer drugs [methotrexate]
What drugs suppress lactation?
- Thiazide diuretics
- Estrogen [in high doses]
What drugs are safe in breast feeding mothers?
- Penicillins, cephalosporins
- Theophylline, salbutamol
- Anticonvulsants
- Antihypertensives (beta blockers, methyldopa)
- Warfarin, heparin
- Tricyclic antidepressants
Describe whic drugs achieve higher concentrations in milk?
Unionized, highly lipid soluble, and with low protein binding
How would drugs pass to the baby during breast feeding?
Most drugs are secreted into milk through passive diffusion and reach to suckling babies
What are the guidelines to minimize drug effects during breastfeeding?
- If possible avoid drugs
- Use the safest effective medicine
- Decrease babies’ exposure via:
- Using the lowest possible dose
- Taking medications immediately after breast feeding
- Alternating breast feeding with bottle feeding
