Teratogenicity Flashcards
How do most drugs cross the placenta?
passive diffusion
What are the characteristics of medications more likely to cross the placenta?
- MW <500 Da
- highly lipid soluble
- unionized
- free drug (low protein binding)
During what weeks is the baby most vulnerable to medications?
weeks 3-8; during organogenesis medications can cause major damage to the developing organs
At what week are most of the major organ systems already developed?
week 16
Which medications are known to impair folate absorption/ increase folate degradation?
- anticonvulsants
- Primidone
- Cyclosporine
What medications interfere with Vit B12?
- cholestyramine
- metformin
What anticonvulsants are associated with the risk of folate deficiency?
- valproate
- phenytoin
- phenobarbital
- carbamazepine
- lamotrigine
- topiramate
Which anticonvulsant is associated with a lower risk of birth defects?
Levetiracetam KEPPRA
What is recommended if a patient cannot D/C a medication associated with decreased folate?
folic acid supplementation (2.5-5 mg/day)
What is folate antagonism/deficiency associated with?
- neural tube defects
- cleft pallet
- limb defects
- developmental delays
What medications are associated with neural crest cell disruption?
- Bosentan (TRACLEER)
- Isotretinoin (CLARAVIS/ACCUTANE)
- Ketoconazole (systemic)
What medications can disrupt sex hormones needed for fetal growth?
- drugs used in fertility treatment
- oral contraceptives
- 5-alpha reductase inhibitors (finasteride)
What precautions should be taken with Finasteride (PROCAR) due to it being a pregnancy category X?
- pregnant females or females trying to conceive should not handle crushed or broken tablets (inhale/absorb)
What medications cause teratogenicity due to oxidative stress?
- class III antiarrhythmic drugs
- Phenytoin
- Terbutaline
- Tetracycline
- Thalidomide
- Valproic acid
What medications cause vascular disruption?
- anti-HTN meds (esp. ACE/ARBs)
- aspirin
- ephedrine
- NSAIDs
When should Aspirin be avoided in pregnancy?
- not recommended at any dose/ trimester for pain/ headache
- regular dose aspirin not recommended in 3rd trimester (FDA category D)
When should ACE/ ARBs be avoided in pregnancy?
2nd and 3rd trimester (FDA category D)
Why might low-dose aspirin be used during pregnancy?
treatment for preeclampsia \; D/C just before delivery to decrease risk of bleed for mother/child
Why should aspirin be avoided in late stages of pregnancy?
- premature closure of ductus arteriosus
- hyperoxygenated blood –> potential for pulmonary HTN and right-sided HF
When should NSAIDs be avoided in pregnancy?
- not recommended in 3rd trimester (cat D)
- cat C in 1st and 2nd
- Tylenol linked to autism?
Why should Statin be D/C as soon as pregnancy is suspected/ wanted?
CI in pregnancy (cat X)
Which SSRI has the highest risk of birth defects?
Paroxetine (cat D)
What are the risks of taking an SSRI during the first trimester of pregnancy?
- cardiac defects
- preterm birth
What are s/s of SSRI withdrawal after birth?
- tremors
- jitteriness
- irritability/agitation
- increased muscle tone
- feeding problems
- colic (cries for a long time)
What SSRIs have the highest incidence of withdrawal in newborns?
- Paroxetine
- Fluoxetine
What is a recommendation to decrease risk of withdrawal symptoms?
taper and D/C SSRI about 2 weeks prior to birth
What antipsychotic had the lowest risk of congenital malformation?
Quetiapine
What are SEs associated with chronic exposure to other antipsychotics during pregnancy?
- abnormal movements
- abnormally increased/decreased muscle tone
- motor restlessness
- hyperreflexia
- agitation
- tremor
- tachycardia
- crying
Which antipsychotics are more likely to cause neonatal toxicity and withdrawal?
first generation and risperidone
What pregnancy cat is warfarin?
When is baby at highest risk?
- cat X
- weeks 6-12
What anticoagulant is first line in pregnant patients?
LMWH does not cross placenta/ cause fetal anticoagulation
What are benefits to the removal of FDA pregnancy categories?
- provides integrated risk summary
- includes men and fertility
What should the pharmacist consult along with using clinical judgment to determine teratogenicity?
package insert
What is the limit for caffeine in pregnancy?
<200-300 mg/day
What are appropriate smoking cessation agents in pregnancy?
- NRT
- bupropion
What opioid cessation treatments are preferred in pregnancy?
- methadone
- buprenorphine
What are s/s of opioid withdrawal in newborns?
- high pitched cry
- sleep/wake disturbances
- alteration in tone/ movement
- feeding difficulties
- GI disturbances
- failure to thrive
What are treatment options for opioid withdrawal in newborns?
- morphine
- methadone
How does THC effect pregnancy and lactation?
- transferred into placenta/ breast milk
- plasma exposure ~10% of maternal THC
What are the complications of cocaine use during pregnancy?
- preterm birth
- low birth weight
- small for gestational age
- miscarriage
- decreased head circumference
What complications are associated with Amphetamine use during pregnancy?
maternal and neonatal morbidity and mortality
