Drugs in Pregnancy Flashcards
How does creatinine clearance change in pregnancy?
Increases
Kidney function is better
How does protein binding change during pregnancy?
Most proteins increase Albumin decreases Alpha-fetoprotein increases T4, TSH stay the same Anemia can occur as red blood cell mass increases
How does gastric emptying change during pregnancy?
Decreases
Which side effects of pregnancy are treated by medications during pregnancy?
Nausea, pre-eclampsia and constipation
How does plasma volume change during pregnancy?
Increases by 50%
How does absorption from the skin change during pregnancy?
Increased due to increased vascularity of the skin from estrogen
How does cardiac output change in pregnancy?
Increases
How does peripheral resistance change in pregnancy?
Decreases
How does diastolic blood pressure change in pregnancy?
Decreases
How does peripheral resistance change during pregnancy?
Increase
How does colloid osmotic pressure change during pregnancy?
Decreases until 30-34 weeks and then rises after
How does carbohydrate metabolism change during pregnancy?
Fasting hypoglycemia, postprandial hyperglycemia, hyperinsulinemia, hypercortisolemia
How does blood gas change in pregnancy?
Increased pH, decreased pCO2
What are the major functions of the placenta?
Transfer nutrients and oxygen from mother to fetus
Assist in removal of waste products from fetus to mother
Synthesis of hormones, peptides and steroids
Provides a link between the circulation of 2 individuals
Barrier to protect the fetus from drugs/toxins in the maternal blood
How are drugs transferred across the placenta?
Passive diffusion, active transport and metabolism
What happens once drug gets into the fetal circulation?
It gets metabolized by the liver (metabolites into kidney or gut) and excreted by kidney. Fetal urine in the amniotic fluid may be swallowed again by the fetus
Depends on how well the systems are developed.
How are fetal pharmacokinetics different?
Maternal side blood flow increases to flow through placenta
Liver enzymes are different from mother’s
The kidney is immature so filtration is reduced but increases with gestational age
What are adverse drug reactions that are seen in pregnancy?
Teratogenesis, osteoporosis, uterine stimulation (premature), uterine suppression (overdue), drug dependent infant, breathing difficulties in the neonate and impaired intellectual or social development
What are some manifestations of fetal alcohol syndrome?
Wide set eyes, small, flat bridge of nose
Intellectual slowing
How do you prove a drug is a teratogen?
Must cause a specific set of malformations
Act only between 4-7 weeks of gestation
Incidence should increase with increasing dose and duration of exposure
No proof for teratogenicity does not mean it is safe in pregnancy
Why is it hard to prove if a drug is teratogenic?
Low incidence of congenital anomalies
Animal tests may not be applicable
Exposure often needs to be prolonged
Controlled experiments can’t be done in humans
Neurodevelopmental and behavioural issues are often hard to identify and/or link
What are Shepard’s Principles of Teratology?
The agent must be present during critical periods of development
Acts directly on embryo
Experimental models on corroborating the findings
What do fetal effects from drugs depend on?
Time (when in pregnancy)
Dose (high dose can be lethal or cause abortions and low dose may have no effects)
What happens if teratogenic drugs are taken in the embryonic period (3-8 weeks or first trimester)?
Gross malformations
What happens when drugs are taken in the fetal period (9-40 weeks)?
Function problems (learning deficits and/or behavioural abnormalities) rather than cross anatomy
What drugs have known or suspected teratogenic effects?
Thalidomide, Isotretinoin, Acitretin, Coumarins, Misoprostol, Methotrexate, Diazepam, Tetracyclines, Lithium, Streptomycin, Valproate, Phenytoin, Fluoroquinolones, Sulfamethoxazole-Trimethoprim, Chloramphenicol, ACE inhibitors, NSAIDS, live virus vaccines
What was diethylstilbesterol (DES) used for?
To prevent miscarriages in high risk pregnancies.
What were the fetal effects of DES use in pregnancy?
Vaginal cancer in female offspring (ages 16-20) and vaginal anomalies
Abnormal genitalia and sperm defects in males
What was thalidomide used for?
Anti-emetic, sleeping pill
What were the fetal effects of thalidomide use in pregnancy?
Phocomelia (malformation of limbs), congenital heart defects, eye defects, urogenital defects, GI defects, hearing loss
From single treatment in first trimester
What can use of SSRI’s in pregnancy cause?
4x higher chance of baby being born with a congenital heart defect Excess cardiac malformations Studies contradictory (not well established)
What is a general product monograph for drugs with unknown pregnancy safety?
Safe use in pregnancy has not been established. Therefore, it should not be administered to women of childbearing age unless, in the opinion of the treating physician, the expected benefits to the patient markedly outweigh the possible hazards to the child or fetus
What is done about depression in pregnancy?
Can cause Neonatal Discontinuation Syndrome (jittery in first days of life, difficulty latching)
Women commonly discontinue therapy, but those who are treated have very low doses
What is the risk to women exposed to non-teratogenic drugs?
Women assign a 25% teratogenic risk
Use evidence-based counselling
What should we be worried about radiation in pregnancy?
Diagnostic radiation does not pose too much a risk
Lumbar spine radiograph, 3 hour plane ride is worse than all
