Catch-22

Damned if you do, damned if you don’t

Drugs in pregnancy

Affect both mother & fetus, so drug treatment is all about

balancing risks

Catastrophe Thalidomide causing phocomelia

Physiology of pregnancy Cardiovascular Cardiac output increases by 30-50% from 6 th-30th week,

with increase in HR & stroke volume Blood Total blood volume increases, with plasma volume increasing

more than hematocrit, causing dilutional decrease in hemoglobin

Urinary GFR increases, causing decrease in BUN & creatinine &

increased frequency of urination Renin-angiotensin-aldosterone system activation causes

salt & water retention

continued Respiratory Respiratory rate increases to decrease CO2 & increase O2 GIT GI motility decreases causing dyspepsia & constipation Alkaline phosphatase increases due to release from placenta Endocrine Enlarged pituitary releases more prolactin to ensure lactation Placenta produces

TSH like hormone that increases free T4, CRH increases adrenal hormones promoting edema, HPL & insulinase increase insulin resistance, MSH increases pigmentation- melasma

Periods of fetal development Pre-implantation 1st week Damage causes abortion Organogenesis 2nd-8th week Organs are formed Damage can cause structural malformation Growth or maturation 3rd-9th month Damage may modify function of organs

Placental barrier

Most drugs cross placenta,exception being heparin & insulin

Scientific data

Insufficient, largely due to concern about teratogenecity

Definitely teratogenic drugs Warfarin- 25% Phenytoin- ~6% Carbamazepine- 6% Na valproate- 2% Lithium- 2% Retinoids- high

Fetal ultrasound

At ~10 & ~18 weeks detects most of clinically

significant structural abnormalities

FDA categorization of drugs A- safest, based on human studies B- no risk in animal studies, not enough

human data C- inadequate studies in animals or

humans D- evidence shows harm to fetus, but

benefits may outweigh risks X- risks outweigh benefits, do not use

Safest drugs in pregnancy

Mineral & vitamin supplementsOthers, use if necessary

Important drugs Antibiotics- B- penici l l in, cephalo., metro., NFT, clinda., azithro. C- chloroquine, quinolones, fluconazole, albendazole D- doxycycline, aminoglycosides Cardiovascular- B- LMW heparin C- β-blockers, dihydropyridine CCB, methyldopa,

furosemide, digoxin, heparin D- ACEI, ARB, warfarin, thiazides, diltiazem Other- B- acetaminophen, insulin C- aspirin, clonidine, rofecoxib, glyburide, metformin D- NSAID, diazepam, carbamazepine, valproic acid Vaccines- C- OPV, MMR, BCG, HBV/HAV & rabies vaccine

Smoking in pregnancy Increases risk of- Spontaneous abortion Abruptio placentae, placenta previa, PROM Preterm birth Low birth weight Sudden infant death syndrome Best to quit, may require nicotine

replacement

Alcohol in pregnancy Ethanol freely crosses the placenta Complications are dose related,

worse in first trimester Fetal alcohol syndrome- Growth retardation Facial abnormalities- shortened palpebral fissure,

low-set ears, midfacial hypoplasia, thin upper lip CNS dysfunction- microcephaly, MR, behavioural disturbances Best is no alcohol