Pharmacology of Pregnancy and Breast Feeding

Pharmacology of Pregnancy and Breast Feeding

Pregnancy

·        Risks are often unknown – although usually small

·        Rule of thumb: DON‟T use drugs in pregnancy

·        Most drug induced abnormalities are subtle ® don‟t make link with drug

·        Effects of harmful drugs: 

o   Gametes ® sterility

o   Blastocyst ® death

o  Embryo ® death or major abnormality (heart, limbs, brain, eye form during embryogenesis

o  Fetus ® Functional abnormality

·        Factors affecting dysmorphogenesis:

o  Critical dose

o  Timing of dose during development

o  Fetal susceptibility

o  Fetal environment (eg already at risk due to diabetes, smoking etc) 

o  Placental drug transfer: all drugs get across but in widely varying amounts. Lipid drugs with polar metabolites are bad news (drug crosses in, but metabolites can‟t get out, eg diazepam)

·        Testing safety:

o  Validity of drug models

o  RCTs assess efficacy not safety

o  Can only pick them up with post-market monitoring and careful evaluation in clinical practice

·        Effects of pregnancy on drug handling:

o  30 – 50% delay in gastric emptying

o  Minimal effect on absorption

o  Albumin reduced by 25% by 15 weeks

o  Plasma volume increases by 50%

o  Total body water ­ by 8 litres

o  50% ­ in renal blood flow

·        Fetal renal excretion:

o  Fetal kidney‟s are functionally immature (Ccr = 2 – 4 mls at term – very small)

o  Renal blood flow only 5% of cardiac output (25% in adult)

o  Renal elimination not an important route of drug metabolism (baby swallows it again anyway)

·        Hepatic metabolism:

o  Shunt 30 – 70% of umbilical blood flow (ductus venosus)

o  Oxygenation of the Left lobe (umbilical vein) > than right lobe (portal vein)

o  Slower metabolic rate than adult but extensive CYP450 metabolism

Breast Feeding

·        Transfer affected by:

o  PKa: Base transfers more as pH of milk is lower than blood

o  Lipid solubility

o  Molecular weight (eg high molecular weight heparin doesn‟t cross)

·        Avoid:

o  Excess alcohol

o  Anticoagulants except heparin

o  Anti-thyroid drugs 

o  Antibiotics: chloramphenicol, tetracyclines (affect teeth and growth plates), sulphonamides and quinolones 

o  b-blockers: atenolol, sotalol ® bradycardia.  Other antihypertensives OK

o  Diazepam

o  Lithium

o  Combined OCPs

o  Anti-metabolic agents

o  Ergot derivatives (eg anti-migraine medication)

o  ?Diuretics

o  ?SSRIs

o  Phenytoin

o  NSAIDs – effect breast milk production