9.3 Pregnancy, Pediatrics, Geriatrics & Organ Impairment

Pregnancy

The old FDA letter categories (A, B, C, D, X) have been replaced by a narrative labelling system (the Pregnancy and Lactation Labeling Rule), so modern practice weighs the risk–benefit balance for each drug rather than memorising letters. General principles: use the fewest drugs at the lowest effective dose, avoid non-essential medicines in the first trimester (organogenesis), and never withhold clearly necessary treatment. Folic acid 400 micrograms daily is recommended pre-conception and through the first trimester; 5 mg daily is used in higher-risk women (previous neural tube defect, diabetes, or antiepileptic drugs such as valproate or carbamazepine).

Drugs to Avoid in Pregnancy

Common Pregnancy Problems

• Analgesia: paracetamol is first-line at the lowest effective dose. Avoid NSAIDs, especially in the third trimester (premature closure of the ductus arteriosus, oligohydramnios).
• Nausea and vomiting: start with dietary measures; first-line drug therapy is pyridoxine (vitamin B6) with or without doxylamine. Ondansetron is generally reserved for refractory cases because of a possible small increase in oral clefts with first-trimester use and QT-prolongation cautions.
• Urinary tract infection: all bacteriuria in pregnancy is treated. Avoid trimethoprim in the first trimester (folate antagonism — neural tube defect risk) and avoid nitrofurantoin at term (risk of neonatal haemolytic anaemia). Typical culture-guided choices include amoxicillin-clavulanate or a cephalosporin such as cefalexin.

Breastfeeding

Drug transfer into milk is greatest for drugs that are small (low molecular weight), lipophilic, minimally protein-bound, and weakly basic. As a rule of thumb, a relative infant dose below 10% of the maternal weight-adjusted dose is considered compatible with breastfeeding. Practical advice: choose the shortest-acting agent, dose just after a feed or before the infant's longest sleep, and check a specialist resource (e.g. LactMed) rather than guessing. Codeine is avoided because ultra-rapid CYP2D6 metabolisers convert it to morphine at dangerous rates.

Pediatrics

Children are dosed by weight (mg/kg), with the total capped at the adult dose; body surface area is reserved for specialist uses such as oncology. Use oral syringes for liquids to ensure accurate measurement, and match the formulation to the age band (suspensions and dispersible tablets for young children). Physiology matters too: neonates have immature hepatic enzymes and renal function, so drug clearance is reduced and dosing intervals are extended, while young children often clear drugs faster per kilogram than adults. Always double-check the arithmetic on a paediatric dose — a tenfold error from a misplaced decimal is a recognised cause of serious harm.

Absolute or near-absolute paediatric avoidances:

• Aspirin — avoid in children and adolescents under 16 with viral illness because of Reye's syndrome (acute encephalopathy with liver failure).
• Codeine — contraindicated under 12 years and avoided in 12–18-year-olds with respiratory conditions; ultra-rapid CYP2D6 metabolisers risk morphine toxicity.
• Tetracyclines — avoid under 8 years (tooth discoloration, enamel hypoplasia).
• Chloramphenicol — avoid in neonates: immature glucuronidation causes accumulation and grey baby syndrome (circulatory collapse, cyanosis).
• Fluoroquinolones — generally avoided in children because of cartilage concerns, with defined specialist exceptions.

Geriatrics

Polypharmacy (commonly defined as five or more medicines) drives adverse events, interactions and prescribing cascades, where a side effect is misread as a new disease and treated with another drug. Screening tools frequently examined are the Beers criteria (American Geriatrics Society list of potentially inappropriate medicines in older adults) and STOPP/START — STOPP flags potentially inappropriate prescriptions, START flags omitted but indicated therapies. Watch the anticholinergic burden (cognitive impairment, constipation, urinary retention, blurred vision, falls) from drugs such as oxybutynin, tricyclics and first-generation antihistamines. Falls risk is raised by benzodiazepines, Z-drugs (zolpidem, zopiclone), antipsychotics and aggressive antihypertensives — "start low, go slow."

A key exam point: older adults have reduced muscle mass, so serum creatinine can look normal while renal function is significantly reduced. Always estimate creatinine clearance (Cockcroft-Gault) before dosing renally cleared, narrow-index drugs such as digoxin.

Hepatic and Renal Impairment Dosing Principles

There is no simple creatinine-clearance equivalent for the liver. Severity is graded clinically with the Child-Pugh score — bilirubin, albumin, INR, ascites and encephalopathy — classed A (mild), B (moderate) and C (severe). Principles: avoid hepatotoxic drugs, reduce doses of hepatically cleared agents (especially high-extraction drugs), and be cautious with sedatives and opioids, which can precipitate encephalopathy.

For renal impairment, remember the loading vs maintenance distinction:

• Loading dose depends on the volume of distribution (loading dose = Vd × target concentration ÷ bioavailability), which is usually unchanged in renal impairment — so the loading dose is generally given in full.
• Maintenance dose depends on clearance — it must be reduced, either by lowering each dose (small therapeutic window drugs) or extending the interval (concentration-dependent drugs such as aminoglycosides, hence extended-interval gentamicin).