Dosing in Special Populations
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Direct answer
Drug dosing must be individualised at the extremes of age and in organ failure. Neonates have immature hepatic glucuronidation and low glomerular filtration — chloramphenicol's grey baby syndrome and sulphonamide-induced kernicterus are the classic consequences — while children metabolise many drugs faster per kilogram and need weight-based dosing. In the elderly, reduced renal function, altered body composition and increased receptor sensitivity demand the start-low-go-slow approach, with creatinine clearance estimated by the Cockcroft-Gault equation because serum creatinine alone misleads in sarcopenic patients. Renal impairment extends intervals or reduces doses of renally cleared drugs, hepatic impairment demands caution with high-extraction drugs, and therapeutic drug monitoring guides narrow-index agents.
What you must remember
- Neonatal pharmacokinetics: immature glucuronidation caused the grey baby syndrome with chloramphenicol; reduced albumin and displaced bilirubin explain sulphonamide kernicterus; low glomerular filtration at birth necessitates extended dosing intervals for aminoglycosides.
- Paediatric dosing: mg per kg calculations dominate; young children often clear drugs faster than adults per kilogram (higher mg per kg doses), and G6PD deficiency and growth considerations shape drug choice.
- Geriatric prescribing: reduced renal clearance and increased sensitivity to benzodiazepines, opioids, anticoagulants and anticholinergics; anticholinergic burden and orthostatic hypotension drive falls; deprescribing reviews and criteria such as the Beers list flag hazardous drugs.
- Renal dosing rule: loading doses usually stay unchanged, maintenance doses are reduced or intervals extended for renally eliminated drugs — metformin (avoid eGFR below 30), DOACs, aminoglycosides, vancomycin, digoxin, gabapentin and morphine (active metabolites accumulate).
- Hepatic dosing: high first-pass extraction drugs (propranolol, morphine, lignocaine) reach several-fold higher levels in cirrhosis; lorazepam and oxazepam, cleared by glucuronidation, are preferred; Child-Pugh class informs anticancer decisions.
- Cockcroft-Gault creatinine clearance: estimated from age, weight and serum creatinine — muscle mass loss in the elderly produces deceptively normal creatinine despite poor clearance.
- Therapeutic drug monitoring drugs: digoxin, phenytoin, lithium, aminoglycosides, vancomycin, theophylline, methotrexate, ciclosporin and tacrolimus — narrow therapeutic index plus serious toxicity, with levels guiding dose.
Common confusion
Serum creatinine is persistently mistaken for renal function: a "normal" creatinine of 1.0 in a frail 80-kilogram 85-year-old may reflect a creatinine clearance near 40 mL per minute, needing dose reduction. The second confusion is loading versus maintenance dosing — unreduced maintenance causes accumulation toxicity in organ impairment.
Exam-focused takeaway
Stems include the neonate with grey collapses on chloramphenicol (glucuronidation deficiency), the elderly patient on diazepam falling at night (start-low-go-slow and benzodiazepine caution), the metformin patient with eGFR 25 (stop), the cirrhotic needing sedation (lorazepam), and the list of TDM drugs. Calculations may ask which Cockcroft-Gault inputs matter or which drugs need interval extension in renal failure. Anchoring one signature example per population answers nearly every question.
Frequently asked questions
Why did chloramphenicol cause grey baby syndrome?
Neonates lack mature hepatic glucuronidation, so unconjugated chloramphenicol accumulates, producing grey cyanosis, circulatory collapse and death.
How does ageing change drug handling?
Reduced renal clearance, altered body composition and heightened target-organ sensitivity mean lower starting doses, longer intervals and regular deprescribing review.
Which drugs need dose reduction in renal impairment?
Renally cleared agents — aminoglycosides, vancomycin, digoxin, DOACs, metformin, gabapentin and morphine (via accumulated metabolites) — reduced or interval-extended.
Why estimate creatinine clearance rather than trust serum creatinine?
In sarcopenic elderly patients serum creatinine stays deceptively low despite poor filtration; Cockcroft-Gault combines age, weight and creatinine to reveal true clearance.
Which drugs are monitored by therapeutic drug monitoring?
Digoxin, phenytoin, lithium, aminoglycosides, vancomycin, theophylline, methotrexate and the calcineurin inhibitors, all with narrow therapeutic indices.