Overview
This lecture reviews how pharmacokinetics and pharmacodynamics differ in special populations, specifically pediatric, pregnant, and geriatric patients, and the clinical significance of these changes.
Pediatric Patients
- Newborns have neutral gastric pH (6–8) that returns to normal within 1–2 days, affecting drug absorption.
- Gastric emptying is slower in infants, delaying drug onset and peak concentration.
- Higher volume of distribution for hydrophilic drugs means larger doses (e.g., gentamicin) may be necessary.
- Lower plasma protein (albumin) binding leads to higher free drug fractions in infants.
- Bilirubin can displace drugs from albumin, increasing free drug levels in neonates.
- Drug metabolism matures over the first year; phase II pathways (e.g., glucuronidation) may be underdeveloped.
- Renal function (GFR, secretion) is immature; dose adjustment is challenging and may require specialized formulas or urine collection.
Pregnant Patients
- Pregnancy hormones increase plasma volume, cardiac output, and renal blood flow, altering drug distribution and elimination.
- Progesterone slows GI motility, delaying drug absorption and onset.
- Increased total body water dilutes drugs with small volume of distribution.
- Decreased albumin (from plasma dilution) increases free drug, but increased clearance may counteract effects.
- Placenta and fetus serve as separate compartments affecting drug distribution, metabolism, and potential "ion trapping."
- Fetal organogenesis (first 8–9 weeks) is a critical period; most drugs should be avoided to prevent malformations.
- FDA has moved from rigid pregnancy risk categories to nuanced risk/benefit considerations.
- Warfarin, ACE inhibitors, ARBs, and renin inhibitors are contraindicated in pregnancy; low molecular weight heparin preferred for anticoagulation.
Geriatric Patients
- Decreased gastric motility, GI blood flow, and altered pH affect drug absorption.
- Thinner skin alters topical drug absorption.
- Reduced cardiac output and renal blood flow decrease drug clearance.
- Lower protein (albumin) may result in increased free drug and exaggerated effects.
- Higher body fat changes drug distribution, prolonging effects of lipophilic drugs (e.g., benzodiazepines).
- Hepatic metabolism decreases due to lower liver volume and perfusion.
- GFR declines about 1% per year after age 50, increasing risk of toxicity.
- Polypharmacy and comorbidities heighten risk of drug interactions and adverse effects; Beers list outlines high-risk drugs.
Key Terms & Definitions
- Pharmacokinetics (ADME) — Absorption, Distribution, Metabolism, Elimination of drugs.
- Pharmacodynamics — Effects of the drug on the body.
- Volume of Distribution (Vd) — Measure of drug distribution between plasma and tissues.
- Plasma Protein Binding — The degree to which drugs attach to proteins in the blood.
- Glucuronidation — A liver phase II conjugation pathway for drug metabolism.
- Ion Trapping — Accumulation of drugs in a compartment due to pH differences.
- GFR (Glomerular Filtration Rate) — Indicator of renal function.
- Beers List — A list of drugs to avoid or use with caution in the elderly.
Action Items / Next Steps
- Review and understand ADME changes in pediatric, pregnant, and geriatric populations.
- Identify drugs contraindicated in pregnancy and elderly.
- Read assigned textbook chapter on pharmacology in special populations.