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pharmacokinetics in the elderly

Pharmacology: - increased 1/2life of lipid-soluble drugs - increased peak concentration of hydrophilic drugs - increased time for drug clearance - increased sensitivity to: - benzodiazepines - anticoagulants - thrombolytics - narcotics - calcium channel blockers - diminished sensitivity to: - beta-adrenergic receptor agonists - beta-adrenergic receptor antagonists - factors that alter drug levels in the elderly: a) absorption 1] decreased gastric acidity ? 2] decreased gastric emptying 3] decreased absorptive surface 4] decreased GI blood flow 5] increased intestinal transit time 6] decreased GI active transport 7] decreased liver blood flow 8] decreased liver size 9] generally considered NOT greatly affected by age b) distribution 1] decreased cardiac output 2] decreased total body water 3] decreased lean body mass 4] increased body fat 5] decreased total body size 6] decreased serum albumin a] greater free drug for a given serum drug level b] potential complications with: phenytoin, benzodiazepines, warfarin, etc. 7] increased alpha-1 acid glycoprotein (orosomucoid) a] major serum protein binding basic drugs b] diminished free drug for a given serum drug level c] reduced effectiveness of: quinidine, lidocaine, tricyclic antidepressants c) metabolism 1] decreased hepatic blood flow (10-15% by age 80) 2] decreased liver mass & volume (20-50% by age 80) 3] decreased enzyme activity ? 4] poor nutritional status 5] concurrent drug use (interactions) d) renal excretions 1] decreased filtration rate 2] decreased tubular secretion 3] decreased tubular reabsorption 4] renal disease

General

pharmacokinetics

References

  1. Ambrose P. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  2. Ambrose P. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 25-28, 2002
  3. Taffet GE, Physiology of Aging, In: Geriatric Medicine: An Evidence-Based Approach, 4th ed, Cassel CK et al (eds), Springer-Verlag, New York, 2003