15 - A. Changes in the elderly

A. Changes in the elderly

© SPMM Course 3. Variables affecting pharmacokinetics: A. Changes in the elderly Domains Change Effect Body composition An increase in total body fat. A decrease in total muscle mass (lean body mass). A decrease in total body water. A larger volume of distribution and longer half-life of lipophilic chemicals because of their increased sequestration in fat. e.g. benzodiazepines excretion slower in the elderly Plasma protein Decrease in plasma protein binding capacity in elderly individuals

Nearly 15-25% - due to higher proteinuria and to some extent due to lesser plasma protein synthesis by the liver. Albumin decreased; protein affinity decreased; acid glycoprotein increased. Higher free drug plasma concentration – increased metabolism and clearance of the free drug. More frequent protein binding interactions. Phenytoin is affected Liver Hepatic metabolism not altered much. Decreased hepatic blood flow occurs. Liver withstands aging to considerable extent unless associated physical frailty present. No changes noted up to age 60 - 80. After 80, CYP system declines. Phase 2 (conjugation) metabolism is not affected (Hence lorazepam better than diazepam for elderly). Decreased hepatic first pass effect. Higher oral bioavailability of certain agents. Kidney Decreases in renal blood flow have been approximated at 10% per decade beginning after the fourth decade - leads to reduced creatinine clearance and GFR. More frequent toxicity of renally eliminated agents (e.g. lithium). GI tract Absorption is not greatly affected. GI blood flow is diminished. Gastric pH is increased as acidity drops.

Slower but nearly equal absorption of oral administered drugs. Decreased gastric first pass metabolism noted. A reduction in the gastric wall content of dopa decarboxylase Leads to a 3-fold increase in the concentration of levodopa in the elderly. Brain receptors Decreased number of brain acetylcholine postsynaptic receptors; choline acetyltransferase is diminished, level of brain acetylcholinesterase also decreased during aging. Some of these counterbalance each other. On the whole anticholinergic side effects more pronounced leading to increased frequency of delirium on polypharmacy. Kidney mass has been reported to be substantially reduced in old age, by approximately 20 to 25% between the age of 30 and 80 years. Renal blood flow reduces with age even in those with normal health. Renal blood flow decreases by about 10% per decade after the age of 20. By age 80, RBF