What are the pharmacokinetic and pharmacodynamic changes that occur in the elderly patient?
Pharmacokinetic changes are those that affect the absorption, distribution, protein binding, metabolism and bioavailability, and elimination of a drug. Pharmacodynamic changes relate to alterations in drug-receptor interactions.
Pharmacokinetic and Pharmacodynamic Changes With Aging and Their Effects
| CHANGES | EFFECT | EFFECT ON DRUG USE | |
|---|---|---|---|
| Absorption | Decreased gastric emptying Decreased gastric acid secretion Decreased splanchnic blood flow Decreased absorptive capacity of the small intestine | Decreased drug absorption | Altered oral medication absorption |
| Distribution | Decreased total body water Decreased lean muscle mass Increased body fat | Increased V d for lipophilic drugs Decreased V d for hydrophilic drugs | Lipophilic: Delayed onset of action Prolonged half life Hydrophilic: Increased plasma levels Higher frequency of ASEs |
| Protein binding | Decreased liver mass Decreased protein synthesis | Decreased albumin levels | Increased free drug availability Increased drug-drug interaction |
| Metabolism/bioavailability | Decreased liver mass Decreased liver blood flow Decreased CYTP450 and hepatic enzyme function | Decreased first pass metabolism | Increased bioavailability of drugs with extensive first pass metabolism Decreased bioavailability of prodrugs requiring activation by liver Increased toxicity risk |
| Elimination | Liver: Decreased liver blood flow Kidney: Decreased GFR Decreased renal blood flow Decreased size | Liver: Decreased liver clearance Kidney: Decreased renal clearance | Liver: Decreased clearance for drugs with high extraction ratio Kidney: Dose adjustment |
| Pharmacodynamic | Decreased receptor density Increased receptor affinity | Altered sensitivity to CNS/PNS drugs | Increased sensitivity to centrally acting drugs Decreased sensitivity to adrenergic/cholinergic receptor-specific drugs Increased drug-drug and drug-disease interaction |
ASEs , Adverse side effects; CNS , central nervous system; CYTP450 , cytochrome P450; GFR , glomerular filtration rate; PNS , peripheral nervous system; V d , volume of distribution.
