Pharmacokinetic and Pharmacodynamic Changes With Aging

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

CHANGESEFFECTEFFECT ON DRUG USE
AbsorptionDecreased gastric emptying
Decreased gastric acid secretion
Decreased splanchnic blood flow
Decreased absorptive capacity of the small intestine
Decreased drug absorptionAltered oral medication absorption
DistributionDecreased total body water
Decreased lean muscle mass
Increased body fat
Increased for lipophilic drugs
Decreased for hydrophilic drugs
Lipophilic:
Delayed onset of action
Prolonged half life
Hydrophilic:
Increased plasma levels
Higher frequency of ASEs
Protein bindingDecreased liver mass
Decreased protein synthesis
Decreased albumin levelsIncreased free drug availability
Increased drug-drug interaction
Metabolism/bioavailabilityDecreased liver mass
Decreased liver blood flow
Decreased CYTP450 and hepatic enzyme function
Decreased first pass metabolismIncreased bioavailability of drugs with extensive first pass metabolism
Decreased bioavailability of prodrugs requiring activation by liver
Increased toxicity risk
EliminationLiver:
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
PharmacodynamicDecreased receptor density
Increased receptor affinity
Altered sensitivity to CNS/PNS drugsIncreased 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; , volume of distribution.

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