PDA

View Full Version : [Nephrology] Describe age-related changes that might affect drug pharmacokinetics



TomHsiung
Mon 9th September '13, 4:56pm
Absorption

Most drugs are absorbed via passive diffusion, ad age-related physiologic changes appear to have little influence on drug bioavailablility. But drugs require active transport for absorption, so their bioavailability may be reduced.

First-pass effect on hepatic and/or gut wall metabolism has decreased with age, therefore the bioavailability of drugs that have first-pass effect increase and higher plasma concentrations will be resulted in.Distribution

The distribution of medications depends on factors such as blood flow, plasma protein binding, and body composition, each of which may be altered with age. Generally, the volume of distribution of water-soluble drugs is decreased, whereas lipophilic drugs exhibit an increased volume of distribution.

Also the elderly may also exhibit differences in the distribution of drugs to their sites of action.Metabolism

The most remarkable characteristic of hepatic function in older adults is the increase in interindividual variability compared with other age groups, a feature that may obscure true age-related changes.

Phase I metabolism declines due to reduced hepatic volume rather than reduced hepatic enzymatic activity. Phase II metabolism of medications appears to be relatively unaffected by advancing age.

Hepatic enzyme induction or inhibition dose not appear to be affected by the aging process.

Age-related decreases in hepatic blood flow can decrease significantly the metabolism of drugs with high hepatic extraction ratios.Elimination

Renal excretion is the primary route of elimination for many drugs. Generally, the renal elimination declines with advancing age because of reduced renal function.

TomHsiung
Fri 13th September '13, 12:40pm
Altered Pharmacodynamics

There is some evidence of altered drug response or "sensitivity" in older adults. Four possible mechanisms have been suggested

1.Changes in receptor numbers;

2.Changes in receptor affinity;

3.postreceptor alterations;

4.Age-related impairment of homeostatic mechanisms.