Changes in metabolism with age

The liver is one of the major routes of drug elimination. There are several changes that can occur with advanced age that may affect drug metabolism:

(1) Liver mass decreases

(2) Hepatic blood flow decreases

         (Both liver mass and blood flow
decrease about 40%)

(3) Decreased first pass metabolism

(4) Phase I metabolic reactions decline.
(a) Hydroxylation (phenytoin)
(b) Dealkylation (benzodiazepines)
(c) Sulfide oxidation (chlorpromazine)
(d) Hydrolysis (aspirin)
(e) Nitro reduction (chloramphenicol)

These changes influence the pharmacokinetics of numerous agents used by the elderly. Drugs with a high intrinsic clearance (eg propranolol) have hepatic blood flow as a rate-limiting step. Such drugs would have an increased bioavailability when both hepatic blood flow and extraction are diminished. Therefore, drugs with a high bioavailability such as antiarrhythmics should be administered at the lowest recommended doses and monitored carefully.

Other factors such as polypharmacy, alcohol use, smoking etc may influence metabolism more significantly than age alone.

[Agents known to have decreased hepatic clearance in the elderly]: acetaminophen, antiarrhymics, anticonvulsants, antidepressants, antipsychotics, benzodiazepines, indomethacin, theophylline, warfarin, some beta blockers.



Geriatric issues

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Changes in metabolism with age