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Changes in metabolism with age
  

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
-References-


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Feely J, Coakley D.  Altered pharmacodynamics in the elderly.  Clin Geriatric Med. 1990; 6:269-283.

Greenblatt DJ, Sellers EM, Koch-Weser J. Importance of protein binding for the interpretation of serum or plama drug concentrations. J Clin Pharmacol. 1982;22:259-263.

Hammarlund ER, Ostrom JR, Kethley AJ. The effects of drug counseling and other educational strategies on drug utilization in the elderly. Med Care. 1985;23:165-170.

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Levy RA.  Therapeutic inequivalence of pharmaceutical alternates.  Amer Pharm.  1985; April: 28-39.

MacLennan WJ, Martin P, Mason BJ. Protein intake and serum albumin levels in the elderly. Gerontology. 1977;23:360-367.

Schmucker DL. Aging and drug disposition: An update. Pharmacol Rev. 1985;37:133-148.

Thoreson J. Drug Metabolism and Drug/Drug Interactions from a Geriatrics Perspective. Clin Ger. 1997; 5: 57-74.

Tregaskis BF, Stevenson IH.  Pharmacokinetics in old age.  Br Med Bulletin. 1990; 46: 9-21.

Wilcox SM, Himmelstein, Inappropriate drug prescribing for the community-dwelling elderly. JAMA. 1994; 272:292-296  

 

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