Geriatric Quick Consult Medications to Avoid in the Elderly Do #6
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| Though it is more difficult to measure than the decline in renal function, oxidative metabolism of drugs through the P-450 enzyme system in the liver may be significantly diminished in older patients.
CYP3A, the largest component of the P-450 enzyme family, is responsible for metabolizing 60% of all prescribed medications. For example, diazepam (Valium®), and its active metabolite desmethyldiazepam, may profoundly affect older patients for as long as 72 hours. A normal serum creatinine can result when both creatinine formation and elimination are reduced. Several algorithms have been proposed to estimate creatinine clearance. This oxidative metabolism problem is more pronounced in heart failure, which reduces liver blood flow and produces hepatocyte ischemia by passive congestion, and in liver disease, which can be occult. |
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| All older patients, particularly those with congestive heart failure, should be presumed to have impaired hepatic oxidative metabolism.
You should reduce the dose of drugs that are cleared by this mechanism. Glucuronidation is the other main hepatic drug clearance mechanism, and it is usually not affected by age. Usually, you do not need to adjust the dosage of drugs cleared by glucuronidation in older patients. Also, note that many drugs interact with liver metabolic pathways. For example, some anticonvulsants induce (increase) the activity of oxidative enzyme pathways, and therefore reduce the effects of other drugs that are cleared by these pathways. Routinely consult a pharmacist about older patients with complicated regimens involving multiple drugs. |
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