Chapter 17 Implications of Drug-Nutrient Interaction and Pharmacology

BOX 17.4 Drugs That Deplete Folic Acid Aspirin

Barbiturates Carbamazepine Celecoxib

Cholestyramine Cimetidine Colestipol

Corticosteroids Famotidine

Hydrochlorothiazide Indomethacin

Methotrexate NSAIDs

Oral contraceptives Phenytoin Primidone Ranitidine Salsalate Triamterene Trimethoprim Valproic acid

in the blood. Low albumin levels, which are common in the older adult, result in clinically significant decreases of drug binding sites. This may increase the free fraction of highly protein-bound drugs. In an indi- vidual with hypoalbuminemia (less than 3g/dL), there exist fewer binding sites for highly protein-bound drugs such as phenytoin (Dilantin) (90% bound) and warfarin (Coumadin) (99% bound). For warfarin, this can induce bleeding, while higher unbound phenytoin levels can cause central nervous system toxicity. Therefore, older adults with hypoalbuminemia require lower doses of a highly protein-bound drug as com- pared to the usual dose for those with normal albumin to decrease the possibility of developing toxic drug levels, especially for medications with a narrow thera- peutic index (warfarin, sulfamide, theophylline, and lithium).

Metabolism

Metabolism is the process by which the drug/nutrient is chemically changed by the action of enzymes in the liver or intestinal tract, with the stomach playing only a minor role. Hepatic function and perfusion tend to be diminished in older adults; however, standard liver function tests do not predict hepatic metabolism. Diminished hepatic oxidative metabolism reduces the clearance of many drugs in the older adult. During the metabolism of orally administered drugs, there are opportunities for drug-nutrient interactions. Reduced hepatic blood flow can increase the half-life of some medications, such as diazepam and phenobarbital. One of the more important enzyme systems responsible for the oxidative metabolism of a very wide range of nutri- ents and drugs is the cytochrome P450 enzyme system. Food, including dietary supplements, may increase or inhibit the activity of this enzyme system. Because of

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the changes, the rates and extent of drug metabolism may be altered. A decrease in the metabolic clearance of drugs such as antipyrine, barbiturates, diazepam, and phenylbutazone is indicative of reduced oxidative drug-metabolizing enzyme activity in older adults. In summary, the process of metabolism is to transform a drug from a lipid-soluble to a more water-soluble com- pound that can be handled more easily by the kidneys and excreted in the urine.

Excretion

Excretion is the process by which the drug/nutrient or its metabolites are removed from the body, primarily by the kidneys. In some instances, drugs and drug metabolites may be eliminated in feces, bile, and other body fluids. Changes in renal function can affect drug clearance. After age 40, the glomerular filtration rate falls approximately 1 mL/min each year. The reduction of renal function and the decrease in nephrons and renal mass underlie the slower rate of drug elimination in older adults. Congestive heart failure, dehydration, hypotension, and diabetes can further reduce renal elimination of drugs. Foods and nutrients may also alter the renal excretion of some drugs and affect blood levels of others. It should be emphasized that the dose of a drug generally assumes normal liver and kidney function. Table 17.1 gives an overview of the four parameters of pharmacokinetics (see page 245); Table 17.2 details drug classes and treatment uses (see pages 246–247).

MODIFICATION OF MEDICATION ACTION

Certain foods or food additives that exhibit effects similar to those of a medication can enhance the effects or toxicity of a medication.

Pressor Amines/Monoamine Oxidase Inhibitors

Amines are nitrogen-containing organic compounds that are naturally present in foods. Some amines are biologically active. Monoamines are called pressor amines or vasoactive amines because of their action of constricting blood vessels. Examples of pressor amines include tyramine, histamine, dopamine, sero- tonin, and norepinephrine. Biologically active amines do not normally pose a health hazard because they are broken down by oxidases. However, certain drugs called oxidase inhibitors inhibit the work of the oxi- dases in the body. Monoamine oxidase inhibitors (MAOIs) are a group of drugs that interfere with the work of monoamine oxidase (MAO). MAO is found in the liver, in the GI tract, and in adrenergic nerve endings. It metabolizes (oxidizes) tyramine,