Chapter 17 Implications of Drug-Nutrient Interaction and Pharmacology

families involved with the majority of drug metabolism in humans are CYP3A, CYP2D, and CYP2C.

Alterations in Cytochrome P450

Enzyme Genetics CYP3A accounts for approximately 30% of hepatic P450 content and is involved in over 50% of drug metabolism in drugs such as antidepressants, antipsy- chotics, anxiolytics, calcium channel blockers, che- motherapeutics, immunosuppressants, macrolide antibiotics, opiates, and statins (28). Metabolism of St. John’s wort and the antituberculosis agent rifam- pin and azole antifungals may also be affected. Levels of CYP3A affect more African Americans (29). CYP2D6 is responsible for the metabolism of 25% to 30% of prescription medications but represents about 2% to 5% of total CYP content of the liver (30). Poor metabolizers of CYP2D6 do not have the ability to break down medications. This will cause medication levels in the blood to rise to possibly toxic levels. Consequently, the individual may have an exaggerated response and adverse effects. As an example, fluoxetine (Prozac), which has a geriatric indication, is metabo- lized by CYP2D6. Someone who is a poor CYP2D6 metabolizer will have higher levels of fluoxetine with usual doses. This may lead to greater toxicity and adverse effects, such as tremor, anorexia, dizziness, insomnia, or photosensitivity.

Ultra-rapid CYP2D6 metabolizers break down medications more quickly. This will result in lower levels of the medication in the blood, possibly causing the individual to have a poor therapeutic response. One such example is the response to tamoxifen therapy in women with breast cancer.

CYP2C19 is responsible for the metabolism of phenytoin with the same results—some metabolize at a greater extent than others, depending on genetic traits. Several pharmacological inhibitors of CYP2C19 exist, including cimetidine and fluoxetine. The impact of CYP2C19 metabolic variation has also been high- lighted in studies involving individuals being treated with clopidogrel (27).

CYP2C9 is responsible for the metabolism of several drugs, including phenytoin and warfarin. Variations in the metabolism of CYP2C9 lead to the wide variability in dosing requirements of warfarin, the most commonly prescribed anticoagulant. Table 17.6 has common genetic variants in phase I drug metabo- lizing enzymes (see page 242).

PRACTICAL ASPECTS FOR THE REGISTERED DIETITIAN NUTRITIONIST

Food-Drug Interactions with Diuretics RDNs must consider the following when caring for patients taking diuretics and antihypertensive agents:

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Electrolyte loss: sodium, potassium, magnesium, phosphate, bicarbonate, and calcium (with loop diuretics).

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Electrolyte retention: calcium (with thiazide diuretics).

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Hyponatremia, hypokalemia, hypomagnesemia may be of clinical significance.

●●A low-sodium diet may not be indicated. ●●

Caution should be used with calcium/vitamin D supplements (or excess dietary calcium) with thiazide diuretics; hypercalcemia has rarely occurred.

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High potassium and magnesium diet and/or sup- plements are indicated.

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Thiazide diuretics may complicate glucose control in diabetes (reason unknown).

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Natural licorice may cause sodium and water retention.

Food-Drug Interactions with Other Antihypertensive Agents ●●

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A low-sodium, low-fat diet may be appropriate to treat hypertension.

Natural licorice may cause sodium and water retention, antagonizing the antihypertensive effects of all agents.

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Calcium/vitamin D supplements may decrease the effect of verapamil.

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Avoid salt substitutes, potassium supplements, and potassium-sparing diuretics (eg, spironolac- tone [Aldactone]) with ACE inhibitors and angio- tensin II receptor blockers (ARBs); hyperkalemia may result from the combination.

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Avoid intravenous iron (iron dextran) with ACE inhibitors; severe systemic reactions may occur. This does not apply to oral iron supplements.

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Avoid alcoholic beverages with ACE inhibitors and dihydropyridine calcium channel blockers, as additive vasodilation may occur.

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Use caution with grapefruit/grapefruit juice with felodipine, nicardipine, nifedipine, nisoldipine; decreased intestinal metabolism may increase drug effect.