Chapter 17 Implications of Drug-Nutrient Interaction and Pharmacology BOX 17.5 Caffeine: Clinical Guidelines

Drug-Nutrient Interaction Issues Caffeine may enhance the adverse effects of the

following drugs: ●●

●● Anticonvulsants

Antipsychotics, antidepressants, antianxiety medications

●●Antiulcer agents ●●Bronchodilators

●●

Cardiac regulators: calcium-channel blockers, antihypertensives, H2

antagonists

●● Decongestants ●●Diuretics

●● Insulin/oral hypoglycemics ●●NSAIDs/pain relievers ●● Potassium supplements ●● Stimulants/sedatives

Clinical Excess Signs/Symptoms ●●

Chest pain ●●Confusion

●●Decreased calcium absorption ●●Decreased iron absorption

●●Hyperglycemia in individuals with diabetes ●●Hallucinations

●● Increased free fatty acid concentrations ●● Increased gastric acid secretion/GI irritation ●● Irregular or increased heartbeat ●● Increased urination ●● Insomnia ●● Irritability ●●Nervousness

●● Pressor activity ●● Trouble breathing

●●Uncontrollable muscle movement ●● Vomiting

Clinical Withdrawal Signs/Symptoms ●●

Constipation ●●Depression

●● Flulike symptoms ●●Headache ●● Insomnia ●● Irritability

●● Lack of concentration ●● Lethargy ●● Sleepiness

●● Stiffness, muscle pain

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amiodarone (Cordarone) by impeding activity of cyto- chrome P450 3A4 isoenzymes in the intestinal wall. Serum drug levels increase and can become toxic. More than 85 prescription medications have demon- strated interactions with grapefruit. Of these, 43 can have serious adverse effects, including sudden death, kidney failure, GI bleeding, and rhabdomyolysis (24). “The mechanisms and magnitudes of the interac- tions can be influenced by the concentrations of furanocoumarins and flavonoids in the grapefruit product, the volume of juice consumed, and the inher- ent variability of specific enzymes and transporter components in humans.” It is truly challenging to predict the extent of grapefruit-drug interactions. The clinical significance of interactions also depends on the disposition and toxicity profile of the drug being administered (25). It appears this interaction is clini- cally significant for drugs with low oral bioavailabil- ity, which are substantially metabolized and inactivated in the intestinal tract. When grapefruit or grapefruit juice is ingested, the metabolizing enzyme is irreversibly inhibited, which reduces the drug’s normal metabolism. This allows more of the drug to reach the systemic circulation; the increase in blood levels of unmetabolized drug results in a greater phar- macological effect and possible toxicity (26).

Vitamin K

Foods, nutrients, and natural products that affect war- farin action include vitamin E at doses over 400 IU or vitamin A at levels above 3,000 μg/d, onions greater than 60 g, garlic, ginger, ginkgo, ginseng, saw palmetto or horse chestnut, quinine, papaya, mango, and possi- bly cranberry (multiple studies have found no interac- tion with less than 250 mL cranberry juice). Each of these can cause bleeding reactions because they have either antiplatelet activity or intrinsic fibrinolytic activ- ity. Vitamin K significant dietary sources can be found in Table 17.5 (see page 240).

Foods, nutrients, and natural products that decrease the anticoagulant action of warfarin include CoQ10, Saint John’s wort, and avocado. Ingestion of these products may lead to therapeutic failure of warfarin.

PHARMACOGENOMICS: INDIVIDUAL DIFFERENCES IN DRUG DISPOSITION

“Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will