Understanding the FOOD-DRUG Relationship

The medications we take can alleviate our pain, lower our blood pressure and cholesterol, improve our mood disorders, and generally give us a sense of well-being; yet they can also cause serious health problems and even death. Adverse drug interactions represent one of the most important challenges facing pharmacists today, and they can be truly mind-boggling. These interactions are of great concern to all health care providers, especially pharmacists, who are considered experts in the field and, for the most part, are the most accessible health care professionals. It is difficult today for a busy physician to take the time to monitor and research every possible drug interaction for each and every patient, so it is common for patients to ultimately rely on the pharmacist for counseling on drug therapy. Essentially, drug interactions are extremely complex and linked to phar-macokinetics, which involve drug absorption, distribution, metabolism, and excretion.

Role of Food and Nutrition

There is a dynamic relationship between what we eat and the medications we take. Many of the foods we eat can substantially interfere with therapeutic goals and lead to interactions that can change the absorption of a medication into the bloodstream, as well as decrease the effect of the drug. Drug-food interactions also can have positive effects that result in a reduction of gastrointestinal irritation and an increase in drug absorption. For instance, griseofulvin and saquinavir (antifungal and antiviral agents, respectively) are best absorbed when taken with foods that are high in fat content. Tetracycline, on the other hand, binds to the calcium in milk to form an insoluble

substance that cannot be absorbed by the body.

Generally speaking, certain drugs and food do not mix well. In fact, when taken during the same period of time, some foods and drugs can interfere with the body?s ability to utilize a particular food or drug, which explains why some drugs are prescribed ?with food? or ?on an empty stomach? (empty stomach usually means 1 hour before or 2 hours after a meal). Many foods can eliminate the benefits of certain medications by interfering with proper absorption. Other drugs, such as aspirin and other anti-inflammatory agents, while best absorbed without food, are so irritating to the stomach that they can cause pain, diarrhea, and nausea (Table 1).

Effects of Alcohol, Caffeine, and Tea

Alcohol, caffeine, and some teas can increase the effect of certain drugs. Hypnotics, antidepressants, and antianxiety drugs are greatly affected by alcohol, resulting in enhanced central nervous system side effects. Alcohol can also affect patients taking beta blockers by causing a drastic decrease in blood pressure. When combined with hypo-glycemic drugs, alcohol can alter blood sugar levels. Caffeine can interact with ciprofloxacin and theophylline to produce increased stimulant effects.

Common Drug-Nutrient InteractionsAnticoagulants

Anticoagulants (eg, warfarin) help reduce the formation of blood clots. Vitamin K is essential for the production of clotting factors that help the blood clot and thus prevent bleeding. Anticoagulants exert their effect by blocking vitamin K in the production of these clotting factors. Certainly, an increased intake of foods high in vitamin K can antagonize the anticoagulant effect and prevent the medication from working. Nevertheless, it is not necessary to avoid all foods containing vitamin K, but rather to keep a consistent diet to avoid fluctuations in the levels of drug in the body. Table 2 lists foods with a high content of vitamin K.

Penicillins

Drugs of this class are best absorbed on an empty stomach, but may be taken with food to reduce stomach upset. They should not, however, be taken with acidic foods, fruit juices, colas, or other acidic beverages, because increased stomach acid can interfere with their absorption.

Cephalosporins

Most cephalosporins should be taken on an empty stomach 1 hour before or 2 hours after meals, but may be taken with food to reduce stomach upset. Cefuroxime (Ceftin) is an exception, because absorption of the drug is increased when administered with food.

QuinolonesAs with several other antibacterial agents, quinolones are taken on an empty stomach, but may be taken with food to reduce stomach upset. Avoid high intake of calcium-containing products, such as yogurt, milk, vitamins, or minerals containing iron, or antacids, because these can decrease drug levels in the body (Table 3). Since these drugs may affect elimination of caffeine from the body, caffeine-containing products may increase caffeine levels, causing extreme nervousness.

Allopurinol This antigout agent does not decrease elimination of uric acid but rather its production by inhibiting xanthine oxidase, the enzyme responsible for uric acid conversion. Purines are metabolized to uric acid in the body. Allopurinol acts on catabolism of purine, thereby reducing the production of uric acid. Dietary considerations include a reduction in the intake of such foods as liver, kidney, peas, lentils, excessive amounts of red meat, and alcohol.

Theophylline

This bronchodilator, which opens air passages of the lungs, is indicated for relief or prevention of bronchial asthma and bronchospasm related to emphysema and chronic bronchitis. Blood levels are routinely monitored to achieve maximum therapeutic levels with low toxicity. Levels above 35

mcg/mL can result in serious cardiac arrhythmias and tachycardia. A diet low in carbohydrates and high in protein, as well as charcoal-broiled beef, increases the elimination of theophylline, resulting in poor control of asthma and other conditions. Therefore, a high-carbohydrate, low-protein diet will halt the elimination of theophylline, leading to optimal therapeutic effect. Both theophylline and caffeine stimulate the central nervous system. Therefore, the effect of theophylline may be increased by caffeine-containing beverages, such as cola, coffee, tea, and even some over-the-counter pain medications, causing an increase in side effects.

DigoxinThis agent is indicated for congestive heart failure and atrial fibrillation. When taken after a meal, the rate of absorption is delayed. In addition, high-fiber foods, such as whole wheat products, raw vegetables, bran cereal, and fruits, inhibit its absorption and decrease its effect.

It is important to maintain normal magnesium and potassium levels when taking digoxin. A depletion in magnesium or potassium (which may be caused by thiazide and loop diuretics, for instance) sensitizes the myocardium to digoxin, causing toxicity. Conversely, the combination of digoxin and a potassium-depleting diuretic could present problems. Signs of digoxin toxicity include visual disturbances, headache, confusion, and nausea. Natural licorice is to be avoided, because it can interact with digoxin to further eliminate potassium from the body.

Itraconazole/Ketoconazole

These antifungal agents require gastric acidity for dissolution and absorption. Any drug that suppresses acid secretion, such as antacids or histamine blockers, decreases their effect, while acidic foods and beverages, such as cola, increase absorption. In fact, a clinical study on patients with achlorhydria showed an increase in absorption when itraconazole was taken with a cola beverage. These drugs should be taken with food.

Alendronate/RisedronateThese widely prescribed drugs are used for the prevention and treatment of osteoporosis, the cause of many bone fractures in the elderly. For adequate absorption, alendronate and risedronate must be taken with 6 to 8 oz of plain water one-half hour before the day?s first food, beverage (eg, coffee, tea, mineral water, juice), or medication. The patient should not ingest any food or beverage for 30 minutes to avoid a decrease in absorption. Esophageal irritation is avoided by remaining upright for 30 minutes after taking the medication.

Note: Counsel patients that adequate supplementation of calcium and vitamin D while taking these drugs is still essential.

Monoamine Oxidase Inhibitors (MAOIs)

Phenelzine and tranylcypromine are examples of these effective antidepres-sants, which gained popularity in the 1950s and 1960s. They have been gradually replaced by selective serotonin reuptake inhibitors, which have markedly less side effects. One of the classic and most significant drug interactions occurs when MAOIs are combined with tyramine-rich foods. Tyramine is a central nervous system stimulant that is metabolized by monoamine oxidase before entering the bloodstream. In patients taking MAOIs, the enzyme becomes impaired, which can result in a hypertensive crisis marked by severe headache, fever, and overall confusion. Tyramine is especially high in such foods as chicken livers, avocados, bananas, Chianti wine, certain cheeses, pickled herring, figs, fish, processed meats, tofu, soybeans, coffee, caviar, and lima beans.

Levodopa High-protein foods, as well as vitamin B₆ (pyridoxine), may decrease the absorption of levodopa, thus decreasing the levels of dopamine and impairing its antiparkinsonism effects. Proteins in certain foods may be degraded into amino acids that compete with levodopa for transport to the brain. Instead of cutting down on the amount of protein intake, it is advisable to spread it out throughout the day.

Diuretics

Loop and thiazide diuretics are considered ?potassium wasting? and can cause electrolyte disturbances. Triam-terene, on the other hand, is considered ?potassium sparing,? because it may impair the excretion of potassium by the kidneys. Potassium-rich foods include figs, orange juice, and bananas. Licorice could also interact with these drugs and deplete potassium from the body. Beware of salt substitutes (rich in potassium) when taking these drugs.

Grapefruit Juice

Grapefruit juice interacts with many drugs because it inhibits the oxidative metabolism by cytochrome P450 (mainly 3A4) isoenzymes in the gut wall or liver. This inhibition causes higher levels of drug in the body and consequently an increase in adverse effects and/or toxicity. The following drugs should not be taken with grapefruit juice:

• Calcium channel blockers (dihydropyridine family): amlodipine (Norvasc), felodipine (Plendil), and nifedipine (Adalat, Procardia)
• Cyclosporine (Neoral, Sandimmune)
• Midazolam (Versed): Note: No effect when administered intravenously.
• Buspirone (Buspar)
• Triazolam (Halcion)
• Carbamazepine (Tegretol)
• Cilostazol (Pletal)
• Cholesterol-lowering agents (?statins?): lovas-tatin (Mevacor), fluvastatin (Lescol), and atorvastatin (Lipitor). Note: No significant interaction with prava-statin (Pravachol).

Guidelines for Patient Counseling Pharmacists today have an excellent opportunity to participate in a patient?s drug therapy program, as well as to counsel on the complexities and nuances of drug interactions. A good, overall sound method for counseling should include the following:

• Role of drug therapy and duration of course
• Dosing schedule and administration (with food, without food, morning vs evening, etc)
• Effect of nutrients on therapy (eg, warfarin with foods high in vitamin K)
• Alcohol interactions with mood-altering medications, metronidazole, etc
• Effect of caffeine, antacids, and sodium
• Restrictions and modifications of certain nutrients (eg, foods high in tyramine, potassium in combination with diuretic agents, etc)
• Potential adverse effects and ways to minimize them

In general, pharmacists should strive toward educating patients and ensuring that they understand their course of therapy. This will ultimately result in patient compliance and optimal results with low adverse effects.