ABSTRACTThe effect of a drug on a person may be different since the drug may interact with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.

e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Physicians and pharmacists recognize that some drugs when taken simultaneously with some food  can alter the body’s ability to utilize a particular food or drug, or cause serious side effects. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions.

This review gives information about various interactions between different foods and drugs which  will help physicians and pharmacists to prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient.INTRODUCTIONIf anytime food or beverage changes the effects of a drug, the change results in a food-drug interaction.  Certain foods and specific nutrients present in foods, if ingested concurrently with some drugs, may affect the overall bioavailability, pharmacokinetics, pharmacodynamics and therapeutic efficacy of the medications. Food can alter the time of medications  reaction in the body and the total amount of medication delivered. Moreover, the therapeutic efficacy of many drugs depends on the nutritional status of the individual. In other words, the presence or absence of some nutrients in the gastrointestinal tract and/or in the body’s physiological system, such as in the blood, can enhance or impair the rate of drug absorption and metabolism.Food-drug interactions can occur with prescription drugs, over-the-counter drugs, herbal products, and dietary supplements.    Drug–food interactions can be a major source of inconvenience for the patient and non-adherence through disruptions in a patient’s daily schedule.

Unless advised to the contrary, patients often take drugs with meals as a suitable adherence reminder and to lessen gastrointestinal (GI) side effects. Lack of knowledge of potentially significant drug–food interactions can lead to poor clinical outcomes.  UNDERLYING MECHANISMS OF FOOD EFFECT ON  DRUG EXPOSUREPhysiological and Physiochemical MechanismsDietary substances can alter drug absorption, distribution, metabolism, and/or excretion (ADME) via physiologic and physicochemical mechanisms. Physiologic/mechanical mechanisms include delayed gastric emptying, stimulated/increased bile or splanchnic blood flow, and GI pH or flora changes. Alterations of such processes can lead to reduced absorption of some drugs (e.g., penicillins, angiotensin-converting enzyme inhibitors) .

Physicochemical mechanisms include binding of the drug by the food. For example, enteral nutrition formulas are incompatible with the antiepileptic agent, phenytoin, which can bind to proteins and salts in enteral formulations, resulting in reduced phenytoin absorption and potentially inadequate seizure control . Some tetracyclines and fluoroquinolones can bind to divalent cation-containing products (e.g., calcium in dairy), resulting in reduced drug absorption and potential therapeutic failure. High fat meals can increase drug absorption by improving solubility, such as with some antiretroviral protease inhibitors Biochemical MechanismsBiochemical mechanisms include interference with co-factor formation or function, potentiation of drug pharmacodynamics , and modification of drug metabolizing enzyme/transporter function by the dietary substance .

For example, vitamin K-rich foods interfere with co-factor function and should be consumed cautiously with the anticoagulant, warfarin, as they can disrupt vitamin K metabolism and increase risk of bleeding or clot formation . Isoniazid and monoamine oxidase inhibitors, used to treat tuberculosis and depression, respectively, inhibit the breakdown of endogenous and dietary amines; a tyramine-rich diet can potentiate a hypertensive crisis. EFFECT OF DRUG FOOD INTERACTION A food-drug interaction can: ?    Alter the intended response of medication?    Cause a side effect from a medicine to get worse or better ?    Alter the normal nutritional status of the body?    They can create a new unintended effectFoods can interfere with the stages of drug action in a number of ways :-The most common effect is for foods to interfere with drug absorption.Absorption is the transfer of a drug from its site of administration to the blood stream. Food may affect drug absorption in the GI tract by altering gastric pH,secretion, gastrointestinal motility and transit time.

This may result in a change in the rate of absorption or extent of drug absorption or both and drugs get less effective because less drug gets into the blood and to the site of action. Second, nutrients or other chemicals in foods can affect how a drug is used in the body. Drugs are eliminated from the body either unchanged through the kidneys and bile, or theymay undergo some chemical changes that allow them to be more easily excreted. The processof undergoing chemical changes is called biotransformation, or metabolism.

Food may alter the hepatic metabolism of some drugs.Third, excretion of drugs from the body may be affected by foods, nutrients, or other substances. When a drug is taken into and distributed throughout the body, it must be subsequently removed, or concentrations of the drug would continue to rise with each successive dose. The complete removal of the drug from the body is referred to as elimination.

Foods may alter the urinary pH, which can affect the activity of certain drugs. The half-lives of some medications can be significantly changed by alterations in urinary pH. Therefore, the half-life of acidic drugs will be extended in acidic urine because the drug is in its unionized form. With some medications, it’s important to avoid taking food and medication together because the food can make the drug less effective in the body . For other drugs, it may be good to take the drug with food to prevent stomach irritation.FACTORS  AFFECTING   EXTEND  OF   INTERACTION  BETWEEN   DRUG  AND  FOOD.The impact of drug-food interactions depends on a variety of intervening factors like dosage of the drug, person’s age, size and state of  health. Apart from these, the time at which foods and the medications are taken also play an important role.

Avoidance of drug interactions does not necessarily mean avoiding drugs or foods. In the case of tetracycline and dairy products, these should simply be taken at different times; rather than eliminating one or the other from the diet. Sufficient information about the medications and timing of medications around food intake can help to avoid drug interaction problems.MAJOR DRUG FOOD INTERACTIONSFOOD    DRUG    DEMERITS1. Calcium – rich  foods?    Dairy products such as milk,yogurt,and cheese.

     Antibiotics•    Cephalexin(Keflex)•    Amoxicillin(Amoxil)•    Clindamycin(Clepcin)•    Metronidazole(Elagyl)•    Ciprofloxacin(Cipro)•    Levofloxacin(Levaquin)•    Amoxicillin potassium clavulanate(Augmentin)    These antibiotics may bind to the calcium in the milk which forms an insoluble substance in the stomach and upper small intestine that the body is unable to absorb.Antibiotics works better if taken 1 hour or 2 hours before or after eating.2.

Pickle,Cured and Fermented Foods•    Red wine,hard cheese,chocolate,aged cheese, Brewer’s yeast, yeast extracts , pickled herring    MAIOs antidepressants    These food contains tyramine which causes dangerous increase in blood pressure among patients taking certain medications for Parkinsons disease.3. Vitamin k – rich foods?    Broccoli, Brussels sprouts, cabbage, kale, spinach and other leafy greens    Warfarin(Coumadin)    Warfarin is a blood-thinning medication that helps to treat and prevent blood clots. Consuming certain foods, especially those rich in vitamin K, can diminish warfarin’s effectiveness.

4. Grapefruit and Grapefruit Juice    Statins•    simvastatin (Zocor)•     lovastatin (Altoprev)•      atorvastatin (Lipitor),     Statins are highly effective cholesterol-lowering drugs. eating grapefruit or drinking grapefruit juice causes increase in medication potency by interacting with enzymes in the small intestine and liver.5. Alcohol    Insulin, Oral Diabetic Agents    It increase or prolongs the effects of insulin or oral diabetic agents (pills) and thus leads to hypoglycemia.

6. High-Fiber Diets(wheat bran )    Digoxin(Digitalis, Digitek, Lanoxin)    Digoxin  is used to strengthen the contraction of the heart muscle, slow the heart rate, and promote the elimination of fluid from body tissues.Dietary fiber can slow down the absorption of digoxin and lessen its effectiveness. 7.Grapefruit    Calcium Channel Blockers •    felodipine (Plendil)•     nicardipine (Cardene)•    nisoldipine (Sular)  •    weaker with amlodipine (Norvasc), diltiazem (Cardizem), and nifedipine (Adalat).    Calcium channel blockers are prescribed for high blood pressure. Grapefruit alters the breakdown of the calcium channel blockers, possibly results in excessively high blood levels of the drug along with an increased risk of serious side effects.8.

Cinnamon    Anti diabetics    This spice in large amounts can lower blood sugar which is similar to the actionof  diabetes drugs which results in dangerous lowering of blood sugar. A sprinkle of cinnamon in cooking is safe, but avoid consuming high-dose supplements.9. Fish oil supplements    Blood thinners    Large amounts of fish oil also can thin the blood. Combined with these kinds of medications , this can pose a health risk.

10.Iodine-Rich Foods?    seafood and seaweed, such as kelp and nori.    Antithyroid Drugs    Antithyroid drugs prevents iodine absorption in the stomach. A high-iodine diet requires higher doses of antithyroid drugs which result in  side effects that include rashes, hives, and liver disease.11. Alcohol    NSAIDS•    aspirin and ibuprofen    stomach bleeding and serious damage to your liver.12.Bananas     ACE inhibitors•    ramipril (Altace)•    captopril (Capoten)•    moexipril (Univasc)•    perindopril (Aceon)•     trandolapril (Mavik)•    benazepril/hctz (Lotensin)•    lisinopril (Prinivil, Zestril)•    enalapril maleate (Vasotec)•    fosinopril sodium (Monopril)•    quinapril hydrochloride (Accupril)    High amounts of potassium can cause heart palpitations and an irregular heartbeat13.

Black Licorice    Hypertensive drugs    Black liquorice contains glycyrrhiza which causes an irregular heartbeat or even death, when combined with digoxin.Black liquorice reduces the effectiveness of most blood pressure drugs, intensify the side effects of blood thinners and lower potassium levels when consumed with birth-control pills.14.Soybean flour, walnuts    Thyroid drugs such as levothyroxine (Levothroid, Levoxyl, Synthroid).    These high-fiber foods can prevent ones body from absorbing the medications.

15.Potassium (bananas, apricots, coconut, dates, prunes, peaches, grapefruit, tomatoes, and oranges.)     Spironolactone (aldactone)    Spironolactone, a potassium-sparing diuretic, in combination with foods high in potassium, could result in hyperkalemia16.Cow’s milk    Antitumor Drugs  (Mercaptopurine)    Xanthine Oxidase present in milk may potentially reduce bioavailability of mercaptopurine.17.

Coffee    Bronchodilators    Stimulate the CNS and causes Hyperexcitation18.High fat meals    Anti-fungal agents•    Griseofulvin    Griseofulvin has a significantly increased absorption when taken with high fat meals.DIFFERENT WAYS TO MINIMIZE DRUG FOOD INTERACTIONS•     The number of food-drug interactions with harmful results is small. However, to be safe, one should carefully read the labels of all prescription and over-the-counter drugs to check for interactions.

•    In addition, always talk with the doctor or pharmacist about any known food (or drug) interactions with ones medications and clarify treatment options.•     If the medications do not seem to produce the desired effects, or if one experience unwanted side effects (particularly if the effects change during the course of treatment), review ones diet with the doctor or pharmacist to assess for food-drug interactions.•    It is usually best to take medication with a full glass of water. This may help to prevent stomach irritation and improve absorption.But don’t stir the medication into food or drink unless adviced by the doctor or pharmacist.ROLE  OF  PHARMACISTS  IN  PREVENTION  OF  DRUG FOOD INTERACTIONSPharmacists have an extensive knowledge of how drugs work, their side effects, and the medications, supplements, and foods they interact with.

A pharmacist plays a pivotal role in the identification, detection,prevention, and management of  drug-food interactions and pharmacists in practice setting need to be vigilant in monitoring for potential drug-food interactions.This can be done by thoroughly screening the patient’s medication profile.Pharmacists should  advise the  patients regarding foods or beverages to avoid when taking certain medications.

It is important for pharmacists to keep up-to-date on potential drug-food interactions of medications, especially today’s newly released drugs, so that they may counsel the patients properly.                      In providing drug information to patients, pharmacists often discuss potential side effects of the drugs and how the medication should be taken. It is important to provide nformation to patients on when to take their medications in relation to food intake. Patients should be given instructions and counseling regarding the potential for drug-food interactions before their hospital discharge. Elderly patients taking three or more medications for chronic conditions such as  hypertension, depression, diabetes, high cholesterol or congestive heart failure are at a high risk of drug food interaction and should be monitored for possible such interactions.

BENEFITS OF  MINIMIZING  DRUG FOOD  INTERACTIONS•    Medications achieve their intended effects.•    Patients do not discontinue their drug.•    The need for additional medications is minimized.•    Fewer caloric or nutrient supplements are required.•    Adverse side effects are avoided.•    Optimal nutritional status is preserved.

•    Accidents and injuries are avoided.•    Disease complications are minimized.•    The cost of health care services is reduced.•    There is less professional liability.•    Licensing agency requirements are met.

STUDIES CONDUCTED ON DRUG FOOD  INTERACTIONS•    Sudies were conducted on  food-drug interactions by collecting seventy five outpatient prescriptions at a random from various local hospitals in Karachi.In the present work, out of thirty four drugs prescribed to 34 patients , food drug                                       interactions were found in twenty seven cases. It means that absorption of approximately 80% of the drugs found to be affected by food.     It was also found that only few studies have been carried out so far on the effect of food on drug disposition in the Asian population. Thus more studies on food-drug interactions particularly in the local population is recommended in order to determine the effect of food and foodcomponents on drug disposition.•    A Questionnaire Study of Food -Drug Interaction was conducted to access the Knowledge of people from diverse backgrounds in Hyderabad,India.

A total of 345 respondents were enrolled in the study. The data was analysed and the results were expressed in percentages.Out of 252 respondents which are valid 85.68% believed that they were aware of food drug interactions while 14.28% were unaware.

Knowledge of Clinical Pharmacologists on food drug interactions was better than doctors,nurses and pharmacy students. The otheroutcome of this survey showed that individuals from non medical field had a limited awareness on food drug interactions. This survey also found that people from non-medical field use herbal supplements concomitantly with prescription and OTC medication.  CONCLUSIONInteractions between drugs and food products occur in various ways and in various steps ranging from ingestion, absorption, metabolism, and excretion of both the drug and food product. Some of the effects induced by food-drug interactions, such as an increase in the blood drug level, may have potential therapeutic benefits while some interactions may result in detrimental physiological effects.Like drugs, foods are not tested as comprehensively so they may interact with prescription or over-the-counter drugs.

It is therefore important to understand and examine the potential interactions between foods and drugs and their specific effects at an individual level

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