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Food drug interactions

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Qussai Abbas + Kinda Sharrouf

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Food drug interactions

  1. 1. Toxicology Qussai & Kinda
  2. 2. 1 Syrian Arab Republic Damascus University Faculty of Pharmacy Biomedical Science department, Syria ,2018. Edited by: Qussai Abbas & Kinda Sharrouf Supervised by: Dr. Sophie Barakel & Dr. Alia Omran FOOD AND DRUG INTERACTIONS
  3. 3. 2 Contents Contents...........................................................................................................................................................................................2 Introduction....................................................................................................................................................................................3 Definitions.......................................................................................................................................................................................5 Underlying factors:......................................................................................................................................................................6 Classification of drug-food interactions:.........................................................................................................................7 EFFECTS OF FOOD ON DRUG.......................................................................................................................................8 I. Pharmacokinetic interactions.............................................................................................................................8 II. Pharmacodynamics Interactions....................................................................................................................13 EFFECTS OF DRUGS ON NUTRITION STATUS.....................................................................................................14 Most common food drug interactions...........................................................................................................................18 Grapefruit juice...................................................................................................................................................................18 St. John’s wort.....................................................................................................................................................................21 Other examples..................................................................................................................................................................27 Alcohol and Medication Interactions......................................................................................................................36  Specific Alcohol-Medication Interactions.......................................................................................................38 Summary of some signifiant Food-Drug Interactions............................................................................................45 References:....................................................................................................................................................................................52
  4. 4. 3 Introduction Medicinescan treat and curemany health problems. However, they must be taken properly to ensure that they are safe and effective. Medicationsshould be extremely specific in their effects, have the same predictable effect for all patients, never be affected by concomitantfood or other medications, exhibit linear potency, be totally non-toxic in any dosage and require only a single dose to affect a permanent cure. However, this ideal drug is still to be discovered. Many medicineshavepowerful ingredientsthat interact with the human body in different ways. Diet and lifestyle can sometimes have a significant impact on drugs. A drug interaction is a situation in which a substance affects the activity of a drug when both are administered together i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interactionsbetweendrugscome to mind (drug-drug interaction). However, interactions may also exist between drugs and foods (drug-food interactions), as well as drugs and medicinal plants or herbs (drug-plant interactions). People taking antidepressant drugs such as monoamine oxidase inhibitors should not take food containing tyramine as hypertensive crisis may occur (an example of a drug-food interaction). These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Drug interactionsmaybetheresult ofvariousprocesses. Theseprocessesmay includealterationsinthepharmacokineticsofthedrug, such as alterationsin the absorption, distribution, metabolism, and excretion (ADME) of a drug. Alternatively, drug interactions may be the result of the pharmacodynamic propertiesofthedrug, e.g., additive, synergistic, or antagonisticeffects(when co-administration of a receptor antagonist and an agonist for the same receptor) of a drug. Drug interactions(DIs) represent an importantand widely under recognized source of medication errors. Interactions between food and drugs may inadvertently reduce or increase the drug effect. Some commonly used herbs, fruits as well as alcohol may causefailureof thetherapyup a point of to seriousalterationsofthepatient’s health. The majority of clinically relevant food-drug interactions are caused by food induced changesin the bioavailabilityof the drug. Major side-effects of some diet (food) on drugs include alteration in absorption by fatty, high protein and fiber diets. Bioavailability is an important pharmacokinetic parameter which is correlated with theclinicaleffect ofmost drugs. However, inorder toevaluate the clinicalrelevance of a food-drug interactiontheimpact of food intake on
  5. 5. 4 theclinicaleffect of the drug hasto bequantified aswell. The most important interactionsare those associated with a high risk of treatment failurearising from a significantly reduced bioavailability in the eating state. Such interactions are frequently caused by chelation with components in food. In addition, thephysiologicalresponse to food intake, in particular, gastricacid secretion, may reduce or increase the bioavailability of certain drugs. The gastrointestinal absorption of drugs may be affected by the concurrent use of other agentsthat have a largesurfacearea upon which the drug canbe absorbed, bind or chelate, alter gastric pH, alter gastrointestinal motility, or affect transport proteins such as P-glycoprotein. A reduction only in absorption rate of a drug is seldom clinically important, whereasa reductioninthe extent of absorptionwill be clinicallyimportant if it results in sub therapeutic serum levels. Coenzyme Q-10 (CoQ10) is very widely consumed by humans as a food supplement becauseof itsrecognitionby the public as an importantnutrient in supporting humanhealth. It interfereswith intestinalefflux transporterP- glycoprotein (P-gp) and as result food-drug interactions arise. The interaction of natural products and drugs is a common hidden problem encountered in clinical practice. The interactions between natural products and drugs are based on the same pharmacokinetic and pharmacodynamic principles as drug-drug interactions. Several fruits and berries have recently been shown to contain agents that affect drug-metabolizing enzymes. Grapefruit isthemost well-knownexample, but alsosevillianorange, pomelo and star fruit contain agents that inhibit cytochrome P450 3A4 (CYP3A4), which is the most importantenzyme in drug metabolism. Thestudy of drug- drug, food-drug, and herb-drug interactions and of genetic factors affecting pharmacokineticsand pharmacodynamicsisexpected toimprovedrug safety and will enable individualized drug therapy. Drugs can show their efficacy only if administered in appropriatequantitywith appropriatecombinationof drugs and foods and at appropriate time. In contrast to the easy access to information on drug-drug interactions, the information about food-drug interactionisnot always availableconveniently. It isa difficult and complex problem to accurately determine the effects of food and nutrients on a particular drug.
  6. 6. 5 Definitions Food/Drug Interactions: Foods 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. This can make a drug less effective because less gets into the blood and to the site of action. Second, nutrients or other chemicalsinfoods canaffect how a drug is used in the body. Third, excretionof drugs from the body may be affected by foods, nutrients, or other substances. With somedrugs, it’simportant toavoid taking food and medicationtogether becausethefood can makethedrug less effective. For other drugs, it maybegood totakethedrug with food toprevent stomach irritation. Drug/Nutrient Interactions: It is also possible for drugs to interfere with a person’s nutritional status. Somedrugsinterferewith theabsorptionofa nutrient. Other drugsaffect the body’s use and/or excretionof nutrients, especiallyvitaminsand minerals. If less of a nutrient is available to the body because of these effects, this may lead to a nutrient deficiency. Sometimes drugs affect nutritional status by increasing or decreasing appetite. This affects the amount of food (and nutrients) consumed. Synergy and antagonism When the interaction causes an increase in the effects of the drug the interaction is called a synergistic effect. The oppositeeffect to synergy is termed antagonism: Whenthe interaction causes a decrease in the effects of one or both of the drugs.
  7. 7. 6 Underlying factors: By studying the conditions that favour the appearance of interactions it should be possible to prevent them or at least diagnose them in time. The factorsor conditionsthat predisposeor favour theappearanceofinteractions include: High-risk patients, such as the elderly patients taking three or more medications for chronic conditions, patients suffering from diabetes, hypertension, depression, high cholesterol or congestive heart failure should be especially monitored for such drug-food interactions. Insufficient nutritional status can impair drug metabolism. Some people at higher risk for drug- nutrient interactions. They are who: • have impaired hepatic, renal or gastro-intestinal function. • are nutritionally compromised due to chronic disease. • have recent weight loss or dehydration. • are on multiple and prolonged drug therapy. • areat the extremesofage with changesinlean bodymass, totalbodyfluids and plasma protein concentration.
  8. 8. 7 Classification of drug-food interactions: Drug-nutrient interactions could be classified into one of five broad categories. The many types of drug-nutrient interactions could thus be categorized with each having an identified precipitating factor and an object of the interaction. In some cases, the drug is the precipitating factor (i.e., causing changes to nutritional status), while in others the drug is the object of the interaction (i.e., changes in drug disposition or effect result from a nutrient, food, or nutritional status). In the event of the precipitating factor produces significant change in the object of the interaction, drug-nutrient interactionsareconsidered as important. Interactionsthat need to be totally avoided are not common; instead close monitoring with modification to the dosing schedules is usually all that is necessary.
  9. 9. 8 EFFECTS OF FOOD ON DRUG I. Pharmacokinetic interactions Modifications in the effect of a drug are caused by differences in the absorption, transport, distribution, metabolism or excretion of the drug. These changesare basicallymodificationsinthe concentration of the drugs. 1- Absorption interactions:  Reduced or delayed drug absorption: The presence of food may decrease or delay drug absorption and that could be due to:  The formation of insoluble complexes  Delayed gastric emptying  Increased viscosity due to the presence of food Some examples of drug-food interactions that delay and reduce the absorption of drugs Drug Mechanism Counseling Acetaminophen High pectin foods act as adsorbant and protectant Take on empty stomach if not contraindicated Digoxin High–fiber, high–pectin foods bind drug Take drug same time with relation to food, Avoid taking with high-fiber foods Glipizide Mechanism unknown Affects blood glucose; more potent when taken half hour before meals Isoniazide Food raises gastric pH preventing dissolution and absorption Take on empty stomach if tolerated Levodopa Drug competes with amino acids for absorption transport Avoid taking drug with high–protein foods Methyldopa Competitive absorption Avoid taking with high- protein foods If anorally administereddrug harmsthestomach lining or decomposesinthe acidic environment of the stomach, a tablet or capsule of the drug can be coated with a substanceintended toprevent it from dissolving untilit reaches thesmallintestine. Theseprotectivecoatingsaredescribed asenteric coating. For these coatingsto dissolve, they must comein contact with theless acidic environment of the small intestine or with the digestive enzymes there. One
  10. 10. 9 example is aspirin, when food delays gastric emptying this delays aspirin absorption.  Increased drug absorption: Increased drug absorption due to the presence of food has been frequently reported. Accumulated evidencesuggest that morecompletedrugdissolution due to the presence of food itself, or as a result of food induced gastrointestinalsecretionsor delayed gastricemptying, oftenhasa significant positive effect on absorption, particularly for fat soluble compounds.  In particular, poorly water soluble drugs (e.g. griseofulvin, mebendazoleand halofantrine), whentaken asa solid formulationmay not enter solution readilyin thestomach. Administrationofsuch drugs with very fatty foods can increase bioavailability, possibly by such mechanisms as the formation of solutions in the dietary oil.  Bioavailability of Axetil (Ceftin), an antibiotic, is 52% after a meal and 37% in the fasting state.  Absorptionoftheantiretroviraldrug saquinavir isincreasedtwofold by food.  Taking ketoconozoleand delavirdinewith orangeor cranberryjuicecan reduce stomach pH and increase absorption, however in the case of warfarin, patients who are taking warfarin should limit or avoid completely drinking cranberry juice. Some examples of drug-food interactions that accelerate the absorption of drugs Drug Mechanism Counseling Carbamazepine Increased bile production, enhanced dissolution and absorption Dicumerol Increased bile flow, delayed gastric emptying permits dissolution and absorption Take with food Erythromycin Unknown Griseofulvin Drug is lipid soluble, enhanced absorption with high- fat foods. Take with high- fat foods Hydralazine, Labetalol and Metaprolol Food may reduce first-pass extraction and metabolism Nitrofurantoin, Phenytoin and Propoxyphene Delayed gastric emptying improves dissolution and absorption Propranolol Food may reduce first-pass extraction and metabolism Take with food Spironolactone Delayed gastric emptying permits dissolution and absorption, bile may solubilize the drug
  11. 11. 10 2- Metabolism interactions: Types of drug metabolism interaction:  Enzyme induction  Enzyme inhibition Alteration in activities of enzymes that metabolize drugs can result in:  Increased blood concentration of drug (stronger physiological effects)-ex. Grapefruit and statins  Decreased effectiveness of drug (ex. Warfarin and vitK) CYP450: Cytochrome P450 is a very large family of hemoproteins that are characterized by their enzymatic activityandtheir roleinthe metabolism of a large number of drugs. Of the various families that are present in human beings the most interesting in this respect are the 1, 2 and 3, and the most important enzymes are CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. The majority of the enzymes are also involved in the metabolism of endogenous substances, such as steroids or sex hormones, which is also important should there be interference with these substances. Fruit-drug interactions Fruit Molecular target Drug interactions Grapefruit inhibits CYP3A4, CYP1A2, MRP2, OATP-B and P-glycoprotein calcium channel antagonist, central nervous system modulators, HMG-CoA reductase, immunosuppressants, antivirals, phosphodiesterases-5 inhibitor, antihistamines, and antibiotics Sevilla orange inhibits CYP3A4, P-glycoprotein, OATP-A, OATP-B vinblastine, fexofenadine, glibenclemida, atenolol, ciprofloxacine, ciclosporine, celiprolol, levofloxacin and pravastatin Grapes inhibits CYP3A4 and CYP2E1 cyclosporine Mango inhibits CYP1A1, CYP1A2, CYP3A1, CYP2C6, CYP2E1, P- glycoprotein midazolam, diclofenac, chlorzoxazone, verapamil Apple inhibits CYP1A1, OATP family Fexofenadine
  12. 12. 11 Papaya inhibits CYP3A4 not documented
  13. 13. 12 Vegetable-drug interactions Vegetable Molecular target Drug interactions Broccoli inhibits CYP1A1, CYP2B1/2, CYP3A4, CYP2E1, hGSTA1/2, MRP1, MRP2, BCRP, UDP, glucorosytransterases, dulfotransferases, quinone reductses phenolsulfotransferases induces: UDP- glucuronosyltransferases, (UGTs), sulfotransferases (SULTs) and quinone reductase (QRs) not documented Spinach possible inhibition of CYP1A2 heterocyclic aromatic amines Tomato inhibits CYP1A1, CYP1B1, UGP increases UGT and CYP2E1 diethylnitrosamine, N-methyl- ,-N- nitrosourea and 1,2 dimethylhydrazine Carrot induces phenolsulfotransferases and ethoxycoumarin O- deethylase ECD inhibits CYP2E1 not documented Red pepper inhibits CYP1A2, CYP2A2, CYP3A1, CYP2C11, CYP2B1, CYP2B2, CYP2C6 in vitro and in vivo 3- Excretion interactions Only the free fraction of a drug that is dissolved in the blood plasma can be removed through the kidney. Therefore, drugs that are tightly bound to proteins are not available for renal excretion, as long as they are not metabolized when they may be eliminated as metabolites. Theexcretionofdrugsfrom thekidney's nephronshasthe samepropertiesas that of any other organic solute: passive filtration, reabsorption and active secretion. In thelatter phasethe secretionofdrugsis an activeprocessthat is subject to conditions relating to the saturability of the transported molecule and competition between substrates. Therefore, these are key sites where interactionsbetweendrug and nutritioncould occur. Filtrationdependson a number of factors including the pH of the urine, it having been shown that the drugs that act as weak bases are increasingly excreted as the pH of the urine becomes more acidic, and the inverse is true for weak acids.
  14. 14. 13 II. Pharmacodynamics Interactions Foods may interact with medications by altering their pharmacologic actions.  Diets high in vitamin K may cause antagonism of warfarin and decreased therapeutic efficacy of the anticoagulant. Foods rich in vitamin K include green leafy vegetables (kale, turnip greens, spinach and broccoli), cauliflower, chick peas, green tea, pork liver and beef liver. Garlic can cause additive antiplatelet effect in combination with warfarin, heparin, and low molecular weight heparin (LMWH), and cause increased risk of bleeding.  Alcoholic beverages may increase the central nervous system depressant effects of medications such as benzodiazepines, antihistamines, antidepressants, antipsychotic, muscle relaxants, narcotics or any drug with sedative actions.  An example of a food potentiating the effect of a medication is coffee, as caffeine has additive effects on theophylline. It has been reported that caffeine increased serum theophylline levels by 20%–30% and increased the half-life of theophylline by decreasing clearance. Patients may complain of nervousness, tremor or insomnia. Caffeine has some bronchodilator effects, which may enhance the effects of theophylline. A lower dosage of theophylline may be necessary for those patients who consume excessive quantities of coffee (more than 6 cups daily).
  15. 15. 14 EFFECTS OF DRUGS ON NUTRITION STATUS Some drugs can have an effect on a patient’s nutritional status. The mechanisms for these effects are varied and are usually due to drug side effects. A drug canenhance or inhibit nutrientbioavailability. Thus, it affects the nutritional status of individuals. For instance, elderly people, who are taking multiple medications for a long period of time are often found to be deficient in one or more nutrients. Other age groups, such as young children and adolescents, are also particularly at risk. There is a potential problem with drug-nutrient interactions in adolescents becausetheir nutrient needsare higher thanthoseofadults. Pregnant women and infants are the other groups also at particular risk. The reason of these deficiencies is not only based on the chemical reactions between drugs and nutrients but also on the dose and duration of treatment or exposure to the drug. Drugs can interfere with nutrient at several sites starting from the ingestion of the food to the final stage of excretion. The influence of medicationonoverall nutritionalstatuscanbe due to many factors: • Appetite changes • Oral taste and smell • Nausea • Dry mouth • Gastrointestinal effects • Organ system toxicity • Glucose levels Examples of drug categories that may affect appetite:  Decrease Appetite:  Antiinfectives  Bronchodilators  Cardiovascular drugs  Stimulants  Some anorectic drugs are used for weight loss and to treat obesity by reducing appetite. Examplesareadrenergic and serotoninergic agents, which cause satiety, reduce appetite, and increase energy expenditure leading to weight loss. A good example for adrenergic drugs are amphetamines that stimulate secretion of norepinephrine and reduce food intake.
  16. 16. 15  Increase Appetite:  Hormones: Synthetic derivativeofprogesterone, medroxyprogesterone acetate or megestrol acetate, used for the treatment of hormone- sensitive breast and endometrial cancer, may increase appetite, food intake, and weight gain.  Anticonvulsants (caramazepine and valproic acid)  Antihistamines (cyproheptadine hydrochloride – Periactin)  Psychotropic drugs (chlordiazepoxide hydrochloride – Librium, diazepam – Valium, chloromazine hydrochloride – Thorazine, meprobamate – Equanil)  Corticosteroids (cortisone, prednisone).  Dronabinol also known as THC (from tetrahydracannabinols), is also used as an appetite stimulant. 1- Drugs affecting oral cavity, taste and smell  Taste changes: cisplatin, captopril (anti-hypertensive), amprenavir (antiviral), clarithromycin (antibiotic), some hypoglycemic agents like glipizide, the antimicrobials amphotericin B, ampicillin, and antiepileptic phenytoin.  Mucositis: antineoplastic drugs such as interleukin-2, paclitaxel, carboplatin.  Dry mouth: Anticholinergic drugs (tricyclic antidepressants such as amytriptyline, antihistamines such as diphenhydramine, antispasmodics such as oxybutynin). 2- Drugs that affect the GI tract: Drugscandamagethe intestinalabsorptive surfaces including villi, microvilli, brush border enzymes, and the transport system. Also drugs can affect the absorption of nutrients by changing the GI transit time or the overall GI chemical environment. Absorption of micronutrients, vitamins and minerals, as well as macronutrients, protein and fat, are affected by the type, dosage, and strength of some drugs.  Alendronate (Fosamax) anti-osteoporosis drug, patients must sit upright 30 minutes after taking it to avoid esophagitis.  Orlistat – blocks fat absorption, cancauseoily spotting, fecalurgency and incontinence.  Narcotic agents cause constipation.  Drug classes that cause diarrhea:  Laxatives Many laxatives, mineral oil, and cathartic agents reduce transit time in the GI tract and may cause steatorrhea and loss of fat- soluble vitamins, A and E, and possibly calcium and potassium. Also
  17. 17. 16 drugs containing sorbitol, such as theophylline solutions, can induce osmotic diarrhea and so shorten the transit time.  Anti-retrovirals  Antibiotics  Anti-neoplastics  The using of chemotherapeutic agents to treat cancer can affect growing tissues, particularlythelining ofthegastrointestinaltract (GIT). Nausea is a commonsideeffect and caninterferewith eating. Somepatientscanhave oral and esophageal lesions and it can cause pain upon chewing and swallowing (odynophagia). Thus, these formations lead to limits oral intake.  Non-steroidalanti-inflammatoryagents, commonlyused to treat arthritis, including aspirin, cancauseirritationof theupper gastrointestinalmucosa and even causeulcers which cancauseGI bleeding and gastritis, thiscandepressappetiteand produceweight loss.  Antibiotics can suppress commensal bacteria, and this may result in overgrowth of other organisms such as Candida albicans. Overgrowth in the GIT may produce malabsorption and diarrhea. Overgrowth in the mouth may result in candidiasisor thrush, which can reduce oral intake.  Antacids change the pH of the stomach and cause chelating with some minerals, consequently reducing their absorption. Higher pH in the stomach reduces the absorption of iron, calcium, zinc, and magnesium. 3- Drugs that may affect glucose levels:  Decrease glucose levels:  Antidiabetic drugs (acarbose, glimepiride, glipizide, glyburide, insulin, metformin, miglitol, neteglinide, pioglitizone, repaglinide, roiglitizone).  Drugs that can cause hypoglycemia: ethanol, quinine, disopyramide (antiarrhythmic) and pentamidine isethionate (antiprotozoal).  Increase glucose levels:  Anti-retrovirals, protease inhibitors (amprenavir, nelfinavir, ritonavir, saquinavir).  Diuretics, antihypertensives (furosemide, hydrochlorothiazide, indapamide).  Hormones (corticosteroids, danazol, estrogen or estrogen/progesterone replacement therapy, megestrol acetate, oral contraceptives).  Niacin (antihyperlipidemic) baclofen, caffeine, olanzapine, cyclosporine.  Some of the important functions of vitamins and several minerals are being coenzymes/cofactorsinmetabolic processesinthehumanbody. As
  18. 18. 17 a result, certain drugs are targeted to these coenzymes (antivitamins) in order to reduce the activity of some enzymes in related metabolic reactions. Good examples of these drugs are:  Vitamin folate (B6) is a cofactor for the enzyme dihydrofolate reductase, it is necessary for nucleic acid biosynthesis and cell replication. Thisvitaminwillbe excreted becausethedrugsdisplace it from dihydrofolate reductase to reduce cell replication, like methotrexate(MTX) for treating leukemiaand rheumatoidarthritis.  The anticoagulantdrug, warfarin(Coumadin) actsbypreventing the conversion of vitamin K to a useful form, thus a balance or steady state between dose of drug and consumption of vitamin K must be achieved.  Colchicine (gout) para-aminosalicylic acid (TB) sulfasalazine (ulcerative colitis) trimethoprim (antibiotic) and pyrimethamine (antiprotozoal) impair absorption of B12 or folate.  Antibioticscaneffect normalflora and causevitaminBdepletionand antibiotics like cefamendole, cefoperazone, cefotetan can interfere with vitamin K producing bacteria.  Nutrient excretion and altered reabsorption mechanisms can cause drugs to induce nutrient excretion:  D-Penicillamine chelates with toxic metals, and with some other metals like zinc, eliminating it via urine.  Ethylenediaminetetra-aceticacid (EDTA) hasbeenshowntocause urinary excretion of zinc.  Some diuretics, such as furosemide, ethacrynic acid, and triamterene, reduce the reabsorption of electrolytes and minerals such as calcium, magnesium, zinc, and increaserenal excretionof these elements.  The using of thiazide and loop diuretics can often cause sodium loss in the urine.  Phenothiazine antipsychotic drugs (chlorpromazine) increase excretion of riboflavin which can lead to riboflavin deficiency in those with poor intakes  Cisplatin causes nephrotoxicity and renal magnesium wasting resulting in acute hypomagnesemia in 90% of patients (also hypocalcemia, hypokalemia, hypophosphatemia), may require intravenous magnesium supplementation or post-treatment hydration and oral magnesium supplementation and that may persist for months or years after therapy is finished.  Corticosteroids(prednisone) decreasesodium excretion, resulting in sodium and water retention; increase excretion of potassium and calcium (low sodium, high potassium diet is recommended, calcium and vitamin D supplements are recommended with long term steroid use to prevent osteoporosis.
  19. 19. 18 Most common food drug interactions Grapefruit juice Grapefruit juice can be part of a healthful diet—most of the time. It has vitaminCand potassium—substancesyour bodyneedsto workproperly. But it isn't good for you when it affects the way your medicines work. Grapefruit juice and fresh grapefruit can interfere with the action of some prescription drugs, as well as a few non-prescription drugs. This interaction can be dangerous with most drugs that interact with grapefruit juice, "the juice increases the absorption of the drug into the bloodstream, whenthereisa higher concentrationofa drug, you tend tohave more adverse events." For example, if you drink a lot of grapefruit juice while taking certain statin drugs to lower cholesterol, too much of the drug may stay in your body, increasing your risk for liver damageand muscle breakdownthat canlead to kidney failure. Drinking grapefruitjuiceseveralhours before or several hours after you take your medicinemay stillbe dangerous, so it'sbest to avoid or limit consuming grapefruit juice or fresh grapefruit when taking certain drugs. Examples of some types of drugs that grapefruit juice can interact with are: some statin drugs to lower cholesterol, such as Zocor (simvastatin), Lipitor (atorvastatin) and Pravachol (pravastatin)  some blood pressure-lowering drugs, such asNifediac and Afeditab (both nifedipine)  some organ transplant rejection drugs, such as Sandimmune and Neoral (both cyclosporine)  some anti-anxiety drugs, such as BuSpar (buspirone)  some anti-arrhythmia drugs, such as Cordarone and Nexterone (both amiodarone)  some antihistamines, such as Allegra (fexofenadine).
  20. 20. 19 Drugs known to interact with grapefruit juice: Too High or Too Low Drug Levels Many drugs are broken down (metabolized) with the help of a vital enzyme called CYP3A4 in the small intestine. Certain substances in grapefruit juice blocktheactionofCYP3A4, soinstead ofbeing metabolized, moreofthedrug enters the bloodstream and stays in the body longer. The result: potentially dangerous levels of the drug in your body. The amount ofthe CYP3A4 enzymein the intestinevariesfrom one personto another. Some people have a lot, and others have just a little—so grapefruit juice may affect people differently when they take the same drug. While scientists have known for several decades that grapefruit juice can causea potentiallytoxiclevelofcertaindrugsinthebody, morerecent studies have found that the juice has the opposite effect on a few other drugs. "Grapefruit juice reduces the absorption of fexofenadine," decreasing the effectiveness of the drug. Fexofenadine (brand name Allegra) is available in both prescription and non-prescription forms to relieve symptoms of seasonalallergies. Fexofenadinemayalsobelesseffectiveiftakenwith orange or apple juice, so the drug label states "do not take with fruit juices. Why this opposite effect? It involves the transportation of drugs within the body rather than their metabolism. Proteins in the body known as drug transporters help move a drug into cells for absorption. Substancesingrapefruit juiceblockthe action of a specific group oftransporters. Asa result, lessof thedrug isabsorbed and it may be ineffective.
  21. 21. 20 Tips for Consumers:  Ask your pharmacist or other health care professional if you can have fresh grapefruit or grapefruit juice while using your medication. If you can’t, you maywant toask ifyou canhave other juiceswith themedicine.  Read theMedicationGuideor patient informationsheet that comeswith your prescriptionmedicinetofind out if it could interact with grapefruit juice. Some may advise not to take the drug with grapefruit juice. If it’s OK to have grapefruitjuice, therewill be no mentionof it in the guideor information sheet.  Read theDrug Factslabel on your non-prescription medicine, which will let you know if you shouldn’t have grapefruitor other fruit juiceswith it. If you must avoid grapefruitjuicewith your medicine, check the label of bottles of fruit juiceor drinks flavored with fruit juice to make sure they don’t contain grapefruit juice.  Seville oranges (often used to make orange marmalade) and tangelos (a cross between tangerines and grapefruit) affect the same enzyme as grapefruit juice, so avoid these fruits as well if your medicine interacts with grapefruit juice.
  22. 22. 21 St. John’s wort St John's wort (also known as Hypericum perforatum) is a flowering plant in the family Hypericaceae. The common name "St John's wort" maybe used to refer to any speciesof the genus Hypericum. Therefore, Hypericum perforatum is sometimes called "common St John's wort" or "perforate St John's wort" in order to differentiateit. Historically, St. John’s wort has been used for a variety of conditions, including kidney and lung ailments, insomnia and to aid wound healing. Now it isa medicinal herb with antidepressant activityand potent anti-inflammatorypropertiesas an arachidonate 5-lipoxygenase inhibitor and COX-1 inhibitor. 1- St John’s wort isknown toaffect several cytochromeP450 isoenzymes and this accounts for the wide range of drugs with which St John’s wort has been reported to interact. The following is a list of cytochrome P450 isoenzymes that have been assessed with St John’s wort in a clinical setting:  CYP3A4: the main clinically relevant effect of St John’s wort on cytochrome P450 is the induction of CYP3A4. This has been shown to be related to the constituent, hyperforin. Products vary in their hyperforin content; preparations with a high-hyperforin content, given for a long period of time, will induce CYP3A4 activity, and therefore decrease the levels of drugs metabolised by CYP3A4, by a greater extent than preparationscontaininglow-hyperforinlevelstakenfor a shorter period of time. Conventionaldrugsareoftenused asprobesubstratesinorder toestablish the activity of another drug on specific isoenzyme systems.  CYP2C19: there are some clinical reports suggesting that St John’s wort induces CYP2C19.  CYP2C8: St John’s wort may induce CYP2C8.  CYP2C9: St John’swort mayinduce CYP2C9, but themechanism for these interactionsisnot conclusivebecausenot allCYP2C9 substrateshavebeen found to interact.  CYP2E1: St John’s wort may induce CYP2E1 but the general clinical importance of this is unclear.  CYP1A2: St John’swort isalsothoughttobeaninducer ofCYP1A2aslevels of caffeine and theophylline, both of which are CYP1A2 substrates, have been reduced by St John’s wort. However, the generalclinicalimportance of thisis unclear as other studieshave found no clinicallysignificanteffect on these drugs. This may be because St John’s wort only has a minor
  23. 23. 22 inducing effect on CYP1A2, which maydepend on the level of exposureto hyperforin.  CYP2D6: St John’s wort does not appear to affect the activity of CYP2D6 to a clinically relevant extent. 2- P-glycoprotein: St John’s wort is known to affect P-glycoproteinactivity, especiallyintestinal P-glycoprotein, and it isgenerallythought that inhibitiontakesplaceinitially, and briefly, but is followed by a more potent and longer-acting induction. It is the induction that leads to the clinically relevant drug interactions of St John’s wort that occur asa result ofthismechanism. Hyperforinisimplicated as the main constituent responsible for the effect. 3- Serotonin syndrome: St John’s wort inhibits the reuptake of 5- hydroxytryptamine (5-HT, serotonin) and this has resulted in a pharmacodynamic interaction, namely the development of serotonin syndrome with conventionaldrugsthat also have serotonergic properties. Interactions overview St John’s wort is known to interact with manyconventional drugsbecauseof its ability to induce the activity of CYP3A4 and P-glycoprotein, which are involved in the metabolism and distribution of the majority of drugs. Hyperforin is the active constituent believed to be central to the inducing effects of St John’s wort. As St John’s wort preparations and dose regimens are varied, the amount of hyperforin exposure will also vary a great deal, which makespredictingwhether aninteractionwilloccur, and towhat extent, difficult. St John’s wort interaction with Antidiabetics: St John’swort modestlydecreasestheAUCofgliclazideand rosiglitazone. Pioglitazone and repaglinide are similarly metabolised and may therefore be expected to interact similarly. St John’s wort does not affect the metabolism of tolbutamide. Mechanism:  Gliclazide is a substrate of the cytochrome P450 isoenzyme CYP2C9 and St. John’s wort induces this isoenzyme, thereby increasing the metabolism of gliclazide and reducing its levels.  Tolbutamide, anotherCYP2C9 substrate, wasunaffected bySt John’swort suggests that other factors may be involved.  Rosiglitazone is known to be metabolised principally by the cytochrome P450 isoenzyme CYP2C8, and it was therefore concluded that St John’s wort induces this isoenzyme.
  24. 24. 23 St John’s wort interaction with Antiepileptics: St John’s wort modestly increased the clearance of single-dose carbamazepine, but had no effect on multiple-dose carbamazepine pharmacokinetics. St John’s wort increased the clearanceof mephenytoinby about 3-fold and is predicted to reduce the blood levels of phenytoin and phenobarbital. Mechanism:  St John’s wort is a known inducer of CYP3A4, and the results with single- dose carbamazepine are as predicted. However, carbamazepine is also an inducer of CYP3A4, and inducesitsown metabolism (autoinduction). It is suggested that St John’s wort is not sufficiently potent an inducer to further induce carbamazepine metabolism when autoinduction has occurred, and thereforea smallinteractionisseenwith singledosesbut no interaction is seen with multiple doses.  Mephenytoin is a substrate of CYP2C19 and St John’s wort appears to induce this isoenzyme. St John’s wort interaction with Benzodiazepines: Long-term use of St John’s wort decreases the plasma levels of alprazolam, midazolam and quazepam. StJohn’swort preparationstakenasa singledose, or containing low-hyperforin levels, appear to have less of an effect. Mechanism:  Alprazolam, midazolam and quazepam are substrates of the cytochrome P450 isoenzyme CYP3A4. St John’s wort appearsto induce CYP3A4, thus increasing themetabolism oforalmidazolam, alprazolam1and quazepam, and reducing the bioavailability of these benzodiazepines. St John’s wort interaction with Calcium-channel blockers: St John’s wort significantly reduces the bioavailability of nifedipine and verapamil. Other calcium-channel blockers would be expected to interact similarly. Mechanism:  It appears that St John’s wort decreased the bioavailability of both nifedipineand verapamilby inducing their metabolism bythe cytochrome P450 isoenzyme CYP3A4 in the gut. St John’s wort interaction with Chlorzoxazone: St John’s wort increases the clearance of chlorzoxazone. Mechanism:
  25. 25. 24  It appears that St John’s wort increases the clearance of chlorzoxazone by inducing its metabolism by the cytochrome P450 isoenzyme CYP2E1. St John’s wort interaction with Cyclosporine: Marked reductions in ciclosporin blood levels and transplant rejection can occur within a few weeks of starting St John’s wort. Mechanism:  St John’s wort is induces the cytochrome P450 isoenzyme CYP3A4 by which cyclosporine is metabolized. Concurrent use therefore reduces cyclosporine levels. It has also been suggested that St John’s wort affects cyclosporine reabsorption by inducing the drug transporter protein, P- glycoprotein, in the intestine. St John’s wort interaction with Cimetidine: Cimetidine does not significantly alter the metabolism of the constituents of St John’s wort. Mechanism:  Cimetidine is an inhibitor of the cytochrome P450 isoenzymes CYP3A4, CYP1A2 and CYP2D6. This study suggests that St John’s wort is not significantly metabolised by these isoenzymes. St John’s wort interaction with Digoxin: There is good evidence that some preparations of St John’s wort canreducethelevels of digoxinbyabout one-quarter to one-third. Mechanism:  St John’s wort, and specificallyhyperforin hasbeenshown to increase the activity of the P-glycoprotein drug transporter protein in the intestines, which reduces the absorption of digoxin St John’s wort interaction with Imatinib: St John’s wort lowers serum imatinib levels. Mechanism  St John’s wort induces intestinal CYP3A4 and it therefore also reduces imatinib levels. St John’s wort interaction with NNRTIs:
  26. 26. 25 Thereis some evidenceto suggest that St John’swort may decreasethelevels of nevirapine. Delavirdine and efavirenz would be expected to be similarly affected. Mechanism  This finding supports predictions based on the known metabolism of the NNRTIs delavirdine, efavirenz and nevirapine by the cytochrome P450 isoenzyme CYP3A4, of which St John’s wort is a known inducer St John’s wort interaction with Opioids: St John’s wort reduces the plasma concentrations of methadone and withdrawal symptoms may occur. Mechanism:  St John’s wort is metabolised intheliver and inducesthecytochromeP450 enzyme CYP3A4, and so could affect plasma levels of drugsmetabolised in this way, such as methadone. St John’s wort interaction with Protease inhibitors: St John’s wort causes a marked reduction in the serum levels of indinavir, which mayresult inHIV treatment failure. Otherproteaseinhibitors, whether used alone or boosted by ritonavir, are predicted to interact similarly Mechanism:  Not fully understood, but it seems highlylikely that St John’s wort induces theactivityofthecytochromeP450 isoenzymeCYP3A4, therebyincreasing the metabolism of indinavir and therefore reducing its levels. St John’s wort interaction with Proton pump inhibitors: St John’s wort induces the metabolism of omeprazole, and this might result in reduced efficacy. Other proton pump inhibitors are likely to be similarly affected. Mechanism:  St John’s wort increases the metabolism of omeprazole by inducing both CYP2C19 and CYP3A4. St John’s wort interaction with SSRIs: Cases of severe sedation, mania and serotonin syndrome have been reported in patients taking St John’s wort with SSRIs.
  27. 27. 26 Mechanism:  A pharmacodynamic interaction may occur between St John’s wort and venlafaxine because they can both inhibit the reuptake of 5- hydroxytryptamine (serotonin). St John’s wort interaction with Statins: St John’s wort modestly decreases the plasma levels of atorvastatin and simvastatin, but not pravastatin. Mechanism:  The reason for this interactionisunknown, but St John’s wort may reduce the levels of simvastatin and its metabolite, and atorvastatin, by inducing the cytochrome P450 isoenzyme CYP3A4 or by having some effect on P- glycoprotein. St John’s wort interaction with Tricyclic antidepressants: The plasma levels of amitriptylineand itsactivemetabolite, nortriptyline, are modestly reduced by St John’s wort. Mechanism:  Not fully understood. St John’s wort is known to induce the activity of the cytochrome P450 isoenzyme CYP3A4, which is a minor route of metabolism of the tricyclic antidepressants. However, the tricyclics are predominantlymetabolised byCYP2D6, soan effect on CYP3A4 is unlikely to lead to a clinically relevant reduction in their levels. St John’s wort interaction with Warfarin and related drugs: St John’s wort can causea moderatereductioninthe anticoagulanteffectsof phenprocoumon and warfarin. Mechanism: Uncertain, but itissuggested thattheStJohn’swort increasesthemetabolism and clearanceoftheanticoagulantspossiblyby inductionof cytochromeP450 isoenzyme CYP3A4, and possibly also CYP2C9, as both R- and S-warfarin were affected.
  28. 28. 27 Other examples Carbohydrates: The impact ofcarbohydrateson drug metabolism isconflicting. It is known that high-carbohydratedietsmayinducetheexpressionof several glycolytic and lipogenic hepatic enzymes, but some suggest that carbohydrateshave little impact ondrug metabolism. However, noted that antipyrineand theophylline metabolism decreased incarbohydrate-supplemented dietsbut increased inthe protein-enriched diet, suggesting that carbohydratesand proteinhave oppositeeffects on oxidativedrug metabolism. Although many medicationsareoften given to childrenin a sugar syrup, littleresearch has been done on its effect on dispositionand action. Somestudiessuggested that dietarycarb ohydratesand fat may significantlyinfluencethe hepatic drug-metabolizing enzymes. Protein: Several investigators have reported that medications that undergo extensive first-pass effect, such as propranolol, metoprolol and lidocaine, can have enhanced bioavailabilityafter a high-proteinmealowing toenhanced hepatic blood flow. High-extraction drugs can then rapidly pass through the liver, allowing higher drug concentrationsinthesystemic circulation. A decreasein dietaryproteindepressescreatinineclearanceand renalplasma flow. Specific dietaryproteinscanalsoimpacta responsetoa medication. Oneoftheclassic examples is that of the monoamine oxidase inhibitor (MAOI) drug class and the amino acid tyramine that is contained in aged cheeses, pickled/smoked meats, fermented foods, and red wines. Tyramine is an indirect sympathomimetic amine that releases norepinephrine from the adrenergic neurons, causing a significant pressor response. Typically, tyramine is metabolized by the enzyme monoamine oxidase before any significant increases in blood pressure are seen. If the enzyme is blocked, however, severe and potentiallyfatalrises in blood pressure canoccur when tyramine- rich foods are ingested.
  29. 29. 28 Other medications, such as the oxazolidinone antibiotic, linezolid, also have MAOI properties and patients should avoid ingesting large amounts of tyramine while being treated with this antibiotic. Dietaryproteinalsoaffectstherenaltubular transport ofcertaincompounds, although the mechanism by which this occurs is still not understood. The binding of dietary proteins to a drug may underscore changes in bioavailability after a protein meal. For example, increases in both the maximum concentration and area under the curve are seen in patients receiving gabapentin. This enhanced absorption was attributed to trans- simulation, a carrier-mediated processin which increased intestinalluminal amino acid concentrations result in an up-regulation and/or increased activity of the L-amino acid transporter. Dietaryfat: Lipids are an essential part of cell membrane structure and are involved in many of the normal enzymatic activities located within the cell membrane. Diets that are deficient in fat or essential fatty acids decrease the activity of the enzyme systems responsible for the metabolism ofnutrients. Plasma free fatty acid levels become elevated after consumption of a high-fat meal, increasing the potential to become bound to plasma albumin, and subsequently displace albumin bound drugs, increasing the risk of drug toxicity. Dietary fats along with food-stimulated secretions (eg, bile salts) may facilitate the solubility of lipophilic compounds. This may contribute to a reduction in the extent of first past metabolism due to enhanced splanchnic blood flow. Ingestion of diets high in fat has been associated with the induction of CYP2E1. The extent to which this enzyme is up-regulated is dependent upon the type of fat. Polyunsaturated fats such as corn and menhadenoils appear to have thegreatest influencein comparisontolard or olive oils. This can result in enhanced peroxidation of the polyunsaturated fatty acid substrates and contribute to free radical production. The rate of
  30. 30. 29 gastric emptying is also influenced by the fat content of a meal. Fat retards gastric emptying to a greater degree than does protein or carbohydrate. The antiviral agent zidovudine is also impacted by dietary fat. When administered orally, its absorption is reduced when the drug is taken with a high-fat meal in comparison with when taken in the fasted state. It is recommended that zidovudinebetakenonanemptystomach toachievepeak serum concentrations. High-fat, high-cholesterol meals can sharply reduce the effect of ACE inhibitors such as enalapril, as well as statins and other cholesterol medications. Minerals: Some medications, notablybeta blockers such as metoprololthat are used to treat high blood pressure, are greatly inhibited by high levels of calcium or sodium at a meal. Thosenutrients, whilenecessaryin their ownright, bind to the medication and decrease its availability to the body. Others like tetracycline and ciprofloxacin are markedly reduced by milk and other dairy products, because the calcium in the milk binds the antibiotic due to their chelation property that lead to insoluble complex that prevents gut absorption as well as supplemental magnesium, iron, or zinc will decrease these drugs absorption
  31. 31. 30 Vegetables: Diets rich in vegetables and fruit may also impact the response to medications. Both serve as sources of trace minerals that are contained in metalloenzymes, including several antioxidants. Many plants contain flavonoids, isothiocyanates, and allyl sulfides that are potent modulators of the cytochrome monoxygenase system. Phyotochemicals are linked with the modulation of a variety of metabolic pathways. The most frequently sources includecruciferousvegetables, citrus juices, and spices. Dietary supplements and herbs are also associated with this category. There are five major families of phytochemicals: carotinoids (eg, beta carotene, lycopene), alkaloids, phenolics (include flavonoids, coumarins, tannins), nitrogen compounds, and sulfur compounds (eg, isothiocyanates, allylic sulfur). Recent research has focused on how vegetables and fruits can influence a variety of enzymatic pathways. Typically induction of these enzyme systems is rapid and plateaus within days of continued daily ingestions of the food with theenzymeinducing capacity. Cruciferousvegetables, including brussels sprouts, cabbage, turnips, broccoli, cauliflower, and spinach, contain indols that induce arylhydrocarbon hydroxylase enzyme activity as well as the conjugation of phenacetin and acetaminophen. Potatoes, tomatoes, and eggplant contain natural insecticide compounds called solanaceous glycoalkaloids that even in small amounts may greatly slow the metabolism of muscle relaxants and anesthetic agents such as suxamethonium, mivacurium, and cocaine. Cooking does not reduce them and theymayremaininthebodyfor several daysafter ingestion. Solanaceous glycoalkaloids inhibit butyryl cholinesterase, which breaks down many anesthetic agentsand cetylcholinesterase, which breaks down acetylcholine.
  32. 32. 31 Insoluble fibers: High-fiber foods can have unpredictable effects on the absorption of medications. For example, insoluble dietary fiber, the kind found in bran or brown rice, can seriously inhibit body's absorption of the heart medication digoxin. Whole grains can also take a long time to move through digestive tract and that means medicationswhich isbeen takenwith or just before the meal can spend longer than they should in the high-acid environment of the stomach, and their effectiveness can be impaired by the time they reach the intestine. Soluble fibers and gelling agents: Soluble fiber is the kind found in oatmeal and in fiber supplements such as psyllium. It forms a stickygel inthe presenceof moisture, which immobilizes nutrientsand medicationsinthedigestivesystem and slowstheir absorption, it can seriously reduce the absorption of many antibiotics and other drugs such as warfarin. Solublefiber and closely related gelling agentssuch as guar gum and xanthan gum, often found in gluten-free foods, can also slow absorption of many common medications.
  33. 33. 32 Very low calorie diets: In diets involving severe protein-energy restriction, such as extreme slimming diets, the metabolism of drugsmay be affected in one of two ways. First, tissueproteiniscatabolized and used asanenergysource, thusreducing theavailabilityofaminoacidsfor proteinsynthesis, which inturnreducesthe amount of enzymes available for drug metabolism. Second, endogenous substrates derived from carbohydrate and protein such as glucuronide, sulfate, and glycine could also compete for the tissue needs for these nutrients and that of the drug metabolism. Eating habits, especially among dieters that omits or severely restrict whole categoriesoffoods, havea negativeimpactonmicronutrient status. Dietsthat eliminate all animal foods have been associated with other vitamin deficiencies including vitamin C. Moreover, skipping meals and fad diets to lose weight frequently compromise micronutrient intake. It should be routinelyassumed that it isextremelydifficult tomeet alltherequirementsat intakes of less than 1,200 calories per day. Patientswithverylow caloriediet weightlosshaveimproved hyperinsulinism as a result of a reduction in basal insulin production as well as enhanced hepatic insulin extraction. Moreover, it is thought the weight loss through very low calorie diet lowers the hepatic glucuronidation of drugs leading to higher plasma concentrations of the affected drugs. Other dietary restrictions: In additiontocaloric restriction, restrictionof other dietarycomponentscan also impact drug response. In patients who have sodium restricted diets, there is an increased risk of acuterenal failure if these samepatientsare given concomitantangiotensin- converting enzyme inhibitors (ACE inhibitors) or non-steroidal anti- inflammatoryagents (NSAIDS). Thereisenhanced nephrotoxicityinpatients who are sodium depleted and are given cyclosporine or tacrolimus. Sodium restriction can also increase the renal tubular absorption of lithium, leading to toxicity. Patients receiving aminoglycosides, amphotericin, cisplatin, or
  34. 34. 33 radiocontrast mediainconjunctionwith a low-sodium diet haveanincreased risk for hemodynamic nephrotoxic and ischemic acute renal failure. For reasonsstill not known, theefficacyof calcium channelblockersisreduced in patients on a sodium-restricted diet. Vegetarianism: Drug metabolism among vegetarianswillvarydramaticallydepending onthe protein intake. Most research has focused on Asian vegetarians in which the half-livesof drugsthat underwentsignificanthepaticmetabolism (antipyrine, acetaminophen and phenacetin) were significantly longer than in nonvegetarians. Vegetarian diets are also associated with lower circulating concentrations of sex steroids hormones, increased fecal excretion of estrogens and different hormonal profiles in comparison to individuals consuming an omnivorous diet. Vegetable intake may influence total body estrogen load via the modulationofCYP enzymesinvolved inestrogenmetabolism. CYP13C, found in cruciferous vegetables, can increase estrogen hydroxylation. Impact of beverage type on drug bioavailability: The term beveragereferstoany drinkableliquid other thanplainwater. They are typically classified as caffeinated, alcoholic, milk-based, mineral waters, or fruit/vegetables juices. Depending upon the type of fluid taken with a medication, drug absorption may be affected. Mixing drugs with fruit juices or other beverages to mask their taste may impact absorption due to changes in gastric pH. Dairy products decrease the absorption of tetracyclines and reduce their bioavailability due to the formation of insoluble chelates between the drug and the calcium present in the beverage. Similar decreases in bioavailability were noted when fluoride tablets are taken with milk. Tannins present in teas may impair iron absorption. Alcoholic beveragesreducethe absorptionoffolic acid, cyanocobalamin, and magnesium.
  35. 35. 34 Soft drinks, such as colas, may decrease drug absorption for a variety of reasons. The phosphoric acid and sugar present in these drinks can slow gastric emptying and the tendencyto serve them chilled may also reducethe rate of blood flow within the intestines. Moreover, the carbonation may increase mixing and possibly motility. Interestingly, the acidic pH of cola beveragescanbeused tooptimizeclinicalresponses ofboth ketoconazoleand itraconazole in patients with gastric hypochlorhydria, such those patients with AIDS gastropathy. The effects of grapefruit juice on drug disposition have been discussed separately. Liquorice: Liquorice contain glycyrrhizin (glycyrrhizinic or glycyrrhizic acid) which is hydrolyzed in the intestine to pharmacologically active compound glycyrrhetic acid which inhibit 11 betahydroxysteroid dehydrogenase. This increase cortisol in kidney and act as aldosterone (fluid retention, hypokalemia, hypertension), so Liqourice should not be administrated with antihypertensive drugs. Garlic: Aspirin and protease inhibitors are some of the medicines that may cause a negative interaction with garlic. Drug interactions such as these may cause
  36. 36. 35 complications, such asdecreasing themedications' effectivenessor increasing the risk of bleeding. Garlic may exaggerate the activity of medications that inhibit the action of platelets in the body. Examples of such medications include indomethacin, dipyridamole, Plavix, and aspirin, as well as there have been reports of a possible interaction between garlic and warfarin that could increase the risk of bleeding in people taking this blood thinning medication. Garlic may reduce blood levels of protease inhibitors, a medication used to treat people with the human immunodeficiency virus (HIV) which include indinavir, ritinavir, and saquinavir. Iodine-rich foods: Anti-thyroid drugs are compounds that interfere with the body’s production of thyroid hormones, thereby reducing the symptoms of hyperthyroidism. Anti-thyroid drugs work by preventing iodine absorption in the stomach. A high-iodine diet requires higher doses of anti-thyroid drugs. The higher the dose of anti-thyroid drugs, the greater the incidence of side effects that include rashes, hives, and liver disease. The richest dietary sources of iodine are seafood and seaweed, such as kelp and nori. Iodine is also found in iodized salt and to a lesser extent in eggs, meat, and dairy products.
  37. 37. 36 .Alcohol and Medication Interactions Most people who consume alcohol, whether in moderate or large quantities, also take medications, at least occasionally. As a result, many people ingest alcohol while a medication is present in their body or vice versa. A large number of medications—both those available only by prescription and those availableover the counter (OTC)—havethe potentialtointeract with alcohol. Those interactions can alter the metabolism or activity of the medication and/or alcohol metabolism, resulting in potentially serious medical consequences. For example, thesedativeeffectsofboth alcoholand sedativemedicationscan enhanceeach other (i.e., the effectsareadditive), therebyseriouslyimpairing a person’s ability to drive or operate other types of machinery. Most studies assessing alcohol medication interactions focus on the effects of chronic heavy drinking. Relatively limited information is available, however, on medication interactions resulting from moderate alcohol consumption (i.e., one or two standard drinks 1 per day). Researchers, physicians, and pharmacists must therefore infer potentialmedicationinteractionsat moderatedrinking levels based on observations made with heavy drinkers. In addition, moderate alcohol consumption may directly influence some of the disease states for which medications are.
  38. 38. 37 Common Alcohol-Medication Interactions: Mechanisms of Alcohol-Medication Interactions Interactions between alcohol and a medication can occur in a variety of situationsthatdiffer based onthetiming of alcohol and medicationconsumption. For example, such interactions can occur in people who consume alcohol with a mealshortlybeforeor after taking a medication or who take pain medications after drinking to prevent a hangover. Alcohol-medication interactions fall into two general categories: pharmacokinetic and pharmacodynamic. - Pharmacokinetic interactions are those in which the presence of alcohol directly interferes with the normal metabolism of the medication. This interference can take two forms, as follows:  The breakdown and excretion of the affected medications are delayed, because the medications must compete with alcohol for breakdown by cytochromeP450. Thistypeof interactionhasbeen described mostlyfor metabolic reactions involving CYP2E1, but it also may involve CYP3A4 and CYP1A2.  The metabolism of the affected medications is accelerated, because alcohol enhances the activity of medication-metabolizing cytochromes. When alcohol is not present simultaneously to compete for the cytochromes, increased cytochrome activity results in an increased elimination rate for medications that these enzymes metabolize. - Pharmacodynamic alcohol-medication interactions do not involve enzyme inhibitionor activation, but rather refer totheadditiveeffectsofalcoholand certain medications. In this type of interaction, which occurs most commonly in the centralnervous system (CNS), alcohol alters the effects of the medication without changing the medication’s concentration in the blood. With some medications (e.g., barbiturates and sedative medications called benzodiazepines), alcoholactsonthesamemoleculesinsideor onthe surface of the cell as does the medication. These interactions may be synergistic—that is, theeffectsofthe combined medicationsexceed thesum of the effects of the individual medications. With other medications (e.g., antihistamines and antidepressants) alcohol enhances the sedative effects of those medications but acts through different mechanisms from those agents.
  39. 39. 38  Specific Alcohol-Medication Interactions This section describes different classes of medications and their interactions with alcohol. The potential for the occurrence and relevance of alcohol- medication interactions in moderate drinkers may differ, however, between pharmacokinetic and pharmacodynamic interactions. The number of potential pharmacokinetic interactions with alcohol is great, because the various cytochrome P450 enzymes metabolize many medications. However, many of the pharmacokinetic interactions discussed here were first discovered in heavy drinkers or alcoholics or were studied in animals given large alcohol doses in their diet. Although the potential for such effects certainlyexistseven after low alcohol consumption, researchershavenot yet demonstrated the occurrence and relevance of those effects in moderate drinkers. Conversely, pharmacodynamic interactions can occur with intermittent alcoholconsumptionand evenafter a single episodeof drinking. Accordingly, those interactions clearly pertain to moderate drinkers.  Antibiotics: The package inserts for most antibiotics include a warning for patients to avoid using alcohol with those medications. Therationalefor these warnings isnot entirelyclear, however, becauseonlya few antibioticsappear tointeract with alcohol. For example, although some antibiotics induce flushing, most antibiotics do not. The antibiotic erythromycin may increase alcohol absorptionintheintestine(and, consequently, increaseBALs) byaccelerating gastric emptying. Furthermore, people taking the antituberculosis drug isoniazid should abstain from alcohol, because isoniazid can cause liver damage, which maybeexacerbatedbydailyalcoholconsumption. Asidefrom
  40. 40. 39 these effects, however, moderate alcohol consumption probably does not interfere with antibiotic effectiveness. Possibly, concerns regarding the concurrent use of alcohol and antibiotics grew from research findings indicating that heavy alcohol use can impair the function of certain immune cells and that alcoholics are predisposed to certain infections. These effects, however, are unlikely to occur in moderate drinkers.  Antidepressants Several classes of antidepressant medications exist, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase (MAO) inhibitors, and atypical antidepressants. These classes differ in their mechanism of action in that they affect different brain chemicals. All types of antidepressants, however, have some sedative as well assome stimulating activity. TCAswith a higherratioofsedativeto-stimulant activity (i.e., amitriptyline, doxepin, maprotiline, and trimipramine) will causethemost sedation. AlcoholincreasestheTCAs’ sedativeeffectsthrough pharmacodynamic interactions. In addition, alcohol consumption can cause pharmacokinetic interactions with TCAs. For example, alcohol appears to interferewith thefirst-passmetabolism ofamitriptylineintheliver, resulting in increased amitriptyline levels in the blood. In addition, alcohol-induced liver disease further impairs amitriptyline breakdown and causes significantlyincreased levels of activemedicationin the body (i.e., increased bioavailability). High TCA levels, in turn, can lead to convulsions and disturbances in heart rhythm. SSRIs (i.e., fluvoxamine, fluoxetine, paroxetine, and sertraline), which are currently the most widely used antidepressants, are much less sedating than are TCAs. In addition, no serious interactions appear to occur when these agents are consumed with moderate alcohol doses. In fact, SSRIs have the best safety profile of all antidepressants, even when combined in large quantities with alcohol (e.g., insuicideand overdosesituations). Conversely, peopletaking MAOinhibitors or atypical antidepressants can experience adverse consequences when simultaneously consuming alcohol. Thus, MAO inhibitors (e.g. phenelzine and tranylcypromine) can induce severe high blood pressure if they are consumed together with a substancecalled tyramine, which is present in red wine. Accordingly, people taking MAO inhibitors should be warned against drinking red wine. The atypical antidepressants (i.e., nefazodone and trazodone) may cause enhanced sedation when used with alcohol.  Antihistamines These medications, which are available both by prescription and OTC, are used in the management of allergies and colds. Antihistamines may cause drowsiness, sedation, and low blood pressure(i.e., hypotension), especiallyin elderly patients. Through pharmacodynamic interactions, alcohol can substantially enhance the sedating effects of these agents and may thereby
  41. 41. 40 increase, for example, a person’s risk of falling or impair his or her ability to drive or operate other types of machinery. As a result of these potential interactions, warning labels on OTC antihistamines caution patients about the possibilityof increased drowsinesswhen consuming themedicationwith alcohol. Newer antihistamines (i.e., certrizine and loratidine) have been developed tominimizedrowsinessand sedationwhilestillproviding effective allergy relief. However, these newer medicationsmaystill be associated with an increased risk of hypotension and falls among the elderly, particularly when combined with alcohol. Consequently, patients taking nonsedating antihistamines still should be warned against using alcohol.  Barbiturates These medications are sedative or sleep-inducing (i.e., hypnotic) agents that arefrequentlyused for anesthesia. Phenobarbital, which isprobablythemost commonly prescribed barbiturate in modern practice, also is used in the treatment of seizure disorders. Phenobarbital activates some of the same molecules in the CNS as does alcohol, resulting in pharmacodynamic interactionsbetweenthetwosubstances. Consequently, alcoholconsumption whiletaking phenobarbitalsynergisticallyenhancesthemedication’ssedative side effects. Patients taking barbiturates therefore should be warned not to perform tasks that require alertness, such as driving or operating heavy machinery, particularlyafter simultaneousalcoholconsumption. In addition to thepharmacodynamic interactions, pharmacokineticinteractionsbetween alcohol and phenobarbital exist, because alcohol inhibits the medication’s breakdown in the liver. This inhibition results in a slower metabolism and, possibly, higher blood levels of phenobarbital. Conversely, barbiturates increase total cytochrome P450 activity in the liver and accelerate alcohol eliminationfrom theblood. Thisaccelerationofalcoholeliminationprobably does not have any adverse effect.  Benzodiazepines Like barbiturates, benzodiazepines(BZDs) areclassified assedative-hypnotic agents and act through the same brain molecules as do barbiturates. Accordingly, as with barbiturates, concurrent consumption of BZDs and moderateamountsofalcoholcancausesynergistic sedativeeffects, leadingto substantial CNS impairment. It is worth noting that both barbiturates and benzodiazepines can impair memory, as can alcohol. Consequently, the combination of these medications with alcohol would exacerbate this memory-impairing effect. Infact, thiseffect sometimesisexploited bymixing alcoholic beverages with BZDs, such as the rapid-acting flunitrazepam, an agent implicated in date rape. In addition, the metabolism of certain BZDs involves cytochrome P450, leading to the alcohol-induced changes in metabolism described earlier in this article.
  42. 42. 41  Histamine H 2 Receptor Antagonists (H2RAs) As mentioned earlier in this article, H2RAs (e.g., cimetidine, ranitidine, nizatidine, and famotidine), which reduce gastric acid secretion, are used in the treatment of ulcers and heartburn. These agents reduce ADH activity in the stomach mucosa, and cimetidine also may increase the rate of gastric emptying. Asa result, alcohol consumed with cimetidineundergoeslessfirst- pass metabolism, resulting in increased BALs. For example, in a study of people who consumed three or four standard drinks over 135 minutes while taking cimetidine, BALs rose higher and remained elevated for a longer period of timethaninpeople not taking cimetidine. Not allH2RAs, however, exert the sameeffect on BALs when takenwith alcohol. Thus, cimetidineand ranitidine have the most pronounced effect, nizatidine has an intermediate effect, and famotidine appears to have no effect (i.e., appears not to interact with alcohol). In addition, because women generally appear to have lower first-pass metabolism of alcohol, they may be at less risk for adverse interactions with H2RAs.  Muscle Relaxants Several muscle relaxants (e.g., carisoprodol, cyclobenzaprine, and baclofen), when taken with alcohol, may produce a certain narcotic-like reaction that includesextremeweakness, dizziness, agitation, euphoria, and confusion. For example, carisoprodol is a commonly abused and readily available prescription medication that is sold as a street drug. Its metabolism in the liver generates an anxiety-reducing agent that was previously marketed as a controlled substance (meprobamate). The mixture of carisoprodol with beer is popular among street abusers for creating a quick state of euphoria.  Nonnarcotic Pain Medications and Anti-Inflammatory Agents Many people frequently use nonnarcotic pain medications and anti- inflammatory agents (e.g., aspirin, acetaminophen, or ibuprofen) for headaches and other minor aches and pains. In addition, arthritis and other disorders of the muscles and bones are among the most common problems for which older people consult physicians. Nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, naproxen, indomethacin, and diclofenac) and aspirin are commonly prescribed or recommended for the treatment of these disorders and are purchased OTC in huge amounts. Several potential interactions exist between alcohol and these agents, as follows: • NSAIDs have been implicated in an increased risk of ulcers and gastrointestinal bleeding in elderly people. Alcohol may exacerbate that risk by enhancing the ability of these medications to damage the stomach mucosa.
  43. 43. 42 • Aspirin, indomethacin, and ibuprofen cause prolonged bleeding by inhibiting the function of certain blood cells involved in blood clot formation. This effect also appears to be enhanced by concurrent alcohol use. • Aspirin has been shown to increase BALs after small alcohol doses, possibly by inhibiting first-pass metabolism. An important pharmacokinetic interaction between alcohol and acetaminophen can increase the risk of acetaminophen-related toxic effects on the liver. Acetaminophen breakdown by CYP2E1 (and possibly CYP3A) results in the formation of a toxic product that can cause potentially life- threatening liver damage. As mentioned earlier, heavy alcohol use enhances CYP2E1 activity. In turn, enhanced CYP2E1 activity increases the formation of the toxic acetaminophen product. To prevent liver damage, patients generally should not exceed the maximum doses recommended by the manufacturers (i.e., 4 grams, or up to eight extra-strength tablets of acetaminophen per day). In people who drink heavily or who are fasting (which also increases CYP2E1 activity), however, liver injury may occur at doses as low as 2 to 4 grams per day. The specific drinking levels at which acetaminophen toxicity is enhanced are still unknown. Because acetaminopheniseasilyavailableOTC, however, labels on thepackageswarn people about thepotentiallydangerousalcohol-acetaminophencombination. Furthermore, people should be aware that combination cough, cold, and flu medications may contain aspirin, acetaminophen, or ibuprofen, all of which might contribute to serious health consequences when combined with alcohol.  Opioids Opioids are agents with opium-like effects (e.g., sedation, pain relief, and euphoria) that areused aspainmedications. Alcoholaccentuatestheopioids’ sedating effects. Accordingly, all patients receiving narcotic prescriptions should be warned about the drowsiness caused by these agents and the additive effects of alcohol. Overdoses of alcohol and opioids are potentially lethal becausethey can reducethe cough reflex and breathing functions; asa result, the patientsareat riskofgetting foods, fluids, or other objectsstuckin their airways or of being unable to breathe. Certain opioid pain medications (e.g., codeine, propoxyphene, and oxycodone) are manufactured as combinationproductscontaining acetaminophen. Thesecombinationscanbe particularly harmful when combined with alcohol because they provide “hidden” doses of acetaminophen. As described in the previous section, alcohol consumption may result in the accumulation of toxic breakdown productsofacetaminophen. Therefore, patientsusing opioid-acetaminophen combinationproductsshould becautioned aboutrestricting thetotalamount
  44. 44. 43 of acetaminophen they ingest daily (i.e., they should not take regular acetaminophen in addition to the combination product).  Warfarin The anticoagulant warfarin is used for the prevention of blood clots in patientswith irregular heart rhythmsor artificialheart valves; it is also used to treat clots that form in extremities such as legs, arms, or sometimes the lungs. Its anticoagulant effect is acutely altered by even small amounts of alcohol. In people taking warfarin and ingesting a few drinks in one sitting, anticlotting effects may be stronger than necessary for medical purposes, placing these people at risk for increased bleeding. This excessive warfarin activity results from alcohol related inhibition of warfarin metabolism by cytochrome P450 in the liver. Conversely, in people who chronically drink alcohol, long term alcohol consumption activates cytochrome P450 and, consequently, warfarin metabolism. As a result, warfarin is broken down faster than normal, and higher warfarin doses are required to achieve the desired anticoagulant effect. Thus, alcohol consumption can result in dangerouslyhigh or insufficient warfarinactivity, depending onthe patient’s drinking pattern. Therefore, patients taking warfarin generally should avoid alcohol.
  45. 45. 44 Counseling and Guidance about Drug-Food Interactions: The following information can be given to the patients while dispensing the medicine. 1. Read the prescription label on the container. If you do not understand something or think you need more information, ask your physician or pharmacist. 2. Read directions, warnings and interaction precautions printed on all medication labels and package inserts. Even over-the-counter medications can cause problems. 3. Take medication with a full glass of water. 4. Do not stir medicationintoyour food or takecapsules apart (unlessdirected by your physician). This may affect the efficacy of medication. 5. Do not takevitaminpillsat thesametimeyou takemedication. Vitaminsand minerals can interact with some drugs. 6. Do not mix medicationintohot drinksbecausethe heat from the drink may destroy the effectiveness of the drug. 7. Never take medication with alcoholic drinks. 8. Be sure to tell your physician and pharmacist about all medications you are taking, both prescription and nonprescription. 9. Checkwith thepharmacist onhow food canaffect specific medications taken with the food.
  46. 46. 45 Summary of some signifiant Food-Drug Interactions Condition Drug Use Interactions/Guidelines Examples Allergies Antihistamine To relieve or prevent the symptoms of colds, hay fever and allergies Food: Take with water, if GI distress occurs consumewith food. Exception: Fexofenadine, bioavailability decreases if taken with apple, orange, or grapefruit juice Avoidalcohol Diphenhydrami ne Fexofenadine Loratadine Cetirizine Arthritis and Pain Analgesic/Anti pyretic To treat mild to moderate pain and fever Food: For rapid relief, take on empty stomach Caffeine: May increase the rate of absorption of the drug Avoidalcohol Acetaminophen Non-Steroidal Anti- Inflammatory Drugs (NSAIDS) To reduce, pain, fever and inflammation Food: Take with food, water, or milk to decrease stomach upset. With a high dose of this drug, one may need to increase consumption of vitamin C, vitamin K, and folate Caffeine: Limit intake Supplements: Limit or avoid products that affect blood coagulation (garlic, ginger, gingko, ginseng, or horse chestnut) Avoidalcohol Aspirin Ibuprofen Naproxen Corticosteroid s To relieve inflamed areas of the body, reduce swelling and itching, allergies, rheumatoid Food: Take with food or milk to decrease stomach upset. Limit grapefruitand other citrus fruits. While taking this drug, one may need to decrease sodium, and supplement Methyprednisol on Prednisone Prednisone Cortisone acetate
  47. 47. 46 arthritis, and other conditions the diet with calcium, vitamin D, K, A, C, or protein Caffeine: Limit intake Avoidalcohol Narcotic Analgesic To provide relief for moderate to severepain Food: Take with food or milk to decrease stomach upset Avoidalcohol Codeine combined with acetaminophen Morphine Asthma Bronchodilato rs To treat the symptoms of bronchial asthma, chronic bronchitis, and emphysema Food: Take with food if stomach upset occurs. High-fatmeals may increase the amount of theophylline in the body, while high- carbohydratemeals may decrease it. Different foods may have decrease it. Different foods may have varying effects depending on the doseform Caffeine: Avoid eating or drinking large amounts of foods and beverages that contain caffeine Avoidalcohol Theophylline Albuterol Epinephrine Cardio- Vascular Disorders Diuretics To help eliminate water, sodium and chloride from the body Food: Take on an empty stomach since food reduces drug availability. Take with food or milk if stomach upset occurs. Since some diuretics causeloss of potasium, calcium, and magnesium, supplementation of these minerals may be necessary. Trimtereneis known as a “potassium sparing” diuretic. When taking triamterene avoid eating large amounts of potassium-rich foods Fuorsemide Triamterene Hydrochlorothi azide Bumetamide Metolazone
  48. 48. 47 such as bananas, oranges and green leafy vegetables or salt substitutes. Avoid natural licorice. Cholesterol Lowering Food: Take with food. Do not take with grapefruitor other citrus fruits. Follow a diet low in cholesterol and dietary fat Avoidalcohol Zocor Beta Blockers To decrease the nerve impulses to blood vessels. Food: Take with food to increase bioavailability. Take separately from orangejuice, and avoid natural licorice. Itmay be necessary to decrease dietary calcium and sodium, which may decrease absorption Avoidalcohol Atenolol Metoprolol Propranolol Nadolol Nitrates To relax blood vessels and lower the demand for oxygen by the heart. Food: Take on an empty stomach with water to increase absorption, 1 hour before meals or 2 hours’ after Avoidalcohol Isosorbide dinitrate Nitroglycerin Angiotensin Converting Enzyme Inhibitors (ACEI) To relax blood vessels by preventing angiotension II a vasoconstrict or frombeing formed. Food: High fat meals decrease absorption of quinapril. Ensure adequate fluid intake. Avoid salt, calcium, and natural licorice. Avoid salt, calcium, and natural licorice. Captopril Enalapril Lisinopril Quinapril Moexipri HMG-CoA Reductase Known as “statins” intended to lower cholesterol, and reduce the Food: Avoid grapefruit/related citrus with atorvastatin, lovastatin and simvastatin. Lovastatin should be taken with the evening meal to enhance absorption. Atorvastatin Fluvastatin Lovastatin Pitavastatin Simvastatin
  49. 49. 48 production rate of LDL Decreasedietary fat and cholesterol while taking these medications Supplements: Avoid St. John’s wort Avoidalcohol Anticoagulant s To prevent the formation of blood clots Food: Limit foods with vitamin K, since it produces blood-clotting substances thatreduce the effectiveness of anticoagulants. Do not exceed the upper limit for vitamin E and A Supplements: Avoid garlic, ginger, ginko saw palmetto, and horse chestnut Warfarin Infections Antibacterials /Penicillin To treat infections caused by bacteria and fungi Food: Take on an empty stomach, or 1 hour before or 2 hours after food. If upsetstomach occurs, takewith food. Avoid guar gum Supplements: Use caution when taking vitamin K Penicillin V Amoxicillin Ampicillin Quinolones To treat infections caused by bacteria and fungi Food: Take on an empty stomach, or 1 hour before or 2 hours after food. If upsetstomach occurs, takewith food but not with dairy or calcium-fortified products alone Caffeine: Taking these medications with caffeine-containing products may increase caffeine levels, leading medications with caffeine-containing products may increase Ciprofloxacin Levofloxacin Ofloxacin Trovafloxacin
  50. 50. 49 to excitability and nervousness Cephalosporin s To treat infections caused by bacteria and fungi Food: Take on an empty stomach, or 1 hour before or 2 hours after food. If upsetstomach occurs, takewith food Cefaclor Cefradroxil Cefixime Cefprozil Cephalexin Macrolides To treat infections caused by bacteria and fungi Food: May take with food if stomach upset occurs Exceptions: Zmax should be taken on an empty stomach one hour before or 2 hours after food. Avoid taking with citrus foods, citrus juices, and carbonated drinks Azithromycin (Zmax) Clarithromycin Sulfonamides To treat infections caused by bacteria and fungi Food: Take with food and at least 8 ounces of water Avoidalcohol Sulfamethoxazo le + trimethoprim Tetracyclines To treat infections caused by bacteria and fungi Food: Take with food and at least 8 ounces of water. Avoid taking tetracycline with dairy tetracycline with dairy products, antacids, and vitamin supplements containing iron because they can interfere with the medication’s effectiveness Tetracycline Doxycycline Minocycline Nitromidazole To treat infections caused by bacteria and fungi Food: May take with food to decrease stomach upset, but food decreases bioavailability Avoidalcohol Metronidazole Antifungals To treat infections caused by fungi Food: Take with food to increase absorption. Do not take itraconazole with grapefruitor related citrus with Fluconazole Ketoconazole Itraconazole
  51. 51. 50 grapefruitor related citrus Avoidalcohol Mood Disorders Monoamine Oxidase Inhibitors (MAOI) To treat depression, emotional and anxiety disorders Food: These medications have many dietary restrictions and those taking them should follow the dietary guidelines and physician instructions very carefully. A rapid, potentially fatal increase in blood pressurecan occur if foods or alcoholic beverages containing tyramine are consumed while taking MAO inhibitors. Avoid foods high in tyramine and other pressor amines during drug use and for 2 weeks after discontinuation. These include aged cheeses, aged meats, soy sauce, tofu, fava beans, snowpeas, auerkraut, avocadoes, bananas, yeastextracts, raisins, ginseng, licorice, chocolate, and caffeine Avoidalcohol Phenelzine Tranycypromine Anti-Anxiety Drugs To treat depression, emotional and anxiety disorders Food: May take with food if upsetstomach occurs. Limit grapefruit and citrus consumption Caffeine: May cause excitability, nervousness, and hyperactivity and lessen the anti-anxiety effects of the drugs Supplements: Use caution with sedative Lorazepan Diazepam Alprazolam
  52. 52. 51 herbal products such as chamomile, kava, or stimulants such as caffeine or, Sedative- hypnotic or mate Avoidalcohol Antidepressat Drugs To treat depression, emotional and anxiety disorders. Food: These medications can be with or withoutfood Avoidalcohol Paroxetine Sertraline Fluoxetine Stimulant Food: Take with or without meals. Limit caffeine, and ensure adequate calcium intake. Methylphenidat e Depressant Sedative- hypnotic Food: Do not take with food, or immediately after a meal Zolpidem Stomach Histamine Blockers To relieve pain, promote healing, and prevent irritation from returning Food: These medications can be taken with or without food, with 8 ounces of water. A bland diet is recommended. Take drug 2 hours beforean iron or antacid supplement is consumed. May decrease iron and vitamin B12 absorption Caffeine: Caffeine products may irritate the stomach Avoidalcohol Cimetidine Famotidine Ranitidine Nizatadine Seizures Anticonvulsat/ Antiepileptic Therapy Food: Take with food or milk to decrease stomach upset Avoid grapefruitor related citrus fruits, star fruits, or pomegranatejuice. Supplement with calcium and vitamin D Tegretol Equetro Carbatrol
  53. 53. 52 Avoidalcohol References: 1- Stockley’s Drug Interactions; Eighth edition; Edited by Karen Baxter, 2008. 2- Handbook of Food-Drug interactions; Edited by Beverly J. McCabe, Eric H. Frankel and Jonathan J. Wolfe, 2003. 3- Chan LN: Drug-Nutrient Interactions; in Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ (eds): Modern Nutrition in Health and Disease. Baltimore, Lippincott Williams & Wilkins, 2006, pp 1540–1553. 4- Food and drug interactions: general review, Department of Food Engineering, Ege University of Izmir, 35100 Bornova Izmir, Turkey. 5- Pharmacological Sciences: Perspectives for Research and Therapy in the Late 1990s pdf

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