Food Drug Interaction. Prof.Dr Naji Abuirmeileh

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Letitia Lambert
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1 Food Drug Interaction Prof.Dr Naji Abuirmeileh

2 Aims of the Topic for patients care Personal 1 st - Raising awareness of potential interactions to make the integration of nutrition and pharmacotherapy a routine component of patient care. 2 nd - Knowing all potential interactions is impossible, despite that health professionals are familiar with medications of their patient population. 3 rd - Reporting Patient experience could help identify an unknown risk of interaction and inform health care professionals for better and safer advices to their patients regarding food and drug medications management.

3 Introduction : I was motivated to speak on food drug interaction after I witnessed its effect on the health of an ordinary Jordanian young man named Kamal The story of Kamal health deterioration is as follows:

4 Kamal is a 30 year old man considered himself an overweight with abdominal obesity. He was advised to lose weight by drinking grapefruit juice on an empty stomach every morning. He followed the advice and felt that he lost some weight in two weeks time. Unfortunately, he felt also a serious headache.

5 Cont d The doctor examined his blood pressure and found it extremely high 230/140 and prescribed an anti-hypertensive drug ( Adalat ). In a week time his blood pressure mildly decreased but abruptly felt kidney pain followed by kidney failure. He is now on artificial kidney 6 hours a day 3 times a week.

6 Adalat by it self had nothing to do with his health problem, but the interaction between Adalat and Grapefruit juice had caused the problem.! Because of the drug accumulation beyond its therapeutic window causing kidneys toxicity.

7 For every drug there is a Therapeutic window The dosage range with therapeutic efficacy. Levels below this window may not be effective, and levels above this window may result in toxicity.

9 Drug accumulation in bloodstream Drug accumulation in bloodstream Intestinal P glycoprotein No drug back absorption to lumen Inhibit Grapefruit and Grapefruit juices Inhibit Cytb 450 3A4 No drug Metabolism Inhibit Hepatic HMGCOA R ase Inhibitor Simvastin or Atorvastin so High Cholesterol Synthesis Grapefruit Component 6,7 dihydroxybergamottin is the active inhibitor

10 There are other examples of course which show how medications and nutrients can interact. However, this topic is not indented to cover all the possible interactions There are thousands of medications on the market and numerous new medications that come out every year with the possibilities of their interactions with nutrients in food.

11 The interaction can be at the levels of absorption, metabolism and/or excretion of either the drug or nutrients in food. Nutritional status is affected by drugs especially in elderly leading to malnutrition of patients out or in hospitals.

12 Effect of Food on Drug Action :

13 Effect of Food on Drug Action Some foods or nutrients in food can alter a medication s effectiveness by: Decreasing or enhancing medication absorption Interfering with medication metabolism Interfering with medication removal

14 Effect of Food on Drug Absorption Some foods or nutrients in food can increase or decrease medication absorption by: -Decreasing stomach emptying. eg: Fiber, Fat drug absorption - Binding to medications. (Chelation reaction) DA - Competing for absorption DA - Altering acidity or DA - Presence of Food in stomach : drug absorption & GIT : drug absorption

15 Absorbing less than the intended dose lowers the chance a medication will work properly Absorbing more than the intended dose increases the chance of an overdose effect

16 Medications are typically absorbed more quickly when the stomach is empty Having food in the stomach typically will slow down a medications absorption

17 Some medication should be taken with food Some medication should be taken on an empty stomach (1 hour before or 2 hours after eating) Read the directions to see if a medication should or should not be taken with food

18 Examples: Acidity of food or beverage consumed with a medication can affect absorption Some medications are better absorbed in an acidic environment Other medications can be damaged by an acid environment, these types of medications are often available in coated forms to resist stomach acidity

19 Gastric emptying rate : - Prokinetics - Food in stomach / high fat meal - Vomiting, diarrhea - Gastric surgical resection. E.g : Also, delayed gastric emptying by high fiber or high fat meals delay drug absorption which is not significant if the extent of absorption is not affected. However, It is significant in antibiotics and analgesics.

20 Food and Absorption * Presence of food and nutrients in intestinal tract may affect absorption of drug * Antiosteoporosis drugs Fosamax or Actonel: absorption negligible if given with food; 60% with coffee or orange juice

21 Food and Absorption - Absorption of iron from supplements 50% when taken with food - Best absorbed when taken with 2 cups of water on empty stomach - Food may GI upset - If take with food, avoid bran, eggs, fiber supplements, tea, coffee, dairy products, calcium supplements to avoid any decrease in iron absorption.

22 Food and Absorption - Presence of food enhances the absorption of some medications - Bioavailability of Axetil (Ceftin), an antibiotic, is 52% after a meal vs 37% in the fasting state - Absorption of the antiretroviral drug saquinavir is increased twofold by food - Erythromycin absorption is increased also by food.

23 Effect of Food on Drug Action : Metabolism

24 Effect of Food on Drug Metabolism * Some foods or nutrients in foods may interfere with a medication s metabolism or action in the body by: - Affecting enzyme systems - Interacting with medications - Having a similar chemical structure resulting in competition

25 * Examples: * Components in grapefruit juice - Inactivate enzymes that metabolize many medications which can result in increased medication levels * Aged and fermented foods - Contain a chemical called tyramine that interacts with a medication, monoamine oxidase inhibitor, which can result in dangerously high blood pressure * Vitamin K - Structurally similar to the anticoagulant warfarin which can decrease the effectiveness of warfarin

26 Enzyme systems in GIT and liver involve in increasing or decreasing drug metabolism 1- Increasing Drug metabolism E.g : Diet ( pro, CHO food ) : Activate the hepatic enzyme systems which hepatic metabolism of antiasthma drug theophylline causing an increase in drug clearance 2- Decreasing drug metabolism E.g : grapefruit + grapefruit juices : hepatic + intestinal Cytb 450 3A4

27 Grapefruit Inhibits Metabolism of Many Drugs * It inactivates metabolizing intestinal enzyme resulting in enhanced activity and possible toxicity * It s effect persists for 72 hours so it is not helpful to separate the drug and the grapefruit * Therefore,many hospitals and health care centers have taken grapefruit products off the menu entirely

28 Drugs known to interact with grapefruit juice * Anti-hypertensives. * Immunosuppressant's. * Antihistamines. * Protease inhibitors. * Lipid-Lowering Drugs. * Anti-anxiety.

29 Those taking MAOI drug should avoid food sources or limit foods that contain high levels of tyramine, such as : - Aged foods - Alcoholic + non Alcoholic beverages. - Pepperoni. - Caviar - Processed foods ( breakdown of protein to tyramine by bacteria ). - Fermented foods. - Overripe Fruits, beans.

30 * Monoamine oxidase inhibitors (MAOI) interact with pressor agents in foods (tyramine, dopamine, histamine) * Pressers are generally deaminated rapidly by MAO; MAOIs prevent the breakdown of tyramine and other pressers * Significant intake of high-tyramine foods (aged cheeses, processed meats) by pts on MAOIs can precipitate hypertensive crisis as shown below in the Diagrammatic Representation explaining the hypertensive crisis.

31 No Depression Accumulate High Blood Pressure Normal Levels Tyramine Inactive Product Active Dopamine Norepinephrine Serotonin MAO Inactive Product Low Levels Depression Inhibited by MAOI ( Morplan ) Antidepressant Accumulation Cytb 450 3A4 Grapefruit + Juices

32 Vit. K and Warfarin * Warfarin (anticoagulant) acts by preventing the conversion of vitamin K to a usable form * Ingestion of vitamin K in usable form will allow production of more clotting factors, making the drug less effective

33 * Pts must achieve a balance or steady state between dose of drug and consumption of vitamin K; recommend steady intake of vit. K * Other foods with anticlotting qualities may also have an effect (garlic, onions, vitamin E in large amounts, and ginseng)

34 Food/Nutrient Effects on Drugs Excretion

35 Effect of Food on Drug Excretion * Urinary ph: some diets, particularly extreme diets, may affect urinary ph, which affects reabsorption of acidic and basic medications. *- Urine ph ( should be controlled ) - Kidney stones ( should be prevented )

36 # Urinary ph is affected by : - Dietary intake - Kidney function - Lung function - acid base balance - Hydration status - Diseases - Infections # Should evaluate drug dosage intervention include : - Increase in water intake : to facilitate drug excretion - Limiting protein : to reduce load on kidney - Reducing dietary oxalate : to reduce kidney stones

37 Some food or nutrients in foods may interfere with removal of a medication from the body by: * Affecting enzymes involved in preparing medications for removal * Altering urine ph

38 Examples : * Liver enzymes prepare medications for removal from the body - These enzymes require nutrients to work properly - If nutrients are not present the medication may stay active in the body longer than intended * Quinidine is excreted more readily in an acidic urine - Foods that cause the urine to be more basic, such as sodium bicarbonate, may reduce quinidine excretion

39 Drug Effects on Food Action : Absorption

40 Drug Effects on Food Absorption due to : - Complexes - Transit time - GI environment - Adsorption - GI mucosa and GI absorptive surfaces

41 Drug Effects on Food : Absorption * Drug-nutrient complexes : example, ciprofloxacin and tetracycline will complex with calcium, supplemental magnesium, iron, or zinc - Take minerals 2 to 6 hours apart from the drug * Decreased transit time : cathartic agents, laxatives, drugs containing sorbitol, drugs that increase peristalsis

42 ** Drugs can also influence the absorption of nutrients by changing the GI transit time or the overall GI chemical environment, like the ph of the stomach. 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.

43 Drug Effects on Food : Absorption * Change GI environment : - Proton pump inhibitors, H2 receptor antagonists inhibit gastric acid secretion, raise gastric ph; cimetidine reduces intrinsic factor secretion; this impairs B12 absorption; ph may impair absorption of calcium, iron, zinc, folic acid, and B-carotene

44 Drug Effects on Food: Absorption ** Cholestyramine (antihyperlipidemic bile acid sequestrant) also adsorbs fat-soluble vitamins A, D, E, K, possibly folic acid; may need supplements for long term therapy, especially if dosed several times a day ** Mineral oil: ( 2 tbsp/day) absorption of fat soluble vitamins by adsorping them. - take vitamins at least 2 hours after mineral oil

45 Drug Effects on Food : Absorption GI mucosa and adrorpative surfaces : ** Drugs can damage the intestinal absorptive surfaces including villi, microvilli, brush border enzymes, and the transport system GI damage can come from over-the-counter drugs such as aspirin and other acidic drugs, or from antibiotic neomycin or laxatives. The resulting changes in the mucosal lining interfere with optimum absorption of nutrients such as iron, calcium, fat (including some fat-soluble vitamins), protein, sodium, and potassium.

46 Drug Effects on Food : Absorption Damage GI Mucosa : - Chemotherapeutic agents, NSAIDs, antibiotic therapy - Alters ability to absorb minerals m especially iron and calcium - Affect Intestinal Transport Colchicine ( gout ) paraaminosalicylic acid ( TB) sulfasalazine ( ulcerative colitis ) trimethoprim ( antibiotic ) and pyrimethamine ( antiprotozoal ) - Impair absorption of B12 or folate.

47 Drug Effects on Food Action : Metabolism

48 Drug Effects on Nutrition: Metabolism * Some medications can affect nutritional health by interfering with body s ability to metabolize nutrients due to: - Affecting enzyme systems - Competing with enzyme systems

50 Drug Effects on Food : Metabolism Some of the important functions of vitamins and several minerals are their roles as coenzymes/cofactors in metabolic processes in the human body. Therefore, certain drugs are targeted to these coenzymes (antivitamins) in order to reduce the activity of some enzymes in related metabolic reactions.

51 Drug Effects on Food : Metabolism - Phenobarbital and phenytoin increase metabolism of vitamin D, vitamin K, and folic acid *Patients on chronic tx may need supplements - Carbamazepine may affect metabolism of biotin, vitamin D, and folic acid, leading to possible depletion

52 Drug Effects on Food : Metabolism - INH (anti-tuberculosis) blocks conversion of pyridoxine to active form * Patients with low intake at higher risk * May cause deficiency and peripheral neuropathy * Pts on long term tx may need supplements

53 Drug Effects on Food : Metabolism * Methotrexate (cancer and rheumatoid arthritis) and pyrimethamine (malaria ) are folic acid antagonists - May treat with folinic acid (reduced form of folic acid, does not need conversion to active form) or folic acid supplements

54 Drug Effects on Food Action : Excretion

55 Drug Effects on Food : Excretion Some medications can affect nutritional health by increasing nutrient excretion due to: Decreased kidney reabsorption Increased urinary excretion

56 Drug Effects on Food : Excretion Competitive binding and altered reabsorption are the two recognized mechanisms that may cause drugs to induce nutrient excretion D-Penicillamine chelates with other metals such as zinc, eliminating it via urine.

57 Ethylenediaminetera-acetic acid ( EDTA) has been shown to cause urinary excretion of zinc. Some diuretics m such as furosemide, ethacrynic acid, and triamterene, reduce the reabsorption of electrolytes and minerals such as potassium, magnesium, zinc, and calcium and increase renal excretion of these elements.

58 Drug Effects on Food : Excretion Diuretics remove excess fluid from the body Some diuretics may also increase loss of potassium along with fluids Potassium is very important in proper functioning of the heart and other muscles Large amounts of aspirin can cause increased loss of folate

59 Drug Effects on Food : Excretion Loop diuretics ( furosemide ), increases excretion of potassium, magnesium, sodium, chloride, calcium. - Patients may need supplements with long term use, high dosages, poor diets - Electrolytes should be monitored

60 Drug Effects on Food : Excretion * Thiazide diuretics (hydrochlorthiazide) increase the excretion of potassium and magnesium, but reduce excretion of calcium - High doses plus calcium supplementation may result in hypercalcemia

61 * Potassium-sparing diuretics (spironolactone) increase excretion of sodium, chloride, calcium - Potassium levels can rise to dangerous levels if pt takes K+ supplements or has renal insufficiency

62 Drug Effects on Food: Excretion * Corticosteroids (prednisone) decrease sodium 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 (lupus, RA) to prevent osteoporosis

63 Drug Effect on Nutritional Status

64 Nutrition Implications * Little chance taking a medication for a short time will affect your nutritional status * However, using some medications for months or years may affect nutritional health. * the presence of some drugs can significantly affect the food and nutrient metabolism and bioavailability in humans.

65 Drug Side Effects that Affect Nutritional Status - Appetite changes - Oral taste and smell - Nausea - Dry mouth - Gastrointestinal effects - Organ system toxicity - Glucose levels

66 Food Intake * Some medications can affect nutritional health by causing poor food intake due to: - Decreased appetite - Nausea or vomiting - Unpleasant taste or dry mouth - Gastrointestinal sores or inflammation

67 Drugs Effect On Nutritional Status Examples of Drug Categories / Decrease Appetite - Anti-infective - Antineoplastics - Bronchodilators - Cardiovascular drugs - Stimulants

68 Drugs Effect On Nutritional Status Weight Gain * Drugs That May Increase Appetite - Anticonvulsants - Hormones - Psychotropic drugs - Antipsychotics - Antidepressants, tricyclics, MAOIs

69 Drugs Effect On Nutritional Status Examples of Drug Classes That Cause Diarrhea - Laxatives - Antiretrovirals - Antibiotics - Antineoplastics - + liquid medications in elixirs containing sugar alcohols

70 Drugs That May Lower 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)

71 Drugs That Raise Blood Glucose - Antiretrovirals, 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, interferon alfa-2a

72 Drugs Effect On Nutritional Status Nutrition Implications of Excipients in Drugs - Excipients: are inactive ingredients added to drugs as fillers, buffers, binders, disintegrate, flavoring, dye, preservative, suspending agent, coating - Approved by FDA for use in pharmaceuticals - Vary widely from brand to brand and formulation strengths of the same drug

73 Drugs Effect On Nutritional Status Nutrition Implications of Excipients in Drugs - Excipients may cause allergic or health reactions in persons with celiac disease, dye sensitivity, other allergies, inborn errors of metabolism - Examples of excipients that might cause reactions are albumin, wheat products, alcohol, aspartame, lactose, sugar alcohols, starch, sulfites, tartrazine, vegetable oil - Some meds may contain sufficient CHO or protein to put a patient on a ketogenic diet out of ketosis

74 Food/Nutrient Effects on Drugs Enteral Feedings - Most medications should not be mixed with enteral feedings; physical incompatibilities can occur including granulation, gel formation, separation of the feeding leading to clogged tubes - Enteral feedings interfere with phenytoin absorption; window the feeding around drug dose (2 hours before and after)

75 At - Risk Population

76 At-Risk Populations * Elderly - Multiple meds polypharmacy - Both OTC and prescribed - Physiological changes

77 Physiological Change related to Aging : 1) Ratio of Fat tissue / Muscle mass 2) Liver mass. 3) Blood Flow. 4) Impairment of Kidney Function 5) Illness and endocrine dysfunction 6) Malnutrition and Dehydration 7) CNS side effect of Drugs 8) Low albumin level ( < 3 g/dl ) tendency affect drug distribution.

78 At-Risk Populations * Nutrition Support - Tube feedings decrease absorption of some meds - Macronutrients may cause chelation of meds

79 Recommendation - Lower The risk of Drug Nutrient Interactions by : * Eating a Healthy Diet. * Following directions on how to take medications * Reading warning labels. * Not sharing medications.

80 Washing you Best of Health Thank you

Food-Drug Interactions

Food-Drug Interactions Definition of Terms Drug-nutrient interaction: the result of the action between a drug and a nutrient that would not happen with the nutrient or the drug alone Food-drug interaction: