Food Drug Interactions Presentation for attending 1st part of Master Degree of Pharmacology Cairo University Food Drug Interactions By: Ayman M. A. Fkirin, Pharmacology Demonstrator, Fayoum University

Before Starting Important Definition: 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: a broad term that includes drug-nutrient interactions and the effect of a medication on nutritional status (Food- drug interaction, By: Candace Roberts,2008)

To ↓ Food Drug Interactions Therapeutic importance Importance of Studying Food Drug Interaction To ↓ Food Drug Interactions Therapeutic importance 1) Optimum drug efficacy. 2) Improved compliance. 3) ↓ need for adding drugs. 4) Adverse effect are avoided. 5) Optimal nutritional status. 6) The cost of health care services is reduced. 1) Alter the intended response to the medication 2) Cause drug toxicity 3) Alter normal nutritional status (Food- drug interaction, By: Candace Roberts,2008)

MAP 1) Food Affecting Drugs: a) kinetics: * Absorption. * Distribution. * Metabolism. * Execration. b) Dynamic 2) Drug Affecting Food: a) Absorption. b) Distribution. c) Metabolism. d) Execration. 3) Drug Affecting Nutritional state 4) Prevention of interaction 5) Recommendations.

MAP 1) Food Affecting Drugs: a) kinetics: * Absorption. * Distribution. * Metabolism. * Execretion. b) Dynamic 2) Drug Affecting Food: a) Absorption. b) Distribution. c) Metabolism. d) Execration. 3) Drug Affecting Nutritional state 4) Prevention of interaction 5) Recommendations.

Absorption Food Mechanism: Change PH ↑ Digestive secretions Alter rate of Absorption Bind to drug Compete for absorption site. Dilution of drug particles. Formation of physical barrier.

Examples Absorption 1) Grapefruit: - Can cause more of a drug to be absorbed from intestine, even toxic levels. (new Concern)* - Active ingredient*: 1) Naringen. 2) Furano-coumarins 3) Bergamot-tin 2) Orange juice: - Should not consumed with antacid contains AL. - ↓ bioavailability of some antibiotics 3) Dairy products: - Interfere with tetracycline, Antifungal - Exogenous Progesterone may require dairy product to work!! ** 4) Soft drinks or high acid fruit or vegetable juices **: - It is not recommended to take drugs with them. - Can cause excess stomach acidity. Examples *Food-Drug Interactions By: Kamal El din EL Tahir, College of Pharmacy, KSU, 2007 **Food Drug interaction, by: Dr. William Diehl-Jones, University of Manitobia, 2005

Distribution ↓albumin(main blood protein)  ↑ bioavailability of drugs and potentiate their effect: - phenytoin  toxicity - warfarin  bleeding 2) Body composition: - obese or elderly  higher ratio of adipose tissue - So, fat soluble drugs may accumulate in the body ↑ risk of toxicity (Food- drug interaction, By: Candace Roberts,2008) (Food-Medication Interactions 13th edition by Zaneta M. Pronsky)

- Effect persists for 72 hours Metabolism Food--- 1) Act as structural analogue 2) Compete for metabolic enzyme. 3) Alter enzyme Activity Mechanism 1) Alcohol Interact with enzymes  ↓ drugs effect. 2) Grape Fruit  Interfere with: - specific enzyme in the intestine - cytochrome p450. The CYP450 enzymes are essential for the production of numerous agents including cholesterol and steroids. Additionally, these enzymes are necessary for the detoxification of foreign chemicals and the metabolism of drugs. CYP450 enzymes are so named because they are bound to ER and contain a heme pigment (chrome and P) that absorbs light at a wavelength of 450 nm when exposed to carbon monoxide.2 There are more than 50 CYP450 enzymes, mostly in the liver. - Effect persists for 72 hours Food  ↓ first pass metabolism of propranolol. (fraction of lost drug during the process of absorption which is generally related to the liver and gut wall._ Examples (Food- drug interaction, By: Candace Roberts,2008) (Food-Medication Interactions 13th edition by Zaneta M. Pronsky)

Excretion Affect Urinary pH Acidic Food  ↑ excretion of basic drugs. Basic Food ↑ excretion of acidic drugs. Lithium and sodium compete for tubular reabsorption in the kidney. High sodium intake causes more lithium to be excreted. Low sodium intake will cause the kidney to retain lithium (Food-Medication Interactions 13th edition by Zaneta M. Pronsky)

Pharmacodynamic 1) Some foods have additive effects to drugs: - Caffeine containing food and theophylline. - Tyramine (dopamine/epinepherine)containing food and MAOI. (Food and Drug Interaction, by: R. Sudharani, N. Kanmani, P. Augusta, 2007) (Food-Medication Interactions 13th edition by Zaneta M. Pronsky)

Pharmacodynamic 1) Some foods have additives effects to drugs: - Caffeine containing food and theophylline. - Tyramine containing food and MAOI. - Alcohol with: - sedatives. - Beta blockers 2) Some foods have antagonistic effect of drugs: - Vitamin K (or E*) containing food and oral anticoagulant - Caffeine containing food and tranquilizers - High fat diet and antihyperlipidemic drugs - High glucose diet and hypoglycemic drugs. 3) GINKGO ** - It interferes with platelets clotting - Many experts recommend that ginkgo not be combined with NSAID and MAO inhibitors *(Food and Drug Interaction, by: R. Sudharani, N. Kanmani, P. Augusta, 2007) **(Food-Medication Interactions 13th edition by Zaneta M. Pronsky)

MAP 1) Food Affecting Drugs: a) kinetics: * Absorption. * Distribution. * Metabolism. * Execration. b) Dynamic 2) Drug Affecting Food: a) Absorption. b) Distribution. c) Metabolism. d) Execration. 3) Drug Affecting Nutritional state 4) Prevention of interaction 5) Recommendations.

Drug Affecting food Kinetics 1) Absorption: - Drug form complexes with food  ↓ food absorption - Drug alters gastric acidity. - Drug damages mucosal surface. - Alter gastric motility. 2) Distribution: - Drug displace Nutrient from protein binding: e.g. Aspirin displace folate (Food-Medication Interactions 13th edition by Zaneta M. Pronsky)

Drug Affecting food Kinetics 3) Metabolism: - Drug increases the metabolism of nutrients  its deficiency. - Drug causes vitamin antagonism (e.g. INH). 4) Excretion: - Drug increases urinary excretion of nutrients. e.g. Loop diuretics  ↑ excretion of Na, K, Cl, Mg, Ca. - Drug decreases urinary excretion of nutrients. e.g. Thiazide diuretics  ↓ excretion of Ca. (Food-Medication Interactions 13th edition by Zaneta M. Pronsky)

MAP 1) Food Affecting Drugs: a) kinetics: * Absorption. * Distribution. * Metabolism. * Execration. b) Dynamic 2) Drug Affecting Food: a) Absorption. b) Distribution. c) Metabolism. d) Execration. 3) Drug Affecting Nutritional state 4) Prevention of interaction 5) Recommendations.

Drugs Can Affect Nutritional State by: A) At the level of the Mouth: 1) Taste & smell affection - Drug may impair salivary flow - Drug secreted in saliva 2) Drug may suppress natural oral bacteria 3) Drug may cause taste change. M b) At level of stomach and intestine: 1) Drug irritate stomach 2) Drug affect intestinal peristalsis 3) Drug destroy intestinal bacteria C) At level of CNS (Appetite changes) 1) Drug suppress appetite (e.g. SSRI) 2) Drug increase appetite: (e.g. Tricyclic antidepressants)

MAP 1) Food Affecting Drugs: a) kinetics: * Absorption. * Distribution. * Metabolism. * Execration. b) Dynamic 2) Drug Affecting Food: a) Absorption. b) Distribution. c) Metabolism. d) Execration. 3) Drug Affecting Nutritional state 4) Prevention of interaction 5) Recommendations.

Prevention Take pills and capsules with a large glass of water Don’t mix a drug directly into a food or drink Do not stir medication into food or take apart capsules. Avoid taking drugs with hot drinks. Take NO Medicines with Alcohol No Dairy Foods with some drugs. Foods containing tyramine not to be taken with MAOI. Re-asses nutrition status frequently for high risk patients Every drug should be Known Whether Taken on a Full or Empty Stomach

MAP 1) Food Affecting Drugs: a) kinetics: * Absorption. * Distribution. * Metabolism. * Execration. b) Dynamic 2) Drug Affecting Food: a) Absorption. b) Distribution. c) Metabolism. d) Execration. 3) Drug Affecting Nutritional state 4) Prevention of interaction 5) Recommendations.

Recommendations Doctors should know possible food interactions with the prescribed drug i.e. from books, researches, web sites. Doctors should inform patients about it, And write it clearly on the back of prescription. Medication company should write food interaction in drug info section

Summary Before Closing Many people eat foods that have hundred of active substance That may counteract or added to action of many drugs. Food can affect all levels of drug kinetics and dynamics. Drugs can affect food kinetics and Nutritional state of patients. Doctors must take good nutritional history of patients of non-compliance to drugs

Thank You