FOOD-Drug Interactions (FDI)

TOPICS Introduce FOOD-Drug Interactions (FDI) Study different mechanisms resulting in FDI

Food – drug interaction Effect of drug may be DIFFERENT than expected because of INTEREACTION with FOOD Food might increase of decrease effect by various mechanism Clinically significant drug interactions, may result from changes in pharmacokinetic, or pharmacodynamic properties

Mechanism of food-drug interaction FDI PK PD

Mechanism of food-drug interaction PK Interactions Absorption Metabolism Excretion Food Affecting any of these will affect overall exposure of drug

Food affecting drug absorption Food can change Gastric pH Gastric motility Solubility of drug Ultimately affecting the EXTENT of absorption of DRUG

Food affecting drug absorption Food affecting DRUG SOLUBILITY Griseofulvin Drug is lipid soluble, enhanced absorption with high- fat foods Digoxin High–fiber, high–pectin foods bind drug Tetracyclines Binds with calcium ions or iron salts forming insoluble chelates Isoniazide Food raises gastric pH preventing dissolution and Absorption Carbamazepine Increased bile production, enhanced dissolution and absorption

Food affecting drug absorption Food affecting GI Motility Spironolactone FOOD delayed gastric emptying permits dissolution and absorption, bile may solubilize the drug Nitrofurantoin, Phenytoin FOOD delayed gastric emptying improves dissolution and absorption Dicumerol FOOD Increased bile flow, delayed gastric emptying permits dissolution and absorption

Food affecting drug metabolism Food may alter the hepatic metabolism of some drugs Grapefruit Juice is known to INHIBIT CYP Enzymes Bioavailability of Felodipine increased by 3 FOLDS by Grapefruit Juice Add a graph or slide of grapefruit juice example Increase in Concentration due to Grapefruit Juice

Food affecting drug excretion Food may alter the Renal Excretion of some drugs Food is known to affect the pH of Urine Milk, vegetables and citrus fruits can alkalinize urine (Increase pH) Meats, fish, cheese and eggs can acidify the urine (Decrease pH) SO What affect will MILK have on Basic Drugs ?? SO What affect will FISH have on ACIDIC Drugs ?? Acidic drugs – Amplicillin, furosemide etc Basic drugs - quinidine, amitryptiline

Mechanism of food-drug interaction FDI PK PD

Food affecting pd of drugs Foods may interact with medications by altering their pharmacologic actions warfarin Diets high in vitamin K may cause antagonism of warfarin and decreased therapeutic efficacy of the anticoagulant Theophylline Caffeine in coffee adds to effect of Theophylline MAO Inhibitors Food rich in Tyramine (Cheese), breakdown of Tyramine prevented, May lead to Hypertensive crisis Beef liver, leafy Veg are Vit K rich

Assessment of food effect in new drug development Companies developing NEW drugs have to know the effect of Food on Drug Specific Guidance by US-FDA & Europe EMEA on how to do this

Food effect assessment Healthy Volunteers Fasting Group (Drug Only) Food Group (Drug+Food)

Food effect clinical trial With FOOD What Guidance will you give to your patients regarding Food & Drug timing ?? Conc Without FOOD Time

Food effect clinical trial With FOOD What Guidance will you give to your patients regarding Food & Drug timing ?? Conc Without FOOD Time

Guidance on drug information page

Role of pharmacist in preventing food-drug interaction Vigilant in monitoring for potential drug-food interactions Advising patients regarding foods or beverages to avoid when taking certain medications Pharmacists to keep upto-date on potential drug-food interactions of medications

General counselling or advice Read the prescription label on the container. If you do not understand something or think you need more information, ask your physician or pharmacist Take medication with a full glass of water Do not mix medication into hot drinks because the heat from the drink may destroy the effectiveness of the drug Check with the pharmacist on how food can affect specific medications taken with the food

Specific examples of advice ACE inhibitors Take on an empty stomach to improve the absorption of the drugs Digitalis Avoid taking with milk and high fiber foods, which reduce absorption, increases potassium loss

Alcohol-drug interaction Most people who consume alcohol (small, large quantities) also take medicines There is possibility of interaction with alcohol ingested

How is Alcohol metabolised Absorbed from stomach Undergoes some 1st pass metabolism Metabolized in Liver by ADH & CYP enzymes

Alcohol metabolism CYP2E1 involved in alcohol metabolism CYP2E1 metabolized other drugs as acetaminophen, the antibiotic isoniazid, and the barbiturate phenobarbital

Alcohol metabolism OCCASSIONAL DRINKERS: CYP2EI metabolizes small fraction of alcohol HEAVY DRINKERS: CYP2E1 Enzyme activity is increased Later (Induction) During heavy intake of alcohol, Drugs compete with alcohol for enzyme metabolism (Lower clearance) Afterwards due to induction, higher clearance

Alcohol-drug interaction Pharmacodynamic Effect: Most commonly with CNS agents Some drugs, target is common (barbiturates and sedative medications called benzodiazepines) Some drugs, target is not common, antihistamines and antidepressants This leads to synergistic effect through different mechanism

Tobacco drug interactions 1.3 billion cigarette smokers worldwide and this number is still increasing Patients with psychiatric disorders are typically HEAVY Smokers

Tobacco drug interactions TDI PK PD

Tobacco drug interactions Major Interactions are PK Cigarette smoke INDUCES CYP1A2 Heavy Smokers have high CYP1A2 activity

Tobacco drug interactions CYP1A2 Major CYP enzyme responsible for metabolizing several drugs Smoking leads to HIGH clearance of these drugs (HIGH METABOLISM) When patients stop smoking, CYP1A2 activity reverses back in 1 Week Dosing needs to be adjusted for Smokers & after they STOP smoking

Tobacco drug interactions Major Drug Interactions: Clozapine/Olanzapine: Smoking Induces CYP1A2 activity 50% difference in Conc between Smokers & Non-Smokers Re-titration of Dose necessary for patients stop smoking Anti-depressants: Fluvoxamine clearance increased by CYP1A2 induction by smoking Higher than normal doses for Smokers

Tobacco drug interactions Major Drug Interactions: Caffeine Caffeine is metabolized by CYP1A2 Smokers need 4 times MORE caffeine to reach same levels as Non-Smokers

Tobacco drug interactions Pharmacodynamic Interactions: Interactions mostly due to Nicotine present in cigarette smoke METHADONE: Methadone has been shown to increase both smoking rates and smoking satisfaction Nicotine affects the endogenous opioid system BENZODIAZEPINE: Nicotine lowers effect of benzodiazepine sedation by activating CNS 1-2 mg of Nicotine/cig, drug de-addiction programs,

Tobacco drug interactions Other Drugs: Efficacy of inhaled corticosteroids may be reduced in asthmatic patients who smoke Patients might require higher doses of inhaled corticosteroids to attain asthma control Mechanism: Suppression of histone deacetylase expression and activity by cigarette smoking, causing inflammatory gene expression and a reduction in glucocorticoid function

THANK YOU -PHARMA STREET