1. FOOD-Drug Interactions (FDI)

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

3. 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

4. Mechanism of food-drug interaction
FDI PK PD

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

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

7. 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

8. 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

9. 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

10. 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

11. Mechanism of food-drug interaction
FDI PK PD

12. 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

13. 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

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

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

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

17. Guidance on drug information page

18. 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

19. 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

20. 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

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

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

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

24. 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

25. 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

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

27. Tobacco drug interactions
TDI PK PD

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

29. 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

30. 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

31. 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

32. 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,

33. 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

34. THANK YOU -PHARMA STREET