Download FOOD-Drug Interactions (FDI)

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
Food Affecting any of these will
affect overall exposure of drug
Excretion
Food affecting drug absorption
 Food can change
1. Gastric pH
2. Gastric motility
3. 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
Increase in
Concentration due to
Grapefruit Juice
Food affecting drug excretion

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
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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 ??
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
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
Healthy Volunteers
Food effect assessment
Fasting Group
(Drug Only)
Food Group
(Drug+Food)
Food effect clinical trial
With FOOD
Conc
Without FOOD
Time
What Guidance will you give to
your patients regarding Food &
Drug timing ??
Food effect clinical trial
With FOOD
Conc
Without FOOD
Time
What Guidance will you give to
your patients regarding Food &
Drug timing ??
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:
1. Clozapine/Olanzapine:
1. Smoking Induces CYP1A2 activity
2. 50% difference in Conc between Smokers & Non-Smokers
3. Re-titration of Dose necessary for patients stop smoking
2. Anti-depressants:
1. Fluvoxamine clearance increased by CYP1A2 induction by smoking
2. Higher than normal doses for Smokers
Tobacco drug interactions
 Major Drug Interactions:
1. Caffeine
1. Caffeine is metabolized by CYP1A2
2. 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
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
glucocorticoid function
in
THANK YOU
-PHARMA STREET