Food-Drug Interactions By Professor: Kamal El din Hussein EL Tahir and Dr.: Dana M. Bakheet Department of Pharmacology, College of Pharmacy, KSU, Riyadh.

Food-Drug Interactions

By

Professor: Kamal El din Hussein EL Tahir

and

Dr.: Dana M. Bakheet

Department of Pharmacology,

College of Pharmacy, KSU, Riyadh.

IntroductionIntroduction

Drugs are chemicals that are used Drugs are chemicals that are used for treatment of diseases. Their actions for treatment of diseases. Their actions

can be increased or decreased by the can be increased or decreased by the concurrent intake of other drugs or food. concurrent intake of other drugs or food. Such interaction may lead to : Such interaction may lead to :

a) An Increase or loss of the drug effect a) An Increase or loss of the drug effect

or or b) An increase in the drug’s Toxicityb) An increase in the drug’s Toxicity . .

Interactions with Foods

Interactions of Foods with Drugs can occur at different sites: a) In the stomach (By or pH) Affect the stability of the

drugs, e.g

Proteins , milk, gelatin …etc

can buffer the stomach Acidity

b) In the Intesine: b) In the Intesine: ( i ) Delay, Decrease or Increase of ( i ) Delay, Decrease or Increase of Absorption that occurs via diffusion or Absorption that occurs via diffusion or Trans porters ( Influx or Efflux types) Trans porters ( Influx or Efflux types) Influx transporters increase Influx transporters increase absorption absorption e.g Organic Anion Polypeptides e.g Organic Anion Polypeptides Efflux Transporters increase secretion Efflux Transporters increase secretion from intestinal cell into intestinal from intestinal cell into intestinal lumen e.g p-glycoprotein lumen e.g p-glycoprotein

)i i ( Increase or Decrease of Metabolism via cytochrome P 450: CYP3A4

)iii ( Adsorption of the Drug e.g pectins

)iv ( Complex formation: e.g Ca with Tetracyclines or penicillamine

((cc ) )LiverLiver increase or decrease of metabolism via Enzymes increase or decrease of metabolism via Enzymes

inhibition or stimulationinhibition or stimulation..

((dd ) )KidneyKidney : :increase or decrease of Excretion via increase increase or decrease of Excretion via increase or decrease in urinary pHor decrease in urinary pH

((ff ) )Drug ActionDrug Action : : Increase or decrease of the Beneficial ActionsIncrease or decrease of the Beneficial Actions

Increase or decrease of the side effect & ToxicityIncrease or decrease of the side effect & ToxicityPredisposition to Drug - ResistancePredisposition to Drug - Resistance

Examples of Food-Drugs Interactions 1 -Citrus Fruits:

)a (Grape Fruit Juice : Active Constituents

1 -5 - Geranyl oxy furocoumarin ) 0.3 - 6µg/ml juice (

2 -Naringenin (flavonoid) (0.7mg/ml).3 -Bergamottin (25ng/ml).

Effects on Drugs

1 (Bioavailability and t½ (Duration)

2 )Peak Blood-level concentration

in Beneficial and Toxic Actions .

)i (Drugs that are Enhanced

β – Blockers : Celiprolol, Talinolol

Antimalarials : Halofantrine; Quinine

Calcium channel Blockers :

Verapamil; Nifedipine

Felodipine; Nimodipine

Nitrendipine; Nisoldipine

Benzodiazepines: midazolam ; TriazolamAntiarrhy thmics :

Quinidine; Amiodarone Disopyramide; Propafenone

Hypolipoproteinemics: Lovastatin; Simvastatin

AtrovastafinPenile vasodilators:

Sildenafil; Tadalafil; Vardenafil

Anti – Cancer / Immuno-suppressant : Cyclosporin

Antibiotics: Clarithromycin

Anti HIV : Saquinavir

Oral Hypoglycemics Repaglinide

Anorexiogenics:

Sibutramine

Cardiac Blockers:

Carvedilol

Anti – Migraine :

Ergotamine

) ii (Drugs that are Inhibited by Grape Fruit Juice

Anticancers: Etoposide

Angiotensin II Receptor Blocker Losartan

Antiplatelets Clopidogrel

Mechanisms of Action:

)1 (Inhibition of Intestinal and Hepatic CYP450 3A4

"irreversible ”

)2 (of Transporter P-glycoprotein

Dose 250 ml of juice

Problems of Grape JuiceIncrease in Toxicity of Some Drugs

)1(Enhancement of Verapamil – induced Suppression of A – V Conduction

)2 (in Toxicity of Anti – arrhythmics

Amiodarone ; Quinidine Propafenone;

Disopyramide ; )3 (in Toxicity (Cardiac) of Carvedilol

)4 (in Ergotamine – induced gangrene

(5) in Hypotensive effects of Vasodilators

(6) in Halofantrine – induced

Prolongation of Q – T interval

(7) in Lovastatin – induced rhabodmyolysis

) 2 ( Orange Juice Consitiuents:

Dihydrobergamottin Vitamin C

Action :a) Inhibition of Bioavailability of Fexofenadine and Celiprolol Mechamism:

Of Influx Transporters Organic Anion Polypeptides

b) Decrease in Duration of Action of e.g chloroquine Mechanism: Acidification of urine increase in Excretion .

3 )Tangeretin of Citrus Fruits Action: Blocking of Breast Anticancer Effect of Tamoxifen Mechanism: Reduction in Natural Killer T – Lymphocytes (CD8+).

4 )Citrus Flavonoids Kaempferol; Quercetin

Naringenin Action:decrease of Metabolism of 17β – Oestradiol

5 )Citrus aurantium fruit and Citrus grandis pericarp

Constituents: Flavonoids Action: increase in cyclosporin bioavailability &

Increase in maximum peak Blood level Mechanism: Enhancement of Absorption Inhibition of Intestinal metabolism .

Effect of other foods or Drugs

Food Drug Effect 1) Fatty meals Carbamazepine Increase in Bioavailability

Praziquantel, Daiazepam, Phenytoin, Lovastatin

Theophylline Delay of Absorption

Cefaclor // // Indinavir // // Isosorbide mono-nitrate Delay of Absorption

due to delay in Gastric

emptying Ethambutol Decrease in Absorption Rapamy cin Delay of Absorption Metri fonate Delay of Absorption

2) Vitamin A Isotretinoin Increase in Absorption

Food Drug Effect

3( Coca – Cola Phenytoin Absorption Pepsi – Cola Antihypertensives Effect

4( Honey Carbamazepine Absorption 5( Milk Ciprofloxacin

6( Yoghourt Warfarin in Action 7( Garlic and Antiplatelets onion Hypoglycemics in Action

Antihypertesives Anticoagulants

8( Peanut and Antiplatelets sesame oil Anti hypertensives in Action

EffectDrug Food 9) Dietary fibre 9) Dietary fibre Digoxin Decrease in Absorption Digoxin Decrease in Absorption BranBran

10) Cheese 10) Cheese Tranylcypromine Increase in Action Tranylcypromine Increase in Action )Tyramine) )MAO – A lnhibitors) Severe Fever & )Tyramine) )MAO – A lnhibitors) Severe Fever & 11) Soyabean Sause11) Soyabean Sause Convulsions & Convulsions &

HypertensionHypertension

12) Foods Fortified12) Foods Fortified with iron and Ca with iron and Ca 22+ Tetracyclines+ Tetracyclines

PenicillaminePenicillamine in in AbsorptionAbsorption

FoodFood DrugDrug EffectEffect

13) Foods 13) Foods Omeprazole Omeprazole in in ActionAction

)Full stomach) )Full stomach) lansoprazole lansoprazole Itraconazloe Itraconazloe in Bioavailability in Bioavailability

14) Cran berry 14) Cran berry Warfarin Warfarin in Bleeding in Bleeding Juice Juice

15) Vitamin C15) Vitamin C Basic drugs Basic drugs e.g Pseudoephedrine Excretione.g Pseudoephedrine Excretion Tetracyclines Tetracyclines Absorption Absorption

16) Millet 16) Millet Carbimazole Carbimazole in in Action Action

17) Tea and coffee 17) Tea and coffee Analgesics in Action Analgesics in Action ) in PGI2)) in PGI2)

Haloperidol Haloperidol in Action in Action )in )in

metabolism)metabolism) Iron Iron in in

Absorption Absorption β- Blockersβ- Blockers in in

Action Action HydralazineHydralazine in Action in Action

18) Dates 18) Dates Anti-hyperlipedemics in Action Anti-hyperlipedemics in Action

19) Banana19) Banana Cimetidine Cimetidine Ranitidine Ranitidine in in

Action Action

Food Drug Food Drug InteractionInteractionLicoriceLicorice

Organic nitrate actionOrganic nitrate action

Corticosteroids Corticosteroids Retention in NaRetention in Na++

+H+H22OO

FludrocortisoneFludrocortisone

Capsicum Antihypertensive in Capsicum Antihypertensive in actionaction

Cola nut Analgesics in actionCola nut Analgesics in action

Ginger Antiplatelets in Ginger Antiplatelets in BleedingBleeding

Curcum NSAIDs in activityCurcum NSAIDs in activity

KK++ Containing ACEIs Containing ACEIs

Foods AngiotensinFoods Angiotensin

Blockers in Blockers in HyperkalemiaHyperkalemia

CyclosporineCyclosporine

KK++ Sparing Diuretics Sparing Diuretics

Other Diuretics in side Other Diuretics in side effectseffects

Tea Alkaloids e.g. in activityTea Alkaloids e.g. in activity AtropineAtropine

a) High Sodium diet Lia) High Sodium diet Li++ ExcretionExcretion

b) Alfaalfa and Ginger Anticoagulants in b) Alfaalfa and Ginger Anticoagulants in BleedingBleeding

c) Fenugreek Lovastatin in action c) Fenugreek Lovastatin in action ((Antihyperlipedemic effectAntihyperlipedemic effect))

Effect of Drugs on Foods

Drug FoodFood EffectEffect

1) Acarbose 1) Acarbose Sucrose Sucrose Absorption of Absorption of glucose glucose

and and fructosefructose

2) Fluoxetine 2) Fluoxetine Sucrose Sucrose Absorption AbsorptionLeucine Leucine in Absorption in Absorption

) Transporters)) Transporters)3) Metformin 3) Metformin Vitamins Vitamins

glucose of Absorption glucose of Absorption

4) Oral Contraceptive Vitamin B6 4) Oral Contraceptive Vitamin B6 in Excretion in Excretion

5) Tetracyclines 5) Tetracyclines Ca2+ Ca2+ and and and of Absorption and of Absorption Penicillamine Penicillamine Iron Iron