Food-Drug Interactions

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

Drugs are chemicals that are used

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

a) An Increase or loss of the drug effect

or
.b) 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:
( i ) Delay, Decrease or Increase of
Absorption that occurs via diffusion or
Trans porters ( Influx or Efflux types)
Influx transporters increase
absorption
e.g Organic Anion Polypeptides
Efflux Transporters increase secretion
from intestinal cell into intestinal
lumen e.g p-glycoprotein
Increase or Decrease of Metabolism via ) i i ( 
cytochrome P 450: CYP3A4

Adsorption of the Drug e.g pectins ) iii ( 


Complex formation: e.g Ca with ) iv ( 
Tetracyclines or penicillamine
 Liver )c(
increase or decrease of metabolism via Enzymes
.inhibition or stimulation

:Kidney )d(
increase or decrease of Excretion via increase
or decrease in urinary pH

: Drug Action )f(

Increase or decrease of the Beneficial Actions
Increase or decrease of the side effect & Toxicity
Predisposition to Drug - Resistance
 Examples of Food-Drugs Interactions
:Citrus Fruits -1
:Grape Fruit Juice )a(
Active Constituents
Geranyl oxy furocoumarin - 5 -1
)6µg/ml juice - 0.3(
.Naringenin (flavonoid) (0.7mg/ml) -2
.Bergamottin (25ng/ml) -3
Effects on Drugs
Bioavailability and t½ (Duration) )1

Peak Blood-level concentration )2

. in Beneficial and Toxic Actions

Drugs that are Enhanced )i(
β – Blockers : Celiprolol, Talinolol
Antimalarials : Halofantrine; Quinine
:Calcium channel Blockers
Verapamil; Nifedipine
Felodipine; Nimodipine
Nitrendipine; Nisoldipine
Benzodiazepines: midazolam ; Triazolam
:Antiarrhy thmics
Quinidine; Amiodarone
Disopyramide; Propafenone
:Hypolipoproteinemics
Lovastatin; Simvastatin
Atrovastafin
:Penile 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
Drugs that are Inhibited by )ii(
Grape Fruit Juice
:Anticancers
Etoposide
Angiotensin II Receptor Blocker
Losartan
Antiplatelets
Clopidogrel
:Mechanisms of Action

Inhibition of Intestinal and Hepatic )1(

CYP450 3A4
” irreversible "

of Transporter P-glycoprotein )2(

Dose 250 ml of juice

 Problems of Grape Juice
Increase in Toxicity of Some Drugs

Enhancement of Verapamil – induced)1(

Suppression of A – V Conduction

in Toxicity of Anti – arrhythmics )2(

Amiodarone ; Quinidine
; Propafenone; Disopyramide

in Toxicity (Cardiac) of Carvedilol )3(

in Ergotamine – induced gangrene )4(
(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
Tangeretin of Citrus Fruits )3

Action: Blocking of Breast Anticancer

Effect of Tamoxifen

Mechanism: Reduction in Natural

.Killer T – Lymphocytes (CD8+)
Citrus Flavonoids )4
Kaempferol; Quercetin
Naringenin
Action:decrease of Metabolism of 17β – Oestradiol
Citrus aurantium fruit )5
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
 FoodDrug Effect

9) Dietary fibre Digoxin Decrease in Absorption

Bran

10) Cheese Tranylcypromine Increase in Action

(Tyramine) (MAO – A lnhibitors) Severe Fever &
11) Soyabean Sause Convulsions & Hypertension

12) Foods Fortified

with iron and Ca 2+ Tetracyclines
Penicillamine in Absorption
Food Drug Effect

13) Foods Omeprazole in Action

(Full stomach)
lansoprazole
Itraconazloe in Bioavailability

14) Cran berry Warfarin in Bleeding

Juice

15) Vitamin C Basic drugs

e.g Pseudoephedrine Excretion

Tetracyclines Absorption

16) Millet Carbimazole in Action

17) Tea and coffee Analgesics in Action
( in PGI2)
Haloperidol in Action
(in metabolism)

Iron in Absorption

β- Blockers in Action
Hydralazine in Action

18) Dates Anti-hyperlipedemics in Action

19) Banana Cimetidine

Ranitidine in Action
Food Drug Interaction
Licorice
Organic nitrate action

Corticosteroids Retention in Na++H2O

Fludrocortisone

Capsicum Antihypertensive in action

Cola nut Analgesics in action

Ginger Antiplatelets in Bleeding

Curcum NSAIDs in activity

K+ Containing ACEIs
Foods Angiotensin
Blockers in Hyperkalemia
Cyclosporine
K+ Sparing Diuretics

Other Diuretics in side effects

Tea Alkaloids e.g. in activity
Atropine

a) High Sodium diet Li+ Excretion

b) Alfaalfa and Ginger Anticoagulants in Bleeding

c) Fenugreek Lovastatin in action

(Antihyperlipedemic effect)
 Effect of Drugs on Foods

Drug Food Effect

1) Acarbose Sucrose Absorption of

glucose and
fructose
2) Fluoxetine Sucrose Absorption
Leucine in Absorption
( Transporters)
3) Metformin Vitamins
glucose of Absorption

4) Oral Contraceptive Vitamin B6 in Excretion

5) Tetracyclines Ca2+
and and of Absorption
Penicillamine Iron