Drug Interaction

Types of drug interaction:

1. Pharmaceutical “Chemical Interaction” in vitro:
• EPI , erythromycin gluceptate or cephalothin sodium
decomposed in alkaline PH so don’t mix with I.V. solution of
aminophylline
• Phenytoin Na+ will ppt in acidic solution so don’t mix with
dextrose solution
2. Pharmacokinetics = Biopharmaceutical:
• ADME
1) Absorption
2) Distribution
3) Metabolism
4) Excretion

1st Absorption:
• In CHE the F.O.C is , so blood supply to GIT is , so the
absorption of an orally administrated drugs is , so give
Digoxin F.O.C blood supply to GIT ∴ absorption of
drug from GIT .
• EPI make vasoconstriction so absorption of local
anesthetics.
• Purine & Purine antimetabolite compete on the same carrier so
absorption of each other .
2nd Distribution:
• Drug bounds + free “give action”
• VPA displace Phenytoin from plasma proteins binding site so
free Phenytoin conc.∆ ∴ Phenytoin toxicity
• Aspirin displace VPA VPA toxicity
• Quinidine displace Digoxin from plasma proteins binding site so
cause Digoxin free conc.∆ ∴ Digoxin toxicity

3rd Metabolism:
• Inducers :
I. CNS : Phenytoin , CBZ , Phenobarbital
II. Chemical : Tobacco , Chronic alcohol
III. Herb: Grape fruit , Bitter orange , Garlic , St john wart
IV. Antimicrobial: Isoniazid
• Inhibitors:
I.GIT: Omeprazole , Cimetidine
II. Antimicrobial: Ciprofloxacin , Levofloxacin , azole family “ketoconazole”
Ritonavir , Saquinavir , Erythromycin , Metronidazole
III.Others: Verapamil , Haloperidol , Methadone , Gemfibrozil

Ex.Smocking: Theophylline Metabolism cause Theophylline Failure

Ex.Cimetidine: atorvastatin Metabolism ∴ atorvastatin toxicity

4th Excretion “Through Kidney”:

• Filtration:
Theophylline blood supply to kidney so ∴ Glomerular filtration ∴
no time for reabsorption so Theophylline excretion of other drugs

• Active Secretion:

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Probenecid & Penicillin use the same carrier for secretion from the kidney
∴Probenecid Penicillin excretion so prolong its t½ ∴ long acting Penicillin

• Reabsorption:
NaHCO3 is a urine alkalinizer cause amphetamine reabsorpAon & cause
aspirin excretion.

Others example for interactions through absorption:

1- Charcoal
Cholestyramine + Drug absorption

Kaolin ∴ absorption
Bentonite
Acarbose

2- Tetracycline Divalent (Ca+2)

Quinolone
+ Trivalent (Al )+3
Chelation
∴ Absorption
Cation

By Laxative or Prokientic ( Ach)

∴ Absorption amount of controlled release tab

Decrease

3- GIT Motility
By narcotics or anticholinergic

∴ absorption rate

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4- Antacid, PPI ,H2RA ( acidity ) + Ketoconazole
Require acidity for absorption
Ketoconazole absorption

5- GIT Flora digoxin absorption in presence of normal flora

Oral contraceptive requires flora to be absorbed

3. Pharmacodynamic interaction:
• Synergism 1+1=3:
Ex. Sulfamethoxazole + trimethoprim.

• Antagonism 1+1=zero:
Ex. EPi + β.blocker

Ex. Warfarin + Vit.K

Ex. Narcotic + Naloxone

• PotenAaAon 0+1=2 :
Ex. Carbidopa + L.dopa

Ex. Clavulanic acid + Amoxicillin

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Food & Drug Interaction
• Wheat grass, Coenzyme Q10, Spinach, Broccoli.
Provide source of Vit.K ∴a dietary antagonize Warfarin effect.

• Ginger, Garlic, Feverfew Warfarin Effect.

Food May absorption of:-

• Morphine
• Dicumarol oral anticoagulation
• Phenytoin
Fatly Food
• Griseofulvin

Food May absorption of:-

• NSAIDs
• Aspirin
• Acetaminophen
• Antibiotic

Food has no effect on the absorption of:-

• Theophylline
• Metronidazole

Immediate release
Note:
(Food has no effect)
Theophylline
Controlled release
“Bronchodilator”
(Food absorption)
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Note:
Chronic alc. Inducer
Acute Alc. Inhibitor

4. Pharmacogentics:
Poor Intermediate Normal Extensive Ultra Rabid
Metabolizar Metabolizer Metabolizer Metabolizer 2 amplified
“PM” 1 Wild 2 Wild “Em” alleles
2 defecAve 1 DefecAve alleles 1 Wild Doesn’t
allele 1 Amplified affected by
Doesn’t Doesn’t inducer
affected by affected by
inhibitor inducer

Note:
Normal allele = wild

gene responsible for metabolism

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 PM EM

Drug X Drug X

PM

EM

Double
The same
AUC AUC

Drug X + Inhibitor Drug X + Inhibitor

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 Significance of Interaction
1) Trimethoprim & Sulfamethoxazole increase the efficacy of each
other (synergism)
2) Clavulanic acid decrease breakdown of amoxicillin
3) Hydrochlorothiazide & Triamterene neutralize the K+ level
(antagonism)
4) Fatty food Phenytoin absorption (pharmacokinetic)
5) Probenicid Prolong penicillin t½ (pharmacokinetic)

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