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Drug Interaction

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Drug Interaction—when drug is administered a response is obtained. If a second drug or agent (food or environmental) is given then the response of the first drug is altered. This event is known as drug interaction.

 

Classification—

1.    Pharmacokinetic interaction—

a. At the site of absorption

b. At the site of distribution

c.  At the site of metabolism

d.At the site of excretion

2.    Pharmacodynamic interaction

3.    Disease drug interaction

 

 

 

Drug interaction a the level of absorption—

Drug A + Drug B

Result of Interaction

Underlying Mechanism

Digoxin + Antacid (chelating agent)

↓ GIT absorption and

↓ bioavailability of Digoxin

Antacids absorbs Digoxin

Aspirin + Charcoal (chelating agent)

↓ Aspirin absorption

(can be used in Aspirin poisoning)

Charcoal absorbs Aspirin

Tetracycline + Antacid

↓ absorption of Tetracycline

Due to chelation with Antacid

Levodopa + Anti-muscarinic drugs

↓ absorption of Levodopa

Anti-muscarinics ↓ gut motility

 

 

 

Drugs interaction at the level of distribution—

Drug A + Drug B

Result of Interaction

Underlying Mechanism

Sulfonylurea + Sulfonamide

↑ blood level Sulfonylurea and

↑ risk of Sulfonylurea toxicity

Sulfonylureas are displaced from the protein binding site by Sulfonamides

Warfarin + Aspirin

↑ risk of Warfarin induced bleeding

Warfarin is displaced from the protein binding site by Aspirin

Digoxin + Quinidine

↑ level of Digoxin and

↑ risk of Digoxin toxicity

Quinidine displaces Digoxin from its protein binding site in both the tissues and plasma

 

 

 

Drug interaction at the level of metabolism—

Drug A + Drug B

Result of Interaction

Underlying Mechanism

Cimetidine + Theophylline

↑ risk of Theophylline toxicity

cardiac arrhythmia may occur

Cimetidine inhibits the metabolism of Theophylline

Rifampicin + OCP

Failure of contraception

Rifampicin induces the metabolism of OCP

Erythromycin + Terfenadine

H risk of Terfenadine toxicity

Erythromycin inhibits the Terfenadine metabolism

Phenobarbitone + β-blockers

↓ effect of β-blockers

Phenobarbitone induces the β-blocker metabolism

 

 

 

Drug interaction at the level of renal excretion—

Drug A + Drug B

Result of Interaction

Underlying Mechanism

Penicillin + Probenecid

↓ penicillin excretion

Probenecid and Penicillin compete for the same secretory mechanism

Salicylate + NaHCO3

↑ urinary excretion of Salicylates

NaHCO3 alkalinizes the urine and increases ionized fraction of Salicylates

Amphetamine + NH4Cl

↑ urinary excretion of Amphetamine

NH4Cl acidifies the urine and increases the ionized fraction of Amphetamine

Furosemide + NSAID

↓ diuretic and

↓ anti-hypertensive effects

NSAID inhibits renal prostaglandin synthesis

 

 

 

Drug interaction at the pharmacodynamic level—

Drug A + Drug B

Result of Interaction

Underlying Mechanism

Morphine + Naloxone

Amelioration of sign symptoms of Morphine poisoning

Naloxone competitively antagonizes Morphine at same opioid receptors

Neuromuscular blocker

+ Aminoglycosides

Augmented blockade

The antibiotic causes depression of evoked release of acetyl-choline

Penicillin + Aminoglycosides

Synergistic bactericidal action

Penicillin enhances the bacterial cell uptake of Aminoglycosides