Pharmacology Interactions

Pharmacokinetic Interactions

• Quinidine increases the risk of toxicity by increasing tubular passive reabsorption of the object drug.
• Aspirin decreases the clearance of the object drug by decreasing tubular passive reabsorption.
• Drugs that use the same active transport systems in the renal tubules can compete with each other for excretion.

Changes in Active Renal Tubular Excretion

• Penicillins, Cephalosporins, and Quinolones can inhibit organic anion transporters (OATS), increasing the plasma levels of acidic drugs and potentially causing toxicity.
• Probenecid can inhibit the excretion of acidic drugs, leading to increased plasma levels and potential toxicity.

Pharmacodynamic Interactions

• Verapamil can increase digoxin absorption by inhibiting P-glycoprotein.

Distribution Interactions

• Salicylates and Sulfonamides can displace warfarin from its binding sites, increasing the risk of hemorrhage.
• Protein-binding interactions can occur when one drug competes with another for binding sites, depending on concentrations and affinities.

Metabolism Interactions

• Enzyme induction can increase the activity of metabolizing enzymes, leading to increased metabolism of certain co-administered drugs.
• Cytochrome P450 isoenzymes, particularly CYP3A4, are responsible for the metabolism of many drugs.
• Enzyme induction may take up to 3 weeks to develop and wear off.
• Examples of enzyme-inducing drugs include Phenobarbitone, Phenytoin, Carbamazepine, and Rifampicin.

Changes in Gl pH

• Weak bases are more absorbable in basic environments.
• Weak acids are more absorbable in acidic environments.
• Antacids, H₂-receptor antagonists, and Proton pump inhibitors can decrease the absorption of ketoconazole by increasing the pH.

Adsorption, Chelation, and Other Complexing Mechanisms

• Antacids and mineral supplements can decrease the absorption of tetracycline and ciprofloxacin by forming less soluble chelates.

Changes in Gut Motility

• Anticholinergics agents can delay gastric emptying, decreasing the rate of drug absorption.
• Prokinetic agents can increase gastric emptying, increasing the rate of drug absorption.
• Propantheline can delay gastric emptying, decreasing the rate of absorption of paracetamol.
• Metoclopramide and domperidone can increase gastric emptying, increasing the rate of absorption of paracetamol.

Inhibition or Induction of Drug Transporter Proteins

• Rifampin can decrease digoxin absorption by inducing P-glycoprotein.