Introduction
Drug interactions occur when the effect of one drug is changed by the presence of another drug, food or chemical. This interaction may increase or decrease the action of a drug, or create a completely new effect. Understanding drug interactions is important for safe and effective therapy, especially when patients take multiple medicines.
Types of Drug Interactions
Drug interactions are mainly divided into two categories:
- Pharmacokinetic interactions – changes in absorption, distribution, metabolism or excretion of a drug.
- Pharmacodynamic interactions – changes in the drug’s effect at the site of action.
Pharmacokinetic Drug Interactions
These interactions occur when one drug alters the movement of another drug inside the body through absorption, distribution, metabolism or excretion.
1. Absorption Interactions
Drug absorption takes place mainly from the gastrointestinal tract (GIT). Several factors can affect this process:
a) Changes in GI Motility
- Prokinetic drugs (e.g., domperidone) increase GI motility and reduce absorption of other drugs.
- Drugs like atropine decrease motility and may increase absorption.
b) Alteration in pH and Ionisation
- Ionised drugs absorb poorly; non-ionised drugs absorb well.
- Drugs that change gastric pH can reduce or enhance absorption of other drugs.
c) Drug–Food Interactions
High-fat meals may reduce absorption of certain drugs.
d) Formation of Complexes
Some drugs form complexes that cannot be absorbed:
- Tetracyclines bind to calcium.
- Sucralfate binds to proteins.
- Cholestyramine binds to digoxin and thyroxine.
e) P-glycoprotein Interactions
P-glycoprotein pumps drugs back into the intestine. Inhibitors like grape fruit juice increase bioavailability of drugs such as verapamil.
2. Distribution Interactions
Distribution is influenced by plasma protein binding. If two drugs compete for the same binding site, displacement can occur.
- Phenylbutazone or sulphamethoxazole can displace warfarin, increasing warfarin activity.
3. Metabolism Interactions
The majority of metabolism interactions occur through cytochrome P450 (CYP450) enzymes in the liver.
Cytochrome P450 (CYP450) System
- Large family of enzymes involved in drug metabolism.
- Important isoenzymes include CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4.
a) Enzyme Inhibition
Some drugs inhibit CYP enzymes and reduce metabolism of other drugs, leading to toxicity.
- Example: erythromycin inhibits CYP3A4.
b) Enzyme Induction
Some drugs increase enzyme levels and enhance metabolism of other drugs, lowering their effect.
- Examples: rifampicin, phenytoin, barbiturates.
4. Excretion Interactions
These involve renal or biliary excretion.
a) Renal Excretion
Only free (unbound) drugs are filtered through kidneys.
- Urine pH affects excretion: acidic urine enhances excretion of weak bases; alkaline urine enhances excretion of weak acids.
- Alkalinisers like sodium citrate increase excretion of acidic drugs.
b) Biliary Excretion
Large, polar drugs (molecular weight > 300) are excreted in bile.
- Some drugs undergo enterohepatic circulation and may interact with others during reabsorption.
Pharmacodynamic Drug Interactions
These interactions occur at the site of action or receptor level, without affecting drug concentration.
1. Receptor-Level Interactions
a) Homodynamic Interactions
Two drugs act on the same receptor.
- Agonist + antagonist: e.g., morphine and naloxone.
- Partial agonist + full agonist: may reduce overall effect.
b) Heterodynamic Interactions
Two drugs act on different receptors but influence the same physiological process.
- Insulin acts via cAMP signalling.
- Digoxin and furosemide together cause hypokalemia, increasing risk of digoxin toxicity.
2. Physiological Antagonism
Two drugs produce opposite effects by acting on different systems.
- Histamine lowers blood pressure; adrenaline increases blood pressure.
3. Synergism
Drugs may work together to produce a stronger effect.
- Example: combining amoxicillin with clavulanic acid increases antibacterial effect.
4. Potentiation
A drug with no effect on its own may increase the effect of another.
- Example: clavulanic acid potentiates the action of amoxicillin.
Clinical Importance of Drug Interactions
- May increase toxicity.
- May reduce therapeutic effect.
- May improve drug action when used intentionally (e.g., combination therapy).
- Important in elderly and patients taking multiple medications.
Detailed Notes:
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