DRUG INTERACTIONS

Type of drug interactions

Drug Interaction Fundamentals & Assessment

Drug–Drug Interactions (DDIs)

Drug–Herbal Interactions

Drug–Food Interactions

Drug–Laboratory Test Interactions

2 main types of Drug Interaction Fundamentals & Assessment

Precipitant Drug

Object Drug

The drug, agent, or substance that causes the interaction by altering the kinetic or dynamic profile of another drug.

Precipitant Drug

The target drug whose absorption, distribution, metabolism, excretion, or clinical response is affected by the interaction.

Object Drug

Level of Documentation (Degree of Confidence)

Established

Probable

Suspected

Possible

Unlikely

Proven to occur in well-controlled clinical studies; high certainty.

Established

Very likely to occur based on clinical data, but not fully proven in controlled trials.

Probable

Might occur; supported by limited clinical data or well-documented case reports.

Suspected

Could occur; supported by preliminary data or theoretical pharmacokinetic models.

Possible

Doubtful or unverified; lacks reliable evidence or clinical significance.

Unlikely

2 types of Drug–Drug Interactions (DDIs)

Pharmacodynamic Interactions

Pharmacokinetic Interactions

occur when drugs act on the same or related physiological systems, pathways, or receptors, modifying clinical response without necessarily altering systemic drug concentration.

Pharmacodynamic interactions

Interaction types in Pharmacodynamic interactions and their concept formula

Addition (1 + 1 = 2)

Synergism (1 + 1 > 2)

Potentiation (1 + 0 = 2)

Antagonism (1 + 1 = 0)

Electrolyte Changes (Physiological Sensitivity)

Example Drug Combinations under addition

• Benzodiazepine + Antihistamine

• Beta Blocker + Non-DHP CCB

• TCA + Antihistamine

• Antidepressant + Azithromycin

• ACE Inhibitor + K-Sparing Diuretic

Clinical Effect/Outcome under Addition

• Enhanced CNS sedation

• Severe bradycardia/ AV block

• Potentiated anticholinergic toxicity

• Additive QT prolongation / Arrhythmia

• Severe hyperkalemia

Example Drug Combinations under Synergism

• Sulfonamide (-static) + DHFR Inhibitor (-static)

(e.g., SMX-TMP/Cotrimoxazole, Sulfadoxine-Pyrimethamine)

Clinical Effect/Outcome under Synergism

Combined bacteriostatic action yields a potent bactericidal effect

Example Drug Combinations under Potentiation

• Amoxicillin + Clavulanic Acid

• Piperacillin + Tazobactam

• Ampicillin + Sulbactam

• Aminoglycoside + Loop Diuretic (e.g., Ethacrynic acid)

Clinical Effect / Outcome under Potentiation

• Beta-lactamase protection restores beta-lactam efficacy

• Enhanced ototoxicity risk

Example Drug Combinations under Antagonism

• Opioid Agonist + Naloxone (Pharmacologic)

• Glucocorticoid + Oral Hypoglycemic (Physiologic)

• Antipsychotic + Levodopa (Pharmacologic)

• Epinephrine + Acetylcholine / Histamine (Physiologic)

Clinical Effect/Outcome under Antagonism

• Complete reversal of opioid action

• Reduced glycemic control

• Blockade of antiparkinsonian efficacy

• Mutual counteraction of cardiovascular/airway response

Example Drug Combinations under Electrolyte changes

• Diuretic + Digoxin

• Low Sodium (Na+) + Lithium (Li+)

Clinical Effect/Outcome under electrolyte changes

• Digoxin toxicity precipitated by hypokalemia (S/sx: N/V,

xanthopsia, arrhythmias)

• Lithium toxicity secondary to reduced renal sodium (S/sx: coarse tremors)

occur when a precipitant drug alters the ___ profile of an object drug, changing its systemic plasma concentration.

Pharmacokinetic interactions

Absorption, Distribution, Metabolism, or Excretion (ADME)

Types of Pharmacokinetic interactions

Absorption Interactions

Distribution Interactions

Metabolism (Cytochrome P450 Enzymes)

Excretion Interactions