Therapeutic incompatibilities occur when two or more drugs interact, leading to altered effects, reduced efficacy, increased toxicity, or unintended outcomes.
These interactions can affect drug absorption, distribution, metabolism, or excretion.
Types and Causes of Therapeutic Incompatibilities:
1) Antagonism
Definition: When the effect of two drugs is less than the sum of their individual effects, reducing efficacy.
Example: A beta-blocker (e.g., propranolol) reduces the effect of a beta-agonist (e.g., albuterol) due to opposing actions on beta-adrenergic receptors.
2) Synergism
Definition: When the combined effect of two drugs is greater than their individual effects, possibly increasing toxicity.
Example: Combining a sedative (e.g., diazepam) with an opioid (e.g., morphine) can lead to excessive CNS depression and respiratory failure.
3) Altered Absorption
Definition: One drug interferes with the absorption of another, reducing efficacy.
Example: Tetracycline's absorption is reduced when taken with calcium or iron, as they form chelate complexes.
4) Altered Distribution
Definition: One drug alters the distribution of another, affecting its concentration and activity.
Example: Phenytoin displaces warfarin from protein-binding sites, increasing free warfarin and the risk of bleeding.
5) Altered Metabolism
Definition: One drug affects the metabolism of another, often through enzyme induction or inhibition.
Example: Rifampin induces CYP450 enzymes, increasing the metabolism of oral contraceptives, reducing their effectiveness.
6) Altered Excretion
Definition: One drug changes the excretion rate of another, affecting its duration and potency.
Example: Probenecid decreases the renal excretion of penicillin, prolonging its effects by increasing its blood concentration.