Therapeutic incompatibilities

  • 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.
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