Therapeutic incompatibilities refer to interactions between two or more drugs in a formulation or when administered concurrently, which can lead to altered pharmacological effects, reduced efficacy, increased toxicity, or other unintended effects.
These interactions can occur at various stages, including absorption, distribution, metabolism, or excretion of the drugs, or at their site of action.
The causes and reasons for therapeutic incompatibilities include:
1. Antagonism:
Antagonism occurs when the combined effect of two drugs is less than the sum of their individual effects, resulting in reduced efficacy.
This can happen due to competitive or non-competitive inhibition, physiological antagonism, or chemical antagonism. Example:
Concurrent administration of a beta-blocker (e.g., propranolol) and a beta-agonist (e.g., albuterol) can lead to reduced therapeutic effects, as they have opposing actions on the same receptor (beta-adrenergic receptors).
2. Synergism:
Synergism occurs when the combined effect of two drugs is greater than the sum of their individual effects, which can lead to increased toxicity or side effects. Example:
Combining a sedative, such as a benzodiazepine (e.g., diazepam), with an opioid analgesic (e.g., morphine) can lead to increased central nervous system depression, potentially resulting in excessive sedation, respiratory depression, or coma.
3. Altered absorption:
Drug interactions can affect the absorption of one or both drugs, leading to altered therapeutic effects.
This can occur due to changes in pH, chelation, or competition for absorption sites. Example:
Tetracycline antibiotics can form chelate complexes with divalent metal ions (e.g., calcium, iron) present in antacids or dairy products, reducing the absorption and efficacy of tetracycline
4. Altered distribution:
Interactions can affect the distribution of drugs in the body, leading to changes in their concentration at the site of action or in the tissues. Example:
Displacing a highly protein-bound drug, such as warfarin, from its plasma protein-binding sites by another highly protein-bound drug, such as phenytoin, can lead to increased free concentrations of warfarin, increasing the risk of bleeding.
5. Altered metabolism:
Drug interactions can affect the metabolism of one or both drugs, leading to changes in their pharmacological effects.
This can occur due to enzyme induction or inhibition. Example:
Concurrent administration of a CYP450 enzyme inducer, such as rifampin, with an oral contraceptive can lead to reduced efficacy of the contraceptive due to increased metabolism and clearance of the hormones.
6. Altered excretion:
Drug interactions can affect the excretion of one or both drugs, leading to changes in their pharmacological effects.
This can occur due to competition for renal excretion, changes in urinary pH, or alterations in transporter function. Example:
Probenecid, a uricosuric agent, can inhibit the renal tubular secretion of penicillin, resulting in decreased penicillin excretion and increased blood concentrations, prolonging its effects.
