Drug Interactions

• Critical to understand potential drug interactions, given the practice of ‘balanced anesthesia’ and the multiple drugs used to achieve this state.

Drug Interactions

• Common types of Interactions:– Physiochemical

• physical properties of different drugs are sometimes incompatible (ex- formation of a precipitate when pancuronium bromide is added to an IV containing sodium thiopental, forming a non-aqueous soluble salt of the two) (also known as drug incompatibilities)

Drug Interactions

• Common types of Interactions:– Pharmacokinetic

• Occurs when one drug alters the way another drug is handled by the body. (ex- enhanced metabolism of neuromuscular blockers by patients taking anticonvulsants chronically – enzyme induction)

Drug Interactions

• Common types of Interactions:– Pharmacodynamic

• Occurs when a drug increases or decreases the effect of another drug (ex- A decrease in the minimum alveolar concentration required for the volatile anesthetics when opioids are also given)• Considered the most important type of interactions in anesthesiology.

Drug Interactions

• Terms:– Additive – involves two drugs that act by the same mechanism (sometimes different mechanisms) and the effect is equal to what would be expected by direct summation of each effect.– Synergistic – involves effects of two drugs acting by different mechanisms (sometimes the same mechanism) and the effect is greater than the simple sum of each drug effect.– Antagonistic - effect of two drugs where the observed effect is less than additive.

Drug Interactions

• Common causes of drug interactions:– Additive, synergistic, antagonistic actions– Enzyme induction– Enzyme inhibition– Displacement– Absorption interference– Water and ionic disturbances

Drug Interactions

• Anesthesia frequently utilizes specific drug interactions to the benefit of the patient.

– Giving two synergistic drugs to allow decreased doses of each and minimize potential toxicity.

Drug Interactions

• Volatile Anesthetics (or Propofol) and Opioids– Opioids do not cause reliable sedation at doses used to block responses to pain.– Volatile Anesthetics do not block pain responses at doses used to produce unconsciousness.– Either class of agent alone would require a potentially toxic dose to provide a good anesthetic action with proper pain blockade.– Given together, a synergistic interaction occurs, allowing lower doses of each to be used and provide good overall anesthetic and pain blocker.– Ultra-short acting opioids (Remifentanil) together with Propofol provide excellent short acting synergistic anesthesia.

Tolerance

• Seen as an increased need of a drug to elicit the same response.

– both psychological and physiological tolerance types.

• Tachyphylaxis is the rapid development of tolerance.