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

2. 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)

3. 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)

4. 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.

5. 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.

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

7. 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.

8. 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.

9. 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.