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PHARMACEUTICAL INTERACTIONS

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The formulation of drugs is often overlooked but may contribute to bioavailability and desired effects. For example, adding epinephrine to a local anesthetic solution gives the solution a much lower pH due to highly acidic commercial preparations of epinephrine. A more acidic solution of local anesthetic results in lower concentration of the ionized, membrane permeable form of the local anesthetic. This equilibrium change decreases tissue penetration and diminishes the desired effect.

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Propofol is prepared in a lipid emulsion containing soybean oil and egg phosphatide. This hydrophobic solution stabilizes the propofol molecule, but has several clinical consequences. First, it is a ripe environment for microbial growth; so all propofol syringes must be timed and dated and discarded 6 hours after the sterility of the vial is broken. The second issue related to the propofol emulsion is a concern that it will cause anaphylaxis in those with egg or soybean allergy. This is a controversial issue without strong data to support the risk of anaphylaxis; however, it is prudent to avoid propofol in those with allergy to soy, peanut, or egg so long as a suitable alternative is available. The lipid emulsion of propofol also causes burning when administered in small peripheral intravenous lines (IVs).

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The combination of agents in a single intravenous line is another important pharmaceutical interaction. Combination of acidic drugs and basic drugs will form a salt precipitate in the intravenous line. For example, thiopental is acidic and, when mixed with alkaline drugs such as opiates or muscle relaxants, the intravenous tubing may be obstructed by the resulting precipitate.

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Carbon dioxide absorbents such as soda lime and Baralyme allow for removal of exhaled carbon dioxide from the ventilator circuit. These compounds are integral to safe mechanical ventilation, but contain strong bases that can degrade volatile anesthetics. All volatile anesthetics can react with the carbon dioxide absorber to produce carbon monoxide, but this reaction occurs most often with desflurane. A concerning byproduct of sevoflurane interaction with carbon dioxide absorbents is the formation of compound A (pentafluoroisopropenyl fluoromethyl ether) which causes nephrotoxicity in rats. Correlation with nephrotoxicity in humans has not been established, but this side effect is nonetheless concerning.

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PHARMACOKINETIC INTERACTIONS

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Uptake

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Anesthesiologists often manipulate the interaction between epinephrine and local anesthetic when administered for peripheral nerve blocks. When mixed with local anesthetics prior to local injection, epinephrine causes vasoconstriction of muscle and skin, which decreases systemic uptake and results in longer duration of action for the anesthetic. In a similar mechanism, any agent that changes pulmonary blood flow (vasoactive agents, prostaglandins, phosphodiesterase inhibitors, etc) can alter the ventilation/perfusion (V/Q) ratio, thereby altering uptake of volatile anesthetics. Since volatile anesthetic uptake is directly proportional to pulmonary blood flow, the drug’s effect on cardiac output will affect the onset of inhaled anesthetics.

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Several medications alter ...

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