DRUG INTERACTIONS WITH OPIOIDS
General Principles
Opioids are frequently combined with other anesthetic agents to
produce optimal anesthetic conditions. In anesthesia, most concomitantly administered
drugs interact. Although some of these interactions are intentionally sought, others
are unwanted and adverse. There are three general types of mechanisms of drug interactions:
pharmaceutical, pharmacokinetic, and pharmacodynamic.[516]
Pharmaceutical interactions are chemical in nature, as illustrated when an alkaline
solution of thiopental and an acidic solution of succinylcholine precipitate when
simultaneously administered IV.
Pharmacokinetic interactions occur when the administration of
one agent alters the pharmacokinetics or disposition of another. Hemodynamic changes
induced by one agent can affect the pharmacokinetic behavior of the other agent.
The actions of sufentanil, which has a greater hepatic extraction ratio than alfentanil,
are more likely to be affected by decreases in hepatic blood flow. Opioid plasma
levels increase in the presence of propofol.[517]
Decreased opioid metabolism, by the CYP 3A4 isoform of the cytochrome P-450 enzyme
responsible for the oxidative metabolism of more than 50 drugs, may also underlie
pharmacokinetic interactions. Liver enzyme induction by alcohol, antiepileptics,
and barbiturates can also affect the metabolism of anesthetic drugs.
Pharmacodynamic interactions between opioids and inhaled anesthetics
were assessed with classic MAC reduction evaluations in animals and humans. Although
marked synergism between opioids and inhaled anesthetics occurs with analgesic doses
of opioids, there is a ceiling effect to MAC reduction by opioids. The pharmacodynamic
synergism between opioids and sedativehypnotics such as propofol is profound. Choosing
an opioid with a short context-sensitive half-life allows greater doses of that opioid
to be administered, along with reduced doses of propofol, without compromising the
time for recovery from anesthesia. Thus, the optimal plasma level of propofol is
estimated to be approximately 30 percent less when it is combined with remifentanil
instead of alfentanil.[517]
The establishment of drug-dosing regimens and plasma concentrations
of opioids and sedative-hypnotics needed to provide optimal hemodynamic control during
a range of noxious stimuli would be very practical and helpful. However, complicating
our understanding of drug interactions is the observation that the same degree of
interaction does not apply across different types of stimuli.
