Handbook of experimental pharmacology
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Most opioids used in anaesthesia are of the anilidopiperidine family, including fentanyl, alfentanil, sufentanil and remifentanil. While all share similar pharmacological properties, remifentanil, the newest one, is probably the most original, which is the reason this review focusses especially on this drug. ⋯ Consequently, it offers a unique titratability when its effects need to be quickly achieved or suppressed, but it requires specific drug delivery schemes such as continuous infusion, target-controlled infusion and anticipated postoperative pain treatment. Kinetic differences between opioids used in anaesthesia and some clinical uses of remifentanil are reviewed in this chapter.
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Handb Exp Pharmacol · Jan 2008
ReviewHypnotic and opioid anesthetic drug interactions on the CNS, focus on response surface modeling.
This chapter will present the conceptual and applied approaches to capture the interaction of anesthetic hypnotic drugs with opioid drugs, as used in the clinical anesthetic state. The graphic and mathematical approaches used to capture hypnotic/opiate anesthetic drug interactions will be presented. This chapter is not a review article about interaction modeling, but focuses on specific drug interactions within a quite narrow field, anesthesia.
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In this chapter, drawn largely from the synthesis of material that we first presented in the sixth edition of Miller's Anesthesia, Chap 31 (Stanski and Shafer 2005; used by permission of the publisher), we have defined anesthetic depth as the probability of non-response to stimulation, calibrated against the strength of the stimulus, the difficulty of suppressing the response, and the drug-induced probability of non-responsiveness at defined effect site concentrations. This definition requires measurement of multiple different stimuli and responses at well-defined drug concentrations. There is no one stimulus and response measurement that will capture depth of anesthesia in a clinically or scientifically meaningful manner. ⋯ We demonstrate the scientific evidence that profound degrees of hypnosis in the absence of analgesia will not prevent the hemodynamic responses to profoundly noxious stimuli. Also, profound degrees of analgesia do not guarantee unconsciousness. However, the combination of hypnosis and analgesia suppresses hemodynamic response to noxious stimuli and guarantees unconsciousness.
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Nonimmobilizing, inhalational anesthetic-like compounds are experimental agents developed as a tool to investigate the mechanism of action of general anesthetics. Clinically used for more than 150 years, general anesthesia has until now defied all attempts to formulate a theory of its mechanisms that would link, in an uninterrupted logical chain, observations on the molecular level-via effects on the cellular and network levels-to the in vivo phenomenon. Nonimmobilizers, initially termed nonanesthetics, are substances that disobey the Meyer-Overton rule. ⋯ This discovery required not only the introduction of the more precise term "nonimmobilizers," but also excluded one important component of anesthesia, i.e., amnesia, from application of the algorithm. On the other hand, compared to inhalational anesthetics, nonimmobilizers interact with relatively few molecular targets, also limiting the usefulness of the nonimmobilizer algorithm. Nevertheless, nonimmobilizers have not only yielded useful results but can, by virtue of those very properties that make them less than ideal for anesthesia research, be used as experimental tools in the neurosciences far beyond anesthetic mechanisms.