Handbook of experimental pharmacology
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Handb Exp Pharmacol · Jan 2008
ReviewInhibitory ligand-gated ion channels as substrates for general anesthetic actions.
General anesthetics have been in clinical use for more than 160 years. Nevertheless, their mechanism of action is still only poorly understood. In this review, we describe studies suggesting that inhibitory ligand-gated ion channels are potential targets for general anesthetics in vitro and describe how the involvement of y-aminobutyric acid (GABA)(A) receptor subtypes in anesthetic actions could be demonstrated by genetic studies in vivo.
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The heart has a strong endogenous cardioprotection mechanism that can be triggered by short periods of ischaemia (like during angina) and protects the myocardium during a subsequent ischaemic event (like during a myocardial infarction). This important mechanism, called ischaemic pre-conditioning, has been extensively investigated, but the practical relevance of an intervention by inducing ischaemia is mainly limited to experimental situations. Research that is more recent has shown that many volatile anaesthetics can induce a similar cardioprotection mechanism, which would be clinically more relevant than inducing cardioprotection by ischaemia. ⋯ Since ischaemia-reperfusion of the heart routinely occurs in a variety of clinical situations such as during transplant surgery, coronary artery bypass grafting, valve repair or vascular surgery, anaesthetic-induced cardioprotection might be a promising option to protect the myocardium in clinical situations. Initial studies now confirm an effect on surrogate outcome parameters such as length of ICU or in-hospital stay or post-ischaemic troponin release. In this chapter, we will summarize our current understanding of the three mechanisms of anaesthetic cardioprotection exerted by inhalational anaesthetics.
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It is today generally accepted that anesthetics act by binding directly to sensitive target proteins. For certain intravenous anesthetics, such as propofol, barbiturates, and etomidate, the major target for anesthetic effect has been identified as the gamma-aminobutyric acid type A (GABA(A)) receptor, with particular subunits playing a crucial role. ⋯ For the less potent steroid anesthetic agents the picture is less clear, although a relatively small number of targets have been identified as being the most likely candidates. In this review, we summarize the most relevant clinical and experimental pharmacological properties of these intravenous anesthetics, the molecular targets mediating other endpoints of the anesthetic state in vivo, and the work that led to the identification of the GABA(A) receptor as the key target for etomidate and aminosteroids.
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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.