General anesthetics drugs

The anesthesiologist selects the anesthetic drug that will produce safe anesthesia, analgesia (absence of pain), and in some surgeries, effective skeletal muscle relaxation. General anesthesia is most commonly achieved when the anesthetic vapors are inhaled or administered intravenously (IV). Volatile liquid anesthetics produce anesthesia when their vapors are inhaled. Volatile liquids are liquids that evaporate on exposure to air. Examples of volatile liquids include halothane, desflurane, and enflurane. Gas anesthetics are combined with oxygen and administered by inhalation. Examples of gas anesthetics are nitrous oxide and cyclopropane. 

General anesthetic drugs have the ability to reduce the level of consciousness in a dose dependent fashion. The study of the neurobiological mechanisms of action of these drugs may provide insight into the systems that are necessary for the existence of consciousness. It clearly cannot be assumed however, that the systems that underlie the action of these substances are in themselves sufficient for consciousness. Indeed, within a complex neural network, any number of small alterations can disturb the whole. This chapter focuses on what is known about the molecular mechanism of action of drugs that are used clinically for general anesthesia. 

Table 1. The modulatory elFect of general anesthetic drugs on ligand-gated ion channels. The effect of chnicaUy relevant concentrations of general anesthetic drugs. -I- indicates potentiation, 0 indicates no signihcant effect in the majority of studies and -indicates inhibition of activation. indicates insufficient data is available.

The use of inhalational anesthetics is generally reserved for maintenance of anesthesia. The development of an anesthetic concentration in the brain occurs more slowly with inhalational anesthetics than with IV drugs. Once an anesthetic level has been achieved, however, it is easily adjusted by controlling the rate or concentration of gas delivery from the anesthesia machine. The rate of recovery from a lengthy procedure in which inhalational agents are used is reasonably rapid, since inhalational anesthetics are eliminated by the lungs and do not depend on a slow rate of metabolism for their tissue clearance. Thus, inhalational drugs meet the requirement for a relatively prompt return of the patient s psychomotor competence. 

Figure 7.3 Generalized structure of a local anesthetic. Local anesthetics consist of three fundamental structural units a lipophilic part, a hydrogen bonding part, and a terminal amine. The majority of local anesthetic drugs possess these three structural units.

The physiologic state of general anesthesia typically includes analgesia, amnesia, loss of consciousness, inhibition of sensory and autonomic reflexes, and skeletal muscle relaxation. The extent to which any individual anesthetic drug can exert these effects varies with the drug, the dosage, and the clinical situation. 

As pointed out by Anderson et al. (15), starvation, malnutrition, and protein deficiency may all cause differences in drug disposition and thereby differences of drug action. Even relatively minor food deficiencies as observed in Berlin after the second World War (16) caused some unusual reactions, e.g., death from injection of the old and generally safe local anesthetic drug procaine (17). 

The hazard of driving shortly after general anesthesia is still difficult to evaluate. Although abstention from driving has been recommended for 48 hours after general anesthesia (103), it is still difficult to draw clear-cut conclusions from the available data. The matter is also referred to under individual anesthetic drugs. 

The topical anesthetics in general use in the horse are 0.5% proxymetacaine (proparacaine) and 0.5% tetracaine (amethocaine). The rate of onset and duration of clinical anesthesia of the ocular surfaces using these agents in the horse is not known. However, in general, repeated instillations at 30-60 s intervals over a 5 min period will superficially desensitize the normal eye for around 15 min. In the presence of conjunctival hyperemia, there is likely to be accelerated loss of the drug into the systemic circulation and instillation of the anaesthetic agent at shorter intervals for a longer period may be necessary to desensitize the ocular surfaces effectively. 

Mueller RA (1996) General anesthetic drugs. In Munson PL, Mueller RA, Breese GR (eds) Principles of Pharmacology. Chapman and Hall, New York, pp 227-242... 

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