General anesthetics properties

Although most anesthetics are achiral or are adininistered as racemic mixture, the anesthetic actions are stereoselective. This property can define a specific, rather than a nonspecific, site of action. Stereoselectivity is observed for such barbiturates as thiopental, pentobarbital, and secobarbital. The (3)-enantiomer is modestly more potent (56,57). Additionally, the volatile anesthetic isoflurane also shows stereoselectivity. The (3)-enantiomer is the more active (58). Further evidence that proteins might serve as appropriate targets for general anesthetics come from observations that anesthetics inhibit the activity of the enzyme luciferase. The potencies parallel the anesthetic activities closely (59,60). 

Flurothyl [333-36-8] (bis-(2,2,2-trifluoroeth5i)ether) (9), an analeptic having strong convulsant properties, has been used for chemical shock therapy (13). The compound is unique in that it is a volatile fluorinated ether and its stmcture resembles those of many halogenated general anesthetics. Chemical shock therapy is rarely used. 

Several general anesthetics (isoflurane, ketamine, thiopental, etomidate) have one or more chiral carbons and thus exist as pairs ot stereoisomers. In many cases one stereoisomer is more potent than the other at providing anesthesia despite little difference in pharmacokinetics (Christensen Lee, 1973 Benthuysen et ak, 1989 Harris et ak, 1992 Dickinson et ak, 1994). The stereoisomers have equal hydrophobic properties and partition equally into the membrane. 

Actually, it was in the early 1950s that the organic chemistry of fluorine really emerged. Within only two or three years, some major applications were developed such as fluorinated general anesthetics and the antitumor properties of fluorouracil. 

Most local anesthetic agents consist of a lipophilic group (eg, an aromatic ring) connected by an intermediate chain via an ester or amide to an ionizable group (eg, a tertiary amine) (Table 26-1). In addition to the general physical properties of the molecules, specific stereochemical configurations are associated with differences in the potency of stereoisomers (eg, levobupivacaine, ropivacaine). Because ester links are more prone to hydrolysis than amide links, esters usually have a shorter duration of action. 

GHB was first synthesized in 1960 and introduced as a general anesthetic. Because of its narrow safety margin and its addictive potential, it is not available in the USA for this purpose at present. Before causing sedation and coma, GHB causes euphoria, enhanced sensory perceptions, a feeling of social closeness, and amnesia. These properties have made it a popular "club drug" that goes by colorful street names such as "liquid ecstasy,"... 

Analgesic efficacy and clinical use Alfentanil is a shortacting potent opioid with analgesic and anesthetic properties (Larijani and Goldberg, 1987). It is less potent than fentanyl but administration can be better controlled. It is mostly used as a supplement to general anesthesia or as a primary anesthetic e.g. in cardiac surgery. Intra-... 

General anesthetics alter the excitation of the neuronal membrane and modify impulse conduction. Specifically, the general anesthetics have the following common properties (1) They decrease the activity of neurons by increasing their threshold to fire, and (2) they prevent the action potential from rising to a normal rate by interfering with sodium influx (Figure 65.7). 

It was at the turn of the twentieth century that the importance of lipid solubility in drug action was also independently described by Meyer and Overton (the significance of the oil/water partition coefficient was discussed in Chapter 2). The importance of lipid solubility in drug action subsequently became manifested in the lipoid theory of cellular depression. In essence, this theory correlated a pharmacological effect (e.g., CNS depression) with a physical property (i.e., lipid solubility) rather than a structure-activity relationship. In the process, the theory was attempting to explain the diverse chemical structures that exist within the hypnotic and general anesthetic classes of drugs (see Chapter 11). Today, we realize the limitations of the lipoid theory and appreciate that the distinction between physical and chemical factors is illusory, since chemical structure is a determinant of physical properties. 

In 1958, phencyclidine (PCP) was introduced into clinical anesthesia as an injectable anesthetic agent. PCP had physiological properties that made it a useful anesthetic. The most significant of these was that it was quite effective but had no risk of cardiac or respiratory depression, as was typical of classical general anesthetic agents. 

Ethylidene Chloride.—CH3—CHCI2 is a colorless liquid boiling at 57.7°. It does not mix with water and possesses anesthetic properties, though it has no general use as such. It is a by-product in the manufacture of chloral, tri-chlor aldehyde (p. 226). 

Stoddard Solvent is a slight to severe skin irritant depending on the exposure condition and duration. This is related to the defatting properties of the solvent. Little is known regarding the specific mechanisms of action for systemic toxicity to Stoddard Solvent. Its effect on the nervous system at high exposure levels may be due to its general solvent properties and anesthetic effect of hydrocarbons in general. 

Phenol therefore seemed to be an excellent option for treating drooping eyelids. In fact, the general toxicity of phenol is non-existent when treating limited areas, and a local anesthetic is aU that is needed given the anesthetic properties of the phenol itself. 

The ability to dry up bronchial secretions and reduce laryngospasms (induced by some general anesthetics) has been the reason for using atropine and scopolamine as presurgical medication. It should be mentioned that scopolamine, which differs from atropine by the (3-6,7-epoxy bridge (Fig. 8-13), while it generally parallels atropine s pharmacological spectrum, does not share its cerebral and medullary stimulation rather it exhibits CNS depression and amnesia, properties applied to anesthesia in an adjunct capacity. 

In this section drugs used because of their CNS depressant properties will considered. The volatile general anesthetics (gases and low-boiling liquids), fixed general anesthetics (e.g., certain barbiturates), and sedative hypnotics (as defined earlier) will be included. In subse-... 

General anesthetics alter the excitation of the neuronal membrane and modify impulse conduction. Specifically, the general anesthetics have the following common properties ... 

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