General Anesthetics Specific Agents

First, it is clear that nearly all drugs with CNS effects act on specific receptors that modulate synaptic transmission. A very few agents such as general anesthetics and alcohol may have nonspecific actions on membranes (although these exceptions are not fully accepted), but even these non-receptor-mediated actions result in demonstrable alterations in synaptic transmission. 

The physiologic state induced by general anesthetics typically includes analgesia, amnesia, loss of consciousness, inhibition of sensory and autonomic reflexes, and skeletal muscle relaxation. The extent to which any individual anesthetic agent can produce these effects depends on the specific drug, the dosage, and the clinical situation. 

Hence, it is believed that general anesthetics exert most, if not all, of their effects by binding to one or more neuronal receptors in the CNS. This idea is a departure from the general perturbation theory described earlier that is, that the inhaled anesthetics affected the lipid bilayer rather than a specific protein. Continued research will continue to clarify the mechanism of these drugs, and future studies may lead to more agents that produce selective anesthetic effects by acting at specific receptor sites in the brain and spinal cord. 

Anesthetic agents are a diverse class of chemicals which are extremely important in modern medicine. They are generally used to produce a loss of sensation to all stimuli, either in a specific anatomical area, or a total loss of consciousness. Anesthetics differ from analgesics in that analgesics such as aspirin, acetaminophen, ibuprofen, or morphine act to decrease pain, but not other sensations. Anesthetics can be broadly categorized into two general classes, local anesthetics and general anesthetics. These classes are independent as far as indication, chemical class, routes of administration, and toxicity, and thus will be considered separately. It will be noted when one compound within a class differs from the others. 

A. Inhalation. The toxic air level is quite variable, depending on the specific agent (see Table IV-4, p 532). Freon 21 (dichlorofluoromethane TLV 10 ppm [42 m m ) is much more toxic that freons 12 and 22 (TLV 1000 ppm). In general, anesthetic or CNS-depressant doses require fairly large air concentrations, which can also displace oxygen, leading to asphyxia. The air level of dichloromonofluoromethane considered immediately dangerous to life or health (IDLH) is 5000. Other TLV and IDLH values can be found in Table IV-4 (p 532). 

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. 

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