Anesthetic state

Neuroleptic analgesia is so called because the combination of a major tranquilizer, a neuroleptic dmg, and a potent opiate produces an anesthetic state characterized by sedation, apathy, and mental detachment (see Psychopharmacological agents) (152). Iimovar [8067-59-2] a combination of droperidol [648-72-2], C22H22FN2O2, (19) and fentanyl (9) citrate, is used for procedures that do not require muscle relaxation. However, the onset of action is slow. 

Ketamine (Ketalar) is a rapid-acting general anesthetic. It produces an anesthetic state characterized by profound analgesia, cardiovascular and respiratory stimulation, normal or enhanced skeletal muscle tone, and occasionally mild respiratory depression. Ketamine is used for diagnostic and surgical procedures that do not require relaxation of skeletal muscles, for induction of anesthesia before the administration of other anesthetic drugp, and as a supplement to other anesthetic drags. 

Inhaled (volatile) anesthetics are delivered to the lungs in gas mixtures in which concentrations and flow rates are easy to measure and control. However, dose-response characteristics of volatile anesthetics are difficult to quantify. Although achievement of an anesthetic state depends on the concentration of the anesthetic in the brain (ie, at the effect site), concentrations in the brain tissue are obviously impossible to measure under clinical conditions. Furthermore, neither the lower nor the upper ends of the graded dose-response curve defining the effect on the central nervous system can be ethically determined because at very low gas concentrations awareness of pain may occur. Moreover, at high concentrations there is a high risk of severe cardiovascular and respiratory depression. Nevertheless, a useful estimate of anesthetic potency can be obtained using quantal dose-response principles for both the inhaled and intravenous anesthetics. 

In contrast to the barbiturates, benzodiazepines do not produce an anesthetized state. They may be used as a preanesthetic in order to lessen anxiety, to be followed by a barbiturate and then the general anesthesia gas such as halothane. 

Desflurane can be made by fluonnation of isoflurane with potassium fluonde [/J] or with bromine tnfluonde [14] (equation 2) Although approximately six times more desflurane than isoflurane is required for anesthesia, it achieves the anesthetic state and the patient recovers from this state more rapidly This feature seems to be of interest to some anesthesiologists One negative property is that it irritates the breathmg passageway, especially in children Desflurane is flammable at higher levels of anesthetic use It is the least metabolized of all the commercial anesthetics, producing tnfluoroacetic acid and fluonde ion [75]... 

Several drugs are used intravenously, alone or in combination with other drugs, to achieve an anesthetic state (as components of balanced anesthesia) or to sedate patients in intensive care units who must be mechanically ventilated. These drugs include the following (1) barbiturates (thiopental, methohexital) (2) benzodiazepines (midazolam, diazepam) (3) opioid analgesics (morphine, fentanyl, sufentanil, alfentanil, remifentanil) (4) propofol (5) ketamine and (6) miscellaneous drugs (droperidol, etomidate, dexmedetomidine). Figure 25-2 shows the structures of... 

Ketamine has indirect sympathomimetic activity. Ketamine s behavioral effects are distinct from those of other anesthetics. The ketamine-induced cataleptic state is accompanied by nystagmus with pupillary dilation, salivation, lacrimation, and spontaneous limb movements with increased overall mnscle tone. Although ketamine does not prodnce the classic anesthetic state, patients are amnestic and nnresponsive to painful stimuli. Ketamine produces profound analgesia, a distinct advantage over other parenteral anesthetics. 

ACTIONS AND MECHANISMS OF GENERAL ANESTHETICS The Anesthetic State... 

General anesthetics produce a behavioral state referred to as general anesthesia, which can be defined as a global but reversible depression of CNS function resulting in the loss of response to and perception of aU external stimuli. However, anesthesia is not simply a deafferented state (e.g., amnesia is an important aspect of the anesthetic state), and not all general anesthetics produce identical patterns of deafferentation. 

Components of the anesthetic state include amnesia, immobility in response to noxious stimulation, attenuation of autonomic responses to noxious stimulation, analgesia, and unconsciousness. General anesthesia is useful only insofar as it facilitates the performance of surgery or other noxious procedures. The performance of surgery usually requires an immobilized patient who does not have an excessive autonomic response to suigery (blood pressure and heart rate) and who has amnesia for the procedure. Thus, the essential components of the anesthetic state are immobilization, amnesia, and attenuation of autonomic responses to noxious stimulation. If an anesthetic produces profound amnesia, it can be difficult in principle to determine if it also produces either analgesia or unconsciousness. 

The ideal anesthetic state is characterized by a loss of all sensations and includes analgesia and muscle relaxation. Neuronal depression in specific areas of the central nervous system is believed to be largely responsible for such an anesthetic state. The areas involved include many cortical regions that are represented by excitatory pyramidal... 

The production and maintenance of the anesthetic state is believed by most to be dependent on the concentration, or partial pressure, of the anesthetic agent in yet unknown areas of the brain. Obviously, the concentration of the anesthetic agent in the gas mixture administered, as well as the rate and depth of respiration of the patient, will influence the rate of anesthesia induction. The rate at which delivery of anesthetic agents to these sites occurs is dependent on their physicochemical properties, particularly their solubility in lipid and blood. 

Reversal of the anesthetic state and recovery requires a reduction in the concentration of the anesthetic in the brain. This is achieved by stopping the delivery of the... 

Many of the short-chain alkanes, alkenes, and alkynes are capable of producing an anesthetic state when administered to patients. Potency generally increases as chain length increases. Because of their flammability and increased propensity to cause cardiovascular toxicity, however, these nonsubstituted hydrocarbons are not useful as anesthetic agents. 

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