Consciousness anesthetics

Anesthetic, general. A compound that, when given systemically, causes a reversible loss of consciousness sufficient to allow surgical procedures. 

Ethanol is classified for medical purposes as a central nervous system (CNS) depressant. Its effects—that is, being drunk—resemble the human response to anesthetics. There is an initial excitability and increase in sociable behavior, but this results from depression of inhibition rather than from stimulation. At a blood alcohol concentration of 0.1% to 0.3%, motor coordination is affected, accompanied by loss of balance, slurred speech, and amnesia. When blood alcohol concentration rises to 0.3% to 0.4%, nausea and loss of consciousness occur. Above 0.6%, spontaneous respiration and cardiovascular regulation are affected, ultimately leading to death. The LD50 of ethanol is 10.6 g/kg (Chapter 1 Focus On). 

Phencyclidine (l-[l-phenylcyclohexyl] piperidine, PCP) was originally developed as an intravenous anesthetic in the 1950s. Used for this indication, it causes a trance-like state without loss of consciousness and was hence classified as a dissociative anesthetic. However, it was soon withdrawn from human use because it produced unpleasant hallucinations, agitation, and delirium. The product was later used in veterinary medicine. Ketamine, a chemically closely related substance, was developed to replace PCP and is stiU in use as a dissociative anesthetic in children. Ketamine is less potent than PCP, and its effects are of shorter duration. However, it may also cause hallucinations (see the section on ketamine in Chapter 7, Club Drugs ). Much of the ketamine sold on the street (special K, cat Valium) has been diverted from veterinarians offices. 

A more complex cyclohexylamine, tiletamine (65), is a useful anesthetic in that injection leads to loss of consciousness without an untoward decrease in blood pressure or heart rate and without undue respiratory depression. Its synthesis15 begins with... 

Backman, S. B., Fiset, P. Plourde, G. (2004). Cholinergic mechanisms mediating anesthetic induced altered states of consciousness. Prog. Brain Res. 145, 197-206. 

The hypothesis of the role of HA in wakefulness stems from the observation that administration of the classical antihistamines (i.e. H3 receptor antagonists) induced sedation. These first-generation antihistamines, used to treat inflammatory reactions, could cross the blood-brain barrier and block the central Hi receptor (White Rumbold, 1988). The first study examining the effect of antihistamines on sleep-wakefulness in cats reported an increase in NREM sleep and a decrease in REM sleep (Jewett, 1968). Similar results were also obtained in dogs (Wauquier et ah, 1981) and humans (Risberg et ah, 1975 Bassano Caille, 1979 Nicholson et ah, 1985 Adam Oswald, 1986). Intraventricular application of HA in the anesthetized rat caused a dose-dependent decrease in the duration of narcosis, whereas intraventricular application of HA in conscious... 

Sokoloff, L., Reivich, M., Kennedy, C. etal. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28 897-916,1977. 

The hypothesis that HNO is not involved during NO-release from sydnonimines was confirmed by the study of NO-release from C78-0652 109, the dimethyl derivative of SIN-1A (Scheme 6.19). This product closely resembles SIN-1A in its biological and pharmacological behavior, showing a clear NO-dependent vasodilating effect on guinea pig pulmonary arteries and hypotensive action in anesthetized and conscious dog models [105]. 

In vivo Hemodynamic and cardiac parameters pressure (arterial, venous, ventricular, e.g., ventricular contractility, cardiac output), HR, peripheral resistance, ECG parameters, body temperature, flow Conscious (restrained or telemetry) and anesthetized Takahara et al. 97 Sato et al. 98 Nekooeian and Tabrizchi99... 

AbdelRahman, A.R., Inadequate blockade by hexamethonium of the baroreceptor heart rate response in anesthetized and conscious rats, Arch. Int. Pharmacodyn. Ther., 297, 68-85, 1989. 

Tsukada et al. (2002) 4 Macada mulatto monkeys C-Raclopride PET (B/1) IV nic (B/I) Slight j, BP (indicating f DA concentration) in anesthetized, but not conscious monkeys, in dorsal striatum... 

Excess consumption of alcohol is not healthful, as many people will testify. Ethanol is a depressant and can be a mild tranquilizer or a general anesthetic, depending on how much is consumed over what period of time. At low doses, ethanol depresses some of the brain s inhibitory systems and acts as a social lubricant. It can also exacerbate seizure disorders such as epilepsy by depressing the inhibitory systems in the brain that suppress seizures and convulsions. At higher doses, alcohol leads to the classical symptoms of intoxication unsteady walk, slurred speech, altered sensory perception, slow reaction times, bizarre behavior, and finally, loss of consciousness. Consnmption of a fiffh of a gallon of hard liqnor over a short time period can be fatal. 

Naloxone is used for rapid opioid detoxification in conjunction with anesthetic agents for conscious sedation. 

In regional anesthesia (spinal anesthesia) with a local anesthetic (p. 204), nociception is eliminated, while consciousness is preserved. This procedure, therefore, does not fall under the definition of general anesthesia... 

Substances from different chemical classes suspend consciousness when given intravenously and can be used as injectable anesthetics (B). Unlike inha-lational agents, most of these drugs affect consciousness only and are devoid of analgesic activity (exception ketamine). The effect cannot be ascribed to nonselective binding to neuronal cell membranes, although this may hold for propofol... 

Methoxyflurane is an extremely powerful inhalation anesthetic that is an excellent skeletal muscle relaxant. However, its use is somewhat limited by its relatively high solubility, which causes the patient to make a slow transition back into consciousness. Another disadvantage of methoxyflurane is that fluorine ions are the product of its biotransformation, which may lead to the development of renal failure. Therefore, it is recommended to use methoxyflurane for anesthesia during interventions of no more than 2 h. A very common synonym for methoxyflurane is penthrane. 

These drugs, unlike general anesthetics, cause a loss of feeling in specific areas while keeping the patient conscious. 

General anesthesia - Remifentanil is not recommended as the sole agent in general anesthesia because loss of consciousness cannot be assured and because of a high incidence of apnea, muscle rigidity, and tachycardia. Remifentanil is synergistic with other anesthetics and doses of thiopental, propofol, isoflurane, and midazolam have been... 

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