Central nervous system anesthetics

Affects the blood, kidney, and central nervous system anesthetic effect from large doses testicular atrophy and teratogenic oral LD50 value (rabbits) 890 mg/kg combustible liquid flash point (closed cup) 42° C (107°F) LEL and UEL values 2.5 and 19.8% by volume, respectively forms peroxides. See Section 20.2 for a detailed discussion. 

Toxicity. 1,1-Dichloroethane, like all volatile chlorinated solvents, has an anesthetic effect and depresses the central nervous system at high vapor concentrations. The 1991 American Conference of Governmental Industrial Hygienists (ACGIH) recommends a time-weighted average (TWA) solvent vapor concentration of 200 ppm and a permissible short term exposure level (STEL) of 250 ppm for worker exposure. The oral LD q of... 

Trichloroethylene is acutely toxic, primarily because of its anesthetic effect on the central nervous system. Exposure to high vapor concentrations is likely to cause headache, vertigo, tremors, nausea and vomiting, fatigue, intoxication, unconsciousness, and even death. Because it is widely used, its physiological effects have been extensively studied. 

Overexposure to tetrachloroethylene by inhalation affects the central nervous system and the Hver. Dizziness, headache, confusion, nausea, and eye and mucous tissue irritation occur during prolonged exposure to vapor concentrations of 200 ppm (15). These effects are intensified and include incoordination and dmnkenness at concentrations in excess of 600 ppm. At concentrations in excess of 1000 ppm the anesthetic and respiratory depression effects can cause unconsciousness and death. A single, brief exposure to concentrations above 6000 ppm can be immediately dangerous to life. Reversible changes to the Hver have been reported foUowing prolonged exposures to concentrations in excess of 200 ppm (16—22). Alcohol consumed before or after exposure may increase adverse effects. 

Inhalation is the most common means by which ethers enter the body. The effects of various ethers may include narcosis, irritation of the nose, throat, and mucous membranes, and chronic or acute poisoning. In general, ethers are central nervous system depressants, eg, ethyl ether and vinyl ether are used as general anesthetics. 

The toxic effect depends both on lipid and blood solubility. I his will be illustrated with an example of anesthetic gases. The solubility of dinitrous oxide (N2O) in blood is very small therefore, it very quickly saturates in the blood, and its effect on the central nervous system is quick, but because N,0 is not highly lipid soluble, it does not cause deep anesthesia. Halothane and diethyl ether, in contrast, are very lipid soluble, and their solubility in the blood is also high. Thus, their saturation in the blood takes place slowly. For the same reason, the increase of tissue concentration is a slow process. On the other hand, the depression of the central nervous system may become deep, and may even cause death. During the elimination phase, the same processes occur in reverse order. N2O is rapidly eliminated whereas the elimination of halothane and diethyl ether is slow. In addition, only a small part of halothane and diethyl ether are eliminated via the lungs. They require first biotransformation and then elimination of the metabolites through the kidneys into the... 

Drugs Central nervous system drugs - Anesthetic gases... 

Many alkaloids have pronounced biological properties, and a substantial number of the pharmaceutical agents used today are derived from naturally occurring amines. As a few examples, morphine, an analgesic agent, is obtained from the opium poppy Papaver somnifemm. Cocaine, both an anesthetic and a central nervous system stimulant, is obtained front the coca bush Erythroxylon coca, endemic to upland rain forest areas of Colombia, Ecuador, Peru, Bolivia, and western Brazil. Reserpine, a tranquilizer and antihypertensive, comes from powdered roots of the semitropical plant Rauwolfia serpentina. Ephedrine, a bronchodilator and decongestant, is obtained front the Chinese plant Ephedra sinica. 

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). 

Other anesthetics susceptible to abuse, such as ether and chloroform, have received far less attention, because they are considered to be less commonly abused substances. Nonetheless, when inhaled, ether and chloroform are also rapidly absorbed and distributed in the central nervous system (CNS), inducing a rapid euphoria. Ether and chloroform inhalation is facilitated by the fact that they have a low boiling point (i.e., approximately 34°C) (Delteil et al. 1974). 

In the past, trichloroethylene was used as a human anesthetic. Trichloroethylene has also been used by individuals who intentionally inhale it for its narcotic properties. Therefore, most of the information regarding the effects of trichloroethylene in humans comes from case studies and experiments describing effects of trichloroethylene after inhalation exposure. These studies indicate that the primary effect of exposure to trichloroethylene is on the central nervous system. Effects include headache, vertigo, fatigue, short-term memory loss, decreased word associations, central nervous system depression, and anesthesia. 

The ability of the anesthetic agent to function is related to the partial pressure of the drug in the brain. Two major factors dictate the concentration of anesthetic agent in the neural tissue (1) the pressure gradients from lung alveoli to the brain (i.e., inhaled gas —> alveoli — bloodstream —> brain) and (2) the lipid solubility of the drug that enables it to pass between the blood-brain barrier to the central nervous system. 

Uncertainty factor 3 severe headaches are known to occur in angina patients medicated with nitroglycerin and the threshold for vasodilatation does not vary greatly among individuals. The effect was also a threshold effect for central nervous systems depression (no change in cognitive abilities slight imbalance in one of several sensitive motor tests). Individual variation in susceptibility to central nervous system depressants such as anesthetics varies no more than 2-fold. 

GHB, short for its chemical name gamma hydroxybutyrate, is a potent sedative and a depressant of the central nervous system. GHB was first synthesized in the 1920s, although it was not specifically designed to mimic another existing drug. In the 1960s, GHB was developed for possible use as an anesthetic. However, the makers of GHB later withdrew it from consideration for approval by the U.S. FDA because of severe side effects reported by patients. 

More specifically regarding petroleum and petroleum products, the alkanes in gasoline and some other petroleum products are central nervous system depressants. In fact, gasoline was once evaluated as an anesthetic agent. However,... 

Herbai sedatives and anxioiytics are a diverse group of plant drugs that commonly act as depressants of the central nervous system (CNS) (table 6.1). Pharmaceutical CNS depressants are used as anxiolytics, anti-epiieptics, sedatives, sleep-inducers (sedatives or hypnotics), general anesthetics, and recreationai drugs (e.g., ethanol) (table 6.2). CNS... 

Neurological Effects. Neurological effects in hrnnans after acute inhalation exposure to chloroform are well documented because chloroform has been used as an anesthetic for surgery. Inhaled chloroform acts as a depressant on the central nervous system. Chronic inhalation exposure to chloroform resulted in exhaustion, lack of concentration, depression, and irritability in occupationally exposed people (Challen et al. 1958). In a case study, chloroform inhalation for 12 years resulted in psychotic episodes, hallucinations, and convulsions (Heilbmnn et al. 1945). Central nervous system toxicity was observed in humans after oral exposure to chloroform, which suggests that the effects of inhalation and oral exposure are similar. In case reports of patients who intentionally or accidentally ingested several ounces of chloroform, deep coma with abolished reflexes occurred within a few minutes (Piersol et al. 1933 Schroeder 1965 Storms 1973). 

The clinical effects of chloroform toxicity on the central nervous system are well documented. However, the molecular mechanism of action is not well understood. It has been postulated that anesthetics induce their action at a cell-membrane level due to lipid solubility. The lipid-disordering effect of chloroform and other anesthetics on membrane lipids was increased by gangliosides (Harris and Groh 1985), which may explain why the outer leaflet of the lipid bilayer of neuronal membranes, which has a large ganglioside content, is unusually sensitive to anesthetic agents. Anesthetics may affect calcium-dependent potassium conductance in the central nervous system (Caldwell and Harris 1985). The blockage of potassium conductance by chloroform and other anesthetics resulted in depolarization of squid axon (Haydon et al. 1988). 

Although this drug is categorized as a local anesthetic, I have chosen to put it in with the hallucinogens because of the psychotomimetic effects that it produces. Cocaine is not a phenylethyl-amine, but it produces central nervous system arousal or stimulant effects which closely resemble those of the amphetamines, the methylenedioxyamphetamines in particular. This is due to the inhibition by cocaine of re-uptake of the norepinephrine released by the adrenergic nerve terminals, leading to an enhanced adrenergic stimulation of norepinephrine receptors. The increased... 

A matter of philosophical rather than practical significance is the close similarity in the optimal hydrophobicity for the random-walk process in plants and animals. In a series of papers dating bact to 1968, Hansch ( 3) has shown that drugs acting rather non-specifically in the animal central nervous system, such as anesthetics and barbiturates, also have an optimal log P in the 2.0 to 2.5 range (Table V). 

Halothane is used as a clinical anesthetic, and all levels of central nervous system depression can be expected, including amnesia, analgesia, anesthesia, and respiratory depression. Levels ranging from 5000 to 3 0,000 ppm can induce anesthesia, whereas 5000-15,000ppm can maintain it. A 30-minute exposure to 4000 ppm caused amnesia and impairment of manual dexterity, whereas similar exposure to 1000 ppm did not alter the outcome on various psychomotor tests. ... 

When used as a topical anesthetic in medical applications, iodoform produced central nervous system depression with vomiting, coma, and damage to the kidneys, liver, and heart. ... 

Toxicology. Trichlorofluoromethane is toxic by several mechanisms It can sensitize the myocardium to catecholamines, resulting in ventricular arrhythmias it can have an anesthetic effect on the central nervous system... 

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