Anesthesia/anesthetics

Anesthesia. Materials that have unquestionable anesthetic properties are chloral hydrate [302-17-0] paraldehyde, dimethoxymethane [109-87-5] and acetaldehyde diethyl acetal. In iadustrial exposures, however, any action as an anesthesia is overshadowed by effects as a primary irritant, which prevent voluntary inhalation of any significant quantities. The small quantities which can be tolerated by inhalation are usually metabolized so rapidly that no anesthetic symptoms occur. 

The narcotic potency and solubiUty in oHve oil of several metabohcaHy inert gases are Hsted in Table 10. The narcotic potency, ED q, is expressed as the partial pressure of the gas in breathing mixtures requited to produce a certain degree of anesthesia in 50% of the test animals. The solubiUties are expressed as Bunsen coefficients, the volume of atmospheric pressure gas dissolved by an equal volume of Hquid. The Hpid solubiHty of xenon is about the same as that of nitrous oxide, a commonly used light anesthetic, and its narcotic potency is also about the same. As an anesthetic, xenon has the virtues of reasonable potency, nonflammability, chemical inertness, and easy elimination by the body, but its scarcity and great cost preclude its wide use for this purpose (see Anesthetics). 

The onset of action is fast (within 60 seconds) for the intravenous anesthetic agents and somewhat slower for inhalation and local anesthetics. The induction time for inhalation agents is a function of the equiUbrium estabUshed between the alveolar concentration relative to the inspired concentration of the gas. Onset of anesthesia can be enhanced by increasing the inspired concentration to approximately twice the desired alveolar concentration, then reducing the concentration once induction is achieved (3). The onset of local anesthetic action is influenced by the site, route, dosage (volume and concentration), and pH at the injection site. 

The membrane enzyme luciferase, responsible for light emission in fireflies, is sensitive to anesthetics (20,21), and the concentrations of inhalational agents which inhibit luciferase are the same as those which cause general anesthesia. Studies of various classes of inhalational agents and luciferase demonstrated that above a certain chain length in a homologous series, a point is reached where higher members are not anesthetic. The same cut-off effect in efficacy is observed in anesthesia (22). This effect is not explainable by Hpid theory. 

The agent should be odorless, nonflammable at concentrations which are likely to be used in the operating room, and stable both on storage and to soda lime, which is used as the CO2 absorber in the anesthetic circuit. Induction of, and recovery from, anesthesia should be rapid, and minimal side effects... 

Nitrous Oxide. Nitrous oxide, described by Priesdy in 1772, was first used to reHeve severe dental pain in the latter part of the 18th century. Sometime in the mid-1800s N2O was successfully used as an anesthetic, and its widespread usage coincided with the development of anesthesia machines. Nitrous oxide is a nonflammable, colorless, odorless, and tasteless gas that can exist as a Hquid under pressure at room temperature. It is normally stored in cylinders. However, it supports combustion. 

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

Methohexital [18652-93-2] (Brevital), C 4H gN202, (2) is a barbiturate iv anesthetic iaduction agent that has a slightly faster onset than thiopentone and less accumulation. The recovery from anesthesia is also slightly faster and better. However, iaduction is associated with an iacreased iacidence of excitatory phenomena. Methohexital also causes respiratory and cardiovascular depression and is unstable ia solution, necessitating reconstitution before use (99). 

Local anesthetics produce anesthesia by blocking nerve impulse conduction in sensory, as well as motor nerve, fibers. Nerve impulses are initiated by membrane depolarization, effected by the opening of a sodium ion channel and an influx of sodium ions. Local anesthetics act by inhibiting the channel s opening they bind to a receptor located in the channel s interior. The degree of blockage on an isolated nerve depends not only on the amount of dmg, but also on the rate of nerve stimulation (153—156). 

Specific Local Anesthetic Agents. Clinically used local anesthetics and the methods of appHcation are summarized in Table 5. Procaine hydrochloride [51-05-8] (Novocain), introduced in 1905, is a relatively weak anesthetic having along onset and short duration of action. Its primary use is in infiltration anesthesia and differential spinal blocks. The low potency and low systemic toxicity result from rapid hydrolysis. The 4-arninobenzoic acid... 

Lidocaine hydrochloride [73-78-9] (Xylocaine), is the most versatile local anesthetic agent because of its moderate potency and duration of action, rapid onset, topical activity, and low toxicity. Its main indications are for infiltration, peripheral nerve blocks, extradural anesthesia, and in spinal anesthesia where a duration of 30 to 60 min is desirable. Because of its vasodilator activity, addition of the vasoconstrictor, epinephrine, increases the duration of action of Hdocaine markedly. It is also available in ointment or aerosol preparations for a variety of topical appHcations. 

The total U.S. market value for the anesthetic agents Hsted was 299.9 million ia 1990 (162). General inhalation agents, valued at 154.5 million, comprised over half (51.5%) of the 1990 market. General iv anesthetics were valued at 111.5 million (37.2%). Local iajectable agents, at 33.9 million, represented the smallest portion of the market (11.3%). U.S. sales for selected anesthesia pharmaceuticals are given ia Table 6. 

Use of isopropyl alcohol in industrial appHcations does not present a health hazard. The alcohol produces anesthetic effects in high vapor concentration. Consequently, the OSHA permissible exposure limit (PEL) and the ACGIH threshold limit value (TLV) have been estabUshed at 400 ppm (0.098 mg/L) for an 8-h exposure (TWA) (138). This level causes a mild irritation of the eyes, nose, and throat (139). However, the TLV level does not produce symptoms of anesthesia (140). The OSHA and ACGIH short-term exposure limits (STELs) are 500 ppm. The odor threshold for isopropyl alcohol ranges from 3 to 200 ppm, which is the minimum concentration having identifiable odor (141). 

Combinations of barbiturates and benzodiazepine tranquilizers or even antihistaminergics having sedative properties are sometimes used. Furthermore, infusion of anesthetics can be used to provide long-term anesthesia for intensive care medicine. The antagonist flumazenil (18) is available to reverse the effects of anesthetics of the benzodiazepine class. 

Another injectable anesthetic widely used in feline and primate practice is ketamine hydrochloride [1867-66-9]. Ketamine, a derivative of phencychdine, can be chemically classified as a cyclohexamine and pharmacologically as a dissociative agent. Analgesia is produced along with a state that resembles anesthesia but in humans has been associated with hallucinations and confusion. For these reasons, ketamine is often combined with a tranquilizer. The product is safe when used in accordance with label directions, but the recovery period may be as long as 12—24 h. 

Halothane and methoxyflurane are volatile and are used in a vaporizer and deflvered to the animal via an oxygen carrier. Both agents can be dehvered with nitrous oxide [14522-82-8], a mild anesthetic that when combined with halothane or methoxyflurane can induce anesthesia faster than... 

It must be remembered that all anesthetics and tranquilizers are used by the practitioner following a risk—benefit evaluation. General anesthesia, even being adininistered by an experienced practitioner, can result in death through cardiac or respiratory depression. The veterinarian is acutely aware of these risks and chooses the dmg and method of adininistration considering the patient s health status, the nature of and need for the procedure, and the likelihood of success. 

Anesthetics. Ethyl amiaobenzoate [94-09-7] (benzocaiae), C2H22NO2, is the only anesthetic candidate that might allow spawned-out broodstock carcasses to be used for pet or human food. Studies are still required to determine which residues remain ia the carcasses (9). Electronarcosis is an alternative to chemical anesthesia that uses varying electrical frequencies to rapidly anesthetize fishes and allow gentie recovery. Electronarcosis has been used effectively on tilapia (Oreochromis sp.) and the common carp Cyprinus carpid) and the technique is being tested with other fishes (23,24). 

Ethylene is slightly more potent as an anesthetic than nitrous oxide, and the smell of ethylene causes choking. Diffusion through the alveolar membrane is sufficiendy rapid for equilibrium to be estabUshed between the alveolar and the pulmonary capillary blood with a single exposure. Ethylene is held both ia cells and ia plasma ia simple physical solution. The Hpoid stroma of the red blood cells absorb ethylene, but it does not combine with hemoglobin. The concentration ia the blood is 1.4 mg/mL when ethylene is used by itself for anesthesia. However, ia the 1990s it is not used as an anesthetic agent. 

Anesthesia Anesthesia is a loss of sensation or feeling. Anesthesia (or "anesthetics") is often used deliberately by doctors and dentists to block pain and other sensations during surgical procedures. Treatment for pre- or postoperative pain is called analgesia. 

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... 

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