Halothane muscle effects

The anesthesiologist selects the anesthetic drug that will produce safe anesthesia, analgesia (absence of pain), and in some surgeries, effective skeletal muscle relaxation. General anesthesia is most commonly achieved when the anesthetic vapors are inhaled or administered intravenously (IV). Volatile liquid anesthetics produce anesthesia when their vapors are inhaled. Volatile liquids are liquids that evaporate on exposure to air. Examples of volatile liquids include halothane, desflurane, and enflurane. Gas anesthetics are combined with oxygen and administered by inhalation. Examples of gas anesthetics are nitrous oxide and cyclopropane. 

Halothane exerts a pronounced hypotensive effect, to which a negative inotropic effect contributes. Enflurane and isoflurane cause less circulatory depression. Halothane sensitizes the myocardium to catecholamines (caution serious tachyarrhythmias or ventricular fibrillation may accompany use of catecholamines as antihypotensives or toco-lytics). This effect is much less pronounced with enflurane and isoflurane. Unlike halothane, enflurane and isoflurane have a muscle-relaxant effect that is additive with that of nondepolarizing neuromuscular blockers. 

The following agents may be affected by theophylline Benzodiazepines, -agonists, halothane, ketamine, lithium, nondepolarizing muscle relaxants, propofol, ranitidine, and tetracyclines. Probenecid may increase the effects of dyphylline. 

The duration of exposure to the anesthetic can also have a significant effect on the recovery time, especially in the case of the more soluble anesthetics (eg, halothane and isoflurane). Accumulation of anesthetics in muscle, skin, and fat increases with prolonged exposure (especially in obese patients), and blood tension may decline slowly during recovery as the anesthetic is slowly eliminated from these tissues. Although recovery may be rapid even with the more soluble agents following a short period of exposure, recovery is slow after prolonged administration of halothane or isoflurane. 

Halothane, isoflurane, and enflurane have similar depressant effects on the EEG up to doses of 1-1.5 MAC. At higher doses, the cerebral irritant effects of enflurane may lead to development of a spike-and-wave pattern and mild generalized muscle twitching (ie, myoclonic activity). However, this seizure-like activity has not been found to have any adverse clinical consequences. Seizure-like EEG activity has also been described after sevoflurane, but not desflurane. Although nitrous oxide has a much lower anesthetic potency than the volatile agents, it does possess both analgesic and amnesic properties when used alone or in combination with other agents as part of a balanced anesthesia technique. 

Inhaled (volatile) anesthetics potentiate the neuromuscular blockade produced by nondepolarizing muscle relaxants in a dose-dependent fashion. Of the general anesthetics that have been studied, inhaled anesthetics augment the effects of muscle relaxants in the following order isoflurane (most) sevoflurane, desflurane, enflurane, and halothane and nitrous oxide (least) (Figure 27-9). The most important factors involved in this interaction are the following (1) nervous system depression at sites proximal to the neuromuscular junction (ie, central nervous system) (2) increased muscle blood flow (ie, due to peripheral vasodilation produced by volatile anesthetics), which allows a larger fraction of the injected muscle relaxant to reach the neuromuscular junction and (3) decreased sensitivity of the postjunctional membrane to depolarization. 

Inhaled anesthetics that are relatively insoluble in blood (low blood gas partition coefficient) and brain are eliminated at faster rates than more soluble anesthetics. The washout of nitrous oxide, desflurane, and sevoflurane occurs at a rapid rate, which leads to a more rapid recovery from their anesthetic effects compared to halothane and isoflurane. Halothane is approximately twice as soluble in brain tissue and five times more soluble in blood than nitrous oxide and desflurane its elimination therefore takes place more slowly, and recovery from halothane anesthesia is predictably less rapid. The duration of exposure to the anesthetic can also have a marked effect on the time of recovery, especially in the case of more soluble anesthetics. Accumulation of anesthetics in tissues, including muscle, skin, and fat, increases with continuous inhalation (especially in obese patients), and blood tension may decline slowly during recovery as the anesthetic is gradually eliminated from these tissues. Thus, if exposure to the anesthetic is short, recovery may be rapid even with the more soluble agents. However, after prolonged anesthesia, recovery may be delayed even with anesthetics of moderate solubility such as isoflurane. 

Kataoka et al. (1994) studied the negative inotropic effects of sevoflurane, isoflurane, enflurane and halothane in canine blood-perfused papillary muscles. 

McMurphy RM, Hodgson DS (1996) Cardiopulmonary effects of desflurane in cats. Am J Vet Res 57 367-370 Mazzeo AJ, Cheng EY, Bosnjak ZJ et al. (1996) Differential effects of desflurane and halothane on peripheral airway smooth muscle. Br J Anaesth 76 841-846 Mitsuhata H, Saitoh J, Shimizu R et al. (1994) Sevoflurane and isoflurane protect against bronchospasm in dogs. Anesthesiol 81 1230-1234... 

The effect of the sympathomimetic drugs on the pregnant uterus is Vciriable and difficult to predict, but serious fetal distress can occur, due to reduced placental blood flow as a result both of contraction of the uterine muscle (a) and arterial constriction (a). Pj-agonists are used to relax the uterus in premature labour, but unwanted cardiovascular actions can be troublesome. Sympathomimetics were particularly likely to cause cardiac arrhythmias (p, effect) in patients who received halothane anaesthesia (now much less used). 

The potentiation of D-tubocurarine block produced by enflurane slowly continues to increase with time, even after the usual equilibration period has passed (SEDA-5, 132) (128). This does not occur with halothane, and the discrepancy is said to mean that more D-tubocurarine will be required in the first hour of enflurane anesthesia than during equipotent halothane anesthesia, but that thereafter less will be required during enflurane anesthesia. It has been suggested that enflurane, unhke halothane, may produce an effect on muscle that takes time to develop. This may also be part of the mechanism, in addition to the... 

Muscle relaxants may also contribute to anesthesia. Pancuronium 0.1 mg/kg has been reported to lower the MAC for halothane by 25% (135). It was conjectured that this could be due to a central effect or peripheral effect, through reduction of afferent input from muscle spindles to the reticular activating system. Recently, however, a similar though not identical study (SEDA-15, 124) (136) failed to confirm that pancuronium, vecuronium, or atracurium lowers the MAC for halothane. 

There are reports that diazepam can produce paradoxical excitability immediately after i.v. administration to humans and small animals. Although this paradoxical effect is not well described in horses, diazepam should be administered with caution to mature horses when used as a sole agent. It can be used as the sole agent for sedation and restraint in young foals. Diazepam is recommended for i.v. use at doses of 0.02-0.1 mg/kg. Diazepam is primarily used in adult horses to provide muscle relaxation and for its anticonvulsant effect prior to anesthetic induction with ketamine. Diazepam (0.04 mg/kg) reduces the MAC of halothane by approximately 29% (Matthews et al 1990). Diazepam is considered the acute treatment of choice for status epilepticus in all species (see Ch. 9). Diazepam (0.02-0.04 mg/kg) is an appetite stimulant in horses, although its effect is of short duration (Brown et al 1976). 

The inhalational anesthetics halothane, isoflurane, and enflu-rane all have been reported to have a positive effect in children and adults with severe asthma that is unresponsive to standard medical therapy. The proposed mechanisms for inhalational anesthetics include direct action on bronchial smooth muscle, inhibition of airway reflexes, attenuation of histamine-induced bronchospasm, and interaction with /32-adrenergic receptors. Well-controlled trials with these agents have not been completed. Potential adverse effects include myocardial depression, vasodilation, arrhythmias, and depression of mucociliary function. In addition, the practical problem of delivery and scavenging these agents in the intensive care environment as opposed to the operating room is a concern. The use of volatile anesthetics cannot be recommended based on insufficient evidence of efficacy. 

Answer D. The pharmacologic action common to both morphine and D-tubocurarine is the release of histamine from mast cells, causing vasodilation. Morphine increases, but D-tubocurarine (via ganglion blockade) decreases, bladder tone. When used in combination with inhalational anesthetics (e.g., halothane), D-tubocurarine has been implicated in malignant hyperthermia. Morphine relaxes the uterus, but D-tubocurarine has no effects on smooth muscle neurotransmission. 

Electrolyte imbalance, and diseases that lead to electrolyte imbalance, such as adrenal cortical insufficiency, alter neuromuscular blockade. Depending on the nature of the imbalance, either enhancement or inhibition may be expected. Magnesium sulfate, used in the management of toxemia of pregnancy, enhances the skeletal-muscle-relaxing effects of pancuronium. Antibiotics such as aminoglycosides, tetracyclines, clindamycin, lincomycin, colistin, and sodium colistimethate augment the pancuronium-induced neuromuscular blockade. Anesthetics such as halothane, enflurane, and isoflurane enhance the action of pancuronium, whereas azathioprine will cause a reversal of neuromuscular blockade. 

Because diethyl ether (commonly known simply as ether) is a short-lived muscle relaxant, it has been widely used as an inhalation anesthetic. However, because it takes effect slowly and has a slow and unpleasant recovery period, other compounds, such as enflurane, isoflurane, and halothane, have replaced ether as an anesthetic. Diethyl ether is still used where there is a lack of trained anesthesiologists, since it is the safest anesthetic to administer by untrained hands. Anesthetics interact with the nonpolar molecules of cell membranes, causing the membranes to swell, which interferes with their permeability. 

Musck Halothane causes some relaxation of skeletal muscle via its central depressant effects and potentiates the actions of nondepolarizing muscle relaxants (curariform drugs see Chapter 9), increasing both their duration of action and the magnitude of their effect. Halothane and the other halogenated inhalational anesthetics can trigger malignant hyperthermia this syndrome frequently is fatal and is treated by immediate discontinuation of the anesthetic and administration of dantrolene. 

Muscle Isoflurane produces some relaxation of skeletal muscle via its central effects. It also enhances the effects of depolarizing and nondepolarizing muscle relaxants. Isoflurane is more potent than halothane in its potentiation of neuromuscular blocking agents. The drug relaxes uterine smooth muscle and is not recommended for analgesia or anesthesia for labor and vaginal delivery. 

Interestingly, anticholinesterases, ACH and ion antagonize competitively pancuronium bromide effectively however, its activity is virtually enhanced by general anaesthetics, for instance halothane, ether, enflurane etc. (see Chapter 4). Therefore, the latter substantial potentiation in pharmacological activity is particularly useful to the anaesthetist due to the faet that it is administered invariably as an adjunct to the anaesthetic procedure in order to cause simultaneous relaxation of the skeletal muscle. 

Halothane (Fluothane) Mechanism unclear. Induces rapid, comfortable anesthesia and skeletal muscle relaxation. i cardiac output, mild T of systemic vascular resistance, typically no effect on heart rate, 1 right atrial pressure, moderate depression of myocardial function, most likely to sensitize myocardium to catecholamines and i baroreceptor reflex. t ventilation control (T tidal volume, >1 rate of breathing, i response to CCfe and hypoxia), bronchodilation (mostpotent), No effect on hypoxic pulmonary vasoconstrictor response, depression of ciliary function and mucous clearance. 

I. Pharmacology. Cimetidine, ranitidine, famotidine, and nizatidine are selective competitive inhibitors of histamine on Hj receptors. These receptors modulate smooth muscle, vascular tone, and gastric secretions and may be involved in clinical effects associated with anaphylactic and anaphylactoid reactions, as well as ingestion of histamine or histamine-like substances (eg, scombroid fish poisoning). Cimetidine, as an inhibitor of cytochrome P-450 enzymes, has been proposed or studied in animals as an agent to block the production of toxic intermediate metabolites (eg, acetaminophen, carbon tetrachloride, halothane. 

Analyses of nerve membranes have brought to light the unusually high ratio of cholesterol to phospholipid, namely about 1 to 3 Chdicko et al. 1976). Because the spinal cord and brain are clad in lipid-rich membranes, a lower dose of a depressant is effective for the central nervous system as compared with the musculature. Thus the partition coefficient of halothane is 6.80 for brain (grey matter), but only 2.92 for muscle (tissue/gas, 37°C) (Lowe, 1968). In detail, the site of action of a general anaesthetic in the central nervous system is not exactly known, some workers favouring the polysynaptic sites, others the cytoplasmic membrane. The physical and molecular nature of this site will be discussed later in this chapter. 

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