Halothane interaction

Kissin et al. (1984) studied the morphine-halothane interaction in rats. 

Kissin I, Kerr CR, Smith LR (1984) Morphine-halothane interaction in rats. Anesthesiol 60 553-561 Krantz Jr. JC, Carr CJ, Forman SE et al. (1941) Anesthesia. IV. The anesthetic action of cyclopropylethyl ether. J Pharmacol Exp Ther 72 233-244... 

Halothane has a mUd depressive effect on cardiac performance (4). In human ventricular myocardium, halothane interacted with L-type calcium channels by interfering with the dihydropyridine binding site this may, at least in part, explain its negative inotropic effect (5). 

Karl HW, Swedlow DB, Lee KW, Downes JJ. Epinephrine-halothane interactions in children. Anesthesiology (1983) 58, 142-5. 

Forni, L.G., Packer, J.E., Slater, T.F. and Willson, KL. (1983). Reactions of the trichloromethyl and halothane derived peroxyl radicals with unsaturated fatty acids a pulse radiolysis study. Chem. Biol. Interact. 45, 171-177. 

The Dp and Dq are the diffusion coefficients of probe and quencher, respectively, N is the number molecules per millimole, andp is a factor that is related to the probability of each collision causing quenching and to the radius of interaction of probe and quencher. A more detailed treatment of fluorescence quenching including multiexponential intensity decays and static quenching is given elsewhere/635 There are many known collisional quenchers (analytes) which alter the fluorescence intensity and decay time. These include O2/19 2( 29 64 66) halides,(67 69) chlorinated hydrocarbons/705 iodide/715 bromate/725 xenon/735 acrylamide/745 succinimide/755 sulfur dioxide/765 and halothane/775 to name a few. 

Other conditions in which ephedra is contraindicated are anxiety disorders, angle-closure glaucoma, prostate adenoma with residual urine volume, pheochromocytoma, and thyrotoxicosis (Gruenwald et al. 1998). Known medications that may interact adversely with ephedrine include heart glycosides, halothane, guanethidine, MAO inhibitors, secale alkaloids, and oxytocin. 

The mechanism of action of inhalational anesthetics is unknown. The diversity of chemical structures (inert gas xenon hydrocarbons halogenated hydrocarbons) possessing anesthetic activity appears to rule out involvement of specific receptors. According to one hypothesis, uptake into the hydrophobic interior of the plasmalemma of neurons results in inhibition of electrical excitability and impulse propagation in the brain. This concept would explain the correlation between anesthetic potency and lipophilicity of anesthetic drugs (A). However, an interaction with lipophilic domains of membrane proteins is also conceivable. Anesthetic potency can be expressed in terms of the minimal alveolar concentration (MAC) at which 50% of patients remain immobile following a defined painful stimulus (skin incision). Whereas the poorly lipophilic N2O must be inhaled in high concentrations (>70% of inspired air has to be replaced), much smaller concentrations (<5%) are required in the case of the more lipophilic halothane. 

Drugs that may interact with labetalol include beta-adrenergic agonists, cimetidine, glutethimide, halothane, and nitroglycerin. 

The arrhythmias associated with halothane or cyclopropane anesthesia have been attributed to the interaction of the anesthetic with catecholamines, and they have been suppressed by IV administration of 1 to 3 mg propranolol. An increase in circulating catecholamines also has been observed in patients with acute myocardial infarction and has been correlated with the development of arrhythmias. 

Halothane and enflurane have direct cardiac inhibitory effects similar to verapamil and diltiazem and these effects may summate. Interaction may also cause an additive effect on conduction with, e.g. isoflurane or halothane. 

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. 

The outcomes of the interaction between a chemical and a target molecule will depend both on the attributes and on the function of the target molecule. Thus, a covalent adduct could be formed, which might be recognized as a neo-antigen (e.g., see sect. "Halothane Hepato toxicity," chap. 7), or a mutation could be caused if the target is DNA [see sect. "Benzo(a)pyrene," chap. 7]. 

Metaproterenol (Alupent, Metaprel) [Bronchodilator/ Beta-Adrenergic Agonist] Uses Asthma reversible bronchospasm Action Sympathomimetic bronchodilator Dose Adults. Neb 0.2-0.3 mL in 2.5-3.0 mL of NS Peds. Neb 0.1-0.2 mL/kg of a 5% soln in 2.5 mL NS Caution [C, /-] Contra Tach, other arrhythmias Disp Aerosol 0.65 mg/inhal soln for inhal 0.4, 0.6% tabs 10, 20 mg syrup 10 mg/5 mL SE Nervousness, tremors (common), tach, HTN Interactions T Effects W/ sympathomimetic drugs, xanthines T risk of arrhythmias W/ cardiac glycosides, halothane, levodopa, theophylline, thyroid hormones T HTN W/ MAOIs effects W/ BBs EMS Separate additional aerosol use by 5 min fewer 3i effects than isoproterenol longer-acting monitor lung sounds before/after administration... 

In cases in which drugs exert their actions by interacting with specific receptors, structural modification dramatically alters the expected effects. However, not all drugs act by interacting with specific receptors. For example, general anesthetics such as thiopental, halothane, cyclopropane, and nitrous oxide have vastly dissimilar structures. 

This question of direct interaction with nerve proteins or indirect interaction via membrane perturbation has also been tackled by ESR spectroscopy. Two types of labeling have been used fatty acids for lipid labeling and maleimide for frog nerve proteins. The anesthetics used were halothane as an example of a general anesthetic and procaine, lidocaine, and tetracaine as examples of local anesthetics. The latter interact primarily with head groups but can also merge into the hydrophobic hydrocarbon... 

There is a long history of controversy in the literature regarding the mode of action of general anesthetics. Experimental results derived from model systems of lipids alone or lipid-cholesterol are somewhat controversial. To mention just a few, using Raman spectroscopy it was found that, at clinical concentrations, halothane had no influence on the hydrocarbon chain conformations, and it was concluded that the interaction between halothane and the lipid bilayer occurs in the head group region [57]. This idea was also supported by 19F-NMR studies. The chemical shifts of halothane in a lipid suspension were similar to those in water and differed from those in hydrocarbons. In contrast, from 2H-NMR experiments, it was concluded that halothane is situated in the hydrocarbon region of the membrane (see also chapter 3.3). 

Inagaki Y, Sumikawa K, Yoshiya I. Anesthetic interaction between midazolam and halothane in humans. Anesth Analg 1993 76(3) 613-7. 

Eliason E, Gardner I, Hume-Smith H, de Waziers I, Beaune P, Kenna JG. Interindividual variability in P450-dependent generation of neoantigens in halothane hepatitis. Chern Biol Interact 1998 116 123-41. 

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