Asthma catecholamines

The modern usage of P2" go Asts for the treatment of asthma dates to 1903 when the effect of injected epinephrine [51-43-4] (adrenaline) C2H23NO2, (1 R = CH3) was investigated (see Epinephrine and norepinephrine) (33). As in some other modem treatments, eg, xanthines and anticholinergics, the roots of P2" go Ast therapy for asthma can be found in historical records which document the use of herbal extracts containing ephedrine [299-42-3] C qH NO, (2) as bronchodilators. Epinephrine and ephedrine are stmcturaHy related to the catecholamine norepinephrine [51-41-2] CgH NO, (1, R = H), a neurotransmitter of the adrenergic nervous system (see Neuroregulators). 

Beta-1, beta-2, and beta-3 adrenergic receptors are G-protein-coupled receptors. Beta-1 and beta-2 receptors mediate the positive inotropic, chronotropic, and dro-motropic effects of the endogenous catecholamines epinephrine and norepinephrine. The beta-3 subtype seems to play a role in regulating thermogenesis and lipid mobilization in brown and white adipose tissue. Several coding and promoter polymorphisms of these receptors have been identified. Clinical studies in asthma... 

P -agonists are invariably used in the symptomatic treatment of asthma. Epinephrine and ephedrine are structurally related to the catecholamine norepinephrine, a neu-... 

Metaproterenol [met a proe TER a nole], although chemically similar to isoproterenol, is not a catecholamine and is resistant to methyla-tion by COMT. It can be administered orally or by inhalation. The drug acts primarily at p2 receptors, producing little effect on the heart. Metaproterenol produces dilation of the bronchioles and improves airway function. The drug is useful as a bronchodilator in the treatment of asthma and to reverse bronchospasm (Figure 6.13). 

INHALATIONAL- HALOTHANE TERBUTALINE, THEOPHYLLINE Cases of arrhythmias when these bronchodilators are co-administered with halothane Possibly due to sensitization of the myocardium to circulating catecholamines by the volatile anaesthetics to varying degrees Risk of cardiac events is higher with halothane. Desflurane is irritant to the upper respiratory tract, and t secretions can occur and are best avoided in patients with bronchial asthma. Sevoflurane is non-irritant and unlikely to cause serious adverse effects... 

Salbutamol, fenoterol, rimiterol, reproterol, pir-buterol, salmeterol, ritodrine and terbutaline are P-adrenoceptor agonists that are relatively selective for p2-receptors, so that cardiac (chiefly p -receptor) effects are less prominent. Tachycardia still occurs because of atrial (sinus node) p -receptor stimulation the P2-adrenoceptors are less numerous in the ventricle and there is probably less risk of serious ventricular arrhythmias than with the use of nonselective catecholamines. The synthetic agonists are also longer-acting than isoprenaline because they are not substrates for catechol-O-methyltransferase, which methylates catecholamines in the liver. They are used principally in asthma, and to reduce uterine contractions in premature labour. 

Indications Cardiac arrest, hay fever, asthma, anaphylaxis Category Catecholamine Sympathomimetic Half-life N/A... 

The xanthine theophylline has been used for several decades in the treatment of asthma. This compound produces different effects at the cellular level, including phosphodiesterase isoenzyme inhibition, adenosine antagonism, catecholamine secretion enhancement, and the modulation of calcium fluxes. Recently, theophylline was found to have both immunomodulatory and anti-inflammatory properties therefore, interest in its use in patients with asthma has been renewed [103]. Recent studies have thus discovered that at low doses, theophylline is able to decrease airway inflammation, accelerate eosinophil apoptosis, and decrease recruitment of lymphocytes and neutrophils to the lungs. Although it is classified as a phosphodiesterase inhibitor, its exact therapeutic mechanism of action remains undetermined [104]. Of the new mechanisms that have been included in the potential mode of action of theophylline, one is the apoptosis of inflammatory cells. In eosinophils and lymphocytes, for example, this effect is due to the compound s ability to inhibit phosphodiesterase, which leads to an even more pronounced increase in intracellular cAMP levels than that which occurs when adenylate cyclase, the enzyme that synthesizes cAMP, is activated. This inhibition and the resulting cAMP level increase thus lead to... 

The agonist isoproterenol is used to treat asthma, because it mimics the effects of catecholamines in relaxing bronchial muscles in the lung it does so by interacting with one specific class of adrenergic receptors (so-called because they bind adrenaline, the old name for epinephrine). 

Catecholamines Epinephrine No Minutes Anaphylaxis, glaucoma, asthma, and to cause vasoconstriction... 

Belcher, N. G., Murdoch, R., Dalton, N., Clark, T. J. H., Ress, P. J., and Lee, T. H., 1988, Circulating concentrations of histamine, neutrophil chemotactic activity, and catecholamines during the refractory period in exercise-induced asthma, J. Allergy Clin. Immunol 81 100-110. 

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