Adrenergic Agents

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b-adrenergic agonists are the preferred initial rescue medication for acute bronchospasm. b-adrenergic receptors are divided into two types: b 1 and b2. Stimulation of b.| receptors increases rate and force of cardiac contraction and decreases small intestine motility and tone. b 2-adrenergic stimulation promotes bronchodilation, vasodilation, uterine relaxation, and skeletal muscle tremor.

The mechanism of bronchodilator action of b-adrenergic drugs involves stimulation of the enzyme adenyl cyclase, which converts intracellular adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). This action enhances the binding of intracellular calcium to cell membranes, reducing the myoplasmic calcium concentration, and results in relaxation of bronchial smooth muscle. In addition to bronchodilation, b-adrenergic drugs inhibit mediator release and promote mucociliary clearance.

The most common side effect of b-adrenergic drugs is skeletal muscle tremor. Patients may also experience nervousness, anxiety, insomnia, headache, hyperglycemia, palpitations, tachycardia, and hypertension. Despite earlier concerns over potential cardiotoxicity, especially when these drugs were used in combination with theophylline, clinical experience has not revealed significant problems. Arrhythmias and evidence of myocardial ischemia are rare, especially in patients without prior history of coronary artery disease.

The b-adrenergic agonists used today are analogues of naturally occurring sympathomimetics ( Tab.l.e... 64-5). The ideal bronchodilator in this class of drugs would possess pure b2-receptor activity—bronchodilation without cardiac effects. The older catecholamine bronchodilators—isoproterenol and epinephrine—are not b 2 specific and have a short duration of action. Isoetharine is more b 2 selective but still has a short duration of action. These drugs have nearly been replaced by newer agents produced by chemical modification of the parent compound. The resorcinol bronchodilators (metaproterenol, terbutaline, and fenoterol) and saligenin bronchodilators (albuterol and carbuterol) share greater b 2 specificity, as well as longer duration of action and effectiveness through the oral route due to resistance to intestinal sulfatases.

Hyperglycemia Intraoperatively

TABLE 64-5 Dosages of Drugs for Asthma Exacerbations in Emergency Medical Care or Hospital

Aerosol therapy with b2-adrenergic drugs produces excellent bronchodilation and is favored over both the oral and parenteral routes. The aerosol route achieves topical administration of a relatively small dose of drug, producing local effects with minimum systemic absorption and fewer side effects. Aerosol delivery may be achieved with a metered dose inhaler (MDI) with spacing device or a compressor-driven nebulizer. A spacing device attached to the inhaler can improve drug deposition when patient technique is inadequate. Even with optimum technique, however, a maximum of 15 percent of the drug dose is retained in the lungs, regardless of the aerosol method used. Dry-powder delivery devices and MDIs using hydrofluoralkane as propellant have recently replaced chlorinated fluorocarbon (CFC)-driven devices.

Aerosol treatments may be administered every 15 to 20 min or on a continuous basis. Epinephrine or terbutaline may be administered subcutaneously to patients unable to coordinate aerosolized or MDI treatments but their use should generally be avoided in patients with a history of cardiovascular disease. Intravenous b-agonist infusions offer no advantage over aerosolized or MDI-delivered agents and carry potential risk. 20

Salmeterol xinafoate is a b2-adrenoreceptor agonist that binds with greater affinity to the b-receptor site than does albuterol. It is indicated for twice-daily maintenance therapy, should never be used more frequently, and is to be avoided for treatment of acute exacerbation. Its bronchodilator effect lasts at least 12 h, and tachyphylaxis has not been reported with long-term use. It is an effective treatment for long-term control of asthma, especially nocturnal asthma. Short-acting b 2-adrenoreceptor agonists are generally added for symptoms that occur despite the use of salmeterol.

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