Asthma adrenoceptor agonists

Methacholine is used to identify bronchial hyperreactivity in patients without clinically apparent asthma. For this indication, the drug is administered by inhalation, and patients who may be developing asthma usually produce an exaggerated airway contraction. Upon completion of the test, a rapid-acting bronchodilator (e.g., inhaled p-adrenoceptor agonist) can be given to counter the bronchoconstrictor effect of methacholine and relieve the patient s discomfort. 

Terbutaline, albuterol, salmeterol and other Pj-adrenoceptor agonists are used primarily in the management of asthma. Terbutaline and albuterol have very rapid onset of action and are indicated for acute symptom rehef Salmeterol, in contrast, has a slow onset of action but a long duration of action. Salmeterol is thus used as prophylactic therapy only, not to reverse acute symptoms. 

A few epidemiological studies suggest that the overuse of p-adrenoceptor agonists is associated with an overall deterioration in disease control and a slight increase in asthma mortality. This apparent trend may be caused by several factors, the most likely of which is that patients rely too heavily on bronchodilator therapy to control acute symptoms at the expense of antiinflammatory therapy to control the underlying disease process. 

Ipratropium bromide (Atrovent) is a quaternary amine derivative that is used via inhalation in the treatment of chronic obstructive pulmonary disease and to a lesser extent, asthma. Ipratropium has a slower onset of action (1-2 hours for peak activity) than Pz-adrenoceptor agonists and thus may be more suitable for prophylactic use. Compared with p2-adrenoceptor agonists, ipratropium is generally at least as effective in chronic obstructive pulmonary disease but less effective in asthma. 

The corticosteroids are effective in most children and adults with asthma. They are beneficial for the treatment of both acute and chronic aspects of the disease. Inhaled corticosteroids, including triamcinolone ace-tonide (Azmflcort),beclomethasone dipropionate (Beclo-vent, Vancerit), flunisolide AeroBid), and fluticasone (Flovent), are indicated for maintenance treatment of asthma as prophylactic therapy. Inhaled corticosteroids are not effective for relief of acute episodes of severe bronchospasm. Systemic corticosteroids, including prednisone and prednisolone, are used for the short-term treatment of asthma exacerbations that do not respond to (32-adrenoceptor agonists and aerosol corticosteroids. Systemic corticosteroids, along with other treatments, are also used to control status asthmaticus. Because of the side effects produced by systemically administered corticosteroids, they should not be used for maintenance therapy unless all other treatment options have been exhausted. 

Which one of the following p-adrenoceptor agonists has such a slow onset of action that it is not indicated for the relief of acute asthma symptoms ... 

D. In all asthma treatment regimens, inhaled 2-adrenoceptor agonists are used as bronchodilators as needed to relieve acute symptoms. As asthma is an inflammatory disease of the airway, inhaled corticosteroids are also used as standard therapy to control symptoms in all but the mildest cases. The potential for dangerous side effects and drug... 

Theophyiiine is the most effective of the methyixanthines as a bronchodiiator. However, it is iess effective than 32-adrenoceptor agonists, has a very narrow therapeutic window and has deciined in importance for the treatment of asthma. A piasma theophyiiine concentration of 20 pg-mL-1 (the upper iimit of the therapeutic range) produces 45-60% of maximum bronchodiiatation compared to the 80-90% that can be achieved with 32-adrenoceptor agonists. 

The drugs most used for management of asthma are adrenoceptor agonists, or sympathomimetic agents (used as "relievers" or bronchodilators) and inhaled corticosteroids (used as "controllers" or anti-inflammatory agents). Their basic pharmacology is presented in detail elsewhere (see Chapters 9 and 39). In this chapter, we review their pharmacology relevant to asthma. 

The 32-selective adrenoceptor agonist drugs, particularly albuterol, are the most widely used sympathomimetics for treatment of the bronchoconstriction of asthma at present (Figure 20-4). These agents differ structurally from epinephrine in having a larger... 

Anderson SD, Brannan JD. Long-acting beta 2-adrenoceptor agonists and exercise-induced asthma lessons to guide us in the future. Paediatr Drugs. 2004 6 161-175. 

Cockcroft DW. As-needed inhaled beta2-adrenoceptor agonists in moderate-to-severe asthma current recommendations. Treat Respir Med. 2005 4 169-174. 

Sears MR, Lotvall J. Past, present and future—beta2-adrenoceptor agonists in asthma management. Respir Med. 2005 99 152-170. 

Corticosteroids and yS2 adrenoceptor agonists form the cornerstone of the management of asthma. Patients requiring very occasional relief from symptoms may be managed with fi2 adrenoceptor agonists alone, but an inhaled corticosteroid such as beclomethasone is added if symptomatic relief is needed more than once daily. 

Asthma. In severe asthma (given i.v.) when (5-adrenoceptor agonists fail to give adequate response and for chronic asthma (orally) to provide a background bronchodilator effect. 

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. 

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