The danger of using beta-adrenergic blockers and particularly those without cardiac selectivity in asthmatic patients has been known for more than 20 years. Even relatively cardioselective agents (including atenolol) have been shown to produce significant bronchoconstriction, and for this reason are strictly contraindicated in asthma. One possible way of overcoming the adverse effects of beta-blockade is to use an agent which has additional beta-2 stimulating qualities (beta-2 intrinsic sympathomimetic activity or beta-2 ISA). The latter could provide a degree of bronchodilation despite existing beta 1 blockade. Celiprolol has been reported to possess such bronchosparing qualities and even to dilate the bronchi in animals and in single-dose human studies. These reports prompted us to evaluate the respiratory effects of this drug in hypertensive asthmatics in a doubleblind crossover comparison with a better-known cardioselective beta-blocker, atenolol.
Patients and Methods
Twelve patients with mild to moderate essential hypertension and reversible airway obstruction were recruited. The trial protocol was approved by the Research Ethics Committee of the University of Cape Town Medical School, and all patients provided signed and informed consent. All subjects were hospital outpatients in whom hypertension control was not optimal on current medication (Table 1). Link
Mild to moderate hypertension was defined as diastolic blood pressure between 95 and 115 mm Hg taken with the patient in the supine position on two or more occasions during the placebo run-in period of two weeks.
Reversible airway obstruction was defined as the combination of a FEV, of 85 percent or less of the patients predicted normal value (according to height and weight); together with either a demonstrated 15 percent increase in the FEV, in response to 200 jig of inhaled salbutamol PC20 to histamine challenge of 8 mg/ml or less.
Table 1 — Batient Characteristics and Pre-trial Treatment
|Patient||Age(yr)||Sex||DurationofAsthma(yr)||DurationofHypertension(yr)||Airway Reactivity (% or mg/ml)*||Maintenance Asthma Therapy||Maintenance Antihypertensive Therapy|
|1||51||M||10||9||20||Salbutamol inhalerf + theophylline, $ 350 mg bd||Amiloride, 5 mg: hydrochlorothiazide, 50 mg daily + prazosin, 2.5 mg bd|
|2||61||M||9||6||26||Salbutamol inhaler||Atenolol, 100 mg; chlorthalidone, 25 mg daily|
|3||29||F||3||6||29||Salbutamol inhaler + theophylline, 125 mg bd||Amiloride, 10 mg; hydrochlorothiazide, 100 mg daily|
|4||63||F||55||3||32||Salbutamol inhaler||Amiloride, 5 mg; hydrochlorothiazide, 50 mg daily + methyldopa, 750 mg daily|
|5||45||F||7||7||3.2 mg/ml||Salbutamol inhaler||Hydrochlorothiazide, 25 mg; triamterene, 50 mg daily + methyldopa, 250 mg bd|
|6||60||M||41||15||1.2 mg/ml||Salbutamol inhaler + theophylline, 350 mg tds + beclomethasone, 50 jigbd||Cyclopenthiazide, 0.50 mg; potassium chloride, 1200 mg daily|
|7||42||F||2||2||16||Intermittent||Cyclopenthiazide, 0.25 mg; potassium chloride, 600 mg daily|
|8||41||F||8||8||1.6 mg/ml||Intermittent||Methyldopa, 500 mg bd|
|9||43||F||6||13||8 mg/ml||Intermittent||Hydrochlorothiazide, 25 mg; triameterene, 50 mg daily + nifedipine, 5 mg bd|
|10||50||M||46||6||20||Intermittent||Amiloride, 5 mg; hydrochlorothiazide, 50 mg daily + prazosin 2.5 mg bd -1- nifedipine 10 mg bd|
|11||38||F||34||7||67||Fenoterol inhaler + theophylline, 350 mg bd + sodium cromoglycate, 20 mg bd||Methyldopa, 250 mg bd|
|12||49||F||6||36||0.8 mg/ml||Intermittent||Hydrochlorothiazide, 25 mg; triamterene, 50 mg daily + prazosin, 1 mg bd|