Bronchial and cardiac beta‐adrenoceptor blockade‐a comparison of atenolol, acebutolol and labetalol.

Self Cite

1 The R-entantiomer of timolol, L-714,465, is considerably less potent as a 1l-and 132-adrenoceptor antagonist in animals than timolol, whilst only slightly less potent in reducing intraocular pressure. If the same was true in man L-714,465 would have potential benefits over timolol in the treatment of glaucoma. 2 The extent of bronchial 1-adrenoceptor blockade following one eyedrop in each eye of timolol 1% and L-714,465 1% was compared in six normal subjects, by measuring the displacement of the bronchodilator dose-response curve to isoprenaline following each drug compared to the isoprenaline dose-response curve after placebo eyedrops (methylcellulose). 3 There was no significant difference between the dose-response curves to L-714,465 and placebo, but a significant displacement of the dose-response curve following timolol. The geometric mean dose ratio following timolol (21) differed significantly from that following L-714,465 (1.6). 4 Heart rate at the end of the isoprenaline dose-response study was lower after timolol, despite the fact that subjects had received higher doses of isoprenaline. The trend was in the same direction after L-714,465 when compared with placebo though less marked. 5 L-714,465 clearly causes less 3-adrenoceptor blockade than timolol when given as 1% eyedrops. The effects of L-714,465 1% on the airways and heart rate did not differ significantly from placebo in these six subjects but the pattern of response would be most consistent with L-714,465 having some ,B-adrenoceptor blocking activity though considerably less than timolol.

Section: Discussionsupporting

confidence: 85%

“…The study design does not allow us to say whether L-714,465 has some P2-adrenoceptor blocking activity albeit less than timolol, or none. The mean dose ratio for L-714,465 is similar to that seen with oral atenolol 100 mg or metoprolol 200 mg in different subjects in previous studies (Gribbin et al, 1981;Tattersfield et al, 1984).…”

Section: Discussionsupporting

confidence: 85%

Bronchial beta‐adrenoceptor blockade following eyedrops of timolol and its isomer L‐714,465 in normal subjects.

Richards¹,

Tattersfield²

1985

Self Cite

“…There are, however, differences in the degree of selectivity of the cardioselective ,-adrenoceptor blockers since they displace to varying extents the bronchial dose-response curves to 32-adrenoceptor stimulants. In clinical studies, atenolol or bisoprolol appeared to be more selective than other compounds, such as acebutolol, metoprolol or oxprenolol (Greefhorst & van Herwaarden, 1982;Gribbin et al, 1981;Lammers et al, 1984;Lawrence et al, 1982;Macquin-Mavier et al, 1988;Perks et al, 1978;Ruffin et al, 1979;Tattersfield et al, 1984). Bronchial rings from a segmental bronchus were prepared and suspended in parallel in Krebs solution under an initial tension of 2.5 g. After 1.5 h of equilibration, the resting tension was between 1 and 2 g. Tensions were measured isometrically with strain gauges, amplifiers and .O.S..-Moise 2 recorder system (Celaster, Celle l'Evescault, 86600 Lusignan, France) (Advenier et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Comparative beta‐adrenoceptor blocking effects of propranolol, bisoprolol, atenolol, acebutolol and diacetolol on the human isolated bronchus.

Naline¹,

Sarriá²,

Ertzbischoff³

et al. 1990

Cedex 06 and 2Laboratoires Lederle, 74, rue d'Arcueil, SILIC 275, 94578 Rungis Cedex, France Five P-adrenoceptor blockers, propranolol, acebutolol, diacebutolol, atenolol and bisoprolol, were tested for their antagonistic effect against isoprenaline on human isolated bronchi. The results showed (1) that only propranolol exerted a competitive antagonistic effect against isoprenaline (pA2 = 9.40 ± 0.22, n = 7) whereas the other drugs did not, and (2) that, in the presence of P-adrenoceptor blockers in the plasma concentrations reported after a single usual therapeutic dose, the doses of isoprenaline giving the same bronchodilator effect must be multiplied by 32.6, 5.51, 4.63, 2.82 and 1.95 respectively with propranolol, diacetolol, acebutolol, atenolol, and bisoprolol. It was concluded that (1) atenolol and bisoprolol were the least potent drugs at bronchial level in therapeutic plasma concentrations and (2) that tests performed on the human isolated bronchus might be a useful screening procedure for new drugs with potential activity on the airways.

“…Another problem when comparing two antihypertensive drugs with different shaped dose response curves is the choice of doses. Atenolol 100 mg is generally felt to have similar antihypertensive effects to labetalol 300 mg (Gribbin et al, 1981), although the latter would have to be given twice daily to maintain its effect for 24 h.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of single doses of atenolol and labetalol on airways obstruction in patients with hypertension and asthma.

Jackson¹,

Beevers²

1983

1 The effects of atenolol (100 mg), a cardioselective 1-adrenoceptor blocking agent, and labetalol (300 mg), a combined a-and non-selective ,8-adrenoceptor blocking agent given in single doses were examined in a double-blind placebo controlled study in 11 asthmatic patients with hypertension.Changes in forced expiratory volume in one second (FEVy) were measured. 2 There were no significant differences between the effects of the active drugs, approximately half the patients having higher FEV, values during each of the two active treatments. When compared with placebo, labetalol significantly reduced the effect of inhaled salbutamol on FEV1.3 Whilst ,8-adrenoceptor blockings drugs cannot be recommended in patients with airways obstruction, should they inadvertantly be given, labetalol like atenolol may be considered relatively safer then pure non-selective ,8-adrenoceptor blocking drugs.