The Effect of Propranolol on Airway Resistance

MacDonald, Alan G.; Ingram, Charles G.; McNeill, R. S.; Fairley, H. Barrie

doi:10.1097/00132586-196904000-00018

Cited by 21 publications

(30 citation statements)

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“…There are however sympathetic nerves terminating on presynaptic cholinergic ganglia (Richardson, 1979) so that increased sympathetic nerve discharge could cause bronchodilatation by inhibiting cholinergic transmission. Previous investigations have suggested that propranolol-induced bronchoconstriction in asthmatic subjects could be both prevented by atropine or other antimuscarinic drugs (Grieco & Pierson, 1971;MacDonald et al, 1967;Ind et al, 1986) or reversed (Grieco & Pierson, 1971;Langer, 1967). However in the present study 72 ,ug inhaled ipratropium bromide caused only partial reversal of the timolol-induced bronchoconstriction and since a further 72 ,ug caused no futher increase in FEV1 in seven patients it is unlikely that the lack of response is due to an inadequate dose.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the airway response to eye drops of timolol and its isomer L‐714,465 in asthmatic subjects.

Richards¹,

Tattersfield²

1987

Brit J Clinical Pharma

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1 The inadvertent administration of timolol to asthmatic patients continues to cause occasional severe and even fatal attacks of asthma. The (R)-entantiomer of timolol, L-714,465, is four times less potent than timolol in reducing intraocular pressure in man. It is 49 times less potent than timolol on 132-adrenoceptors in animals and 13 times less potent on the airways of normal subjects. These findings suggested that L-714,465 might be a safer alternative for the treatment of glaucoma. 2 Ten subjects with mild asthma who bronchoconstricted to timolol eye drops (0.25 or 0.5%) were studied. Airway dose-response curves to timolol (0-2%), L-714,465 (0-4%), and placebo (methyl cellulose) eye drops were performed in a double-blind randomised study in which airway response was measured as change in FEV1 and specific airway conductance (sGaw). 3 L-714,465 and timolol caused dose dependent falls in sGaw and FEV1 with L-714,465 being approximately four times less potent than timolol. The geometric mean dose ratio was 3.89 for FEV1 (95% confidence interval (CI) 1.7-8.7) and 3.93 (95% CI 2-7.8) for sGaw. Since the difference in potency is similar to the reported difference in potency of the two drugs on intraocular pressure we conclude that L-714,465 would not have a greater safety margin than timolol. 4 After completion of the dose-response study eight subjects inhaled ipratropium bromide (72,ug) and this caused an increase in FEV1 from 74% to 80% of baseline. There was no further increase in FEV1 after a further 72 ,ug in seven patients though the FEV1 returned to baseline values after inhaled salbutamol (0.2-2.5 mg). ,B-adrenoceptor antagonist-induced bronchoconstriction is only partially reversed by conventional doses of antimuscarinic drugs.

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Section: Discussionmentioning

confidence: 99%

Comparison of the airway response to eye drops of timolol and its isomer L‐714,465 in asthmatic subjects.

Richards¹,

Tattersfield²

1987

Brit J Clinical Pharma

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“…In addition to the initial bronchospasm, these drugs have been found to increase the sensitivity of the airways to other bronchoconstrictor agents such as histamine and acetylcholine (Zaid & Beall, 1966;Bouhuys, Douglas & Guyatt, 1971). Although these effects have generally been attributed to blockade of airway P-adrenoceptors (Macdonald, Ingram & McNeill, 1967), similar observations with the cardioselective ,3-blockers has led to the suggestion that other factors might be involved (Nicolaescu, Manicatide & Stroescu, 1972). …”

Section: Introductionmentioning

confidence: 91%

Propranolol‐induced airway hyperreactivity in guinea‐pigs

Ney¹

1983

British J Pharmacology

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3 This increased airway sensitivity was not due to P-adrenoceptor blockade because: (a) similar effects were produced by racemic propranolol and its two isomers (+ )-and (-)-propranolol and (b) whilst equal doses of (±)-and (+)-propranolol produced the same potentiation of histamine bronchoconstriction, only (±)-propranolol also caused a measurable P-adrenoceptor blockade in the airways. 4 The enhanced histamine-and 5-HT-induced bronchoconstrictions were antagonized by the leukotriene antagonist FPL 55712 and by the lipoxygenase/cyclo-oxygenase inhibitor BW755c. 5 The results demonstrate that endogenously released leukotrienes can produce not only a direct bronchospasm but may enhance the effects of other bronchoconstrictor agents. 6 The relevance of this leukotriene-mediated hyperreactivity to the non-specific airway hyperreactivity seen in asthmatics is discussed.

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“…It has generally been assumed from the clinical studies that the bronchospasm is due to the blockade of f-adrenoceptors in the smooth muscle thus removing a sympathetic bronchodilator drive to the airways (Macdonald, Ingram & McNeill, 1967) However, because it has been difficult to reproduce the bronchoconstrictor effects in animals, no detailed study of the mechanism of action has been undertaken.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Mechanism of Propranolol‐induced Bronchoconstriction

Maclagan

Ney

1979

British J Pharmacology

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I Dose-related increases in airways resistance (R.W) and decreases in dynamic lung compliance (C,,,.) were recorded in guinea-pigs and rats following intravenous injection of propranolol and of the cardioselective f-adrenoceptor blocking drugs, atenolol and practolol. 2 The bronchoconstriction reached a peak in 2 to 4 min and subsided within 15 min. Repeated injections caused identical responses in the airways.3 The isomer (+)-propranolol, which has only weak ,B-adrenoceptor blocking activity, produced identical responses when given alone or when given after a dose of the racemate, sufficient to cause measurable f-adrenoceptor blockade in the lungs. 4 After the initial bronchospasm had subsided, the f-adrenoceptor blocking drugs and the isomer, (+-propranolol, produced potentiation of the bronchoconstrictor effects of 5-hydroxytryptamine and histamine. 5 Both the bronchospasm and the potentiation occurred in adrenal demedullated rats. 6 The results indicate that the bronchoconstrictor effects of these drugs are unrelated to ,B-adrenoceptor blockade in the airway smooth muscle.

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The Effect of Propranolol on Airway Resistance

Cited by 21 publications

References 0 publications

Comparison of the airway response to eye drops of timolol and its isomer L‐714,465 in asthmatic subjects.

Comparison of the airway response to eye drops of timolol and its isomer L‐714,465 in asthmatic subjects.

Propranolol‐induced airway hyperreactivity in guinea‐pigs

Investigation of the Mechanism of Propranolol‐induced Bronchoconstriction

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