Beta-blocker eye drops lower heart rate and increase respiratory symptoms in asthmatics
The heart rate-lowering effect of timolol liquid and gel drops has been studied in healthy subjects with glaucoma or cataracts. One article «Nieminen T, Lehtimäki T, Mäenpää J ym. Ophthalmic ...»1 summarized clinical results from 18 studies involving a total of 502 patients. Liquid 0.5% timolol had an average lowering effect on resting heart rate of 2-11 beats per minute and 7-22 beats per minute on exercise. Correspondingly, 0.1% timolol in gel form reduced the resting heart rate by an average of 1-9 beats / minute and 5-12 beats / minute on exercise.
Comment: Eye drops travel through the tear ducts to the nasal mucosa and are absorbed into the bloodstream. Drugs bypass the first-pass metabolism of the liver, which may result in a clinically significant systemic effect, even in small amounts. In the instillation technique, closing the upper eyelid and closing the lower tear point for two minutes can reduce the risk of systemic absorption.
A British retrospective registry study «Morales DR, Dreischulte T, Lipworth BJ ym. Respira...»2 collected health registry data on asthma sufferers from more than 5 million people who also used glaucoma drops between 2000 and 2012. At least four non-asthmatic controls were selected for cohort members (18-80 years). The use of beta-blockers was defined as short-term if it had started less than 30 days after the onset of the asthma exacerbation phase or long-term if it had been used for at least 30 days and at least one prescription for the beta-blocker in the previous year. The exacerbation phase of asthma was defined as severe or moderate.
In the case-control setting, short-term use of timolol increased the exacerbation of moderate asthma by 4.8-fold (RR 4.83, 95% CI 1.56-14.94, p = 0.006). The incidence of severe asthma exacerbations was so low that no statistical treatment could be performed.
The same article also included a systematic literature search as well as a meta-analysis of studies in which a single drop of timolol or betaxolol was administered and lung test responses in asthma patients were measured. Out of 203 studies, nine studies were selected for final analysis. A non-selective beta-blocker (the most common timolol) was used by 55 patients (mean age 45 years) and 33 patients used betaxolol (mean age 47 years).
When a non-selective beta-blocker was administered to unselected asthma patients, the mean expiratory capacity per second decreased by 10.9% compared to controls (95% CI -14.9 to -6.9, p <0.001). Correspondingly, a statistically significant difference (risk difference 0.28, 95% CI 0.14 to 0.42, p <0.001) was seen in at least a 20% reduction in expiratory capacity. As an NNT, the result of lung harm could be expressed as three.
When betaxolol was administered to asthma patients who had previously responded to a non-selective beta-blocker, the mean expiratory capacity per second decreased slightly by 6.3% (95% CI -11.7 to -0.8, p = 0.03). In contrast, no statistical difference was observed in the decrease in lung capacity of more than 20% per second (p = 0.11).
Comment: Beta-blockers should be avoided in asthmatics or those with a history of such symptoms. In addition, beta-blocker medication may increase respiratory congestion in previously asymptomatic patients and these symptoms should be actively asked.
The authors wonder whether the lack of chronic use of beta-blockers and exacerbations of asthma may be due to the bias in which symptomatic patients discontinue the medication in question.