Ocular and cardiovascular response to topical carteolol 2% and timolol 0.5% in healthy volunteers.

Abstract

SUMMARY Ocular and cardiovascular effects of carteolol 2%, timolol 0O5%, and dummy eyedrops have been measured in a single dose double-blind crossover study in six healthy volunteers. Both drugs lowered intraocular pressure and reduced exercise-induced tachycardia. Neither produced a significant change in resting heart rate or blood pressure. The two agents appear comparable as regards ocular hypotensive and cardiovascular effects.Topical beta adrenoceptor blocking drugs (beta blockers) are now the first line of treatment in many types of glaucoma, though their use in certain individuals is restricted by adverse cardiovascular or respiratory effects resulting from systemic absorption. Timolol has been reported to cause bradycardia, syncope, arrythmias, and exacerbation of obstructive airways disease.' In theory beta blockers with differing properties such as cardioselectivity, partial agonist activity (intrinsic sympathomimetic activity; ISA) or reduced lipid solubility should offer advantages over timolol with respect to these adverse effects. This paper reports a comparative study of intraocular pressure (IOP) and cardiovascular effects of timolol and the newly introduced topical beta blocker, carteolol. Material and methods SUBJECTSSix healthy subjects, three female and three male, aged 33 to 57 years, took part in this study. None had a previous history of cardiovascular or respiratory disease or was taking drugs of any kind. All had normal eyes, IOPs, blood pressure, peak expiratory flow, electrocardiogram, blood count, and electrolytes. The subjects were phenotyped for debrisoquine hydroxylation,2 and all were extensive metabolisers (range of metabolic ratios 0-2 to 1-7). Non-metabolisers of debrisoquine were excluded because they may be prone to prolonged effects from small systemic doses of certain beta blockers.Each gave written consent to participate and the study was approved by the Ethical Committee of West Lambeth Health Authority. TREATMENTS AND STUDY DESIGNSubjects attended on three occasions at the same time of day separated by at least seven days. On each occasion one of three treatments, carteolol 2%, timolol 0.5%, or a matching dummy solution, was administered double blind as eyedrops in a complete balanced crossover design. Two drops of drug solution (volume 0-027 ml each) were applied one minute apart to one eye, the same eye being used in each volunteer for all treatments. MEASUREMENTSBefore and 2 and 4 hours after treatments the following measurements were made in the order given. The IOP was measured by applanation tonometry under proxymetacaine 0.5% local anaesthesia. Three readings were recorded from each eye on each occasion, the tonometer dial being read by an independent observer. Following a 10-minute supine rest period, the heart rate (HR) was recorded from an electrocardiography (ECG) and blood pressure (BP) measured by sphygmomanometry. The BP was recorded as mean BP (diastolic plus one-third pulse pressure). The HR was then measured during the last 15 seconds of an exercise peri...

Drugs That May Cause or Exacerbate Heart Failure

“…Small case series evaluating topical timolol usually involving young healthy volunteers have variably demonstrated changes in blood pressure and heart rate, which have been considered clinically insignificant. [259][260][261] However, several case series and case reports with topical β-blockers, primarily timolol, have demonstrated clinically significant issues in patients with HF, including arrhythmias such as bradycardia, myocardial ischemia, hypotension, and pulmonary edema. 262,263 In 2 HF patients, topical timolol administration led to an exacerbation of symptoms of HF.…”

Cardiovascular responses to metipranolol and timolol eyedrops in healthy volunteers.

“…Previous studies by ourselves and others have shown that such drugs, though applied to the eye in small quantities, are absorbed into the general circulation sufficiently to produce effects elsewhere in the body (Alvan et al, 1980). As a result, the cardiac response to exercise, for example, may be impaired (Smith et al, 1979;Brazier & Smith, 1988). In clinical practice resultant side-effects may occur in susceptible (particularly elderly) subjects; bradycardia, heart failure, hypotension, bronchoconstriction and pain in the legs on exertion have frequently been reported (Buskirk, 1980;Buskirk & Fraunfelder, 1981;Nelson et al, 1986 This paper reports a comparative healthy volunteer study of intraocular pressure and cardiovascular effects of timolol and the more recently introduced 3-adrenoceptor blocker metipranolol to find out whether the newer drug offers the advantage sought.…”

Ocular Carteolol

“…-A further double-blind crossover study demonstrated comparable decreases in mean lOP of 2.2mm Hg and 2.3mm Hg, respectively, following administration of 2 drops of carteolol 2% or timolol 0.5% in 6 volunteers, significantly greater reductions than achieved with placebo (Brazier & Smith 1988). -A further double-blind crossover study demonstrated comparable decreases in mean lOP of 2.2mm Hg and 2.3mm Hg, respectively, following administration of 2 drops of carteolol 2% or timolol 0.5% in 6 volunteers, significantly greater reductions than achieved with placebo (Brazier & Smith 1988).…”

“…Mean lOP also decreased by approximately 14 to 21% in the untreated eyes of healthy volunteers (Brazier & Smith 1988;Negishi et al 1981), suggesting a crossover effect resulting from systemic absorption of carteolol (see also section 1.3). However, placebo administration also caused a 4 to 11 % decrease in mean lOP in untreated eyes.…”