PubMed1976
In a controlled double-blind crossover study followed by an open longterm continuation period, the antihypertensive effect of timolol (Blocadren), a new beta-receptor antagonist, was investigated in 24 ambulatory patients with mild to moderate essential hypertension who were concomitantly receiving Moduretic as baseline diuretic therapy. The addition of timolol to one tablet daily Moduretic resulted in a clinically and statistically significant further reduction of supine and upright systolic and diastolic blood pressures. The average total daily dosage schedule for timolol ranged between 15 and 20 mg, with the same blood pressure lowering effect whether the divided dose was given twice or three times. Significant sinus bradycardia was consistently observed but well tolerated, with only one patient requiring dose reduction. After 48 weeks of treatment (comprising 46 weeks Moduretic and 36 weeks timolol) 20 of 22 patients were normotensive (supine diastolic blood pressure below 90 mm Hg) while in two the hypotensive response proved inadequate. One patient was dropped from the study after 3 days of timolol treatment because of acute bronchial asthma. When specifically questioned, one-third of the patients admitted experiencing cold extremities. One patient exhibited Raynaud's syndrome which was treated symptomatically while continuing in the study. In terms of electrolyte balance, the fixed combination of hydrochlorothiazide and the antikaluretic amiloride (Moduretic) as baseline therapy essentially proved adequate. On occasion, however, two subject revealed hypokalemia requiring short-term oral potassium supplement. During the initial 10 to 16 weeks a steady decline in serum potassium was observed but this stabilized itself thereafter. The concomitant administration of Moduretic and timolol (Blocadren) was shown to be an effective therapeutic regimen in patients with mild to moderate essential hypertension. This combination is particularly suitable for patient compliance in longterm therapy, as timolol can be given twice daily.