Improved blood pressure control with isradipine in hypertensive patients treated with pindolol.

Isradipine is a new calcium antagonist of the dihydropyridine type with marked vasodilator activity and minimal negative inotropic effects. It is a potent antihypertensive drug when given as monotherapy. This was a randomized double-blind crossover study of 16 weeks' duration, including 80 hypertensive patients with diastolic blood pressures of at least 95 mm Hg who had shown clinically relevant antihypertensive responses, but no normalization of blood pressure during pindolol 10 to 15 mg once daily as monotherapy. Either isradipine or placebo was added to the beta-blocker at doses of either 2.5 mg or 5 mg twice daily, which was doubled after four weeks if the diastolic blood pressure remained more than 90 mm Hg. The addition of isradipine (in either dose regimen) caused a pronounced reduction of blood pressure with no changes in heart rate. Five patients were withdrawn from the study because of adverse events while receiving isradipine compared with three taking placebo. A further three patients withdrew from the study because of adverse events (one patient) or lack of efficacy (two patients) during placebo treatment. These results indicate that isradipine is an effective and well-tolerated adjunct to beta-blockers in hypertensive patients.

Dose-response relationship and incidence of adverse drug reactions with isradipine in patients with essential hypertension.

Based on pooled data from three randomized placebo-controlled dose-finding studies in a total of 489 patients, the dose-response relationship for efficacy and adverse events was estimated, using the Michaelis-Menten equation: Effect = maximal effect multiplied by dose/constant plus dose. Three conclusions were derived from the pooled data: (1) A marked increase in efficacy is seen when the reduction in diastolic blood pressure after one week of treatment is compared with that seen after five weeks of treatment, with both placebo and active treatment. Thus, dose increases should preferably be made at intervals of at least four weeks to avoid unnecessarily high doses. (2) Isradipine 2.5 mg twice daily offers an efficacy of approximately 80 percent of the maximum with an incidence of adverse events which, statistically, is not significantly different from the incidence seen in the placebo groups. (3) With continued treatment, a marked decrease in the incidence of adverse drug reactions is seen between the first and fifth weeks, especially with doses at 1.25 and 2.5 mg twice daily. However, with doses above 10 mg per day, this effect is no longer evident.

A multicenter evaluation of the safety, tolerability, and efficacy of isradipine in the treatment of essential hypertension.

Six hundred outpatients aged between 22 and 84 years with essential hypertension (diastolic blood pressure of at least 95 mm Hg) entered a multinational, multicenter, single-blind trial with dose titration to assess the safety, tolerability, and efficacy of isradipine in doses of 1.25, 2.5, and 5.0 mg twice daily over 12 weeks, following a two-week placebo run-in period. Isradipine alone was taken by 321 patients, the remainder receiving, in addition, other antihypertensive drugs. In valid patients receiving monotherapy, the mean final isradipine dose was 3.4 mg (median, 2.5 mg) twice daily, which normalized supine diastolic blood pressure in 85 percent and 64 percent of patients two to four hours and 10 to 14 hours post-dose, respectively. Overall, 242 patients (40 percent) reported adverse events, 39 (7 percent) of whom withdrew from the study for this reason. The most common side effects were flushing (11 percent), headache (10 percent), and localized edema (4 percent). None of the pathologic changes in hematologic or biochemical values was attributable to isradipine. It is concluded that a slow titration of isradipine by increments at three-week intervals results in an effective and well-tolerated treatment for essential hypertension, both in mono- and combination therapy.

Runaway pacemaker inhibited by external overdrive stimulation: a case report.

A case is described of runaway pacemaker ( Stimulith ) which could be inhibited by external chest-wall overdrive. This pulse generator had been implanted for four years before runaway occurred; the runaway rate was 140/min with capture of the ventricles. Using external chest-wall stimulation at a rate of 170/min, we were able to achieve almost complete inhibition of the faulty generator, while preparing for emergency replacement.

Glucose-insulin-potassium-albumin infusion in the early phase of acute myocardial infarction--a controlled study.

Fifty consecutive patients with acute myocardial infarction admitted to a coronary care unit within 6 hours from onset of symptoms were randomly assigned either to a treatment group (n=27) receiving glucose-insulin-potassium-albumin (GIKA) or to a control group (n=23), comparable regarding clinical data, receiving 5.5% glucose. Both infusions were given intravenously at a rate of 1.2 ml/kg b.wt./hour during 48 hours. The GIKA solution contained 40 mEq K+, 10 ml 20% albumin and 16 IU regular crystalline insulin per 1000 ml 10% glucose. Before the infusion, the treatment group received an i.v. loading dose of 50 ml 50% glucose. Serum time activity curves for creatine kinase (CK) and myoglobin (MG) were established from frequent blood level determinations. A 15-minute single-lead ECG was recorded every fourth hour and subsequently analysed for ventricular arrhythmias. The two patient groups did not differ regarding cumulative MG and CK release. The GIKA group had significantly more patients with high MG/CK ratios (p less than 0.02). No clinically significant difference was found between the two patient groups regarding ventricular arrhythmias, even if ventricular extrasystoles tended to occur less frequently in the GIKA group.