Safety profile of lacidipine: a review of clinical data.

The clinical safety of the new dihydropyridine calcium antagonist lacidipine was assessed in 14 clinical trials, including 1,372 patients treated with lacidipine and 687 treated with an alternative antihypertensive agent. The type and incidence of adverse events seen with lacidipine were characteristic of this class of drug, being mainly those associated with the pharmacologic effect of vasodilation, but with a lower incidence of edema than seen with nifedipine. There were no unexpected adverse effects. Hence, lacidipine is likely to be well accepted in general clinical use. Furthermore, as it has the advantages of a long duration of action and once-daily dosage, the benefit/risk ratio indicates that lacidipine is a suitable agent for the first-line treatment of hypertension across a wide range of patients.

Penetration of nadolol into aqueous humour after a single oral dose.

Nadolol 20 mg was administered orally as a single-blind, single dose to nine patients about to undergo cataract extraction. Intraocular pressures fell by a mean of 24% 3 h after administration. During the operation, aqueous humour and serum samples were taken for measurement of nadolol concentrations. Aqueous nadolol concentrations ranged from 3.8 to 13.4 ng ml-1, and correlated with the serum drug concentrations (r = 0.84). The fall in intraocular pressure did not correlate with either the aqueous humour or plasma concentrations of nadolol.

Termination of focal atrial tachycardia by adenosine triphosphate.

An atrial aneurysm gave rise to incessant atrial tachycardia in a 21 year old Seychellian soldier. This arrhythmia was suppressed by intravenous adenosine triphosphate and ajmaline. Resection of the aneurysm abolished the arrhythmia and re-established sinus rhythm.

A comparison of bepridil with amiodarone in the treatment of established atrial fibrillation.

Fourteen patients with established atrial fibrillation (longer than three months) that was refractory to treatment were studied to compare the clinical and electrophysiological effects of amiodarone and bepridil. All patients initially received bepridil for three weeks (200-600 mg/day), followed by amiodarone for two to three months (100-400 mg/day). Bepridil seemed to be slightly more effective than amiodarone in converting the fibrillation to sinus rhythm (nine of fourteen compared with four of ten). The ventricular response in atrial fibrillation was equally well controlled by bepridil and amiodarone, both at rest and during exercise. Bepridil was associated with the development of ventricular arrhythmias in eight of fourteen patients; two had torsade de pointes, which in one degenerated into fatal ventricular fibrillation. These arrhythmias seemed to be associated with bepridil induced prolongation of the QTc interval. No ventricular arrhythmias were seen during amiodarone treatment. Although bepridil seems to be an effective antiarrhythmic agent for the management of atrial fibrillation, its arrhythmogenic actions make it unsuitable for this purpose.

Assessment of a prototype implantable cardioverter for ventricular tachycardia. Relation between synchronisation of sensing and origin of the tachycardia.

The feasibility of internal cardioversion for ventricular tachycardia using a prototype of an implantable cardioverter which delivers a low energy discharge via an intracardiac lead and its acceptability to the patient were studied. The cardioverting discharge was synchronised to the apical right ventricular electrogram. In 29 episodes of ventricular tachycardia (RR interval 250-700 ms) the apical electrogram was reliably sensed. The interval from the onset of the QRS complex to the marker of sensing of the electrogram was significantly greater in the 15 episodes arising from the left ventricle than in the 14 episodes arising from the right ventricle; in three cases of ventricular tachycardia arising from the left ventricle the interval exceeded 100 ms. In all cases except one, however, sensing occurred within the first 80% of the QRS complex. In two episodes (RR interval 150 and 190 ms--that is, less than the refractory period of the unit) sensing of the electrogram was unreliable. The unit successfully terminated 10 of 15 episodes of ventricular tachycardia using energies ranging between 0.01 and 1.0 J, but 19 of the 23 discharges delivered to conscious patients caused varying degrees of discomfort. Sensing within 100 ms of the onset of the QRS complex (-20% to 83% of QRS) permitted effective and safe termination of ventricular tachycardia. Although there was neither acceleration of tachycardia nor ventricular fibrillation, subthreshold discharges advanced the next local ventricular electrogram in seven instances. An external low energy cardioverter connected to an intracardiac lead is a useful alternative to repeated external direct current shocks.