Forty-seven patients with chronic stable angina pectoris entered a thirteen-week open-label study with a transdermal therapeutic system of nitroglycerin in order to evaluate its clinical efficacy, safety, and patient acceptance. In 19 patients, a beta-blocker and in 17 patients a calcium-channel blocker were continued throughout the study period without alteration of their doses. The study consisted of a two-week run-in period and an eleven-week active drug period. Acute titration was done with nitroglycerin patches on the basis of weekly patient diaries on frequency of angina and sublingual nitroglycerin consumption. Overall, reductions in frequency of angina and in nitroglycerin consumption were statistically significant (p < 0.05). Adverse reactions were common but tolerable. The reported side effects were headache in 32, skin rash in 18, dizziness in 10, palpitation and itching in 9 each, nausea in 7, flushing in 3, and vomiting in 1 patient. In conclusion, the present study demonstrates that individual dose titration with nitroglycerin patches for obtaining significant antianginal effect is essential. The present therapeutic system is convenient to use and well tolerated and had acceptable side effects in our study population.
Every day, thousands of people in the United States receive polycyclic antidepressants (PCAs) prescribed by their primary care physicians. We have examined the cardiovascular manifestations of polycyclic antidepressants in 14 patients with primary depression receiving various antidepressant drugs for a period of six months or more. None had suffered from any systemic illness. All 14 received a commonly prescribed PCA, such as doxepin, amitriptyline, imipramine, desipramine or amoxapine, in therapeutic doses. None developed any significant adverse reaction. Left ventricular function, as determined by M-mode echocardiogram, was within normal limit in all patients. A twenty-four-hour ambulatory electrocardiogram revealed rare supraventricular ectopic beats in 8 patients and ventricular ectopic activity (Lown grade 1) in 4 patients. In 1 patient, who received additional lithium carbonate for treatment of depression, both supraventricular and ventricular ectopic activity developed on rare occasions. In 4 of the 8 patients the plasma concentration of PCA was optimal or near optimal, and in 4 of the 8 patients it was subtherapeutic (even though these 4 patients had shown clinical improvement with continued polycyclic therapy). It appears from the present data that antidepressant therapy with PCAs prescribed in therapeutic doses was well tolerated, without any significant adverse cardiovascular reaction, in otherwise healthy young patients with primary depression.
The preliminary data on efficacy and safety of oral tocainide in refractory ventricular dysrhythmia in 8 patients is described. Two patients died; one within 15 days and the other after 1750 days of continuous tocainide therapy. The cause of death in both patients was unclear. During initial administration and acute titration, oral tocainide was extremely effective in lidocaine-sensitive ventricular dysrhythmia and in patients with Q-T prolongation syndrome. Four out of 8 patients received tocainide in presence of left ventricular dysfunction and 2 out of 4 such patients died suddenly. Minor central nervous system side effects were seen in 2 patients and dermatologic adverse reaction was seen in one patient only.
Metoprolol tartrate (MT) as monotherapy was administered orally in 17 patients with mild hypertension. All other drugs were discontinued 2 weeks prior to MT therapy. The present study group consisted of 10 men and 7 women within the age range of 42 to 71 years (mean * S.D. = 55.8 % 8). MT was administered at an initial dose of 50 mg twice daily.Subsequently, the dose of MT was titrated on a biweekly basis for a period of 12 weeks until the diastolic blood pressure was < 90 mmHg or a maximum daily dose of 300 mg was administered. The blood-pressure-lowering effect of MT was found to be clinically satisfactory and statistically significant (P < 0.05). Mild fatigue and swelling of the extremities were seen in two patients each. Mild headache, transient diarrhea, and mild cloudiness of mind were seen in one patient. From this study it is concluded that MT is a safe and effective first-step antihypertensive agent. The long-term effect of MT as a monotherapy in the treatment of mild hypertension needs further clinical evaluation.
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