Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The electrophysiological effects of diltiazem (0.25 mg/kg), administered by intravenous bolus, have been assessed during intracardiac investigation in 10 patients. Effects on both sinus node and atrioventricular nodal function were measured, as was the influence on reentry atrioventricular tachycardia. There was a tendency for the sinus rate to increase after both diltiazem and verapamil, although with neither drug was this uniform. There was, however, a consistent depression of atrioventricular nodal function with diltiazem which was similar in magnitude to the changes seen after verapamil. With neither drug was there an alteration in His-Purkinje conduction. The drugs had similar effects when given during reentry tachycardia. In six of eight patients, termination occurred, whereas, in the others, both drugs slowed the arrhythmia but failed to terminate it. Diltiazem shows a range of electrophysiological and antiarrhythmic properties similar to those of verapamil. These make it potentially useful for both the acute and chronic treatment of arrhythmias where depression of atrioventricular nodal function is desired.
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PMID:The comparative effects of diltiazem and verapamil on atrioventricular conduction and atrioventricular reentry tachycardia. 683 49

Diltiazem is a calcium slow-channel blocking drug that may be effective in the treatment of chronic stable angina pectoris. To evaluate the therapeutic efficacy 3 hours after a single oral dose of 120 mg, 12 men with chronic stable angina pectoris performed a maximal exercise test on a bicycle ergometer after ingesting either placebo or diltiazem administered in a double-blind fashion. During submaximal exercise at a fixed work load, diltiazem decreased the average heart rate response from 119 +/- 17 to 107 +/- 14 beats/min (p less than 0.01), systolic blood pressure from 182 +/- 15 to 175 +/- 15 mm Hg (p less than 0.05) and the rate-pressure product from 21.8 +/- 4.2 to 18.8 +/- 3.2 x 10(-3) units (p less than 0.01). The average submaximal work load at which significant ST-segment depression (0.1 mV) first appeared was increased from 355 +/- 142 to 525 +/- 143 seconds (p less than 0.01) after diltiazem. At peak exercise after diltiazem, the average depth of ST-segment depression in any one lead and the extent of myocardial ischemia observed in all 12 ECG leads were decreased (p less than 0.01), even though the average work load was increased by 29% (p less than 0.01). Peak heart rate, systolic blood pressure and rate-pressure product were similar with placebo and diltiazem. The plasma diltiazem concentration was 13.9 +/- 29 ng/ml 3 hours after ingestion and was significantly (p less than 0.05) related to the increased time to the onset of important ST-segment depression (r = 0.65) and to the decrease in the extent of myocardial ischemia observed in all 12 ECG leads (r = -0.61) compared with placebo. Thus, diltiazem is effective in treating chronic stable angina pectoris. It decreases myocardial oxygen requirements during upright exercise and appears to increase myocardial oxygen delivery.
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PMID:Increased exercise tolerance and reduced electrocardiographic ischemia with diltiazem in patients with stable angina pectoris. 708 12

The effects of diltiazem, a calcium antagonist drug, we compared with those of placebo on exercise performance during a series of symptom-limited upright exercise tests. Ten patients with chronic stable angina were studied over a period of 7 weeks. The drug was administered in a random double-blind fashion and was evaluated at increasing dose levels of 120, 180 and 240 mg/day. Diltiazem was effective in increasing the total duration of exercise (p < 0.001) and the time the first onset of angina (p < 0.02) and to the first appearance of 1 mm of S-T depression (p < 0.02). These effects were most marked at the highest dose level of diltiazem. The heart rate was reduced at rest (p < 0.05) and during submaximal exercise (p < 0.001). There was a reduction in diastolic blood pressure during submaximal exercise (p < 0.04) but no change in systolic pressure. Pressure-rate product was significantly reduced at submaximal (p < 0.001) but not maximal exercise. The reduction in pressure-rate product is postulated as the mechanism by which diltiazem enhances duration of exercise. There was no reduction in electrocardiographic evidence of myocardial ischemia at peak exercise by either clinical observation or computer analysis of spatial electrocardiographic variables Five of the six patients who continued to take the drug maintained or improved their exercise performance on follow-up study 8 to 10 months later.
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PMID:Improved exercise performance in persons with stable angina pectoris receiving diltiazem. 745 15

Controlled-delivery once-daily diltiazem (qd), 180 mg and 360 mg, was assessed in two multicenter, randomized, double-blind, placebo-controlled trials using a 3 x 3 Latin square design. Both studies compared the controlled-delivery dosage form to the same total daily dose of immediate-release diltiazem administered three times daily (tid) and to placebo. The primary measure of efficacy was the time to termination of the exercise tolerance test (ETT) at 2, 8, and 24 hours after the morning dose. There were no significant differences in time to ETT termination between the qd and tid formulations at any time, except at 24 hours with 180 mg qd versus 60 mg tid. The comparison to placebo showed that diltiazem 180 mg qd, 360 mg qd, and 120 mg tid significantly lengthened the time to ETT termination (p < 0.05) at all time points, while diltiazem 60 mg tid did not differ from placebo at any time point. The qd formulation also increased the time to 1-mm ST-segment depression and reduced the number of angina attacks and the amount of nitroglycerin used when compared to placebo. No new or unusual adverse events were noted. Diltiazem controlled-release capsules administered once daily are safe and effective for the treatment of patients with chronic stable angina.
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PMID:Antianginal efficacy and safety of controlled-delivery diltiazem QD versus an equivalent dose of immediate-release diltiazem TID. 766 99

In a randomized, double-blind, cross-over, multicenter study with a placebo run-in phase, the efficacy and safety of two oral formulations of diltiazem, standard three or four times daily (t.i.d. or q.i.d.) and controlled release twice daily (b.i.d.), were compared in 49 patients with stable angina pectoris. ST-segment depression at maximum exercise 12 h after tablet intake was less frequently observed with diltiazem controlled release than with standard diltiazem (34 of 49, 69% vs. 43 of 49, 88%, p = 0.007). In patients with ST-segment depression after both treatments (n = 33), the average time to 1-mm ST-segment depression was 55.4 +/- 19.9 s longer with diltiazem controlled release than with standard diltiazem [476 +/- 195 vs. 422 +/- 163 s, p = 0.009; 95% confidence interval (CI) 14.8-96 s]. Reduction in mean number of anginal attacks and nitroglycerin (NTG) intake was not significantly different between treatment with standard diltiazem and diltiazem controlled release. The incidence of side effects was low and not different between the two treatments. Both formulations are equally effective in reducing the number of anginal attacks and are well tolerated. Diltiazem controlled release is more effective than standard diltiazem in preventing myocardial ischemia 12 h after tablet intake. Thus, diltiazem controlled release allows twice-daily intake frequency and may therefore be preferable to standard diltiazem in treatment of stable angina pectoris.
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PMID:Comparison of diltiazem standard formulation and diltiazem controlled release in patients with stable angina pectoris: a randomized, double-blind, cross-over, multicenter study. 768 99

The 3-month efficacy and safety of a once-daily controlled formulation of diltiazem (180 to 360 mg/day) were assessed in a study of 54 patients with angina pectoris. This multicenter study was a nonrandomized, placebo run-in, open-label, 3-month trial followed by a 1-week, double-blind, randomized period during which most patients (89%) received placebo. There were only minimal changes in the time to termination (mean change +/- SEM -5.8 +/- 9.6 seconds), time to onset of angina (10.5 +/- 12.2 seconds), and the time to 1 mm ST-segment depression (2.9 +/- 12.5 seconds) from the end of the titration phase to the end of the open-label study. There were, however, statistically significant differences between the end of the 3-month treatment phase and the end of the 1-week randomized placebo phase for those 3 efficacy parameters (-37.3 +/- 11.2, -58.6 +/- 13.6, and -45.6 +/- 16.4 seconds, respectively). Diltiazem significantly decreased the frequency of anginal attacks and nitroglycerin use at the end of the 3-month treatment phase compared with results at the end of the randomized double-blind placebo phase. No new or unusual adverse events were reported during treatment. The present results suggest that there is no loss of efficacy of once-a-day diltiazem when administered for a long period to patients with chronic stable angina pectoris.
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PMID:Three-month efficacy and safety of once-daily diltiazem in chronic stable angina pectoris. 771 May 63

Although calcium channel blockers may preserve function in ischemic myocardium, they may also produce myocardial depression and dysfunction in the presence of decreased coronary flow. This study was designed to examine the issue of possible protection afforded by diltiazem against ischemia-induced myocardial dysfunction during propofol anesthesia. In eight anesthetized and ventilated dogs, regional myocardial (ultrasonic crystals in both left anterior descending [LAD] and left circumflex [LC] perfusion areas) and global ventricular function were evaluated during progressively severe degrees of myocardial ischemia (LAD constriction) before and after intravenous diltiazem (150 micrograms/kg). As coronary flow decreased, heart rate increased, and arterial and coronary perfusion pressures, left ventricular dP/dt, and cardiac output decreased. Systemic vascular resistance was unaffected. Diltiazem without coronary constriction increased heart rate, and decreased diastolic arterial pressures, left ventricular (LV) end-diastolic, coronary perfusion pressures, LV dP/dt max, LAD coronary blood flow, stroke volume, and cardiac output. At all levels of coronary constriction following diltiazem, there were decreases in systolic and diastolic arterial pressures, stroke volume, cardiac output, LV dP/dt, and coronary perfusion pressure. Heart rate increased at critical coronary constriction, and then remained constant relative to the prediltiazem state. The regional muscle effects of the reductions in coronary flow in the LAD perfusion territory included decreased systolic shortening and increased postsystolic shortening before and after diltiazem. Diltiazem did not alter the magnitude of the alterations in systolic or postsystolic shortening brought about by coronary constriction. No changes occurred in the LC area.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diltiazem and regional left ventricular function during graded coronary constriction and propofol anesthesia in the dog. 830 61

Physicians need to weigh the efficacy, adverse effects and cost of first-line antihypertensive agents. Calcium channel blockers lower blood pressure, improve coronary blood flow and depress cardiac contractility by relaxing smooth muscle and cardiac muscle. They have beneficial or neutral effects in hypertensive patients with angina, asthma, chronic obstructive pulmonary disease, postural hypotension, peripheral vascular disease, depression, sexual dysfunction, diabetes and hyperlipidemia. The major adverse effect of some calcium channel blockers is that they may worsen congestive heart failure in some patients. Because calcium channel blockers are metabolized in the liver, the dosage must be lowered in the elderly and in patients with hepatic disease. Diltiazem, verapamil and nifedipine represent prototypes of the three classes of calcium channel blockers, each with slightly different effects.
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PMID:Calcium channel blockers in the treatment of hypertension. 836 95

In isolated rat hearts the calcium paradox, induced by perfusion for 3 minutes in the absence of calcium followed by perfusion for 10 minutes in the presence of calcium, depressed the activation of adenylyl cyclase by l-isoproterenol, NaF and forskolin. The characteristics of the beta-adrenoceptors and the activation of adenylyl cyclase by guanylyl imidodiphosphate were not changed. The findings suggest an uncoupling of beta-adrenoceptors from the catalytic site of the adenylate cyclase complex. Diltiazem, at 0.4 microM in the perfusion medium, greatly reduced the diminution of the activation of adenylate cyclase by isoproterenol and forskolin, and completely prevented the depression of the activation of adenylate cyclase by NaF. These effects may be due to interference by diltiazem with the mechanisms that promote an excessive influx of calcium into the heart during the calcium paradox.
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PMID:Diltiazem prevents the depression of adenylyl cyclase activity induced by the calcium paradox in rat. 840 22

Recent interest in the corneal analgesic properties of diltiazem prompted the present study examining concentration-dependent effects of this calcium channel blocker on C fiber cold receptors and A delta mechanoreceptors. Both afferent fiber types mediate an eye blink reflex, important for protecting the corneal surface. The effects of neuroactive concentrations of diltiazem on corneal would healing were also studied. An in vitro rabbit cornea preparation was used for both electrophysiological recording and wound healing, allowing precise concentration-response analysis. Diltiazem produced a concentration-dependent depression of cold fiber discharge activity (10 to 250 microM), but did not affect mechanoreceptor afferents. In addition, the broad spectrum Ca2+ channel blockers, Ni2+ and Cd2+, did not cause a significant reduction in A delta mechano or C fiber discharge activity. Diltiazem had no effect on corneal epithelial wound healing to a concentration of 50 microM. This is important if diltiazem is to be used for therapeutic control of pain following corneal injury or surgery, because sparing of the eye blink reflexes and wound healing are desirable properties for a corneal analgesic.
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PMID:Diltiazem spares corneal A delta mechano and C fiber cold receptors and preserves epithelial wound healing. 853 62


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