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Asian Journal of Surgery Sep 2018Hemorrhoidectomy is commonly associated with postoperative pain. Calcium channel blockers are known to cause relaxation of gastrointestinal smooth muscle and oral... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemorrhoidectomy is commonly associated with postoperative pain. Calcium channel blockers are known to cause relaxation of gastrointestinal smooth muscle and oral diltiazem has also been shown to reduce the resting anal pressure.
OBJECTIVE
We attempted to analyze efficacy and side effects of topical diltiazem oint. in post-operative pain control.
METHODS
This is a meta-analysis of patients who underwent hemorrhoidectomy using topical diltiazem oint. versus placebo (Vaseline) for pain control. Patients with third or fourth degree hemorrhoids undergoing traditional hemorrhoidectomy were included. Procedures took place in the colorectal division of a hospital in 5 countries. Five randomized control trials (RCTs) published between 2005 and 2016 including 227 patients were included our meta-analysis (Diltiazem (calcium channel block) group = 137; Placebo (Vaseline) group = 90). Pain assessment was performed using a standardized Visual Analogue Scale. Any side effects of surgery or medication use, which were noted by the patient or the surgeon, also were recorded.
RESULTS
A total of 227 patients were included in the meta-analysis. The results revealed that Diltiazem ointment was statistically significant in reducing pain within 48 h, at 72 h, and more than 96 h after operation compared to the placebo group. Regarding overall complications (including headache), there was no statistical significance between diltiazem and placebo group.
CONCLUSIONS
Topical application of diltiazem effectively relieves pain after hemorrhoidectomy with minimal side effects. Further large studies are needed to substantiate its value in clinical practice.
Topics: Administration, Topical; Calcium Channel Blockers; Databases, Bibliographic; Diltiazem; Hemorrhoidectomy; Ointments; Pain, Postoperative; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 28698000
DOI: 10.1016/j.asjsur.2017.06.002 -
Interactive Cardiovascular and Thoracic... Jul 2012Perioperative vasospasm during cardiovascular surgery is a challenging problem. Several vasodilator agents are frequently utilized for its prevention in surgical... (Comparative Study)
Comparative Study
Perioperative vasospasm during cardiovascular surgery is a challenging problem. Several vasodilator agents are frequently utilized for its prevention in surgical practice. Magnesium and diltiazem both have known potential vasorelaxant effects. We planned to compare the efficacy of diltiazem and magnesium in relieving phenylephrine-precontracted rat aortic rings. Ten young adult female Wistar albino rats weighing 230-260 g were used in this study. The aortic rings in the organ bath equilibrated and reached their baseline tension. Precontraction was induced by 0.001 mmol/l phenylephrine and cumulative concentration-relaxation curves were obtained by consecutively increasing the addition of either diltiazem (10(-6)-0.1 mmol/l) or magnesium (0.1-10 mmol/l). The mean maximal relaxation responses observed by diltiazem and magnesium on separate aortic rings were 90 ± 3 and 53 ± 2%, respectively. The calculated EC50 of diltiazem was 0.01035 mmol/l, whereas the EC50 of magnesium was 4.064 mmol/l (P < 0.05). Both magnesium and diltiazem produced vasorelaxation on phenylephrine-precontracted rat aortic rings in this study, but the potency of diltiazem regarding the EC50 value was significantly higher than that of magnesium. Magnesium could be a candidate together with diltiazem to inhibit vasospasm on arterial grafts during coronary bypass surgery.
Topics: Animals; Aorta, Thoracic; Diltiazem; Dose-Response Relationship, Drug; Female; In Vitro Techniques; Magnesium Sulfate; Phenylephrine; Rats; Rats, Wistar; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents
PubMed: 22523136
DOI: 10.1093/icvts/ivs051 -
Brazilian Journal of Cardiovascular... Oct 2020To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside.
OBJECTIVE
To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside.
METHODS
Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis.
RESULTS
Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups.
CONCLUSION
The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.
Topics: Diltiazem; Humans; Mammary Arteries; Nitroprusside; Papaverine; Vasodilator Agents
PubMed: 33118726
DOI: 10.21470/1678-9741-2019-0251 -
Clinical Cardiology Feb 1987To examine the benefits and risks of combined diltiazem and propranolol therapy, 23 patients who had completed a double-blind placebo-controlled cross-over comparison... (Clinical Trial)
Clinical Trial
To examine the benefits and risks of combined diltiazem and propranolol therapy, 23 patients who had completed a double-blind placebo-controlled cross-over comparison between diltiazem and propranolol and who continued to develop angina despite treatment were studied. The patients received the previous dose of diltiazem (180 or 360 mg/day) combined with propranolol 120 mg daily for 4 weeks and if they still developed angina on exercise testing, they went on to propranolol 240 mg daily for a further 4 weeks. Efficacy and safety were evaluated by computer-assisted maximal treadmill tests, ambulatory heart rate monitoring, and resting systolic time intervals at the end of each 4-week treatment period. Low-dose combination therapy abolished treadmill angina in 6 patients, but 2 patients had to be withdrawn. The high-dose combination abolished treadmill angina in 5 of 15 patients. The exercise time and 1-mm ST depression time increased with each increment of combination therapy in patients on both doses of diltiazem. The resting, maximal, and ambulatory heart rates progressively decreased with each increment of combined therapy. Left ventricular function, as evaluated clinically and by the systolic time intervals, was not impaired, but severe sinus bradycardia (heart rate less than 40 beats/min) appeared in 3 patients. Two died during 6 months of follow-up. Only 11 of the 23 patients completed 6 months of combined therapy without an adverse reaction. Although combined diltiazem and propranolol therapy relieved angina and increased exercise tolerance in patients refractory to single drug therapy, it should be used with caution in such patients, since bradycardia can pose serious problems.
Topics: Adult; Aged; Angina Pectoris; Clinical Trials as Topic; Diltiazem; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Monitoring, Physiologic; Propranolol; Systole
PubMed: 3545577
DOI: 10.1002/clc.4960100207 -
Actions of verapamil, diltiazem and other divalent cations on the calcium-current of Helix neurones.British Journal of Pharmacology Sep 19811 Effects of organic Ca(2+)-antagonists, verapamil and diltiazem, and cations, Ni(2+), Mn(2+), Co(2+) and La(3+) on Ca(2+) current (I(Ca)) separated from other ionic...
1 Effects of organic Ca(2+)-antagonists, verapamil and diltiazem, and cations, Ni(2+), Mn(2+), Co(2+) and La(3+) on Ca(2+) current (I(Ca)) separated from other ionic currents in a Helix neurone were studied. A suction pipette technique which allows internal perfusion of the cell body and voltage clamp was used.2 Verapamil and diltiazem (10(-6)-10(-4) M) increased the threshold, and decreased both the amplitude and rate of rise of the soma Ca(2+)-spike. Both agents inhibited I(Ca) over the entire range of the current-voltage (I-V) relationship dose-dependently, without shifting the threshold of the I-V relationship. Increases in external Ca(2+) overcame the inhibitory action of the agents.3 Divalent cations, Ni(2+), Mn(2+), Co(2+) and the trivalent cation, La(3+) inhibited I(Ca) dose-dependently, but induced shifts of the I-V relationship to more positive voltages. The order of potency of inhibition of I(Ca) among these cations was as follows; Ni(2+) > La(3+) > Mn(2+) > Co(2+).4 Double reciprocal plots for peak I(Ca) versus external Ca(2+) concentrations in the presence or absence of both organic and inorganic Ca(2+)-antagonists intersect at the ordinate. Results indicate that both organic and inorganic Ca(2+)-antagonists compete for Ca(2+) at the common binding site for Ca(2+).5 Internal application of the organic Ca(2+)-antagonists (10(-4) M) inhibited I(Ca) in a time-dependent manner to about 40-60% of the control. Ni(2+), when applied internally, also depressed I(Ca).6 The results provide evidence that organic Ca(2+)-antagonists occupy the binding site for Ca(2+) in a competitive manner at the surface of the soma membrane of the Helix neurone, while divalent and trivalent cations, in addition to inhibiting I(Ca) in a similar manner to the organic Ca(2+)-antagonists, change the surface charge of the soma membrane.
Topics: Animals; Benzazepines; Calcium; Calcium Channel Blockers; Cations, Divalent; Diltiazem; Helix, Snails; In Vitro Techniques; Membrane Potentials; Neurons
PubMed: 7272605
DOI: 10.1111/j.1476-5381.1981.tb09958.x -
European Journal of Pharmacology Jan 1988We studied the effects of isosorbide dinitrate and diltiazem on histamine-stimulated 45Ca fluxes and contractions of isolated porcine coronary artery. Isosorbide...
We studied the effects of isosorbide dinitrate and diltiazem on histamine-stimulated 45Ca fluxes and contractions of isolated porcine coronary artery. Isosorbide dinitrate was slightly more potent as an inhibitor of intracellular compared to extracellular calcium-dependent contraction. Isosorbide dinitrate inhibited histamine-stimulated calcium efflux and intracellular calcium-dependent contraction over similar concentration ranges. Isosorbide dinitrate partially inhibited histamine-stimulated calcium influx, but this effect was significant only at high concentration and correlated weakly with inhibition of contraction that was dependent on extracellular calcium. Diltiazem more potently inhibited extracellular vs. intracellular calcium-dependent contraction. Diltiazem partially inhibited histamine-stimulated calcium efflux and intracellular calcium-dependent contraction to similar extents (55-60%) and produced similar concentration-response relationships for inhibition of histamine-stimulated calcium influx and extracellular calcium-dependent contraction. The data suggest that alterations of cellular calcium metabolism are major mechanisms of vascular smooth muscle relaxation by isosorbide dinitrate and diltiazem, but that the specific alterations differ for the two drugs. Isosorbide dinitrate may inhibit contraction primarily by enhancing intracellular calcium sequestration, but possibly also by inhibiting agonist-stimulated calcium influx at high isosorbide dinitrate concentrations. Diltiazem primarily inhibits stimulated calcium influx, but may also inhibit intracellular calcium release.
Topics: Animals; Calcium; Calcium Radioisotopes; Coronary Vessels; Diltiazem; Histamine; In Vitro Techniques; Isosorbide Dinitrate; Muscle Contraction; Muscle, Smooth, Vascular; Swine
PubMed: 3350038
DOI: 10.1016/0014-2999(88)90346-9 -
The American Journal of Cardiology Aug 1991The effect of diltiazem on long-term outcome in patients with acute myocardial infarction with and without a history of systemic hypertension was investigated in 2,466... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Effects of diltiazem on long-term outcome after acute myocardial infarction in patients with and without a history of systemic hypertension. The Multicenter Diltiazem Postinfarction Trial Research Group.
The effect of diltiazem on long-term outcome in patients with acute myocardial infarction with and without a history of systemic hypertension was investigated in 2,466 patients using the Multicenter Diltiazem Postinfarction Trial data-base. The baseline variables were comparable in the diltiazem and placebo-treated patients within the groups with and without hypertension. The initial 60-mg dose of diltiazem was associated with a significant (p less than 0.001) but modest (3%) reduction in blood pressure and heart rate in both groups with and without hypertension. Univariate and multivariate analyses revealed a meaningful overall reduction in first recurrent cardiac events (cardiac death or nonfatal reinfarction, whichever occurred first) and cardiac death in patients with hypertension treated with diltiazem compared with results in those treated with placebo. Similar effects were not observed in patients without a history of hypertension. When first recurrent cardiac events were used as the end point, the diltiazem:placebo hazard ratio (95% confidence limits) was 0.77 (0.58, 1.01) for the total hypertension group, and 0.67 (0.47, 0.96) and 1.32 (0.83, 2.10) for patients with hypertension with and without pulmonary congestion during the acute infarction, respectively. Similar results were observed using cardiac death as the end point. Beta blockers had a negligible effect on the hypertension-diltiazem relation. These findings suggest that diltiazem may exert a long-term beneficial effect in most patients with hypertension who do not have pulmonary congestion during an acute infarction, and a detrimental effect in the minority who have pulmonary congestion.
Topics: Adult; Aged; Diltiazem; Double-Blind Method; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Prognosis; Pulmonary Edema; Retrospective Studies
PubMed: 1872266
DOI: 10.1016/0002-9149(91)90773-e -
Journal of the American College of... Sep 1991This study was designed to investigate whether intracoronary diltiazem given before reperfusion could enhance myocardial salvage in the canine heart. Twenty-five dogs... (Comparative Study)
Comparative Study
This study was designed to investigate whether intracoronary diltiazem given before reperfusion could enhance myocardial salvage in the canine heart. Twenty-five dogs were subjected to 90 min of coronary occlusion followed by 4 h of reperfusion. The dogs were assigned to one of three experimental groups. The early diltiazem group received intracoronary diltiazem into the distal coronary bed at the onset of coronary occlusion and for 60 min after reperfusion. The late diltiazem group received the same amount of drug beginning 15 min before reperfusion and the control group received saline solution for 90 min of occlusion and 60 min of reperfusion. Infarct size expressed as a percent of the area at risk was significantly smaller in the early and late diltiazem groups (15.6 +/- 3.6% and 21.2 +/- 5.1%, respectively) than in the control group (49 +/- 4.6%) (p less than 0.05). Intracoronary diltiazem restored systolic function of the stunned, previously ischemic tissue to essentially normal preocclusion values. Segmental shortening after reperfusion averaged 21.6% in the early diltiazem group versus 0 +/- 1.7% and 7.3 +/- 4% for the control and late diltiazem groups, respectively (p less than 0.05). Low dose intracoronary diltiazem did not alter hemodynamic variables or myocardial blood flow but did improve segmental shortening 2 and 6 h after reperfusion. These data indicate that intracoronary diltiazem given during occlusion or just before reperfusion increases the salvage of myocardium compared with the salvage achieved by reperfusion alone. These results also suggest that intracoronary diltiazem given during the ischemic period enhances systolic contractile function of postischemic stunned myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Coronary Vessels; Diltiazem; Dogs; Drug Administration Schedule; Infusions, Intra-Arterial; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Time Factors
PubMed: 1869751
DOI: 10.1016/0735-1097(91)90814-p -
JACC. Heart Failure Feb 2015
Topics: Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Diltiazem; Female; Heterozygote; Humans; Male; Sarcomeres
PubMed: 25543975
DOI: 10.1016/j.jchf.2014.09.004 -
Journal of General Internal Medicine Dec 2020
Topics: Administration, Intravenous; Atrial Fibrillation; Atrial Flutter; Diltiazem; Humans; Verapamil
PubMed: 32710208
DOI: 10.1007/s11606-020-06051-2