-
Yakugaku Zasshi : Journal of the... Oct 2001Effects of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, simvastatin and atorvastatin, on diltiazem-induced hypotension were examined in... (Comparative Study)
Comparative Study
Effects of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, simvastatin and atorvastatin, on diltiazem-induced hypotension were examined in anaesthetized rats and compared to that of pravastatin. Vehicle, 2 mg/kg/day simvastatin, 2 mg/kg/day atorvastatin, or 4 mg/kg/day pravastatin was administered orally for 4 days. Diltiazem at 3 mg/kg was given orally 2 hours after the final administration of the inhibitors. Arterial blood pressure was measured via a cannula introduced into the left carotid artery, and heart rate was counted from the pulse pressure. In all groups, diltiazem significantly decreased the mean arterial blood pressure without any changes in heart rate. Pretreatment with simvastatin and atorvastatin significantly enhanced the hypotensive effect of diltiazem, while that with pravastatin did not. Heart rate was not modified by pretreatment with the inhibitors. The results indicate that concomitant use of diltiazem with simvastatin or atorvastatin enhances diltiazem-induced hypotension, probably by competitive inhibition of diltiazem metabolism with simvastatin and atorvastatin metabolisms.
Topics: Animals; Antihypertensive Agents; Atorvastatin; Blood Pressure; Diltiazem; Drug Synergism; Drug Therapy, Combination; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Male; Pravastatin; Pyrroles; Rats; Rats, Sprague-Dawley
PubMed: 11676178
DOI: 10.1248/yakushi.121.761 -
Clinical Cardiology Apr 1992The effect of the combined treatment with propranolol 20 mg tid and diltiazem 60 mg tid in patients with chronic atrial fibrillation treated with digoxin was evaluated.... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The effect of the combined treatment with propranolol 20 mg tid and diltiazem 60 mg tid in patients with chronic atrial fibrillation treated with digoxin was evaluated. Thirteen patients entered a double-blind, three-phase crossover study. Heart rate was significantly reduced during rest and at maximal exercise (p less than 0.05) during combined treatment compared with treatment with any single drug. No significant changes in maximal work load, exercise time, systolic blood pressure at maximal work load, or subjective sensation of well-being could be demonstrated during combined drug treatment. The RR distribution pattern was unaffected by the addition of propranolol, diltiazem, or their combination to the chronic digoxin treatment. It is concluded that the combination of diltiazem and propranolol has no advantages over any of these drugs singly, in the moderation of heart rate in patients with atrial fibrillation even combined with basic digitalis treatment, and that the intrinsic AV nodal function is unaffected by these drugs or their combination.
Topics: Atrial Fibrillation; Digoxin; Diltiazem; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Propranolol
PubMed: 1563131
DOI: 10.1002/clc.4960150411 -
Anesthesiology Mar 1991The direct effects of isoflurane, halothane, and enflurane alone or combined with diltiazem were examined in 49 isolated perfused guinea pig hearts. Recording electrodes...
The direct effects of isoflurane, halothane, and enflurane alone or combined with diltiazem were examined in 49 isolated perfused guinea pig hearts. Recording electrodes were placed in the right atrium and left ventricular septal wall to measure spontaneous atrial rate and atrioventricular conduction time (AVCT). The right atrium was paced at 3-7 Hz (n = 10) to examine rate-dependent effects on AVCT, Wenckebach's periodicity, and ventricular response rates with atrioventricular (AV) block. Isovolumetric left ventricular pressure (LVP) was measured with a saline-filled balloon placed through the mitral valve. Hearts were perfused with oxygenated Krebs-Ringer's solution at 55 mmHg equilibrated with low or high concentrations of isoflurane (0.7 and 1.5%), halothane (0.5 and 1%), or enflurane (1.1 and 2.2%). Hearts were also perfused with a low or high concentration of diltiazem (75 and 150 ng/ml) alone and during anesthetic exposure. Significant findings of combined exposure were as follows: 1) the low isoflurane, halothane, or enflurane concentration plus a low or high diltiazem concentration decreased LVP compared with control and diltiazem alone; low isoflurane plus the high diltiazem concentration decreased LVP more than isoflurane alone. The high isoflurane, halothane, or enflurane concentration plus the low or the high diltiazem concentration decreased LVP from control, anesthetics and diltiazem alone. Diltiazem plus halothane or enflurane decreased LVP more than diltiazem plus isoflurane. 2) Diltiazem plus low or high isoflurane, halothane, or enflurane concentrations decreased spontaneous atrial rate from control and the agents alone, except the high isoflurane concentration plus the low diltiazem concentration was not greater than that of isoflurane alone. Diltiazem plus halothane or enflurane decreased atrial rate more than diltiazem plus isoflurane. 3) Low and high diltiazem concentration plus low isoflurane, halothane, or enflurane concentrations did not prolong AVCT more than the individual agents alone, but low or high diltiazem plus high isoflurane, halothane, or enflurane concentrations increased AVCT more than each anesthetic alone. In nonpaced hearts, AV block occurred only with high diltiazem plus low enflurane (23%) concentrations and the high enflurane concentration (31%). 4) In hearts paced at 5 and 6 Hz, AVCT increased above controls during a low or high concentrations of diltiazem, during enflurane, and during the low or high concentration of diltiazem plus enflurane; AVCT increased more with the low concentration of diltiazem plus enflurane than with the low diltiazem concentration alone.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Anesthetics; Animals; Atrioventricular Node; Depression, Chemical; Diltiazem; Enflurane; Guinea Pigs; Halothane; Heart Rate; In Vitro Techniques; Isoflurane; Myocardial Contraction
PubMed: 2001031
DOI: 10.1097/00000542-199103000-00022 -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2012The present study was to investigate the effects of diltiazem, a ghrelin receptor agonist, on food intake and gastrointestinal functions in rats. Rats were...
The present study was to investigate the effects of diltiazem, a ghrelin receptor agonist, on food intake and gastrointestinal functions in rats. Rats were intragastrically administered with diltiazem solution (daily 16 mg/kg, 30 mg/kg or 80 mg/kg, 30 d), and the rats with saline as control. To detect the effects of diltiazem on food intake and body weight, the average daily food intake and body weight were recorded, and the serum metabolic hormones of plasma growth hormone (GH) and neuropeptide Y (NPY) were tested by radioimmunoassay. By means of the spectrophotometer and the modified Mett's method, the effects of diltiazem on rat's gastrointestinal function and pepsin activity were tested, respectively. In addition, the gastric juice's acidity of rats was detected by titration and the secretion amount was calculated. The results showed that the food intake and body weight were maximally promoted by diltiazem at the dose of 30 mg/kg daily (30 d). The average daily food intake and body weight were significantly increased, and the serum concentrations of GH and NPY were also remarkably increased in diltiazem-treated groups compared with those in control group. The results also showed that the gastric emptying rate, gastric acid secretion and the activity of pepsin were significantly increased in diltiazem-treated group compared with those in control group. These results suggest that diltiazem induces enhancement of eating, in the same time, it can also stimulate the gastrointestinal function and regulate growth of rat.
Topics: Animals; Body Weight; Diltiazem; Eating; Female; Gastric Emptying; Gastrointestinal Motility; Gastrointestinal Tract; Growth Hormone; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Receptors, Ghrelin
PubMed: 22513469
DOI: No ID Found -
Japanese Journal of Pharmacology Dec 1982The effects of diltiazem on the cerebral blood flow and cerebrovascular spasm were studied in pentobarbital anesthetized animals. In Rhesus monkeys, the common carotid...
The effects of diltiazem on the cerebral blood flow and cerebrovascular spasm were studied in pentobarbital anesthetized animals. In Rhesus monkeys, the common carotid and internal carotid blood flow were measured by an electromagnetic flowmeter. Diltiazem (10-300 micrograms/kg, i.v.) dose-dependently increased both the common carotid and internal carotid blood flow, and the increase in internal carotid blood flow persisted for a longer period than that in the common carotid blood flow. In dogs, regional blood flow in the cerebral cortex (rCBF) was measured by means of the hydrogen gas clearance method. Diltiazem (20 micrograms/kg/min, i.v.) increased rCBF by about 20% of the control during the infusion, and the increase in rCBF was still continued 40 min after the infusion was stopped. In cats, the basilar artery was exposed by craniotomy through the transcervico-transclival approach, and vasospasm was induced by topical administration of 5-HT, PGF2 alpha and incubated blood. Diltiazem, either applied topically to the artery (100 micrograms/ml) or infused continuously into the femoral vein (20 or 40 micrograms/kg/min), suppressed the vasoconstriction evoked by the spasmogen.
Topics: Administration, Topical; Anesthesia; Animals; Benzazepines; Cats; Cerebrovascular Circulation; Diltiazem; Dogs; Female; Injections, Intravenous; Macaca mulatta; Male; Parasympatholytics; Vasodilator Agents
PubMed: 7161959
DOI: 10.1254/jjp.32.1033 -
Acta Medica Iranica Jul 2016To determine whether the medical Treatment of anal fissure can be an effective alternative for surgery Methods: Retrospectively, we randomly selected 190 Patients being... (Comparative Study)
Comparative Study Randomized Controlled Trial
To determine whether the medical Treatment of anal fissure can be an effective alternative for surgery Methods: Retrospectively, we randomly selected 190 Patients being treated for anal fissure between the years 2005-2010 in 3 equal groups: group A: Patients who received medical treatment with topical nitroglycerin, group B: Patient treated with topical diltiazem, and group C: Patients underwent surgery. The results were then correlated with the statistical program SPSS using chi-square test. Main complaints of the patients were first anal pain and then bleeding. The response to treatments for relieving pain was: 77% in A, 83% in B, and 98% in group C. Response of treatments for fissure healing, in order of groups A, B and C was: 74%, 83%, and 94%. Despite good response to medical treatment, surgical treatment was more effective and medical treatment of choice in patients who are willing to have surgery.
Topics: Administration, Topical; Adult; Aged; Anal Canal; Chronic Disease; Digestive System Surgical Procedures; Diltiazem; Female; Fissure in Ano; Humans; Male; Middle Aged; Nitroglycerin; Pain Management; Retrospective Studies; Treatment Outcome; Vasodilator Agents; Young Adult
PubMed: 27424014
DOI: No ID Found -
Medicine Oct 2022Diltiazem (DZ) is widely prescribed in transplant recipients because of its drug-drug interactions with calcineurin inhibitors (CNI). However, these interactions have...
Diltiazem (DZ) is widely prescribed in transplant recipients because of its drug-drug interactions with calcineurin inhibitors (CNI). However, these interactions have been primarily investigated in renal transplantation, and data regarding the long-term efficacy and safety of DZ in orthotopic heart transplantation (OHT) are still sparse. Our study aimed to elucidate the extent to which the co-prescription of DZ reduces the dose required to maintain adequate blood levels of cyclosporine A (CsA) and the resulting effect on morbidity and mortality in OHT recipients. We performed a retrospective single-center analysis of OHT recipients on a long-term immunosuppressive regimen based on CsA and mycophenolate mofetil (MMF). The study population consisted of 95 adult OHT recipients with a mean follow-up of 15.8 ± 6.7 years. DZ was co-prescribed in 39 subjects (41.1%) and was associated with a 28.6% reduction of the mean CsA daily dose (P < .001). Patients on DZ had less frequent rejection episodes (P = .002), better renal function (P = .009) and a lower rate of end-stage renal disease (P = .008). Additionally, they developed later cardiac allograft vasculopathy (CAV). We observed no prognostic relevance of DZ co-prescription in univariate and multivariate Cox-regression analyses. In addition to reducing the CsA dose required to maintain adequate blood through levels, DZ may have nephroprotective properties in OHT. The co-administration of DZ may decelerate the development of CAV and reduce the frequency of the rejection episodes. However, the beneficial influence on morbidity has no impact on mortality.
Topics: Adult; Calcineurin Inhibitors; Cyclosporine; Diltiazem; Drug Tapering; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Mycophenolic Acid; Retrospective Studies
PubMed: 36254022
DOI: 10.1097/MD.0000000000031166 -
Journal of Psychiatry & Neuroscience :... May 2000To examine the efficacy of a slow-release formulation of diltiazem as adjunctive therapy in patients with treatment-resistant bipolar disorder. (Clinical Trial)
Clinical Trial
OBJECTIVE
To examine the efficacy of a slow-release formulation of diltiazem as adjunctive therapy in patients with treatment-resistant bipolar disorder.
DESIGN
Retrospective study.
PATIENTS
Eight female patients with treatment-resistant bipolar disorder.
INTERVENTIONS
Patients were administered diltiazem and monitored for a 6-month period before starting diltiazem and a 6-month period after starting the drug.
OUTCOME MEASURES
All patients were seen at least monthly and usually every 2 weeks. The frequency and severity of both depressive and manic episodes were examined during the 6-month period after starting diltiazem, and compared with those during the 6-month period before diltiazem treatment.
RESULTS
There was a statistically significant decrease in the frequency and severity of both manic and depressive episodes in these patients after they started treatment with diltiazem, compared with the period before they started treatment with diltiazem (p < 0.001). There was no evidence of side effects requiring patient withdrawal or of drug interactions.
CONCLUSIONS
The results support previous suggestions that calcium-channel antagonists may be an effective adjunctive treatment in the management of bipolar disorder. Further controlled clinical studies are needed to confirm this small, open-label, retrospective study.
Topics: Antidepressive Agents; Bipolar Disorder; Calcium Channel Blockers; Diltiazem; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Retrospective Studies; Severity of Illness Index
PubMed: 10863888
DOI: No ID Found -
Beneficial hemodynamic effects of intravenous and oral diltiazem in severe congestive heart failure.Journal of the American College of... Apr 1984Concern persists about the potential negative inotropic effects of calcium channel blockers in patients with severely depressed myocardial function. Therefore,... (Comparative Study)
Comparative Study
Concern persists about the potential negative inotropic effects of calcium channel blockers in patients with severely depressed myocardial function. Therefore, intravenous diltiazem (100 to 200 micrograms/kg per min infusion) was administered for 40 minutes followed by oral diltiazem (90 to 120 mg/8 hours) for 24 hours to patients with advanced congestive heart failure (New York Heart Association class III to IV, mean ejection fraction 26 +/- 4 [SD]). Intravenous diltiazem (eight patients) increased cardiac index 20% (2.05 +/- 0.8 to 2.47 +/- 0.8 liters/min per m2, p less than 0.01), stroke volume index 50% (22 +/- 9 to 33 +/- 12 ml/m2, p less than 0.001) and stroke work index 27% (19 +/- 10 to 24 +/- 10 g-m/m2, p less than 0.05); while reducing heart rate 23% (97 +/- 18 to 75 +/- 11 beats/min, p less than 0.01), mean arterial pressure 18% (95 +/- 13 to 78 +/- 7 mm Hg) and pulmonary wedge pressure 34% (29 +/- 9 to 19 +/- 7 mm Hg), without altering maximal first derivative of left ventricular pressure (dP/dtmax). Oral diltiazem (seven patients) produced equivalent hemodynamic effects. Transient junctional arrhythmias were observed in three of eight patients with intravenous diltiazem and one of seven patients with oral diltiazem. It is concluded that intravenous and short-term oral diltiazem improve left ventricular performance and reduce myocardial oxygen demand by heart rate and afterload reduction without significantly depressing contractile function in severe congestive heart failure. Caution should be exercised to avoid potential adverse, drug-induced electrophysiologic effects in such patients.
Topics: Administration, Oral; Adult; Benzazepines; Diltiazem; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Nifedipine; Verapamil
PubMed: 6707341
DOI: 10.1016/s0735-1097(84)80365-4 -
British Journal of Pharmacology Dec 19891. The electrophysiological effects of bepridil, its quaternary derivative, CERM 11888 (methylpyrrolidinium bromide) (both 2.5 mg kg-1 i.v.) and those of verapamil and... (Comparative Study)
Comparative Study
1. The electrophysiological effects of bepridil, its quaternary derivative, CERM 11888 (methylpyrrolidinium bromide) (both 2.5 mg kg-1 i.v.) and those of verapamil and diltiazem (0.2 mg kg-1 i.v.) were studied in closed chest anaesthetized dogs at doses used in clinical studies. 2. The four drugs caused a bradycardia with the following order of potency: bepridil greater than CERM 11888 greater than diltiazem greater than verapamil. 3. All the compounds slowed conduction in the AV node, increased the refractory period (RP) and decreased Wenckebach rates with the following order: verapamil much greater than diltiazem greater than bepridil greater than CERM 11888. 4. Verapamil and diltiazem did not affect conduction or the RP in atria while bepridil weakly slowed the former and markedly increased the latter. CERM 11888 caused a lengthening of RP but this was a delayed effect. 5. In the ventricle, bepridil and CERM 11888 caused a small increase in the QRS and a more pronounced increase in the RP. Both compounds increased QTc but did not modify HV. Verapamil and diltiazem had no significant effects at the ventricular level. 6. Our results confirm that the main sites of action of calcium antagonists are the SA and AV nodes. Bepridil has a broader spectrum of activity and also acts at the atrial and ventricular levels. A comparison of the effects of bepridil with those of its quaternary derivative suggests the involvement of an intracellular action in the electrophysiological effects of bepridil.
Topics: Anesthesia; Animals; Bepridil; Blood Pressure; Calcium Channel Blockers; Diltiazem; Dogs; Electrocardiography; Electrophysiology; Female; Heart; Heart Rate; Hemodynamics; In Vitro Techniques; Male; Sinoatrial Node; Time Factors; Verapamil
PubMed: 2611495
DOI: 10.1111/j.1476-5381.1989.tb12684.x