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Indian Heart Journal 2022Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid ventricular rate (AF-RVR) in the emergency department.
OBJECTIVES
To compare the efficacy of intravenous diltiazem and metoprolol for rate control and safety with respect to development of hypotension and bradycardia in patients with AF-RVR.
METHODS
For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane databases, and the clinicaltrials.gov registry between database inception and 30th May 2021. Articles were included if they compared efficacy and safety of diltiazem versus metoprolol in critically ill adult patients hospitalized with AF-RVR. Outcome measures were achievement of rate control, development of new hypotension, and bradycardia after drug administration.
RESULTS
Of 86 records identified, 14 were eligible, all of which had a low to moderate risk of overall bias. The meta-analysis (Mantel-Haenszel, random-effects model) showed that diltiazem use was associated with increased achievement of rate control target compared to metoprolol [14 studies, n = 1732, Odds Ratio (OR): 1.92; 95% Confidence Intervals (CI):1.26 to 2.90; I = 61%]. In the pooled analysis, no differences were seen in hypotension using diltiazem vs metoprolol [12 studies, n = 1477, OR: 0.96; 95% CI:0.61 to 1.52; I = 35%] or bradycardia [9 studies, n = 1203, OR: 2.44; 95% CI: 0.82 to 7.31; I = 48%].
CONCLUSIONS
Intravenous diltiazem is associated with increased achievement of rate control target in patients with AF-RVR compared to metoprolol, while both medications are associated with similar incidence of hypotension and bradycardia.
Topics: Adult; Humans; Diltiazem; Atrial Fibrillation; Metoprolol; Bradycardia; Hypotension; Heart Rate
PubMed: 36334652
DOI: 10.1016/j.ihj.2022.10.195 -
The Yale Journal of Biology and Medicine Mar 2020Diltiazem is a calcium-channel blocker commonly used for the treatment of hypertension. Common adverse effects include dizziness, headache, and edema. Fewer than 20...
Diltiazem is a calcium-channel blocker commonly used for the treatment of hypertension. Common adverse effects include dizziness, headache, and edema. Fewer than 20 cases of diltiazem-associated photodistributed hyperpigmentation have been reported in the literature. Here, we present the case of a 71-year-old woman with new-onset facial hyperpigmentation 6 months after initiating treatment with diltiazem.
Topics: Aged; Biopsy; Calcium Channel Blockers; Dermatologic Agents; Diltiazem; Female; Humans; Hyperpigmentation; Hypertension; Ointments; Photosensitivity Disorders; Skin; Tacrolimus; Treatment Outcome; Withholding Treatment
PubMed: 32226335
DOI: No ID Found -
The Cochrane Database of Systematic... Mar 2018Schizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Schizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments.
OBJECTIVES
To determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication.
DATA COLLECTION AND ANALYSIS
We independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE.
MAIN RESULTS
Previous versions of this review included no trials. From the 2015 search, we identified three cross-over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD -0.71, 95% CI -2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients.
AUTHORS' CONCLUSIONS
Available evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic-induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well-designed randomised trials.
Topics: Antipsychotic Agents; Calcium Channel Blockers; Diltiazem; Dyskinesia, Drug-Induced; Flunarizine; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 29578611
DOI: 10.1002/14651858.CD000206.pub4 -
PLoS Pathogens Feb 2022The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated...
The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Cav1.2 pore-forming subunit (Cav1.2 α1c) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. Cav1.2 α1c interacts with SARS-CoV-2 spike protein and ACE2, and affects the attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem has potential as a drug against SARS-CoV-2 infection and that Cav1.2 α1c is a promising target for antiviral drug development for COVID-19.
Topics: A549 Cells; Animals; COVID-19; Cells, Cultured; Chlorocebus aethiops; Diltiazem; Disease Models, Animal; Female; HEK293 Cells; HeLa Cells; Humans; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; SARS-CoV-2; Vero Cells; Virus Attachment; Virus Internalization; COVID-19 Drug Treatment
PubMed: 35176124
DOI: 10.1371/journal.ppat.1010343 -
Journal of General Internal Medicine Dec 2013
Topics: Antihypertensive Agents; Diltiazem; Female; Humans; Hyperpigmentation; Middle Aged
PubMed: 23846341
DOI: 10.1007/s11606-013-2530-1 -
BioMed Research International 2015Currently, there is still a lack of an optimal treatment for no reflow phenomenon (NRP). We analyzed the efficacy and safety of using nondihydropyridine calcium channel... (Meta-Analysis)
Meta-Analysis Review
Currently, there is still a lack of an optimal treatment for no reflow phenomenon (NRP). We analyzed the efficacy and safety of using nondihydropyridine calcium channel antagonists (NDHP, verapamil/diltiazem) in patients suffering from NRP. Eight RCTs with 494 participants were eligible for analysis. The pooling analysis showed that intracoronary verapamil/diltiazem injection significantly decreased the occurrence of the coronary NRP (RR: 0.3, 95% CI: 0.16-0.57; P = 0.0002) and reduced corrected thrombolysis in myocardial infarction (TIMI) frame Count (WMD = -9.24, 95% CI -13.91-4.57; P = 0.0001) in patients with NRP. Moreover, verapamil/diltiazem treatment showed superiority in reducing wall motion index (WMI) compared to the control at day 1 (WMD = 0.11, 95% CI: 0.02-0.20; P = 0.02) (P < 0.05). There was also a significantly greater decline at occurrence of the major adverse cardiac events between verapamil/diltiazem and control groups (WMD: 0.4, 95% CI: 0.19-0.84; P = 0.02). However, using verapamil/diltiazem did not provide additional improvement of left ventricular ejection fraction post procedure (at 7 days, WMD, 0.1; 95% CI, -2.43-2.63; P = 0.94; at 30 days, WMD, 0.42; 95% CI, -2.09-2.92; P = 0.75). NDHP use is beneficial in attenuating NRP and reducing 6-month MACEs in patients with NRP.
Topics: Calcium Channel Blockers; Cardiovascular Agents; Diltiazem; Humans; No-Reflow Phenomenon; Randomized Controlled Trials as Topic; Verapamil
PubMed: 26504804
DOI: 10.1155/2015/382086 -
Molecular Pharmacology Oct 2019Diltiazem is a widely prescribed Ca antagonist drug for cardiac arrhythmia, hypertension, and angina pectoris. Using the ancestral Ca channel construct CaAb as a...
Diltiazem is a widely prescribed Ca antagonist drug for cardiac arrhythmia, hypertension, and angina pectoris. Using the ancestral Ca channel construct CaAb as a molecular model for X-ray crystallographic analysis, we show here that diltiazem targets the central cavity of the voltage-gated Ca channel underneath its selectivity filter and physically blocks ion conduction. The diltiazem-binding site overlaps with the receptor site for phenylalkylamine Ca antagonist drugs such as verapamil. The dihydropyridine Ca channel blocker amlodipine binds at a distinct site and allosterically modulates the binding sites for diltiazem and Ca Our studies resolve two distinct binding poses for diltiazem in the absence and presence of amlodipine. The binding pose in the presence of amlodipine may mimic a high-affinity binding configuration induced by voltage-dependent inactivation, which is favored by dihydropyridine binding. In this binding pose, the tertiary amino group of diltiazem projects upward into the inner end of the ion selectivity filter, interacts with ion coordination Site 3 formed by the backbone carbonyls of T175, and alters binding of Ca to ion coordination Sites 1 and 2. Altogether, our results define the receptor site for diltiazem and elucidate the mechanisms for pore block and allosteric modulation by other Ca channel-blocking drugs at the atomic level. SIGNIFICANCE STATEMENT: Calcium antagonist drugs that block voltage-gated calcium channels in heart and vascular smooth muscle are widely used in the treatment of cardiovascular diseases. Our results reveal the chemical details of diltiazem binding in a blocking position in the pore of a model calcium channel and show that binding of another calcium antagonist drug alters binding of diltiazem and calcium. This structural information defines the mechanism of drug action at the atomic level and provides a molecular template for future drug discovery.
Topics: Allosteric Regulation; Amlodipine; Animals; Binding Sites; Calcium Channel Blockers; Calcium Channels; Crystallography, X-Ray; Diltiazem; Humans; Models, Molecular; Protein Conformation; Verapamil
PubMed: 31391290
DOI: 10.1124/mol.119.117531 -
CMAJ : Canadian Medical Association... Dec 2016
Review
Topics: Adenosine; Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Calcium Channel Blockers; Catheter Ablation; Diltiazem; Disease Management; Electric Countershock; Electrocardiography; Humans; Practice Guidelines as Topic; Tachycardia, Supraventricular; Verapamil
PubMed: 27777258
DOI: 10.1503/cmaj.160079 -
Journal of the American College of... Feb 1987Fifteen patients with coronary artery spasm completed a double-blind placebo-controlled trial comparing diltiazem and nifedipine. Increasingly, higher daily doses... (Clinical Trial)
Clinical Trial Comparative Study
Fifteen patients with coronary artery spasm completed a double-blind placebo-controlled trial comparing diltiazem and nifedipine. Increasingly, higher daily doses (diltiazem, 90 to 360 mg; nifedipine, 30 to 120 mg) were administered to achieve optimal clinical effects. Daily diaries and ambulatory electrocardiographic recordings were used to assess efficacy and side effects. Both drugs significantly decreased angina frequency compared with that in the preceding placebo period (diltiazem 1.4 +/- 0.4 [mean +/- SEM] to 0.4 +/- 0.2 episodes per day; nifedipine 1.4 +/- 0.3 to 0.4 +/- 0.1 episodes per day; both p less than 0.05). Ambulatory electrocardiographic recordings showed fewer ST shifts than were expected during all treatment periods (0.02/h recorded during placebo, none during diltiazem and 0.02/h during nifedipine therapy). Although some patients responded better to one drug than the other, neither drug resulted in a clearly superior clinical response. Diltiazem was discontinued in one patient because of urticaria, but the total number of side effects was higher with nifedipine (12 of 15 patients) than with diltiazem (5 of 15, p less than 0.01). Nine patients remained symptomatic on single drug treatment and entered open label treatment with the combination of diltiazem and nifedipine. Three patients did not tolerate the combination because of important side effects; the other six also had side effects, but these were relatively minor. Four patients received no more benefit from the combination than from a single agent; the condition of two patients improved. Both diltiazem and nifedipine provide effective antianginal therapy for coronary spasm, but diltiazem has fewer side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Aged; Clinical Trials as Topic; Coronary Vasospasm; Diltiazem; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nifedipine
PubMed: 3543092
DOI: 10.1016/s0735-1097(87)80397-2 -
Journal of Veterinary Internal Medicine 1996The i.v. and apparent steady-state kinetics of diltiazem HCI (DLT) and slow-absorption long-acting diltiazem (CD) given p.o. were investigated in cats. The effects of... (Comparative Study)
Comparative Study
The i.v. and apparent steady-state kinetics of diltiazem HCI (DLT) and slow-absorption long-acting diltiazem (CD) given p.o. were investigated in cats. The effects of p.o. diltiazem on heart rate and PR interval were also studied. Plasma diltiazem concentrations were determined by ultraviolet high-performance liquid chromatography (UV-HPLC), using verapamil as the internal standard. Heart rate and PR interval determinations were evaluated over a 24-hour period for the PO formulations and compared with values under diltiazemfree conditions. The mean systemic clearance and apparent volume of distribution of i.v. diltiazem were 15.0 mL/min/kg and 2.70 L/kg, respectively. The elimination half-life of diltiazem after i.v. and p.o. DLT administration were approximately 120 minutes. In contrast, the terminal half-life of CD was 460 minutes. The mean apparent bioavailability of DLT p.o. was 71%, which was significantly higher than that observed with CD (36%). Heart rate and PR intervals in cats receiving the 2 formulations at steady-state were not different from those measured in the drug-free state. We conclude that DLT at 1 mg/kg p.o. tid and CD at 10 mg/kg p.o. sid provide plasma concentrations that are known to have pharmacodynamic effects in other species.
Topics: Animals; Cardiovascular Agents; Cats; Delayed-Action Preparations; Diltiazem; Female; Half-Life; Heart Rate; Hemodynamics; Metabolic Clearance Rate
PubMed: 8884718
DOI: 10.1111/j.1939-1676.1996.tb02069.x