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Annals of Cardiac Anaesthesia 2023In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation... (Clinical Trial)
Clinical Trial
OBJECTIVES
In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation (AF) following off-pump coronary artery bypass grafting (CABG).
BACKGROUND
AF after CABG is common and contributes to morbidity and mortality. Various pharmacological preventive measures including magnesium, amiodarone, diltiazem, and combination therapy among others have been tried to lower the incidence of AF. Most of the studies have been performed in patients undergoing conventional on-pump CABG. In this uncontrolled trial, efficacy of magnesium alone or in combination with amiodarone and / or diltiazem has been studied in patients undergoing off-pump CABG.
METHODS
One hundred and fifty patients undergoing off-pump CABG were divided into 3 groups, Group M (n=21) received intraoperative magnesium infusion at 30mg/ kg over 1 hour after midline sternotomy; Group MD (n=78) received magnesium infusion in similar manner with diltiazem infusion at 0.05 μg/kg/hr throughout the intraoperative period; Group AMD (n=51) received preoperative oral amiodarone at a dose of 200 mg three times a day for 3 days followed by 200 mg twice daily for another 3 days followed by 200 mg once daily till the day of surgery along with magnesium and diltiazem infusion as in other groups. AF lasting more than 10 min or requiring medical intervention was considered as AF.
RESULTS
The overall incidence of postoperative AF was 12.6% with 11.7% in group AMD, 19% in group M, and 11.5% in group MD, which was not statistically significant.
CONCLUSIONS
It is concluded that the use of amiodarone and/or diltiazem in addition to magnesium did not result in additional benefit of lowering the incidence of AF.
Topics: Humans; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Coronary Artery Bypass; Diltiazem; Magnesium; Postoperative Complications; Treatment Outcome
PubMed: 37861573
DOI: 10.4103/aca.aca_35_23 -
Journal of Veterinary Internal Medicine Nov 2022Acute kidney injury (AKI) in dogs has a high case fatality rate. Diltiazem might improve renal function, but effect of intravenous infusion has not been adequately...
BACKGROUND
Acute kidney injury (AKI) in dogs has a high case fatality rate. Diltiazem might improve renal function, but effect of intravenous infusion has not been adequately studied in dogs.
HYPOTHESIS/OBJECTIVES
To determine if an intravenous infusion of diltiazem improves renal function through changes in glomerular filtration rate (GFR), fractional excretion of sodium (FENa), and urine output (UOP) in healthy dogs.
ANIMALS
Ten healthy adult dogs.
METHODS
Prospective, unmasked, crossover study. Dogs were randomized to receive diltiazem (loading dose of 240 μg/kg followed by 6 μg/kg/min for 300 min) or the same volume of 5% dextrose in water (D5W). The opposite treatment was given after a 7-day washout period. GFR and FENa were obtained at baseline and after infusion. UOP was measured starting 1 hour before diltiazem administration.
RESULTS
GFR did not significantly increase from baseline with diltiazem (before diltiazem median = 2.371 mL/min/kg, range = 1.605-4.359; after diltiazem median = 2.305 mL/min/kg, range = 1.629-4.387; median difference = 0.080 mL/min/kg, 95% confidence interval [CI] = -0.417 to 0.757; P = .85), and there was no difference in D5W GFR before and after diltiazem (median = 2.389 mL/min/kg, range = 1.600-3.557; median difference = 0.036 mL/min/kg, 95% CI = -0.241 to 1.112; P = .69). FENa did not increase from baseline after administration of diltiazem (median difference = 0%, 95% CI = -0.1 to 0.1; P = .81), and there was no difference in D5W FENa (median difference = 0.1%, 95% CI = -0.1 to 0.2; P = .26). UOP did not increase with diltiazem (P = .06).
CONCLUSION AND CLINICAL IMPORTANCE
Intravenous administration of diltiazem does not improve markers of renal function in healthy dogs. Further studies are needed in dogs with AKI.
Topics: Dogs; Animals; Glomerular Filtration Rate; Diltiazem; Infusions, Intravenous; Kidney; Cross-Over Studies; Prospective Studies; Electrolytes; Acute Kidney Injury; Dog Diseases
PubMed: 36354148
DOI: 10.1111/jvim.16575 -
British Journal of Clinical Pharmacology Nov 1997To study the dose-response relationship of the pharmacokinetic interaction between diltiazem and cyclosporin in kidney transplant recipients.
AIMS
To study the dose-response relationship of the pharmacokinetic interaction between diltiazem and cyclosporin in kidney transplant recipients.
METHODS
Eight stable kidney transplant recipients maintained on cyclosporin but not taking diltiazem, were given increasing doses of diltiazem to a maximum dose of 180 mg day(-1). Following a 2 week period on each dose of diltiazem, thirteen blood samples were taken over a 24 h period to allow morning and evening AUCs to be determined for cyclosporin, diltiazem and three metabolites of diltiazem.
RESULTS
Mean cyclosporin AUC(0, 24 h) increased sharply following the lowest dose of diltiazem used (10 mg day(-1)), the rate of increase slowed after 30-60 mg day(-1) but continued to increase up to the maximum dose tested. The effect of a single morning dose of DTZ was evident over both morning (0-12 h) and evening (12-24 h) cyclosporin AUCs. There was considerable interpatient variation in response to DTZ.
CONCLUSIONS
The dose of diltiazem required to increase cyclosporin AUC (and hence allow significant reduction in cyclosporin dose) is less than that currently used for many patients. Lower doses of diltiazem should result in fewer adverse effects and may allow its use in situations where it was hitherto contraindicated. Because of the significant interpatient variation in response, we recommend individual patient blood cyclosporin concentration monitoring both before and after the introduction of diltiazem.
Topics: Adult; Area Under Curve; Calcium Channel Blockers; Cyclosporine; Diltiazem; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged
PubMed: 9384468
DOI: 10.1046/j.1365-2125.1997.t01-1-00616.x -
Pharmacological Reports : PR 2011The purpose of this study was to investigate the possible effects of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, on the pharmacokinetics... (Comparative Study)
Comparative Study
Effects of simvastatin on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, after oral and intravenous administration in rats: possible role of P-glycoprotein and CYP3A4 inhibition by simvastatin.
The purpose of this study was to investigate the possible effects of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats. HMG-CoA reductase inhibitors and diltiazem are sometimes prescribed as a combination therapy for the prevention or treatment of cardiovascular diseases. The effect of simvastatin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Simvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with a 50% inhibition concentration (IC(50)) of 3.0 μM. In addition, simvastatin significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. The pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined after oral and intravenous administration of diltiazem to rats in the presence and absence of simvastatin (0.3 and 1.0 mg/kg). The areas under the plasma concentration-time curve (AUC) and the peak concentration (C(max)) of diltiazem were significantly (p < 0.05, 1.0 mg/kg) increased by 45.2% and 35.2%, respectively, in the presence of simvastatin compared to control. Consequently, the absolute bioavailability (AB) values of diltiazem in the presence of simvastatin (1.0 mg/kg) were significantly (p < 0.05) higher (44.8%) than that of the control group. Moreover, the relative bioavailability (RB) of diltiazem was 1.21- to 1.45-fold greater than that in the control group. The metabolite-parent AUC ratio (MR) in the presence of simvastatin (1.0 mg/kg) significantly decreased compared to the control group. This result implied that simvastatin effectively inhibited the metabolism of diltiazem. The increase in diltiazem oral bioavailability might be attributable to enhanced absorption in the small intestine via the inhibition of P-gp and to reduced first-pass metabolism of diltiazem via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver rather than renal elimination of diltiazem by simvastatin.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Administration, Oral; Animals; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Diltiazem; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Infusions, Intravenous; Male; Rats; Rats, Sprague-Dawley; Simvastatin
PubMed: 22358108
DOI: 10.1016/s1734-1140(11)70724-1 -
Gut Nov 1999Topical nitrates lower anal sphincter pressure and heal anal fissures, but a majority of patients experience headache. The internal anal sphincter has a calcium... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Topical nitrates lower anal sphincter pressure and heal anal fissures, but a majority of patients experience headache. The internal anal sphincter has a calcium dependent mechanism to maintain tone, and also receives an inhibitory extrinsic cholinergic innervation. It may therefore be possible to lower anal sphincter pressure using calcium channel blockers and cholinergic agonists without side effects.
AIMS
To investigate the effect of oral and topical calcium channel blockade and a topical cholinomimetic on anal sphincter pressure.
METHODS
Three studies were conducted, each involving 10 healthy volunteers. In the first study subjects were given oral 60 mg diltiazem or placebo on separate occasions. They were then given diltiazem once or twice daily for four days. In the second and third studies diltiazem and bethanechol gels of increasing concentration were applied topically to lower anal pressure.
RESULTS
A single dose of 60 mg diltiazem lowered the maximum resting anal sphincter pressure (MRP) by a mean of 21%. Once daily diltiazem produced a clinically insignificant effect but a twice daily regimen reduced anal pressure by a mean of 17%. Diltiazem and bethanechol gel produced a dose dependent reduction of the anal pressure; 2% diltiazem produced a maximal 28% reduction, and 0.1% bethanechol a maximal 24% reduction, the effect lasting three to five hours.
CONCLUSIONS
Topical diltiazem and bethanechol substantially reduce anal sphincter pressure for a prolonged period, and represent potential low side effect alternatives to topical nitrates for the treatment of anal fissures.
Topics: Administration, Oral; Administration, Topical; Adult; Anal Canal; Bethanechol; Calcium Channel Blockers; Diltiazem; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Gels; Humans; Male; Middle Aged; Muscarinic Agonists
PubMed: 10517908
DOI: 10.1136/gut.45.5.719 -
The Western Journal of Emergency... Mar 2018Atrial fibrillation (AF) is a common diagnosis of patients presenting to the emergency department (ED). Intravenous (IV) diltiazem bolus is often the initial drug of... (Observational Study)
Observational Study
INTRODUCTION
Atrial fibrillation (AF) is a common diagnosis of patients presenting to the emergency department (ED). Intravenous (IV) diltiazem bolus is often the initial drug of choice for acute management of AF with rapid ventricular response (RVR). The route of diltiazem after the initial IV loading dose may influence the disposition of the patient from the ED. However, no studies exist comparing oral (PO) immediate release and IV continuous infusion diltiazem in the emergency setting. The objective of this study was to compare the incidence of treatment failure, defined as a heart rate (HR) of >110 beats/min at four hours or conversion to another agent, between PO immediate release and IV continuous infusion diltiazem after an initial IV diltiazem loading dose in patients in AF with RVR.
METHODS
This was a single-center, observational, retrospective study conducted at a tertiary academic medical center. The study population included patients ≥18 years old who presented to the ED in AF with a HR > 110 beats/min and received an initial IV diltiazem loading dose. We used multivariate logistic regression to assess the association between routes of administration and treatment failure.
RESULTS
A total of 111 patients were included in this study. Twenty-seven percent (11/41) of the patients in the PO immediate-release group had treatment failure compared to 46% (32/70) in the IV continuous-infusion group. The unadjusted odds ratio (OR) of treatment failure with PO was less than IV at 0.4 (95% confidence interval [CI] [0.18, 0.99], p = 0.046). When we performed a multivariate analysis adjusted for race and initial HR, PO was still less likely to be associated with treatment failure than IV with an OR of 0.4 (95% CI [0.15, 0.94], p = 0.041). The median dose of PO diltiazem and IV continuous infusion diltiazem at four hours was 30 mg and 10 mg/h, respectively.
CONCLUSION
After a loading dose of IV diltiazem, PO immediate-release diltiazem was associated with a lower rate of treatment failure at four hours than IV continuous infusion in patients with AF with RVR.
Topics: Administration, Oral; Atrial Fibrillation; Diltiazem; Emergency Service, Hospital; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Retrospective Studies; Treatment Failure
PubMed: 29560075
DOI: 10.5811/westjem.2017.10.33832 -
Anesthesiology Feb 1987The effects of the calcium entry blocker diltiazem (iv loading dose 0.4 mg/kg, iv maintenance dose 0.4 mg/min) and subsequent isoflurane-induced hypotension to mean...
The effects of the calcium entry blocker diltiazem (iv loading dose 0.4 mg/kg, iv maintenance dose 0.4 mg/min) and subsequent isoflurane-induced hypotension to mean aortic pressures of 70 and 55 mmHg on global and regional right ventricular (RV) and left ventricular (LV) performance (ultrasonic dimension technique), on coronary (electromagnetic flow probes) and systemic hemodynamics, and on electrophysiologic parameters (PR, QRS, QTc intervals) were studied in eight open-chest dogs, anesthetized and paralyzed by continuous infusions of fentanyl and pancuronium. Diltiazem at a plasma concentration of 282 +/- 33 ng/ml (mean +/- SE) caused significant (P less than 0.05) increases in coronary blood flows, and decreases in coronary and systemic vascular resistances with only little effect on global and regional RV and LV function. However, the PR interval increased by 40%, and three animals developed II degrees atrioventricular block type I. At stable diltiazem plasma levels, administration of isoflurane caused dose-dependent decreases in myocardial segment shortening and stroke volume with unchanged LV or increased RV preload, and little changed RV or reduced LV afterload indicating myocardial depression. Coronary and systemic vascular resistances remained unaffected. At the higher concentration of isoflurane (mean inspired 1.3 +/- 0.2%), seven animals developed intermittent sinus node arrests with pauses up to 12 s followed by intermittent junctional escape or sinus rhythms. Similar interactions might develop in patients on diltiazem receiving isoflurane.
Topics: Animals; Diltiazem; Dogs; Drug Interactions; Electrocardiography; Female; Heart; Hemodynamics; Homeostasis; Hypotension; Infusions, Intravenous; Isoflurane; Male
PubMed: 3813073
DOI: 10.1097/00000542-198702000-00002 -
Journal of Pharmacological Sciences Jul 2020We investigated whether benzothiazepines could produce anxiolytic effects via allopregnanolone (ALLO) biosynthesis in mice. We compared the behavioral effects caused by... (Comparative Study)
Comparative Study
We investigated whether benzothiazepines could produce anxiolytic effects via allopregnanolone (ALLO) biosynthesis in mice. We compared the behavioral effects caused by benzothiazepines to those caused by carbamazepine and sodium valproate. We found that a pretreatment with finasteride (a 5 alpha-reductase inhibitor) suppressed carbamazepine-induced anxiolytic effects but not the effects of sodium valproate. Similar to carbamazepine, diltiazem and JTV-519 displayed anxiolytic effects that were suppressed by a pretreatment with finasteride. We clearly demonstrate that the benzothiazepines, diltiazem and JTV-519, exert an anxiolytic-like effect via ALLO biosynthesis in mice.
Topics: 5-alpha Reductase Inhibitors; Animals; Anti-Anxiety Agents; Behavior, Animal; Carbamazepine; Diltiazem; Dose-Response Relationship, Drug; Finasteride; Male; Mice, Inbred C57BL; Neurosteroids; Pregnanolone; Thiazepines; Valproic Acid
PubMed: 32249061
DOI: 10.1016/j.jphs.2020.03.003 -
British Journal of Pharmacology Aug 1986A low concentration (0.2 nM) of oxytocin induced phasic tension development in the isolated uterus of the day-22 pregnant rat. Tonic spasm was also induced by higher...
A low concentration (0.2 nM) of oxytocin induced phasic tension development in the isolated uterus of the day-22 pregnant rat. Tonic spasm was also induced by higher concentrations of oxytocin (2 and 20 nM). Spasmogenic responses to bradykinin and potassium chloride (KCl) also contained phasic and tonic components while acetylcholine induced tonic spasm only. The phasic component of the responses to oxytocin and to bradykinin and both components of the response to KCl were inhibited by (+)-cis diltiazem (0.1 and 1 microM). The tonic component of the responses to oxytocin and to bradykinin and the responses to acetylcholine were only reduced by (+)-cis diltiazem at concentrations greater than 10 microM. (-)-cis Diltiazem was less potent than (+)-cis diltiazem as an inhibitor of calcium (Ca2+)-induced spasm in a depolarizing medium and of the phasic spasms induced by oxytocin. The two isomers were of similar potency as inhibitors of oxytocin-induced tonic spasm. Spasmogenic responses to oxytocin, bradykinin, acetylcholine and KCl were decreased when uteri were bathed in media which were Ca2+-free or of low Na+ content. However, there was no correlation between the rank order of sensitivity of the four spasmogens to the changed media and to their inhibition by (+)-cis diltiazem. Oxytocin (0.2 nM) increased the frequency, duration and amplitude of spike activity, measured by extracellular electrical recording, in parallel with enhancement of phasic tension development. With higher concentrations of oxytocin (2 and 20 nM) spike firing was initially continuous but often subsequently ceased despite the associated tonic contracture. After incubation in (+)-cis diltiazem (10 microM), oxytocin (0.2, 2 and 20 nM) produced graded tonic spasm without spike activity. Oxytocin (0.2 nM) produced a small increase in 45Ca2+ influx into myometrium as assessed by the 'lanthanum method'. Higher concentrations of oxytocin (2 and 20 nM) did not increase 45Ca2+ influx. It is concluded that the phasic component of the response of the uterus to oxytocin and bradykinin is associated with Ca2+ influx via voltage-dependent Ca2+ channels. The tonic component is due to another mechanism(s) which does not appear to involve Ca2+ influx. All of the spasmogenic response to KCl can be explained by Ca2+ influx through voltage-dependent Ca2+ channels. These channels do not appear to be involved in the spasmogenic response to acetylcholine.
Topics: Acetylcholine; Animals; Bradykinin; Diltiazem; Drug Resistance; Female; Lanthanum; Oxytocin; Potassium Chloride; Pregnancy; Rats; Rats, Inbred Strains; Uterine Contraction; Uterus
PubMed: 3742162
DOI: 10.1111/j.1476-5381.1986.tb16264.x -
British Heart Journal Jan 1985The antianginal effects of diltiazem 180 mg/day and propranolol 240 mg/day, alone and in combination, were investigated in 15 patients with effort related angina in a... (Clinical Trial)
Clinical Trial Comparative Study
The antianginal effects of diltiazem 180 mg/day and propranolol 240 mg/day, alone and in combination, were investigated in 15 patients with effort related angina in a double blind placebo controlled crossover trial, with each period of treatment lasting four weeks. Patients performed a symptom limited treadmill exercise test at the end of each period of treatment. Mean (SEM) time to onset of angina was increased from 293(32) s when receiving placebo to 347(38) s when receiving diltiazem alone, to 350(30) s when receiving propranolol alone, and further to 421(34) s when receiving diltiazem and propranolol combined. Similar changes occurred in the duration of exercise testing and time to 1 mm ST segment depression. The sum of ST segment depression at peak exercise was reduced by both diltiazem and propranolol alone compared with placebo, and combination treatment produced a further significant improvement. Rate pressure product was significantly reduced at rest and at peak exercise after propranolol alone and combination treatment. The study clearly showed the superior value of diltiazem and propranolol combined in effort related angina when compared with either drug used alone.
Topics: Aged; Angina Pectoris; Benzazepines; Clinical Trials as Topic; Diltiazem; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Humans; Male; Middle Aged; Propranolol
PubMed: 3881104
DOI: 10.1136/hrt.53.1.43