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Medicine Oct 2023Currently, there is no gold standard for monitoring noxious stimulation during surgery, and the surgical pleth index (SPI) is only one of many monitoring methods. It is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Currently, there is no gold standard for monitoring noxious stimulation during surgery, and the surgical pleth index (SPI) is only one of many monitoring methods. It is commonly used in the monitoring of conventional opiate anesthesia, but its effectiveness in opioid-free anesthesia (OFA) has not been evaluated. Therefore, the aim of this study was to observe the guidance value of the surgical pleth index in opioid-free anesthesia for patients undergoing lower abdominal or pelvic surgery.
METHODS
A total of 122 patients who underwent lower abdominal or pelvic surgery in our hospital between March 2021 and July 2022 were selected and equally divided into OFA (F) and control (C) groups according to the random number table method. Both groups underwent ultrasound-guided unilateral/bilateral quadratus lumborum block in the supine position according to the surgical field. In group F, 0.50% lidocaine and 0.20% ropivacaine (in 20 mL of 0.9% normal saline) were injected on each side. In group C, 20 mL 0.9% normal saline was injected on each side. Group F received general anesthesia without opioids and group C received general anesthesia with opioids. BP, pulse oxygen saturation, PETCO2, reactionentropy, stateentropy, and SPI values; Steward score; dosage of propofol, dexmedetomidine, rocuronium, and diltiazem; extubation time; and awake time were monitored in both groups.
RESULTS
There were no significant differences in the general data between the 2 groups (P > .05). There were no significant differences in SPI values at T0, T1, T2, T3, T4, and T5 or the number of cases requiring additional remifentanil, propofol, and diltiazem between the 2 groups (P > .05). The stateentropy, reactionentropy, and Steward scores were higher in group F than in group C at T4 and T5, while the extubation and awake times were lower in group F than in group C (P < .05). The heart rate and SPI of group F were lower than that of group C at T3 (P < .05).
CONCLUSION
The guiding value of SPI in OFA was similar to its use in opiated anesthesia. Its clinical efficacy is exact, vital signs are stable, enabling rapid, and complete regaining of consciousness.
Topics: Humans; Analgesics, Opioid; Anesthesia, General; Diltiazem; Propofol; Saline Solution
PubMed: 37904423
DOI: 10.1097/MD.0000000000035172 -
Journal of Veterinary Internal Medicine 2009Atrial fibrillation (AF) with excessively high ventricular rates (VR) occurs in dogs with advanced heart disease. Rate control improves clinical signs in these patients.... (Randomized Controlled Trial)
Randomized Controlled Trial
Combination therapy with digoxin and diltiazem controls ventricular rate in chronic atrial fibrillation in dogs better than digoxin or diltiazem monotherapy: a randomized crossover study in 18 dogs.
BACKGROUND
Atrial fibrillation (AF) with excessively high ventricular rates (VR) occurs in dogs with advanced heart disease. Rate control improves clinical signs in these patients. Optimal drug therapy and target VR remain poorly defined.
HYPOTHESIS
Digoxin-diltiazem combination therapy reduces VR more than either drug alone in dogs with high VR AF.
ANIMALS
Eighteen client-owned dogs (>15 kg) with advanced heart disease, AF, and average VR on 24-hour Holter > 140 beats per minute (bpm).
METHODS
After baseline Holter recording, dogs were randomized to digoxin or diltiazem monotherapy, or combination therapy. Repeat Holter evaluation was obtained after 2 weeks; dogs were then crossed over to the other arm (monotherapy or combination therapy) for 2 weeks and a third Holter was acquired. Twenty-four hour average VR, absolute and relative VR changes from baseline, and percent time spent within prespecified VR ranges (>140, 100-140, and <100 bpm) were compared. Correlations between serum drug concentrations and VR were examined.
RESULTS
Digoxin (median, 164 bpm) and diltiazem (median, 158 bpm) decreased VR from baseline (median, 194 bpm) less than the digoxin-diltiazem combination (median, 126 bpm) (P < .008 for each comparison). With digoxin-diltiazem, VR remained <140 bpm for 85% of the recording period, but remained >140 bpm for 88% of the recording period with either monotherapy. Serum drug concentrations did not correlate with VR.
CONCLUSIONS AND CLINICAL IMPORTANCE
At the dosages used in this study, digoxin-diltiazem combination therapy provided a greater rate control than either drug alone in dogs with AF.
Topics: Animals; Atrial Fibrillation; Cardiovascular Agents; Chronic Disease; Cross-Over Studies; Digoxin; Diltiazem; Dog Diseases; Dogs; Drug Therapy, Combination; Heart Rate
PubMed: 19645836
DOI: 10.1111/j.1939-1676.2009.0301.x -
British Journal of Pharmacology Mar 1985The effect of intravenous administration of the calcium-entry blocking drugs, diltiazem and nifedipine, on renal haemodynamic and tubular function was examined in...
The effect of intravenous administration of the calcium-entry blocking drugs, diltiazem and nifedipine, on renal haemodynamic and tubular function was examined in denervated kidneys of pentobarbitone-anaesthetized rats. Infusion of vehicle for the compounds had no effect on renal function which was stable for the duration of the experiments. Diltiazem was infused at 5, 10 and 20 micrograms kg-1 min-1. Blood pressure did not change following 5 micrograms kg-1 min-1 diltiazem but was significantly reduced, by 12 mmHg, after 10 micrograms kg-1 min-1 and by 17 mmHg after 20 micrograms kg-1 min-1. Renal blood flow was not affected by any dose of diltiazem while at the lowest dose of drug, glomerular filtration rate (g.f.r.) was significantly increased, by 24%. Absolute and fractional sodium excretion were increased significantly, 154% and 77% respectively, by 5 micrograms kg-1 min-1 diltiazem, 20% and 24% respectively, by 10 micrograms kg-1 min-1 diltiazem, but were unchanged by 20 micrograms kg-1 min-1. Infusion of nifedipine at 0.5, 1.0 and 2.0 micrograms kg-1 min-1 decreased systemic blood pressure by 9, 9 and 20 mmHg, respectively. Renal blood flow was increased (7%) by 1.0 microgram kg-1 min-1 only, while g.f.r. did not change at any dose. Urine flow, absolute and fractional sodium excretions were increased, 127%, 96% and 90% respectively, by 0.5 microgram kg-1 min-1 nifedipine, 127%, 197% and 194% respectively, by 1.0 microgram kg-1 min-1, while these variables remained unchanged by a dose of 2.0 micrograms kg-1 min-1. 6 These data show that doses on diltiazem and nifedipine, which had little or no effect on blood pressure, had minimal actions on renal haemodynamics. However, at 5 and 10 jig kg-1 min- diltiazem and 0.5 and 1.0 jig kg-' min-' nifedipine these compounds exhibited direct tubular actions, causing both a diuresis and natriuresis, while at the highest dose of each drug these actions were masked by a concomitant reduction in blood pressure.
Topics: Animals; Benzazepines; Blood Pressure; Denervation; Diltiazem; Diuresis; Glomerular Filtration Rate; Hemodynamics; Infusions, Parenteral; Inulin; Kidney; Male; Natriuresis; Nifedipine; Rats; Rats, Inbred Strains; Renal Circulation
PubMed: 3986432
DOI: 10.1111/j.1476-5381.1985.tb16153.x -
Journal of Affective Disorders Sep 2022Improved treatments for bipolar disorder (BD) are needed. Drug repurposing aims to find novel targets for drugs that have been used for other indications. This study... (Observational Study)
Observational Study
BACKGROUND
Improved treatments for bipolar disorder (BD) are needed. Drug repurposing aims to find novel targets for drugs that have been used for other indications. This study investigated the risk of psychiatric hospitalization associated with use of calcium-channel blockers (CCBs; dihydropyridines, diltiazem, verapamil) and adenosine modulators (allopurinol, dipyridamole) in BD in within-individual design.
METHODS
Individuals diagnosed with BD (ICD-10: F30-F31) were identified from the inpatient, specialized outpatient, sickness absence, and disability pension registers during 1996-2018 in Finland (N = 60,045). The main outcome was hospitalization due to affective symptoms (ICD-10: F30-F39). Within-individual models in stratified Cox regression were used and adjusted hazard ratios (aHR) with 95 % confidence intervals (CIs) reported.
RESULTS
Use of CCBs was associated with a decreased risk of hospitalization due to affective symptoms (aHR 0.83, 95 % CI 0.78-0.88) when all CCBs were analyzed together. Of specific CCBs, use of diltiazem (0.71, 0.55-0.91) and dihydropyridines (0.83, 0.78-0.89) were associated with a decreased risk but verapamil was not (0.93, 0.73-1.19). Use of adenosine modulators in general was associated with a decreased risk of hospitalizations due to affective symptoms (0.87, 0.79-0.96). Both allopurinol (0.85, 0.74-0.97) and dipyridamole (0.89, 0.78-1.00) were associated with a marginally decreased risk. Thiazide diuretic use as a negative control was not associated with the risk of hospitalization due to affective symptoms (0.97, 0.83-1.13).
LIMITATIONS
Due to the observational nature of this study, causation cannot be confirmed.
CONCLUSIONS
Dihydropyridines and diltiazem were associated with a decreased risk of psychiatric hospitalization in bipolar disorder. Results for allopurinol and dipyridamole were inconclusive.
Topics: Adenosine; Allopurinol; Bipolar Disorder; Calcium Channel Blockers; Cohort Studies; Dihydropyridines; Diltiazem; Dipyridamole; Humans
PubMed: 35753501
DOI: 10.1016/j.jad.2022.06.040 -
The American Journal of Cardiology Mar 1990The a priori hypothesis that diltiazem would reduce the frequency and repetitiveness of ventricular arrhythmias was tested 3 months after myocardial infarction in... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The a priori hypothesis that diltiazem would reduce the frequency and repetitiveness of ventricular arrhythmias was tested 3 months after myocardial infarction in patients participating in the Multicenter Diltiazem Postinfarction Trial. After 3 months of follow-up, 1,546 of the 2,466 patients enrolled had a 24-hour continuous electrocardiographic recording that contained greater than or equal to 12 hours of analyzable data. They were similar to the patients who survived 3 months but chose not to have a 24-hour electrocardiographic recording (i.e., they were representative of the entire group that survived 3 months). After 3 months of follow-up, there were no significant differences between the diltiazem and placebo groups in the prevalence of atrioventricular block, the frequency of atrial arrhythmias or the frequency or repetitiveness of ventricular arrhythmias. Heart rate was significantly lower (67 +/- 12 vs 71 +/- 12 beats/min) and there was a significantly greater proportion of patients with sinus pauses greater than or equal to 2 seconds in duration in the diltiazem group (6%) than in the placebo group (3%). Comparison with placebo revealed no evidence either for an anti- or proarrhythmic effect of diltiazem. There was no reduction in sudden or arrhythmic death attributable to diltiazem treatment; the fraction of total deaths that were arrhythmic by the Hinkle classification was 41% in the placebo group and 42% in the diltiazem group. It may be that the lack of effect of diltiazem on ventricular arrhythmias is partially responsible for its lack of effect on mortality after myocardial infarction.
Topics: Adult; Aged; Arrhythmias, Cardiac; Diltiazem; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Contraction; Myocardial Infarction; Randomized Controlled Trials as Topic
PubMed: 2178379
DOI: 10.1016/0002-9149(90)91028-5 -
Cell Death & Disease Jan 2022Hereditary degeneration of photoreceptors has been linked to over-activation of Ca-permeable channels, excessive Ca-influx, and downstream activation of Ca-dependent...
Hereditary degeneration of photoreceptors has been linked to over-activation of Ca-permeable channels, excessive Ca-influx, and downstream activation of Ca-dependent calpain-type proteases. Unfortunately, after more than 20 years of pertinent research, unequivocal evidence proving significant and reproducible photoreceptor protection with Ca-channel blockers is still lacking. Here, we show that both D- and L-cis enantiomers of the anti-hypertensive drug diltiazem were very effective at blocking photoreceptor Ca-influx, most probably by blocking the pore of Ca-permeable channels. Yet, unexpectedly, this block neither reduced the activity of calpain-type proteases, nor did it result in photoreceptor protection. Remarkably, application of the L-cis enantiomer of diltiazem even led to a strong increase in photoreceptor cell death. These findings shed doubt on the previously proposed links between Ca and retinal degeneration and are highly relevant for future therapy development as they may serve to refocus research efforts towards alternative, Ca-independent degenerative mechanisms.
Topics: Animals; Calcium; Calcium Channel Blockers; Calcium Channels; Cell Death; Cyclic GMP; Cyclic Nucleotide-Gated Cation Channels; Diltiazem; Ion Channel Gating; Kinetics; Mice; Proteolysis; Retinal Cone Photoreceptor Cells; Retinal Degeneration; Retinal Rod Photoreceptor Cells
PubMed: 35013127
DOI: 10.1038/s41419-021-04482-1 -
Journal of Pharmaceutical and... Jan 2024A number of medical conditions are identified as risk factors for suicide death; in particular, cardiovascular illnesses are recognized as a major suicide risk factor....
A number of medical conditions are identified as risk factors for suicide death; in particular, cardiovascular illnesses are recognized as a major suicide risk factor. In this case, self-poisoning is the common method of suicide and cardiovascular drugs are among the major medications associated with fatal overdose, with calcium channel blockers being one of the most common agents. The present study describes two different fatal suicide cases involving four cardiovascular drugs: carvedilol, doxazosin and amlodipine (case 1) and diltiazem (case 2). The concentrations of the target cardiovascular drugs in the different biological specimens (central and femoral blood, urine, liver, brain) are presented, giving information about the potentially fatal data and the distribution of the drugs in the body. The study led to the implementation of a fast, sensitive and simple method for the detection and quantification of the four commonly prescribed cardiovascular drugs in post-mortem specimens including fluids and tissues for forensic purposes. The method was fully validated. The toxicological results of the studied cases are discussed, along with the autopsy results, histopathological evidence, and circumstances of death. The toxicological findings presented in the study provide new data regarding cardiovascular drugs in different post-mortem specimens, which will contribute to the currently limited knowledge about the toxicological profile of cardiovascular drugs and their distribution.
Topics: Humans; Amlodipine; Diltiazem; Carvedilol; Doxazosin; Cardiovascular Agents; Suicide
PubMed: 37980865
DOI: 10.1016/j.jpba.2023.115831 -
Cardiovascular Therapeutics 2008The purpose of this study was to investigate the effects of resveratrol, an antioxidant, on the pharmacokinetics of diltiazem and its active metabolite,...
The purpose of this study was to investigate the effects of resveratrol, an antioxidant, on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. The pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined after an oral administration of diltiazem (15 mg/kg) to rats in the presence and absence of resveratrol (0.5, 2.5, and 10 mg/kg). Compared to the control group, the presence of resveratrol significantly (P < 0.05) increased the area under the plasma concentration-time curve (AUC) of diltiazem, except for resveratrol 0.5 mg/kg. Consequently, the absolute bioavailability (AB) of diltiazem in the presence of resveratrol (2.5 and 10 mg/kg) was significantly (P < 0.05) higher (10.2-11.1%) than that of the control (6.9%). The relative bioavailability (RB) of diltiazem in the presence of resveratrol (2.5 and 10 mg/kg) was increased by 1.48- to 1.60-fold. Resveratrol did not alter absorption rate constant (K(a)) and the time to reach the peak concentration (T(max)) of diltiazem. The AUC of desacetyldiltiazem was increased significantly (P < 0.05) in the presence of 10 mg/kg of resveratrol. The metabolite-parent AUC ratio (MR) in the presence of resveratrol was decreased but did not show significant change. In conclusion, resveratrol significantly increased the bioavailability of diltiazem due to the inhibition of both the cytochrome P450 (CYP) 3A4-mediated metabolism and the efflux pump P-glycoprotein (P-gp) in the intestine and/or liver. Based on these results, if these results would be confirmed in clinical experiments, the dosage of diltiazem should be readjusted when diltiazem is used concomitantly with resveratrol.
Topics: Administration, Oral; Analysis of Variance; Animals; Antioxidants; Area Under Curve; Biological Availability; Calcium Channel Blockers; Chromatography, High Pressure Liquid; Diltiazem; Dose-Response Relationship, Drug; Drug Interactions; Injections, Intravenous; Male; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes
PubMed: 19035878
DOI: 10.1111/j.1755-5922.2008.00060.x -
European Journal of Pharmacology Sep 2013Accumulating evidence suggests that L-type calcium channel blockers (CCBs) attenuate the expression of opioid withdrawal and the dihydropyridine L-type CCB isradipine... (Randomized Controlled Trial)
Randomized Controlled Trial
Accumulating evidence suggests that L-type calcium channel blockers (CCBs) attenuate the expression of opioid withdrawal and the dihydropyridine L-type CCB isradipine has been shown to block the behavioral effects of naloxone in opioid-maintained humans. This study determined whether two prototypic L-type CCBs with differing chemical structures, the benzothiazepine diltiazem and the phenylalkamine verapamil, attenuate the behavioral effects of naloxone in methadone-maintained humans trained to distinguish between low-dose naloxone (0.15 mg/70 kg, i.m.) and placebo under an instructed novel-response drug discrimination procedure. Once discrimination was acquired, diltiazem (0, 30, 60, 120 mg) and verapamil (0, 30, 60, 120 mg), alone and combined with the training dose of naloxone, were tested. Diltiazem alone produced 33-50% naloxone- and novel-appropriate responding at 30 and 60 mg and essentially placebo-appropriate responding at 120 mg. Verapamil alone produced 20-40% naloxone- and 0% novel-appropriate responding. Diltiazem at 60 mg decreased several ratings associated with positive mood and increased VAS ratings of "Bad Drug Effects" relative to placebo, whereas verapamil increased ratings associated with euphoria. When administered with naloxone, diltiazem produced 94-100% naloxone-appropriate-responding with 6% novel-appropriate responding at 60 mg (n=3). When administered with naloxone, verapamil produced 60-80% naloxone- and 0% novel-appropriate responding (n=5). Diltiazem decreased diastolic blood pressure and heart rate whereas verapamil decreased ratings of arousal relative to placebo. These results suggest that CCBs with different chemical structures can be differentiated behaviorally, and that diltiazem and verapamil do not attenuate the discriminative stimulus effects of naloxone in humans at the doses tested.
Topics: Adult; Calcium Channel Blockers; Calcium Channels, L-Type; Diltiazem; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Self Report; Substance Withdrawal Syndrome; Verapamil
PubMed: 23524089
DOI: 10.1016/j.ejphar.2013.03.007 -
The Primary Care Companion For CNS... Feb 2023
Topics: Humans; Clozapine; Fluoxetine; Diltiazem; Antipsychotic Agents; Drug Interactions
PubMed: 36763815
DOI: 10.4088/PCC.22cr03288