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Background: In silico modeling could soon become a common method of pro-arrhythmic risk assessment in drug research. Each drug simulation was repeated with two separate IC50 datasets, as well as a recently released state-dependent model of hERG and a recently released state-dependent model of hERG and hERG block to determine the impact of variability in IC50 measurements and the effects of including state-dependent drug binding dynamics. Conclusions: Dofetilide and sotalol results for experimental and simulations for specific compounds showed good agreement between experimental and simulations for specific compounds, but more research is needed to investigate the more complex electrophysiological effects of these multichannel blocking drugs.
Source link: https://doi.org/10.3389/fphys.2017.00597
The short QT syndrome is a rare cardiac disorder that can cause arrhythmias and sudden death. The rapid response corrected rectifier current, IKr, was under SQTS version 1, in which treatment with Na+ and K+ anti-arrhythmic agents has demonstrated some success. On action potential and multicellular tissue models, simulations of multi-channel block by disopyramide and quinidine, which include binding kinetics and altered potency of the IKr/hERG channel block in SQT1 and state-dependent block of sodium channels, were demonstrated. This computational modeling report provides new insight into the clinical efficacy of disopyramide and quinidine in the case of SQT1; it also deconstructs the underlying ionic mechanisms that underpin QT and ERP prolongation. Both drugs have proved efficacy in halting the SQT1 phenotype, according to our findings, disopyramide, as an alternative to quinidine in the treatment of SQT1, warrants further investigation as an alternative to quinidine.
Source link: https://doi.org/10.3389/fphys.2017.00759
Short QT syndrome is an inherited disorder that causes abnormally short QT intervals and an elevated incidence of atrial and ventricular arrhythmias. ten Tusscher et al. (2000) The ten Tusscher et al. investigated the potential effects of E-4031, disopyramide, and quinidine on SQT1's ventricular electrophysiology using a mathematical model of human ventricular electrophysiology. Based on experimental results of the kinetics of the human ventricular action potential of the N588K mutation of the IKr channels' KCNH2-encoded subunit of the IKr channels, a more comprehensive model of the human ventricular action potential was updated to include IKr Markov chain formulations based on experimental results of the human ventricular action potential's kinetics. The drugs' channel-blocking effect in healthy and SQT1 cells was predicted using half-maximal inhibitory concentrations and Hill coefficient values from literatures. The effects of drugs on cell AP duration, the common refractory period, and pseudo-ECG traces were determined. The drugs E-4031 and disopyramide had no effect on the ventricular cell APD at 90% repolarization, compared to quinidine, which caused significant delay in APD90 at the single cell level. Quinidine prolonged and reduced maximal transmural AP heterogeneity, contributing to APD's decreased transmural heterogeneity across the 1D strand's reduced transmural heterogeneity. Quinidine exhibited significantly higher therapeutic results on SQT1 than E-4031 and disopyramide, according to the simulated pharmacological effects on SQT1, rather than E-4031 and disopyramide. This research substantiates a causal link between quinidine and QT interval prolongation in SQT1 and QT1 extension, indicating that quinidine may be a potential pharmacologic agent for treating SQT1 patients.
Source link: https://doi.org/10.1371/journal.pone.0179515
We discuss the clinical characteristics of two south Indian children with KCNT1-related epileptic encephalopathy. In these children, the Pharmacological reaction to quinidine is described. Case 1 had a 30% decrease in seizure burden at 20 mg/kg/day and an 80 percent decrease at 36 mg/kg/day, with a 30 percent reduction at 20 mg/kg/day; case 2 had 30 percent less at 20 mg/kg/day and an 80 percent decrease at 20 mg/kg/day; case 2 had 30 percent less at 20 mg/kg/day and 80% reduction at 20 mg/kg/day; and 80% less at 30 mg/kg/day; case 2 had 30 percent at 20 mg/day and 80 percent and 80 mg/day and a reduce at 30 mg/day and 80% reduction at 36 mg/day; and 80% reduction at 30 mg/kg/day; case 2 had 30 mg/day; 80% reduction at 20 mg/kg/day at 20 mg/kg/day at 20 mg/kg/day; 80% at 20 mg/kg/day; 20 mg/kg/kg/kg/kg/day; 30 mg/kg/day; and 80% reduction at 20 mg/kg/kg/day; With quinidine, a critical review of the current status of targeted treatment of KCNT1-related epileptic encephalopathies is attempted.
Source link: https://doi.org/10.4103/aian.AIAN_229_18
For more than four decades, Cinchona bark has been used as an antimalarial treatment. Quinine was first isolated in 1820 and is still active in the treatment of chloroquine-resistant falciparum malaria in lower doses; in lower doses, quinine has been used as a treatment for leg cramps since the 1940s. Here we discuss the effects of the quinoline derivatives quinine, quinidine, and chloroquine's effects on human adult and fetal muscle nicotinic acetylcholine receptors. The present findings add to the pharmacological characterization of muscle cramps and reveal that quinine is safe at therapeutic blood concentrations required for the treatment and prophylaxis of nocturnal leg cramps, indicating that the clinically proven efficacy of quinine could be based on targeting nAChRs.
Source link: https://doi.org/10.3389/fphar.2018.01339
The quinidine component of DM/Q inhibits dextromethorphan's metabolic conversion of dextromethorphan to its active metabolite dextrorphan, boosting dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug rather than the adverse effects of the dextrorphan metabolite. However, because dextrorphan and quinidine concentrations are lower than those used in clinical trials with these drugs administered alone, some of the reported safety issues may not be relevant with this low dose combination drug. Patients with PBA have a variety of health problems and are on many other drugs, so they may not be able to tolerate DM/Q adverse effects, or may be at risk of drug interactions. DM/Q therapy should be started with caution in patients with underlying risk factors for torsade de pointes and those taking drugs that may interact with DM/Q.
ABSTRACT: Epilepsy of infants with migrating focal seizures is a crippling pediatric neurologic disorder that often results in medication-resistant seizure activity and developmental delay. We cover the case of an infant with 2 KCNT1 mutations who died of minor relief with quinidine and explore the drug's important link to phenobarbital.
Source link: https://doi.org/10.1016/j.curtheres.2019.02.002
To overcome these difficulties, we have created a computerized version of the isolated perfused rat small intestine, in which all of these signs can be investigated simultaneously. PAF's vascular bolus brought thromboxane and peptidoleukotrienes from the vain and lymphatic bed, intestinal edema formation, loss of intestinal peregrination, and reduced galactose uptake. PAF's effects were knocked out by PAF-receptor antagonist ABT491's PAF-receptor antagonist ABT491. The COX and LOX inhibitors ASA and AA861 did not have barrier-protective properties, and the eicosanoid rivals SQ29548 and MK571 only moderately attenuated the absence of vascular fluid, the redistribution of the lumen, and the transfer of FITC dextran to the lumen. The therapeutic use of quinidine for intestinal disorders needs to be investigated further.
Source link: https://doi.org/10.1371/journal.pone.0120802
Conclusions: Amiodarone and quinidine orally administered to each rat and decreased eliglustat secretivity in the rats determined by our UPLC-MS/MS method, raising the main pharmacokinetic parameters of eliglustration significantly and reducing clearance rapidly.
In patients with Brugada Syndrome, the use of an implantable cardiac defibrillator has been promoted as the only safe therapy for ventricular fibrillation management. A problematic problem in this patient population is intermittent, recalcitrant VF for which lifesaving cardioversion occurs. Quinidine is well-known in Brist as a reliable antiarrhythmic, though isoproterenol has gained some traction as well. Thus, further prospective studies should be conducted to determine the success of quinidine and ISP in this patient population for prophylactic management and long-term reduction of VF in BrS.
Source link: https://doi.org/10.1155/2015/753537
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