Quinidine. Medical search

Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood.Procainamide: A class Ia antiarrhythmic drug that is structurally-related to PROCAINE.Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.Cytochrome P-450 CYP2D6: A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population.Disopyramide: A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.Cinchona Alkaloids: Alkaloids extracted from various species of Cinchona.Dextromethorphan: Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity.Oxidoreductases, O-Demethylating: Drug metabolizing enzymes which oxidize methyl ethers. Usually found in liver microsomes.Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.Sparteine: A quinolizidine alkaloid isolated from several FABACEAE including LUPINUS; SPARTIUM; and CYTISUS. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest as an indicator of CYP2D6 genotype.Debrisoquin: An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.Pseudobulbar Palsy: A syndrome characterized by DYSARTHRIA, dysphagia, dysphonia, impairment of voluntary movements of tongue and facial muscles, and emotional lability. This condition is caused by diseases that affect the motor fibers that travel from the cerebral cortex to the lower BRAIN STEM (i.e., corticobulbar tracts); including MULTIPLE SCLEROSIS; MOTOR NEURON DISEASE; and CEREBROVASCULAR DISORDERS. (From Adams et al., Principles of Neurology, 6th ed, p489)Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Cinchona: A genus of rubiaceous South American trees that yields the toxic CINCHONA ALKALOIDS from their bark; QUININE; QUINIDINE; chinconine, cinchonidine and others are used to treat MALARIA and CARDIAC ARRHYTHMIAS.Dictionaries, Medical Dictionaries as Topic: Lists of words, usually in alphabetical order, giving information about form, pronunciation, etymology, grammar, and meaning.Dictionaries, Chemical Arrhythmias, Cardiac: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.Malaria: A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.Tablets: Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed)Biological Availability: The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Orosomucoid Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.Drug Labeling: Use of written, printed, or graphic materials upon or accompanying a drug container or wrapper. It includes contents, indications, effects, dosages, routes, methods, frequency and duration of administration, warnings, hazards, contraindications, side effects, precautions, and other relevant information.Drug Repositioning: The deliberate and methodical practice of finding new applications for existing drugs.Product Labeling: Use of written, printed, or graphic materials upon or accompanying a product or its container or wrapper. It includes purpose, effect, description, directions, hazards, warnings, and other relevant information.United States Food and Drug Administration: An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc.Prescription Drugs: Drugs that cannot be sold legally without a prescription.Search Engine: Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.Tachycardia, Supraventricular: A generic expression for any tachycardia that originates above the BUNDLE OF HIS.Wolff-Parkinson-White Syndrome: A form of ventricular pre-excitation characterized by a short PR interval and a long QRS interval with a delta wave. In this syndrome, atrial impulses are abnormally conducted to the HEART VENTRICLES via an ACCESSORY CONDUCTING PATHWAY that is located between the wall of the right or left atria and the ventricles, also known as a BUNDLE OF KENT. The inherited form can be caused by mutation of PRKAG2 gene encoding a gamma-2 regulatory subunit of AMP-activated protein kinase.Tachycardia, Paroxysmal: Abnormally rapid heartbeats with sudden onset and cessation.Tachycardia, Atrioventricular Nodal Reentry: Abnormally rapid heartbeats caused by reentry of atrial impulse into the dual (fast and slow) pathways of ATRIOVENTRICULAR NODE. The common type involves a blocked atrial impulse in the slow pathway which reenters the fast pathway in a retrograde direction and simultaneously conducts to the atria and the ventricles leading to rapid HEART RATE of 150-250 beats per minute.Atrial Flutter: Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DC-shock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias.Formularies as Topic: Works about lists of drugs or collections of recipes, formulas, and prescriptions for the compounding of medicinal preparations. Formularies differ from PHARMACOPOEIAS in that they are less complete, lacking full descriptions of the drugs, their formulations, analytic composition, chemical properties, etc. In hospitals, formularies list all drugs commonly stocked in the hospital pharmacy.Economics, Pharmaceutical: Economic aspects of the fields of pharmacy and pharmacology as they apply to the development and study of medical economics in rational drug therapy and the impact of pharmaceuticals on the cost of medical care. Pharmaceutical economics also includes the economic considerations of the pharmaceutical care delivery system and in drug prescribing, particularly of cost-benefit values. (From J Res Pharm Econ 1989;1(1); PharmacoEcon 1992;1(1))Drug Industry: That segment of commercial enterprise devoted to the design, development, and manufacture of chemical products for use in the diagnosis and treatment of disease, disability, or other dysfunction, or to improve function.Academies and Institutes: Organizations representing specialized fields which are accepted as authoritative; may be non-governmental, university or an independent research organization, e.g., National Academy of Sciences, Brookings Institution, etc.Security Measures: Regulations to assure protection of property and equipment.Legislation, Food: Laws and regulations concerned with industrial processing and marketing of foods.Library Services: Services offered to the library user. They include reference and circulation.Libraries, Medical Injections: Introduction of substances into the body using a needle and syringe.Heart Diseases: Pathological conditions involving the HEART including its structural and functional abnormalities.Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)Malaria, Falciparum: Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.Heart: The hollow, muscular organ that maintains the circulation of the blood.

Transport of fluid by lens epithelium. (1/618)

We report for the first time that cultured lens epithelial cell layers and rabbit lenses in vitro transport fluid. Layers of the alphaTN4 mouse cell line and bovine cell cultures were grown to confluence on permeable membrane inserts. Fluid movement across cultured layers and excised rabbit lenses was determined by volume clamp (37 degrees C). Cultured layers transported fluid from their basal to their apical sides against a pressure head of 3 cmH2O. Rates were (in microliter. h-1. cm-2) 3.3 +/- 0.3 for alphaTN4 cells (n = 27) and 4.7 +/- 1.0 for bovine layers (n = 6). Quinidine, a blocker of K+ channels, and p-chloromercuribenzenesulfonate and HgCl2, inhibitors of aquaporins, inhibited fluid transport. Rabbit lenses transported fluid from their anterior to their posterior sides against a 2.5-cmH2O pressure head at 10.3 +/- 0.62 microliter. h-1. lens-1 (n = 5) and along the same pressure head at 12.5 +/- 1.1 microliter. h-1. lens-1 (n = 6). We calculate that this flow could wash the lens extracellular space by convection about once every 2 h and therefore might contribute to lens homeostasis and transparency. (+info)

Effects of dauricine, quinidine, and sotalol on action potential duration of papillary muscles in vitro. (2/618)

AIM: To compare the characteristics of dauricine, sotalol, and quinidine on action potential duration (APD). METHODS: Using intracellular microelectrode method to record APD in guinea pig papillary muscles. RESULTS: Dauricine 20 mumol.L-1 prolonged action potential at 90% repolarization, the percent of APD prolongation were 22 +/- 8, 11 +/- 6, 9 +/- 5, 7 +/- 5, 6 +/- 3, 4.3 +/- 2.8, 4.5 +/- 2.8 at the cycle lengths of 200-2000 ms, dauricine became more effective in lengthening APD at short cycle lengths. The effect of dauricine on prolonging APD exhibited normal use-dependence, whereas quinidine 1 mumol.L-1 and sotalol 10 mumol.L-1 were less effective in lengthening APD at short cycle lengths. The effect of quinidine and sotalol on APD exhibited reverse use-dependence. CONCLUSSION: The effect of dauricine on APD depends on activation frequency. (+info)

In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes. (3/618)

The aim of this study was to evaluate the (3S)-3-hydroxylation and the N-oxidation of quinidine as biomarkers for cytochrome P-450 (CYP)3A4 activity in human liver microsome preparations. An HPLC method was developed to assay the metabolites (3S)-3-hydroxyquinidine (3-OH-Q) and quinidine N-oxide (Q-N-OX) formed during incubation with microsomes from human liver and from Saccharomyces cerevisiae strains expressing 10 human CYPs. 3-OH-Q formation complied with Michaelis-Menten kinetics (mean values of Vmax and Km: 74.4 nmol/mg/h and 74.2 microM, respectively). Q-N-OX formation followed two-site kinetics with mean values of Vmax, Km and Vmax/Km for the low affinity isozyme of 15.9 nmol/mg/h, 76.1 microM and 0.03 ml/mg/h, respectively. 3-OH-Q and Q-N-OX formations were potently inhibited by ketoconazole, itraconazole, and triacetyloleandomycin. Isozyme specific inhibitors of CYP1A2, -2C9, -2C19, -2D6, and -2E1 did not inhibit 3-OH-Q or Q-N-OX formation, with Ki values comparable with previously reported values. Statistically significant correlations were observed between CYP3A4 content and formations of 3-OH-Q and Q-N-OX in 12 human liver microsome preparations. Studies with yeast-expressed isozymes revealed that only CYP3A4 actively catalyzed the (3S)-3-hydroxylation. CYP3A4 was the most active enzyme in Q-N-OX formation, but CYP2C9 and 2E1 also catalyzed minor proportions of the N-oxidation. In conclusion, our studies demonstrate that only CYP3A4 is actively involved in the formation of 3-OH-Q. Hence, the (3S)-3-hydroxylation of quinidine is a specific probe for CYP3A4 activity in human liver microsome preparations, whereas the N-oxidation of quinidine is a somewhat less specific marker reaction for CYP3A4 activity, because the presence of a low affinity enzyme is demonstrated by different approaches. (+info)

Pseudo second degree atrioventricular block with bradycardia. Successful treatment with quinidine. (4/618)

Pseudo second degree atrioventricular block resulting from blocked His premature beats was successfully treated with quinidine. The diagnosis was proved by His bundle electrogam which showed both blocked and conducted His premature beats. The blocked His prematures produced second degree atrioventricular block by making the atrioventricular junction refractory. Quinidine abolished both conducted and blocked His extrasystoles. There has been no recurrence of arrhythmia during a one-year follow-up. (+info)

Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. (5/618)

In the present study, functional characteristics of organic cation transporter (OCTN)1, which was cloned as the pH-dependent tetraethylammonium (TEA) transporter when expressed in mammalian human embryonic kidney (HEK)293 cells, were further investigated using Xenopus oocytes as well as HEK293 cells as gene expression systems. When OCTN1-derived complementary RNA was injected into Xenopus oocytes, pH-dependent transport of [14C]TEA was observed as the same in HEK293 cells. In contrast, a replacement of sodium ions with potassium ions in the surrounding medium did not cause any change in [14C]TEA uptake in Xenopus oocytes expressed with OCTN1. In addition, when OCTN1 was expressed in HEK293 cells, efflux of TEA from the cells was pH dependent, with an accelerated rate at acidic external medium pH. Accordingly, membrane potential or sodium ions are suggested to have no influence on [14C]TEA transport and the transport activity of OCTN1 is directly affected by pH itself. Furthermore, addition of the unlabeled TEA in external medium enhanced the efflux of preloaded [14C]TEA. These observations suggest that OCTN1 is a pH-dependent and bidirectional TEA transporter. OCTN1-mediated [14C]TEA uptake was inhibited by various organic cations such as cimetidine, procainamide, pyrilamine, quinidine, quinine, and verapamil. In addition, uptakes of cationic compounds such as [3H]pyrilamine, [3H]quinidine, and [3H]verapamil and zwitterionic L-[3H]carnitine were increased by expression of OCTN1 in Xenopus oocytes. Accordingly, OCTN1 was functionally demonstrated to be a multispecific and pH-dependent organic cation transporter, which presumably functions as a proton/organic cation antiporter at the renal apical membrane and other tissues. (+info)

Effects of a novel cardioprotective drug, JTV-519, on membrane currents of guinea pig ventricular myocytes. (6/618)

We investigated effects of a novel cardioprotective drug, JTV-519 (4-[3-(4-benzylpiperidin-1-yl)propionyl]-7-methoxy-2,3,4,5-tetrahy dro-1,4-benzothiazepine monohydrochloride) on membrane currents of guinea pig ventricular myocytes by whole-cell voltage and current clamp methods. The fast Na+ current (iNa) was activated by ramp pulses from various holding potentials of -90, -80 or -60 mV to 10 mV with various intervals. At 0.2 Hz, JTV-519 inhibited iNa in a concentration-dependent manner with an IC50 of approximately 1.2 and 2 microM at the holding potential of -60 and -90 mM, respectively, implicating a voltage-dependent block. Increasing the pulse frequency from 1 to 2 or 3.3 Hz in the presence of 1 microM JTV-519 shortened the time-course and increased the level of iNa block, indicating a frequency-dependent block. The time-course of iNa blocking by JTV-519 was slower than that of lidocaine and similar to that of quinidine. Ca2+ current (iCa) and the inwardly rectifying K+ current (iK1) were also inhibited by JTV-519. JTV-519 decreased the duration and the height of the plateau of the action potential. We conclude that JTV-519 has frequency- and voltage-dependent blocking effects on iNa as well as inhibition of iCa and iK1. (+info)

Alkalinization-induced K+ current of the mouse megakaryocyte. (7/618)

We have recently found that mouse megakaryocytes responded to extracellular alkalinization to pH > 8.0, generating a K+ current under voltage-clamped conditions with the whole cell recording mode of the patch-clamp technique. The purpose of this study was to physiologically and pharmacologically characterize the alkaline-dependent K+ conductance of the megakaryocyte membrane. The alkalinization-induced K+ current (I(ALK)) did not seem to be Ca2+-dependent since I(ALK) was allowed to be generated under intracellularly Ca2+-buffered conditions with 10 mM EGTA, which completely prevented the generation of caffeine-induced Ca2+-activated currents of mouse megakaryocytes; and no [Ca2+]i elevation was evoked by the alkalinization protocol in contrast to a significant increase in [Ca2+]i in response to caffeine when [Ca2+]i was measured with a fura 2 ratiometry. I(ALK) was strongly suppressed with tetraethylammonium (TEA), 4-aminopyridine (4-AP) and streptomycin (SM), but was completely resistant to quinidine (QND). The values of IC50 for the suppression of I(ALK) with TEA, 4-AP and SM were 5.6, 0.47 and 1.5 mM, respectively. Voltage-gated K+ currents (I(K)) of the same megakaryocyte preparation were weakly suppressed with TEA and 4-AP, while they were significantly suppressed with either SM or QND. These results suggest that mouse megakaryocytes possess K+ conductance that was activated by extracellular alkalinization and that probably differs from conventional K+ conductance in its pharmacological properties. (+info)

Enhancing effects of salicylate on tonic and phasic block of Na+ channels by class 1 antiarrhythmic agents in the ventricular myocytes and the guinea pig papillary muscle. (8/618)

OBJECTIVE: To study the interaction between salicylate and class 1 antiarrhythmic agents. METHODS: The effects of salicylate on class 1 antiarrhythmic agent-induced tonic and phasic block of the Na+ current (INa) of ventricular myocytes and the upstroke velocity of the action potential (Vmax) of papillary muscles were examined by both the patch clamp technique and conventional microelectrode techniques. RESULTS: Salicylate enhanced quinidine-induced tonic and phasic block of INa at a holding potential of -100 mV but not at a holding potential of -140 mV; this enhancement was accompanied by a shift of the hinfinity curve in the presence of quinidine in a further hyperpolarized direction, although salicylate alone did not affect INa. Salicylate enhanced the tonic and phasic block of Vmax induced by quinidine, aprindine and disopyramide but had little effect on that induced by procainamide or mexiletine; the enhancing effects were related to the liposolubility of the drugs. CONCLUSIONS: Salicylate enhanced tonic and phasic block of Na+ channels induced by class 1 highly liposoluble antiarrhythmic agents. Based on the modulated receptor hypothesis, it is probable that this enhancement was mediated by an increase in the affinity of Na+ channel blockers with high lipid solubility to the inactivated state channels. (+info)