Quinine bisulfate

746.91

746.33500

208-970-9

667852|10004|5362

Occurs as fine, needle-like, white crystals which frequently cohere in masses or as a fine, white powder.

174.16000

6.65020

1136.7ºC at 760mmHg

641.2ºC

INDEX OF REFRACTION ALPHA 1.565; BETA 1.607; GAMMA 1.670. OPTIC SIGN +, EXTINCTION PARALLEL, ELONGATION +

Slightly sol in water and soluble in alcohol.

Very bitter taste

ODORLESS; VERY BITTER TASTE; SOLN ARE NEUTRAL OR ALKALINE TO LITMUS|Rods; soluble in 8 parts water with blue fluorescence. /Quinidine acid sulfate tetrahydrate/

III

6.1(b)

1544

PROTECT FROM LIGHT; DARKENS ON EXPOSURE TO LIGHT /DIHYDRATE/

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl quinidine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act.

Anderson JL; Clinical implications of New Studies in the Treatment of Benign, Potentially Malignant and Malignant Ventricular Arrhythmias. Am J Cardiol 65 (4): 36B-42B (1990). For purposes of clinical management, ventricular arrhythmias have been divided into risk categories of benign, prognostically important (potentially malignant) and malignant. For malignant arrhythmias, class IA agents (procainamide and quinidine) continue to be the standard of treatment. /Quinidine/|Kim SY, Benowitz NL; Poisoning Due to Class IA Antiarrhythmic Drugs: Quinidine, Procainamide and Disopyramide. Drug Saf 5 (Nov-Dec): 393-420 (1990). A review of poisoning due to quinidine is presented, including the mechanism of toxicity, clinical features, pharmacokinetics, drug interactions, and clinical management with sodium bicarbonate and potassium and accelerated drug removal with dialysis. /Quinidine/|Kirchbaum DW; Combination Drug Therapy for Ventricular Arrhythmias. Clin Pharm 7(Nov): 808-19 (1988). The use of combined therapy with antiarrhythmic agents in patients with ventricular arrhythmias in whom single drug therapy has been ineffective or poorly tolerated is reviewed. Pairs of drugs showing the most promise have been a class IA drug (procainamide, quinidine or disopyramide) with a class IB drug (usually mexiletine) or a class IA drug with a beta blocker. /Quinidine/|Knobler H et al; Quinidine Induced Hepatitis: Common and Reversible Hypersensitivity Reaction. Arch Intern Med 146 (Mar): 526-8 (1986). A review of 33 cases of hepatitis attributed to quinidine occurring over a 10 yr period at one hospital was presented. Clinical and histological features of the syndrome were described. A hypersensitivity mechanism was suggested for the reaction. /Quinidine/|Huang SK, Marcus FI; Antiarrhythmic Drug Therapy of Ventricular Arrhythmias. Curr Probl Cardiol 11 (4): 177-240 (1986). Congestive heart failure is associated with hypoperfusion to various organs including the sites of drug clearance, ie the liver and kidneys. It also leads to organ congestion as seen in the liver and gut. Not all adverse reactions to drugs that may occur in heart failure are the result of alterations in pharmacokinetics; rather, some may be due to important drug interactions. An interaction may occur directly eg reduction of renal clearance of digoxin by captopril and quinidine; or indirectly, eg through diuretic induced hypokalemia, which exacerbate arrhythmias associated with digoxin and antiarrhythmics such as quinidine and procainamide. /Quinidine/

|Danger|H315 (98.45%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P272, P280, P285, P302+P352, P304+P340, P304+P341, P305+P351+P338, P312, P321, P332+P313, P333+P313, P337+P313, P342+P311, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 129 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H302 (11.11%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 45 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P272, P280, P301+P312, P302+P352, P321, P330, P333+P313, P363, and P501

IDENTIFICATION: Quinidine is a class lA antiarrhythmic drug. Origin of the substance: Quinidine is the d- isomer of quinine. Quinidine is an alkaloid that may be derived from various species of Cinchona. Cinchona barks contain 0.25 to 3.0% quinidine. Quinidine is also prepared from quinine. Quinidine is a powder or white crystals, odorless with a bitter taste. Quinidine bisulfate is colorless crystals which is odorless and has a bitter taste. Quinidine gluconate is a white powder which is odorless and has a bitter taste. Quinidine poly-galacturonate is a powder. Quinidine sulfate is a white powder or odorless crystals with a bitter taste. Indications: Description: Premature ventricular extrasystoles and ventricular tachycardia; supraventricular arrhythmia; maintenance of sinus rhythm after cardioversion of atrial flutter or fibrillation. HUMAN EXPOSURE: Main risks and target organs: Cardio-toxicity is the main risk of quinidine poisoning. Quinidine may induce central nervous system symptoms. Summary of clinical effects: Toxic effects appear within 2 - 4 hours after ingestion but the delay may vary according to the quinidine salt and to the preparation forms. Symptoms may include disturbances of cardiac rhythm (especially in patients with underlying cardiovascular disease), neurotoxicity and respiratory depression. Diagnosis: Cardiac disturbances: circulatory arrest, shock, conduction disturbances, ventricular arrhythmias, ECG changes, Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsions, delirium. Respiratory depression. Quinidine concentrations may be helpful in diagnosis but are not useful for clinical management. Contraindications: Allergy or idiosyncrasy to cinchona alkaloids; atrioventricular or complete heart block; intraventricular conduction defects; absence of atrial activity; digitalis intoxication; myasthenia gravis and ventricular dysrhythmia of the torsades de pointes type Precautions include the following: Congestive heart failure, hypotension, renal disease, hepatic failure; concurrent use of other antiarhythmic drugs; old age and breast-feeding. Routes of entry: Oral: Oral absorption is the most frequent cause of intoxication. Parenteral: Intoxication after IV administration is rare but has been reported in patients treated with IV quinidine for cardiac dysrhythmia. Absorption by route of exposure: Oral: Quinidine is almost completely absorbed from the gastrointestinal tract. However, because of hepatic first-pass effect, the absolute bioavailability is about 70 to 80% of the ingested dose and may vary between patients and preparations. The time to plasma peak concentration is 1 to 3 hours for quinidine sulfate, 3 to 6 hours for quinidine gluconate and about 6 hours for quinidine polygalacturonate. Sustained-release quinidine is absorbed continuously over 8 to 12 hours. Parenteral: Absorption of quinidine after intramuscular injection may be erratic and unpredictable with incomplete absorption of the administered dose, probably due to precipitation of drug at the site of injection. Other studies indicate no difference between the rate of quinidine absorption when given by intramuscular injection or oral absorption. Distribution by route of exposure: Oral: Protein binding: About 70 to 80% of the drug is bound to plasma protein. Plasma protein binding is decreased in patients with chronic liver disease. Tissue: Quinidine concentrations in liver are 10 to 30 times higher than those in plasma. Skeletal and cardiac muscle, brain and other tissues contain intermediate amounts. The red cell plasma partition ratio is 0.82. Biological half-life by route of exposure: Elimination half-life: The half-life is about 6 to 7 hours. It is increased in chronic liver disease and in the elderly. It does not appear to be altered in congestive heart failure or renal failure. Metabolism: 50 to 90% of quinidine is metabolized in the liver to hydroxylated products. Metabolites include 3-hydroxyquinidine, 2 oxoquinidinone, 0-desmethylquinidine, quinidine-N-oxide. The principal metabolite is 3 hydroxyquinidine which exerts similar effects to quinidine and may account for part of the observed antiarrhythmic effects. The elimination kinetics of hydroxyquinidine appear to be similar to those of quinidine. Elimination by route of exposure Kidney: The amount excreted unchanged in urine is variable but is about 17% of an administered dose. Up to 50% of a dose of quinidine (unchanged + metabolites) is excreted in urine within 24 hours after administration. Renal excretion is dependent upon the pH of the urine. Excretion varies inversely with urine pH. Excretion is reduced in renal insufficiency and in congestive heart failure. Liver: 50 to 90% of a dose of quinidine is metabolized in the liver. Bile: Approximately 1 to 3% is excreted in the feces via the bile. Breast milk: Quinidine is excreted in breast milk. Mode of action Toxicodynamics: Quinidine reduces the permeability of heart muscle to electrolytes (membrane stabilizer) and is a general cardiac depressant. It has a negative inotropic effect; inhibits the spontaneous diastolic depolarization; slow conduction; lengthens the effective refractory period; and raises the electrical threshold. This results in depression of contractility, impaired conductivity (atrioventricular and intraventricular) and decreased excitability but with possible abnormal stimulus re-entry mechanism. Quinidine has an anticholinergic effect and peripheral vasodilator properties. In experimental studies the following progression changes was observed: ECG: bradycardia, prolongation of the PR interval, lengthening of the QT interval, widening of the QRS with development of an idioventricular rhythm and then in ventricular standstill. Sometimes the terminal event was ventricular fibrillation. Blood pressure decreases progressively. A significant decrease of blood pressure was noted with the appearance of QRS widening and blood pressure was close to zero when slow idioventricular rhythm appeared. Electrolytes abnormalities: decrease in plasma concentrations of potassium, sodium and magnesium with the development of acidosis. Electrolytes: Hypokalaemia may occur and is probably related to an intracellular transport of potassium by a direct effect on cellular membrane permeability. Neurologic symptoms: Syncope and convulsions may represent a direct toxic effect on CNS or may be related to cerebral ischaemia due to circulatory or respiratory failure. Pharmacodynamics: Quinidine slows the rate of firing of the normal and of ectopic rhythmic foci; it raises the threshold for electrically induced arrhythmias; it protects against ventricular arrhythmias; and it prevents or terminates circus movement flutter. Teratogenicity: Quinidine has been implicated as a cause of light cranial nerve damage to the fetus at doses much larger than those needed to treat arrhythmias. Interactions: Several interactions have been reported. Quinidine has a synergistic action with warfarin (decrease of prothrombin level). Quinidine potentiates both non-depolarizing and depolarizing neuromuscular blocking agents. The cardiodepressant effects of other antiarrhythmic agents are increased by concurrent use of quinidine; amiodarone increases quinidine concentrations in the blood. Quinidine concentrations are reduced by: rifampicin, anticonvulsants, nifedipine and acetazolamide. Quinidine concentrations are increased by antacids, cimetidine, verapamil and amiodarone; the risk of quinidine toxicity is increased by terfenadine, astemizole, and thiazide and loop diuretics. Quinidine increases the plasma concentrations of propafenone and digoxin. Main adverse effects: Numerous adverse effects during quinidine therapy have been reported. Cardiovascular: Hypotension after IV administration; Syncope; proarrhythmic effect: "torsades de pointes"; and ECG: widening of QRS interval; prolongation of PR and QT intervals. CNS: Cinchonism: headache, fever, visual disturbances, mydriasis, tinnitus, nausea, vomiting and rashes. Gastrointestinal: Nausea, vomiting, diarrhoea, colic have been reported. Hepatic: Granulomatous hepatitis or hepatitis with centrilobular necrosis. Skin: Skin rashes with drug fever and photosensitivity may result. Hematologic: Thrombocytopenia (immunologic reaction) has been noted. Clinical effects: Acute poisoning: Ingestion: Severity of quinidine poisoning is related to the cardiotoxic effects. Symptoms appear usually within 2 to 4 hours and may include: cardiovascular symptoms: hypotension, cardiogenic shock, cardiac arrest. ECG may show: decrease of T wave; prolongation of QT and QRS intervals; atrioventricular block; ventricular dysrhythmia (torsade de pointes). Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsion, blurred vision and diplopia. Respiratory symptoms: hypoventilation and apnea. Cardiotoxicity may be enhanced if other cardiotoxic drugs have been ingested (antiarrhythmic drugs, tricyclic antidepressants). Parenteral exposure: After IV administration symptoms appear more rapidly. Chronic poisoning: Ingestion: The most relevant symptoms of chronic poisoning are: ECG disturbances; syncope due to ventricular dysrhythmia, (torsade de pointes) and cinchonism gastrointestinal disturbances Course, prognosis, cause of death: The usual course of quinidine poisoning is dominated by the cardiovascular disturbances which usually occur within 2 to 4 first hours but may first appear as late as 12 hours after exposure (and perhaps even later after ingestion of a slow- release preparation). Symptoms may last for 24 to 36 hours. Patients who survive 48 hours after acute poisoning are likely to recover. Death may result from cardiac arrest by asystole or electromechanical dissociation and, rarely, by ventricular fibrillation. Systematic description of clinical effects: Cardiovascular: Acute: Cardiovascular symptoms are the major features of quinidine toxicity. Tachycardia due to anticholinergic effects is usually observed initially or in moderate intoxication. In severe intoxication, bradycardia due to atrioventricular block may occur. Hypotension and shock: hypotension due to peripheral vasodilation is common. In severe intoxication, cardiogenic shock with increased central venous pressure is usually observed and is related to decreased cardiac contractility. Cardiac arrest may occur, which may be related to electromechanical dissociation, ventricular dysrhythmia or asystole. Cardiac dysrhythmias are common and may include: atrioventricular block, idioventricular rhythm, ventricular tachycardia and fibrillation, torsades de pointes. ECG changes are always present in symptomatic intoxication: repolarization abnormalities, decreased T wave, increase of U wave, prolongation of QT and PR intervals, widening of QRS complexes (> 0.08 sec), atrioventricular block. Syncope due to torsade de pointes may occur. Chronic: ECG changes with repolarization abnormalities, decreased T wave and increase of QT interval are a common feature during quinidine therapy. Syncope is related to transient torsade de pointes and occurs in 1 to 8% of patients receiving quinidine. The occurrence of torsade de pointes is not correlated with plasma quinidine levels but is favored by an increase in the QT interval. Respiratory: Acute: Respiratory depression or apnea is mostly associated with severe cardiac disturbances such as shock or ventricular dysrhythmia. Pulmonary edema with normal pulmonary capillary wedge pressure following an attempted suicide has been documented. Neurological: CNS: Acute: Drowsiness, delirium, coma and convulsions may appear without cardiac symptoms. However, cardiac failure should always be considered when CNS symptoms appear. Cinchonism may sometimes appear. Chronic: Cinchonism. Delirium has been reported. Peripheral nervous system: Chronic: Quinidine can potentiate the neuromuscular blocking action of some skeletal muscle relaxants and may cause the return of respiratory paralysis if it is given shortly after recovery from neuromuscular blockade. Autonomic nervous system: Acute: Quinidine has an anticholinergic effect. However, this effect is usually limited to the vagal system. Skeletal and smooth muscle: Chronic: An increase in serum concentrations of skeletal muscle enzymes has been reported in a man treated with quinidine. Gastrointestinal: Acute: Nausea and vomiting may occur. Chronic: Gastrointestinal toxicity (nausea, vomiting, diarrhea and colic) is the most frequent side effect of quinidine. Hepatic: Chronic: Hepatotoxicity has been reported, with an increase in serum concentrations of transaminases, LDH, alkaline phosphatase, and cholestasis. Renal: Acute: No direct nephrotoxic effect has been reported. Acute renal failure related to cardiogenic shock may occur. Dermatological: Chronic: Skin lesions have been attributed to the use of quinidine and include skin rash, photosensitivity and lichen planus. Eye, ear, nose, throat: local effects: Acute: Cinchonism is rarely observed in acute poisonings. Toxic amblyopia, scotoma and impaired color perception may occur at toxic doses. Chronic: Chronic cumulative overdose may cause cinchonism: headache, tinnitus, vertigo, mydriasis, blurred vision, diplopia, photophobia, deafness, and corneal deposits have been reported in a patient who took quinidine for two years. Hematological: Chronic: Thrombocytopenia and hemolytic anemia of immunologic origins have been reported. Immunological: Chronic: Quinidine may cause several immunologic mediated reactions: thrombocytopenia, hemolytic anemia, angioneurotic edema, skin rash, fever. Metabolic: Acid-base disturbances: Acute: Metabolic acidosis may occur in severe intoxication with shock. Fluid and electrolyte disturbances: Acute: Hypokalemia is frequently observed. Special risks: Pregnancy: Chronic: Quinidine has been implicated as a cause of cranial nerve damage to the fetus at doses much larger than those needed to treat arrhythmia. In a neonate born to a woman taking quinidine throughout pregnancy, serum levels were equal to that of the mother. The child's ECG was normal and there was no evidence of teratogenicity. Breast-feeding: Chronic: Quinidine is present in breast milk at levels slightly lower than serum levels. The dose of quinidine received by an infant taking 1l of milk would be below therapeutic doses. However, breast-feeding is not recommended because of potential quinidine accumulation in the immature newborn liver. /Quinidine/

THE ADMIN OF QUINIDINE RESULTS IN AN INCREASE IN THE PLASMA CONCN OF THE GLYCOSIDE IN OVER 90% OF DIGITALIZED PATIENTS. THE DEGREE OF CHANGE IS PROPORTIONAL TO THE DOSE OF QUINIDINE; THE AVERAGE CHANGE IS ABOUT TWO-FOLD. ... THE INITIAL EFFECT OF QUINIDINE MAY BE DUE TO THE DISPLACEMENT OF DIGOXIN FROM BINDING SITES IN TISSUES. /QUINIDINE/|DRUGS ... SUCH AS PHENOBARBITAL OR PHENYTOIN ... MAY SIGNIFICANTLY SHORTEN DURATION OF ACTION OF QUINIDINE BY INCR RATE OF ELIMINATION. ... NITROGLYCERIN CAN CAUSE SEVERE POSTURAL HYPOTENSION IN PATIENTS WHO ARE TAKING QUINIDINE. /QUINIDINE/|QUINIDINE IS WEAK BASE EXCRETED ... BY KIDNEY & ITS BIOLOGICAL HALF-LIFE MAY BE PROLONGED ... IF PH OF URINE IS INCREASED. ... CARBONIC ANHYDRASE INHIBITORS, SODIUM BICARBONATE, & THIAZIDE DIURETICS, ALL OF WHICH INCR URINARY PH MAY SERVE TO INCR LIPID SOLUBILITY & TUBULAR REABSORPTION OF QUINIDINE & THUS PROLONG ITS THERAPEUTIC EFFECT. /QUINIDINE/|QUINIDINE (300 MG), SLOWLY ADMIN IV, CAUSED RETURN OF PARALYSIS INDUCED BY SUCCINYLCHOLINE (40 MG IV). QUINIDINE MAY ENHANCE OR CAUSE A RECURRENCE OF NEUROMUSCULAR EFFECTS OF TUBOCURARINE. /QUINIDINE/|For more Interactions (Complete) data for QUINIDINE SULFATE (30 total), please visit the HSDB record page.

Quinidine should be used with extreme caution, if at all, in patients with incomplete atrioventricular nodal block, since complete heart block and asystole may result. IM or iv administration of quinidine is especially hazardous in the presence of atrioventricular block, in the absence of atrial activity, and the patients with extensive myocardial injury. Hypokalemia, hypoxia, and disorders of acid base balance must be eliminated as potentiating factors in patients who require large doses of antiarrhythmic agents to control ventricular arrhythmias.|Quinidine should be used with extreme caution in patients with cardiac glycoside intoxication, since cardiac glycoside intoxication may cause serious impairment of cardiac conduction and produce arrhythmias which may contraindicate use of quinidine. Conversely, quinidine may cause unpredictable, abnormal rhythms and decreased contractility in the presence of cardiac glycoside intoxication.|Since quinidine-induced decreases in cardiac contractility and blood pressure may aggravate congestive heart failure or preexisting hypotension, the drug should be used cautiously, if at all, in patients with these conditions. If hypotension or congestive heart failure is caused or aggravated by an arrhythmia treatable with quinidine, the drug may be useful, but the potential risks and benefits must be considered.|Quinidine should be used with caution in patients with preexisting asthma, muscle weakness, or infection with fever, since hypersensitivity reactions to the drug may be masked. The drug should also be used with caution in patients with hepatic and/or renal (particularly if renal tubular acidosis is present) insufficiency, since systemic accumulation of quinidine potentially may result.|INDIVIDUALS WITH THE LONG Q-T SYNDROME OR THOSE WHO RESPOND TO LOW CONCENTRATIONS OF QUINIDINE WITH MARKED LENGTHENING OF THE Q-T INTERVAL APPEAR TO BE PARTICULARLY AT RISK /OF SYNCOPE OR SUDDEN DEATH/ AND SHOULD NOT BE TREATED WITH THIS DRUG. /QUINIDINE/

Treatment of pseudobulbar affect (uncontrollable laughing and/or crying)

MEDICATION (VET): OF 6 ANTIARRHYTHMICS TESTED, QUINIDINE BISULFATE GAVE NO PROTECTION AGAINST THE INDUCED ARRHYTHMIA IN DOGS.|... IS EFFECTIVE FOR SHORT- AND LONG-TERM TREATMENT OF SUPRAVENTRICULAR AND VENTRICULAR ARRHYTHMIAS. /QUINIDINE/|FOR PRACTICAL PURPOSES, QUINIDINE IS ONLY GIVEN ORALLY, ALTHOUGH IT CAN BE ADMINEITHER IM OR IV UNDER SPECIAL CIRCUMSTANCES. THE USUAL ORAL DOSE OF QUINIDINE SULFATE IS 200 TO 300 MG THREE TO FOUR TIMES A DAY. ... FOR PATIENTS WITH PREMATURE ATRIAL OR VENTRICULAR CONTRACTIONS OR MAINTENANCE THERAPY. HIGHER AND/OR MORE FREQUENT DOSES CAN BE USED FOR LIMITED PERIODS FOR TREATMENT OF PAROXYSMAL VENTRICULAR TACHYCARDIA.|Quinidine is used primarily as prophylactic therapy to maintain normal sinus rhythm after conversion of atrial fibrillation and/or flutter by other methods. The drug is also used to prevent the recurrence of paroxysmal atrial fibrillation, paroxysmal atrial tachycardia, paroxysmal atrioventricular junctional rhythm, paroxysmal ventricular tachycardia, and atrial or ventricular premature contractions.|For more Therapeutic Uses (Complete) data for QUINIDINE SULFATE (7 total), please visit the HSDB record page.

OCCASIONALLY PATIENTS TAKING QUINIDINE EXPERIENCE SYNCOPE OR SUDDEN DEATH. ... MAY BE RESULT OF HIGH CONCENTRATIONS OF QUINIDINE IN PLASMA OR RESULT OF COEXISTING DIGITALIS TOXICITY. /QUINIDINE/|INDIVIDUALS WITH THE LONG Q-T SYNDROME OR THOSE WHO RESPOND TO LOW CONCENTRATIONS OF QUINIDINE WITH MARKED LENGTHENING OF THE Q-T INTERVAL APPEAR TO BE PARTICULARLY AT RISK /OF SYNCOPE OR SUDDEN DEATH/ AND SHOULD NOT BE TREATED WITH THIS DRUG. /QUINIDINE/|EXCESSIVE CONCENTRATION OF DRUG IN PLASMA WILL CAUSE ADVERSE EFFECTS IN ANY PATIENT. BECAUSE QUINIDINE HAS LOW THERAPEUTIC RATIO, CONSTANT VIGILANCE IS THUS REQUIRED IN EVERY PATIENT TAKING THIS DRUG. /QUINIDINE/|Quinidine should be used with extreme caution, if at all, in patients with incomplete atrioventricular nodal block, since complete heart block and asystole may result. Im or iv administration of quinidine is especially hazardous in the presence of atrioventricular block, in the absence of atrial activity, and the patients with extensive myocardial injury. Hypokalemia, hypoxia, and disorders of acid base balance must be eliminated as potentiating factors in patients who require large doses of antiarrhythmic agents to control ventricular arrhythmias.|For more Drug Warnings (Complete) data for QUINIDINE SULFATE (24 total), please visit the HSDB record page.

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)|A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358) (See all compounds classified as Muscle Relaxants, Central.)|A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)|Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. (See all compounds classified as Adrenergic alpha-Antagonists.)|Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)|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. (See all compounds classified as Anti-Arrhythmia Agents.)|Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. (See all compounds classified as Muscarinic Antagonists.)|A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS. (See all compounds classified as Analgesics, Non-Narcotic.)|Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2D6. (See all compounds classified as Cytochrome P-450 CYP2D6 Inhibitors.)

ABOUT 90% OF QUINIDINE IN PLASMA IS BOUND TO PLASMA PROTEINS (ALPHA/ACID GLYCOPROTEIN AND ALBUMIN) THE DRUG ENTERS ERYTHROCYTES & ... BINDS TO HEMOGLOBIN; AT STEADY STATE, CONCN OF QUINIDINE IN PLASMA & ERYTHROCYTES ARE APPROXIMATELY EQUAL. QUINIDINE ACCUMULATES RAPIDLY IN MOST TISSUES EXCEPT BRAIN, & ... VOL OF DISTRIBUTION IS 2-3 L/KG. /QUINIDINE/|METABOLITES AND SOME OF THE PARENT DRUG (20%) ARE EXCRETED IN URINE; ELIMINATION HALF-TIME IS ABOUT 6 HR. /QUINIDINE/|LIVER METABOLISM & RENAL EXCRETION ARE THE MAIN ROUTES OF ELIMINATION. ENTEROHEPATIC CIRCULATION WOULD NOT SIGNIFICANTLY ALTER ABSORPTION KINETICS AS REFLECTED BY BLOOD CONCENTRATION.|PEAK PLASMA CONCN OF 0.29 UG/ML OF QUINIDINE WERE MEASURED @ 4 HR AFTER ADMIN OF SUSTAINED RELEASE CAPSULE (250 MG QUINIDINE BISULFATE) AND DECLINED STEADILY DURING THE NEXT 8 HR, WHILE AFTER ADMIN OF SUSTAINED RELEASE TABLET (300 MG QUINIDINE SULFATE) THEY WERE FAIRLY EVEN DURING 2-10 HR AFTER DOSING. PLASMA CONCENTRATIONS WERE HIGHER AT LATER TIMES FOR THE CAPSULE THAN FOR THE TABLET. THE BIOAVAILABILITY OF QUINIDINE FROM THE CAPSULES DURING 12 HR WAS 184% COMPARED TO THE TABLET. MEAN QUINIDINE PLASMA CONCN WERE SIGNIFICANTLY GREATER @ 3, 4, 6, 8, & 10 HR AFTER ADMIN OF THE CAPSULE THAN AFTER THE TABLET.|For more Absorption, Distribution and Excretion (Complete) data for QUINIDINE SULFATE (24 total), please visit the HSDB record page.

QUINIDINE YIELDS 2'-HYDROXYQUINIDINE AS METABOLITE IN MAN. /QUINIDINE; FROM TABLE/|MOST URINARY METABOLITES ARE HYDROXYLATED AT ONLY ONE SITE, EITHER ON THE QUINOLINE RING OR ON THE QUINUCLIDINE RING; SMALL AMOUNTS OF DIHYDROXY COMPOUNDS ARE ALSO FOUND. THE FRACTION OF A DOSE OF QUINIDINE THAT IS METABOLIZED & THE METABOLIC PATHWAY APPEAR TO VARY CONSIDERABLY FROM PATIENT TO PATIENT.|Quinidine is metabolized in the liver, principally via hydroxylation to 3-hydroxyquinidine and 2-quinidinone. The metabolites may be pharmacologically active. Approximately 10-50% of a dose is excreted in urine (probably by glomerular filtration) as unchanged drug within 24 hr. /Quinidine/

THE ELIMINATION HALF-LIFE OF QUINIDINE RANGES FROM 4 TO 10 HR IN HEALTHY PERSONS, WITH USUAL MEAN VALUE OF 6 TO 7 HR. HALF-LIFE IS SIGNIFICANTLY PROLONGED IN ELDERLY PERSONS, EVEN WHEN THEY ARE APPARENTLY HEALTHY. /QUINIDINE/|... EXCRETED IN URINE; ELIMINATION HALF-TIME IS ABOUT 6 HR. /QUINIDINE/|Quinidine generally has a plasma half-life of 6-8 hr in healthy individuals, but half-life may range from 3-16 hr or longer. In one study in patients with Plasmodium falciparum malaria, the elimination half-life of the drug averaged 12.8 hr (range: 6.6-24.8 hr). /Quinidine/

IN EXPERIMENTAL ANIMALS, QUINIDINE HAS VERY SIGNIFICANT ATROPINE LIKE ACTION, BLOCKING EFFECTS OF VAGAL STIMULATION OR OF ACETYLCHOLINE. ... ALSO HAS ALPHA-ADRENERGIC BLOCKING PROPERTIES. THIS CAN CAUSE VASODILATATION &, VIA BARORECEPTORS, ACTIVE SYMPATHETIC EFFERENT ACTIVITY. TOGETHER, CHOLINERGIC BLOCKAGE & INCR BETA-ADRENERGIC ACTIVITY CAUSED BY QUINIDINE CAN INCR SINUS RATE & ENHANCE ATRIOVENTRICULAR NODAL CONDUCTION. /QUINIDINE/|CAN CAUSE SEVERE DEPRESSION OF SINUS NODE IN PATIENTS WITH THE SICK SINUS SYNDROME ... QUINIDINE CAN INCR SINUS RATE BY CHOLINERGIC BLOCKADE OR BY REFLEXLY INCR SYMPATHETIC ACTIVITY. ... THERAPEUTIC CONCN OF QUINIDINE ... DECR FIRING RATE OF CARDIAC PURKINJE FIBERS BY DIRECT ACTION ... DECR SLOPE OF PHASE 4 DEPOLARIZATION AND SHIFTS THRESHOLD VOLTAGE TOWARD ZERO. /QUINIDINE/|... INCR DIASTOLIC ELECTRICAL CURRENT THRESHOLD IN ATRIAL & VENTRICULAR MUSCLE & IN PURKINJE FIBERS ... ALSO INCR FIBRILLATION THRESHOLD IN ATRIA & VENTRICLES. /QUINIDINE/|REENTRANT ARRYTHMIAS ARE ABOLISHED BY /QUINIDINE/. THEIR EFFECT ON EFFECTIVE REFRACTORY PERIOD, RESPONSIVENESS, & CONDUCTION. FOR EXAMPLE, WHEN VENTRICULAR PREMATURE DEPOLARIZATIONS ARE CAUSED BY REENTRY IN LOOPS OF PURKINJE FIBERS, ONE WAY BLOCK CAN BE CONVERTED TO TWO WAY BLOCK, THUS MAKING REENTRY IMPOSSIBLE. /QUINIDINE/|For more Mechanism of Action (Complete) data for QUINIDINE SULFATE (9 total), please visit the HSDB record page.

Commercially available quinidine salts contain not more than 20% of the respective dihydroquinidine salt, 1% of the respective quinine salt, and 1% of the respective dihydroquinine salt as impurities. /Quinidine/

General management is similar to that described for other drug overdoses. Because of potentially slow absorption, emesis or lavage and charcoal should be used even many hours after ingestion. Similarly, evaluation of intoxicated patients must continue until it is clear that the patient is stable and absorption is complete. Seizures should be treated with intravenous administration of diazepam initially and then phenytoin. /Quinidine/|Hypotension may be due to decreased systemic vascular resistance (particularly with quinidine) or to decreased cardiac output secondary to myocardial depression. The latter is most significant in cases of severe intoxication, in which cardiogenic shock may be a cause of death. Cautious use of fluids is usually effective in managing hypotension due to vasodilating or adrenergic blocking agents /including quinidine/. If blood pressure does not respond to fluids, vasoconstrictor drugs such as norepinephrine or dopamine should be used. ... Differentiating hypotension caused by vasodilation from that caused by myocardial depression and selecting appropriate therapy require measurement of cardiac output. Thus placement of a pulmonary arterial catheter is desirable. If cardiac output is low and cardiac filling pressure is also low, more fluids are necessary. If cardiac output is low despite adequate filling pressures, inotropic agents should be administered. Animal studies have shown isoproterenol to be most effective in reversing disopyramide-induced myocardial depression. Dobutamine should also be considered. If cardiac output is adequate but vascular resistance is low, vasopressors should be administered. ... In severe cases of quinidine poisoning with low-output shock due to myocardial depression, inotropic drugs may not improve contractility. Yet, in contrast to the situation of cardiogenic shock due to myocardial infarction, if the patient can be supported for several hours until the intoxicating drug can be eliminated, myocardial function will return to normal. Thus, drug-induced cardiogenic shock is an ideal situation for use of extracorporeal circulatory assistance techniques. /Quinidine/|Hemodialysis and hemoperfusion remove relatively little quinidine ... because of extensive tissue distribution of the drug. But when the usual routes of drug elimination are depressed or absent, such as when renal or hepatic failure complicates procainamide or quinidine overdose, respectively, or when extracorporeal circulation is used to support a failing circulation, ... hemoperfusion should be strongly considered because, even though not terribly effective it may offer the only route of drug elimination. /Quinidine/|Serious poisoning may present early with cardiovascular collapse. Therefore iv lines, oxygen, and cardiac monitoring are first priorities. Convulsions are often responsive to diazepam. Failure to respond to the usual anticonvulsant drugs is an indication to check serum electrolytes (particularly calcium) and glucose levels. Respiratory distress may result from either respiratory depression, aspiration pneumonia, or the development of the adult respiratory distress syndrome. In patients with underlying cardiovascular disease, pulmonary edema may result from depressed myocardial contractility. The usual measures of emesis/lavage, activated charcoal, and cathartics within the first several hours (longer if sustained-release preparations are ingested) are indicated. Repeated doses of activated charcoal (every 3 to 4 hr) may enhance the elimination of quinidine trapped in the acid media of the stomach. Although renal excretion of unmetabolized quinidine increases in acid urine, the usefulness of acid diuresis has not been clinically evaluated. Dialysis does not remove a clinically significant amount of quinidine, because of the high degree of protein binding, and should be used only in the presence of renal failure. Hemoperfusion may be useful if hepatic failure reduces metabolism. Glucagon has a positive inotropic effect in dogs, but its clinical efficacy has not been evaluated. Bretylium antagonizes quinidine-induced toxic effects on ventricular fibers, but it may enhance quinidine-induced reduction in atrioventricular conduction.Hypotension should be treated initially with fluids, pneumatic trousers, and, if required, vasopressors. Both isoproterenol and norepinephrine have been used successfully, and a resistant case has responded to the placement of an intra-aortic balloon pump. Persistent hypotension should be managed with a pulmonary catheter and arterial lines in coronary care unit. Treat ventricular dysrhythmias with class IB drugs (lidocaine, phenytoin), and avoid class IA drugs (procainamide, isopyramide). Bretylium should be used with caution because of synergistic atrioventricular nodal suppression. When atypical ventricular tachycardia presents, the goal is to reduce the QT interval. Isoproterenol infusion, 2 to 8 ug/min, may be effective, but usually overdrive pacing (120 to 140/min) is necessary. Lidocaine and procainamide are not effective and may be deleterious. Be sure to correct electrolyte imbalances (especially hypokalemia). /Quinidine/|For more Antidote and Emergency Treatment (Complete) data for QUINIDINE SULFATE (8 total), please visit the HSDB record page.

... COMPLICATION OF QUINIDINE WHEN DRUG IS USED TO TREAT ATRIAL FIBRILLATION IS ... PARADOXICAL INCR IN VENTRICULAR RATE. ... QUINIDINE CAUSES SUBSTANTIAL DECR IN THE ATRIAL RATE. IF THE ATRIAL RATE DECR SUFFICIENTLY, VENTRICULAR RATE MAY ABRUPTLY RISE ... . /QUINIDINE/|QUINIDINE CAN CAUSE SIGNIFICANT HYPOTENSION, PARTICULARLY WHEN GIVEN IV. ... HEMODYNAMIC STUDIES ... REVEALED THAT HYPOTENSION DUE TO QUINIDINE IS CAUSED BY VASODILATATION WITHOUT SIGNIFICANT DECREASE IN CARDIAC OUTPUT. /QUINIDINE/|... QUINIDINE CAN CAUSE CINCHONISM. SYMPTOMS ... INCL TINNITUS, LOSS OF HEARING, SLIGHT BLURRING OF VISION, & GI UPSET. IF TOXICITY IS SEVERE, HEADACHE, DIPLOPIA, PHOTOPHOBIA, & ALTERED COLOR PERCEPTION ... CONFUSION, DELIRIUM, & PSYCHOSIS. SKIN ... HOT AND FLUSHED, NAUSEA, VOMITING, DIARRHEA, & ABDOMINAL PAIN. /QUINIDINE/|RARELY, QUINIDINE CAUSES ANAPHYLACTIC REACTIONS, WHICH REQUIRE USUAL EMERGENCY MEASURES. THROMBOCYTOPENIA IS AN UNCOMMON BUT POTENTIALLY LETHAL OUTCOME OF TREATMENT WITH QUINIDINE. ... ASTHMA-LIKE RESPIRATORY DIFFICULTY OR VASCULAR COLLAPSE CAN OCCUR AS RESULT OF HYPERSENSITIVITY. /QUINIDINE/|For more Human Toxicity Excerpts (Complete) data for QUINIDINE SULFATE (29 total), please visit the HSDB record page.

Adaquin|Biquinate

QUINIDINE SULFATE CONTAINS 82% OF QUINIDINE BASE BY WEIGHT ... .|QUINIDINE SULFATE AVAILABLE ... CAPSULES, CONTAIN 100 ... MG OF THE DRUG; TABLETS OF QUINIDINE POLYGALACTURONATE CONTAIN 275 MG, EQUIVALENT TO 200 MG OF QUINIDINE SULFATE. PREPN FOR SLOW ABSORPTION ARE ALSO AVAILABLE AS 300 MG EXTENDED RELEASE TABLET OF QUINIDINE SULFATE & A 324 MG TABLET OF GLUCONATE. QUINIDINE SULFATE IS ALSO AVAILABLE AS AN INJECTION IN 1 ML AMPULE CONTAINING 200 MG/ML. THE NECESSARY DOSE IS DILUTED TO 800 MG/50 ML IN 5% GLUCOSE SOLUTION AND IS INJECTED AT THE RATE OF 16 MG/MIN, WITH CONTINUOUS OBSERVATION OF THE PATIENT & OF THE ECG.|Oral Tablets extended release 324 mg (equivalent to quinidine 202 mg), Quinaglute Dura-Tabs, Berlex, Quinatime, CMC; 330 mg (equivalent to quinidine 206 mg), Duraquine (with povidone), Warner Chilcott; Parenteral injection, 80 mg (equivalent to quinidine 50 mg) per ml, quinidine gluconate injection (with edetate disodium and phenol). Lilly /Quinidine Gluconate/|Oral Tablets 275 mg (equivalent to quinidine sulfate 200 mg), Cardioquin (with povidone; scored), Purdue Frederick. /Quinidine polygalacturonate/|For more Formulations/Preparations (Complete) data for QUINIDINE SULFATE (7 total), please visit the HSDB record page.

Cinchonan-9-ol, 6'-methoxy-, (8.alpha.,9R)-, sulfate (1:1): INACTIVE|Cinchonan-9-ol, 6'-methoxy-, (9S)-, sulfate (1:1): INACTIVE|Cinchonan-9-ol, 6'-methoxy-, (8.alpha.,9R)-, sulfate (1:?): INACTIVE

GLC DETERMINATION OF QUINIDINE FROM PLASMA AND WHOLE BLOOD. THE LIMIT OF DETECTABILITY IS 0.05 UG/ML OF QUINIDINE IN PLASMA AND THE METHOD IS ADEQUATE FOR FOLLOWING BLOOD PROFILES OF 200 MG QUINIDINE SULFATE DOSES IN HUMANS.|QUINIDINE WAS DETERMINED IN PLASMA AFTER IV INJECTION OF QUINIDINE SULFATE (12.5 & 25 MG/KG AS QUINIDINE BASE) INTO RATS. THE UNCHANGED QUINIDINE WAS DETERMINED BY SPECTROFLUORODENSITOMETRY, EXCITATION AND EMISSION AT 350 AND 450 NM.

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