Quinidine

324.424

324.42

200-279-0

ITX08688JL

2811

DTXSID4023549

C793

CRYSTALS WITH 2.5 MOL WATER OF CRYSTALLIZATION; CRYSTALS FROM DILUTE ALCOHOL

N07XX59|C - Cardiovascular system

2933990090

45.6

2.9

Crystals or white powder. (NTP, 1992)

1.2±0.1 g/cm3

174 °C

495.88°C at 760 mmHg

253.7±27.3 °C

1.638

H2O: 19mg/L(25 ºC)

You should store this material in the refrigerator.

LD50 in rats (mg/kg): 30 i.v., 263 orally (Dietmann)

Specific optical rotation @ 15 °C/D + 230 deg (concn by volume = 1.8 in chloroform); specific optical rotation @ 17 °C/D + 258 deg (alcohol); +322 deg (concn by volume = 1.6 in 2 M HCl); UV absorption spectrum is identical with that of quinine; blue fluorescence in dilute H2SO4.

8.56(at 25 °C)

8.56 (at 25 °C)|pK1 @ 20 °C = 5.4; pK2 = 10.0|pKa = 8.56 @ 25 °C

175.8 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

Rods; soluble in 8 parts water with blue fluorescence /Acid sulfate tetrahydrate/|Crystals from water; decomposes at 115 °C; specific optical rotation at 15 °C/D + 223 deg (0.4 molar solution). /Quinidine dihydrobromide trihydrate/|Crystals; MP: 175-176.5 °C; sol in 9 parts water, 60 parts alcohol /Gluconate/

Insoluble in water.

Alcohols and Polyols

Ⅲ

6.1(b)

2811

3

6.1

S36-S22

VA4725000

Xn:Harmful;

Stable. Incompatible with strong oxidizing agents.

P301 + P310

H301

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl quinidine gluconate and quinidine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Quinidine gluconate and quinidine sulfate/|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).

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.|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.|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.|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.|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, e.g., through diuretic induced hypokalemia, which exacerbate arrhythmias associated with digoxin and antiarrhythmics such as quinidine and procainamide.

Flash point data for this compound are not available. It is probably combustible. (NTP, 1992)

|Danger|H301 (99.51%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 205 companies from 4 notifications to the ECHA C&L Inventory.

Fires involving this compound can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for disposal Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the comtaminated area until safty officer has verified that the area has been properly cleaned.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 5,000 lb or 2270 kg. The toll- free- telephone number of the NRC is (800) 424-8802; in the Washington metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.6 (see section IV. D.3.b).

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 antiarrhythmic 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.

Chronic therapy with quinidine is associated with a low rate of serum enzyme elevations, which are usually mild, asymptomatic and self limited even without alteration in dose. In addition, there have been many reports of acute hypersensitivity reactions to quinidine that include hepatic involvement. The reactions usually arise after 1 to 2 weeks of therapy, but can appear within 24 hours of restarting quinidine or with rechallenge. The clinical features are marked by fatigue, nausea, vomiting, diffuse muscle aches, arthralgias and high fever. Blood testing at an early stage shows increases in serum aminotransferase and alkaline phosphatase levels as well as mild jaundice, which can deepen for a few days even after stopping quinidine. The pattern of serum enzymes elevations is typically cholestatic or mixed. Rash is uncommon and eosinophilia is not typical, despite the presence of other signs of hypersensitivity (fever, arthralgias). Autoantibodies are not typically found. Liver biopsies usually show mild injury and small epithelioid granulomas, as are often found in many organs during systemic hypersensitivity reactions. A similar clinical signature of liver injury occurs with quinine, an optical isomer of quinidine that is used predominantly as an antimalarial agent. In recent years, there have been few reports of liver injury attributed to quinidine, probably because it is now rarely used.

The combination of propranolol and quinidine resulted in increased beta-blockade measured by reduction in exercise heart rate and prolongation of the QTc and PR intervals ... quinidine stereoselectively inhibits the metabolism of propranolol through inhibition of the debrisoquin isozyme. The increased concentration of propranolol produced by quinidine results in increased beta-blockade.|Ethacrynic acid and furosemide /diuretics/ increase lipid solubility and tubular reabsorption of quinidine and thus prolong its therapeutic effects/ ...but will not alkalinize urine... .|Quinidine may potentiate the effects of both nondepolarizing and depolarizing skeletal muscle relaxants such as pancuronium bromide, succinylcholine chloride, and tubocurarine chloride. Neostigmine methylsulfate does not appear to reverse these effects.|Quinidine should be used with caution, if at all, in patients with myasthenia gravis and the dose of anticholinesterase drugs such as neostigmine and pyridostigmine may have to be increased. Since quinidine antagonizes the effect of vagal excitation on the atria and AV node, the administration of cholinergic drugs or any other procedures to enhance vagal activity may fail to terminate paroxysmal supraventricular tachycardia in patients receiving quinidine. The anticholinergic effects of quinidine may be additive with those of anticholinergic drugs.|For more Interactions (Complete) data for QUINIDINE (24 total), please visit the HSDB record page.

LD50 Rat iv 30.0 mg/kg|LD50 Rat i.v. 23 mg/kg|LD50 Rat oral 263 mg/kg|LD50 Mouse i.p. 170 mg/kg|For more Non-Human Toxicity Values (Complete) data for QUINIDINE (7 total), please visit the HSDB record page.

80-88%

Obtained from various species of Cinchona and their hybrids and from Remijia pedunculata Fluckiger (Fam Rubiaceae).|Quinidine is a stereoisomer of quinine and occurs in cinchona bark in amounts ranging from 0.3 to over 1%, although in some barks it may be practically absent.

Found in quinidine sulfate mother liquors. /Quinidine sulfate/

Since quinidine is distributed into milk, the drug should be used with extreme caution in nursing women.

For the treatment of ventricular pre-excitation and cardiac dysrhythmias|FDA Label|Nuedexta is indicated for the symptomatic treatment of pseudobulbar affect (PBA) in adults. Efficacy has only been studied in patients with underlying amyotrophic lateral sclerosis or multiple sclerosis.|Treatment of pseudobulbar affect (uncontrollable laughing and/or crying)

Quinidine is a natural cinchona alkaloid which has potent antiarrhythmic activity and has been used for decades in the treatment of atrial and ventricular arrhythmias. Quinidine has been associated with fever, mild jaundice and clinically apparent liver injury in up to 2% of treated patients.

Antiarrhythmic Agents

Adrenergic alpha-Antagonists; Anti-Arrhythmia Agents; Antimalarials; Enzyme Inhibitors; Muscarinic Antagonists|Quinidine is indicated in the treatment of recurrent, documented, life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Quinidine should not be used to treat ventricular arrhythmias of lesser severity, such as asymptomatic ventricular premature contractions. /Included in US product labeling/|Quinidine is indicated in the treatment of symptomatic atrial fibrillation or flutter in patients whose symptoms are not controlled by measures to reduce the rate of ventricular response. /US Product Labeling/|Chronic quinidine treatment is indicated for some patients at high risk for symptomatic atrial fibrillation pr flutter, such as those who have had previous episodes taht are so frequent and poorly tolerated as to outweigh the risk of porphylactic therapy with quinidine. /US Product Labeling/|Intravenous quinidine is indicated in the treatment of life-threatening Plasmodium falciparum malaria. /US Product Labeling/

Skin reactions to quinidine are rare and include morbilliform and scarlatiniformeruptions, urticaria, rash, pruritus, exfoliative dermatitis, eczema, severe exacerbation of psoriasis, lichenoid reactions, flushing, pigmentary abnormalities, photodermatitis (photosensitivity), and contact dermatitis.|... Adverse reactions are not related to plasma concentration and include drug fever cholestatic hepatitis, systemic lupus erythematosus, asthma, anaphylaxis, thrombocytopenia, hemolytic anemia (especially in glutcose-6-phosphate dehydrogenase deficiency), and hypoprothrombinemia. Skin changes range from maculopapular eruption to thrombocytopenic purpura, cutaneous vasculitis, photosensitivity, and bullous lesions.|Drug induced agranulocytosisis a clinical entity characterized by a selective reduction of circulating neutrophils, usually to a level less than 0.2X10+9/l in relation to the administration of the drug. Quinidine is an antiarrhythmic agent widely used on an outpatient basis with some well known hematological side effects. Its midterm administration has been related to a few cases of agranulocytosis. The case of a 60 yr old man with atrial fibrillation is described who presented quinidine induced agranulocytosis of abrupt onset only 3 days after the exposure to the drug, recovering normal levels of neutrophils during the third hospitalization day.|Large doses ...increase temporal dispersion of ventricular refractory periods ...may induce idioventricular impulse generation. Caution ...mandatory in ...treatment of ventricular ectopic rhythms; increased dose after therapeutic failure may increase hazard.|For more Drug Warnings (Complete) data for QUINIDINE (34 total), please visit the HSDB record page.

Quinidine, a hydantoin anticonvulsant, is used alone or with phenobarbital or other anticonvulsants to manage tonic-clonic seizures, psychomotor seizures, neuropathic pain syndromes including diabetic neuropathy, digitalis-induced cardiac arrhythmias, and cardiac arrhythmias associated with QT-interval prolongation.

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.)|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.)|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 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.)|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 class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)

When the urine pH is less than 7, about 20% of administered quinidine appears unchanged in the urine, but this fraction drops to as little as 5% when the urine is more alkaline.|2 to 3 L/kg|3 – 5 mL/min/kg [adults]|The volume of distribution of quinidine is 2 to 3 L/kg in healthy young adults, but this may be reduced to as little as 0.5 L/kg in patients with congestive heart failure, or increased to 3 or 5 L/kg in patients with cirrhosis of the liver. At concentrations of 2 to 5 mg/L (6.5 to 16.2 umol/L), the fraction of quinidine bound to plasma proteins (mainly to (alpha)1-acid glycoprotein and to albumin) is 80 to 88% in adults and older children, but it is lower in pregnant women, and in infants and neonates it may be as low as 50 to 70%. Because (alpha)1-glycoprotein levels are increased in response to stress, serum levels of total quinidine may be greatly increased in settings such as acute myocardial infarction, even though the serum content of unbound (active) drug may remain normal. Protein binding is also increased in chronic renal failure, but binding abruptly descends toward or below normal when heparin is administered for hemodialysis.|...Essentially completely absorbed after oral admin; max effects occur within 1-3 hr, and persist for 6-8 more hr. Large fluctuations in plasma concentration... if repeated doses are given at this interval. ...IM admin... gluconate yields peak effects in 30-90 min.|...All administered compound is excreted by kidney, and about 10-50% appears in urine as unchanged quinidine, within 24 hr.|The bioavailability of quinidine is 70 to 80% after oral use but varies between individuals and preparations. The sulfate salt is rapidly absorbed in 60 to 90 minutes. Polygalacturonate salts produce peak quinidine concentrations in 5 to 6 hours; gastrointestinal absorption of gluconate salts is intermediate (peak 3-4 hours).|For more Absorption, Distribution and Excretion (Complete) data for QUINIDINE (14 total), please visit the HSDB record page.

Lactate conjugates of quinidine and its 3-hydroxy metabolite were detected in overdose suicide patient.|Quinidine is metabolized in the liver, principally via hydroxylation to 3-hydroxyquinidine and 2-quinidinone. Some metabolites have antiarrhythmic activity. Approximately 10-50% of a dose is excreted in urine (probably by glomerular filtration) as unchanged drug within 24 hr.|Quinidine metabolites include 3-hydroxyquinidine N-oxide, 2'-oxoquinidinone, desmethylquinidine, and quinidine N-oxide. While metabolism is highly variable between individuals, at least in cases of quinidine-induced torsade de pointes, the metabolites do not appear to contribute to the formation of dysrhythmias.|Quinidine undergoes extensive hepatic oxidative metabolism... One metabolite, 3-hydroxyquinidine, is nearly as potent as quinidine in blocking cardiac sodium channels or prolonging action potentials.|Most quindiidne is eliminated hepatically via the action of cytochrome P450 IIIA.|Quinidine has known human metabolites that include 3-Hydroxyquinidine and Quinidine-N-oxide.

6-8 hours|Quinidine generally has a plasma half-life of 6-8 hr in healthy inividuals, 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).|The usual plasma half-life of approximately 7 hours after intravenous administration is increased in the presence of chronic liver disease.

Quinidine acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers. Quinidine may also act on the slow inward calcium current (ICa), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito.|The exact mechanism of antiarrhythmic action of quinidine has not been determined conclusively, but the drug is considered a class I (membrane stabilizing) antiarrhythmic agent. Like other class I antiarrhythmic agents, quinidine is believed to combine with fast sodium channels in their inactive state and thereby inhibit recovery after repolarization in a time- and voltage-dependent manner, which is associated with subsequent dissociation of the drug from the sodium channels. Quinidine exhibits electrophysiologic effects characteristic of class IA antiarrhythmic agents. The electrophysiologic characteristics of the subgroups of class I antiarrhythmic agents may be related to quantitative differences in their rates of attachment to and dissociation from transmembrane sodium channels, with class IA agents exhibiting intermediate rates of attachment and dissociation.|Like lidocaine and procainamide, quinidine suppresses automaticity in the His-Purkinje system. In usual doses, quinidine may decrease the automaticity of ectopic pacemakers, but the extent of this effect also depends upon the anticholinergic effect of the drug on the sinoatrial node, atria, and atrioventricular node. Extremely high concentrations of quinidine may increase myocardial automaticity. The drug decreases conduction velocity in the atria, ventricles, and His-Purkinje system, and may decrease or cause no change in conduction velocity through the AV node. Quinidine probably suppresses atrial fibrillation or flutter by prolonging the effective refractory period and increasing the action potential duration in atrial and ventricular muscle and in the His-Purkinje system. Because prolongation of the effective refractory period is greater than the increase in the duration of the action potential, the cardiac tissue remains refractory even after restoration of the resting membrane potential. Quinidine shortens the effective refractory period of the atrioventricular node, and the anticholinergic action of the drug may also increase the conductivity of the atrioventricular node. The effects of quinidine on refractoriness and the action potential duration of atrial fibers may be modified by the anticholinergic effects of the drug. Quinidine decreases cardiac excitability, both in diastole and in the relative refractory period, by increasing the threshold potential for electrical excitation. At therapeutic plasma concentrations, quinidine causes prolongation of the QRS complex and QT interval.|Quinidine also exhibits some antipyretic and oxytocic properties. Quinidine has a very weak curare-like action on the myoneural junction and also causes depression of skeletal muscle action potential.|Intravenous quinidine depresses contractility and decreases systemic vascular resistance primarily by alpha-adrenergic receptor blockade. High blood levels of quinidine increase left ventricular end-diastolic pressure through its negative inotropic effect. Cardiovascular collapse has resulted from depression of contractility.|Quindine primarily kills the schizont parasite at the asexual intra-erythrocytic cycle stage of the Plasmodium falciparum malaria protozoan parasite. Quinidine also kills the gametocyte parasite stages of Plasmodium malariae, Plasmodium vivax, and Plasmodium ovale.

Quinidine of commerce is usually accompanied by up to 20% of hydroquinidine.|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.

SYMPTOMS: Symptoms of exposure to this compound may include anorexia, nausea, vomiting, abdominal cramps, diarrhea, tinnitus, impaired hearing, blurred vision, vertigo, severe emotional reactions, pyrexia, skin eruptions, thrombocytopenic purpura, asthma, urticaria, acute hemolytic anemia, heart block, diminished cardiac output, ventricular tachycardia, ventricular fibrillation or acute ventricular asystole, headache, confusion, skin rash and angioedema. ACUTE/CHRONIC HAZARDS: This compound can cause irritation of the skin, eyes and mucous membranes. When heated to decomposition it emits toxic fumes. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Decontamination. 1. Prehospital. Administer activated charcoal if available. Do not induce vomiting because of the risk of abrupt onset of seizures and coma. 2. Hospital. Administer activated charcoal. Consider gastric lavage for large ingestions. /Quinidine and other type Ia antiarrhythmic drugs/

/SIGNS AND SYMPTOMS/ The /cardiac/ conduction velocity decreases progressively as drug concentrations rise, as reflected by increases in the PR interval, QRS duration and QT interval. High plasma quinidine levels cause high-grade atrioventricular block, bundle-branch block, and asystole resembling that of hyperkalemia.|/SIGNS AND SYMPTOMS/ Quinidine is a antiarrhythmic drug in the class 1A category. This drug has a low toxic to therapeutic ratio, and its use is associated with a number of serious adverse effects during long term therapy and life threatening sequelae following acute overdose. ... Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity.|/CASE REPORTS/ A patient is described with quinidine induced acute lymphadenopathy syndrome proven by rechallenge of the drug. Serum markers for systemic lupus were negative.|/CASE REPORTS/ Pulmonary edema developed after a suicidal 8 gram quinidine ingestion with normal pulmonary capillary wedge pressures.|/CASE REPORTS/ Fever is a well-known side effect of quinidine therapy, but an elevated white blood cell count is considered unusual. Two patients are described who had leukocytosis or a marked left shift in the white blood cell count (or both) in association with quinidine fever. Neither patient had evidence of infection. In each of these patients, the temperature and white blood cell count returned to normal within two days after quinidine was discontinued. Although infection should always be considered in a patient with fever, leukocytosis, and a left shift, these may also appear in association with quinidine therapy.

Adaquin

100% AS A CARDIAC DEPRESSANT TO INHIBIT AURICULAR FIBRILLATION (1975)

/Available as/ Capsules: 200and 300 mg; Injection: 200 mg/ml; Tablets: 100, 200 and 300 mg; Sustained-Release Tablets: 300 mg /Quinidine sulfate/, as Injection: 800 mg/10 ml; Extended-Release Tablets: 324 and 330 mg /Quinidine Gluconate/ and as Tablets: 275 mg /Quinidine Polygalacturonate/|Quinaglute Dura-Tabs contain 5 gr quinidine gluconate /per tablet/|Quinidex Exten-tabs contain 300 mg quinidine sulfate /per tablet/|Duraquin contains 330 mg quindine gluconate /per tablet/|For more Formulations/Preparations (Complete) data for QUINIDINE (11 total), please visit the HSDB record page.

Cinchonan-9-ol, 6'-methoxy-, (9S)-: INACTIVE|Most of the material sold today is made by isomerization of quinine.|A long acting quinidine preparation /Quinidine gluconate/

Analyte: quinidine gluconate; matrix: chemical identification; procedure: thin-layer chromatography with detection using short- and long-wavelength ultraviolet light and comparison to standards /Quinidine gluconate/|HPLC AND THIN LAYER CHROMATOGRAPHY DETERMINATIONS OF QUINIDINE AND RELATED ALKALOIDS IN PHARMACEUTICALS.|Analyte: quinidine gluconate; matrix: chemical identification; procedure: solution in dilute sulfuric acid exhibits vivid blue fluorescence, addition of hydrochloric acid, the fluorescenece disappears. /Quinidine gluconate/|Analyte: quinidine gluconate; matrix: chemical purity; procedure: potentiometric titration with comparison to standards /Quinidine gluconate/|For more Analytic Laboratory Methods (Complete) data for QUINIDINE (10 total), please visit the HSDB record page.

QUININE OR QUINIDINE DETECTION IN URINE BY FLUORESCENCE ANALYSIS, TLC.|QUINIDINE DETECTION IN PLASMA OR URINE BY UV SPECTROPHOTOMETRY WITH TLC CONFIRMATION.|GCD OF QUINIDINE IN BLOOD, PLASMA. OVERALL RECOVERY IS 98.27 + OR - 3.61%.|DETERMINATION OF QUINIDINE AND DIHYDROQUINIDINE IN PLASMA BY HPLC.

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