CRYSTALS WITH 2.5 MOL WATER OF CRYSTALLIZATION; CRYSTALS FROM DILUTE ALCOHOL
水溶性：
-3.37
稳定性/保质期：
Quinidine gluconate, quinidine polygalacturonate, and quinidine sulfate darken on exposure to light and should be stored in well-closed, light resistant containers. Solutions of quinidine salts slowly acquire a brownish tint on exposure to light. Only colorless, clear solutions of quinidine gluconate injection should be used. Quinidine gluconate injection should be stored at 15-30 °C. When diluted to a concentration of 16 mg/ml with 5% dextrose injection, quinidine gluconate injection is stable for 24 hours at room temperature and up to 48 hours when refrigerated. /Quinidine salts/
旋光度：
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.
分解：
When heated to decomposition it emits toxic fumes of oxides of nitrogen.
Quinidine is mainly metabolized in the liver by cytochrome P450 enzymes, specifically CYP3A4. The major metabolite of quinidine is 3-hydroxy-quinidine, which has a volume of distribution larger than quinidine and an elimination half-life of about 12 hours. Non-clinical and clinical studies suggest that 3-hydroxy-quinidine has approximately half the antiarrhythmic activity of quinidine; therefore, this metabolite is partly responsible for the effects detected with the chronic use of quinidine.
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.
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.
