56-54-2

Crystals or white powder.

Insoluble in water.

Poison.

Flash point data for this compound are not available. QUINIDINE is probably combustible.

white to light yellow crystal powde

Appearance: Quinidine is commonly used in its sulfate form with white needle-like crystal and bitter smell. It changes color easily when exposed to light. Solubility: It was soluble in ethanol and chloroform. Its water solubility is 0.05?g/100?mL (20?°C). Specific optical rotation: 256° (c?=?1, EtOH). Melting point: 168–172?°C.

In 1820, the French chemists Pierre Pelletier and Joseph Caventou extracted some alkaloids from the cinchona bark, including quinine and quinidine. Subsequently, quinine was demonstrated to play a very important role in the treatment of malaria after a number of scientific researches. Quinidine is the dextroisomer of quinine and has the similar pharmacological properties as quinine, but quinidine’s effects are five to ten times stronger on the heart than quinine.

A dextrorotatory stereoisomer of Quinine. Antiarrhythmic (class IA). Antimalarial

antiarrhythmic, antimalarial

Quinidine occurs in cinchona bark to about0.25–0.3% and also in cuprea bark. It is present in quinine sulfate mother liquor. Itis formed by isomerization of quinine. Itis used in the prevention of certain cardiacarrhythmias.

ChEBI: A cinchona alkaloid consisting of cinchonine with the hydrogen at the 6-position of the quinoline ring substituted by methoxy.

Quinidine acts as a class I antiarrhythmic agent (Ia) in the heart. It was clinically applicable to the treatment of recurrent, documented, life-threatening ventricular arrhythmias .

Duraquin (Warner Chilcott); Quinaglute (Berlex).

Quinidine is an alkaloid obtained from various species of Cinchona or its hybrids, from Remijia pedunculata, or from quinine. Quinidine is the dextrorotatory isomer of quinine.Quinidine (Quinidex) was one of the first clinically used antiarrhythmic agents. Because of the high incidence of ventricular proarrhythmia associated with its use and numerous other equally efficacious agents, quinidine is now used sparingly. Quinidine shares all of the pharmacological properties of quinine, including antimalarial, antipyretic, oxytocic, and skeletal muscle relaxant actions.

Quinidine is more potent than quinine in itsaction on the cardiovascular system. Overdosesmay cause lowering of blood pressure.Gastric effects are lower than quinine. Toxicityis lower relative to quinine; subcutaneouslethal dose in mice is 400 mg/kg against200 mg/kg for quinine.

Class IA antiarrhythmic; potassium channel blocker.

Quinidine generally is administered orally, although slow intravenous administration also is possible . Quinidine is the prototype of class I antiarrhythmics; therefore, substances in this group also are called “quinidine-like.”However, it differs, for example, from lidocaine by the following effects: it increases the duration of the action potential, in the ECG it increases QRS duration and Q– T interval, and the refractory period is markedly prolonged. Quinidine can accelerate the impulse conduction rate in the AV node (atropine-like effect).

Quinidine exhibits all of the pharmacological properties of quinine, including antimalarial, fever-reducing, and other properties. Quinidine is used in various forms of arrhythmia for preventing tachycardia and atrial fibrillation, and particularly for preventing ciliary fibrillation, paroxysmal supraventricular tachycardia, extrasystole, and ventricular tachycardia. However, it is a toxic drug and is used relatively rarely. It is also prescribed under the name cardioquin, duraquin, quinidex, and others.

Primary indications for the use of quinidine include (1) abolition of premature complexes that have an atrial, A-V junctional, or ventricular origin; (2) restoration of normal sinus rhythm in atrial flutter and atrial fibrillation after controlling the ventricular rate with digitalis; (3) maintenance of normal sinus rhythm after electrical conversion of atrial arrhythmias; (4) prophylaxis against arrhythmias associated with electrical countershock; (5) termination of ventricular tachycardia; and (6) suppression of repetitive tachycardia associated with Wolff- Parkinson-White (WPW) syndrome.
Although quinidine often is successful in producing normal sinus rhythm, its administration in the presence of a rapid atrial rate (flutter and possibly atrial fibrillation) can lead to a further and dangerous increase in the ventricular rate secondary to inhibition of basal vagal tone upon the A-V node. For this reason, digitalis should be used before quinidine when one is attempting to convert atrial flutter or atrial fibrillation to normal sinus rhythm.

The most common adverse effects associated with quinidine administration are diarrhea (35%), upper gastrointestinal distress (25%), and light-headedness (15%). Other relatively common adverse effects include fatigue, palpitations, headache (each occurring with an incidence of 7%), anginalike pain, and rash. These adverse effects are generally dose related and reversible with cessation of therapy. In some patients, quinidine administration may bring on thrombocytopenia due to the formation of a plasma protein–quinidine complex that evokes a circulating antibody directed against the blood platelet. Although platelet counts return to normal on cessation of therapy, administration of quinidine or quinine at a later date can cause the reappearance of thrombocytopenia.
The cardiac toxicity of quinidine includes A-V and intraventricular block, ventricular tachyarrhythmias, and depression of myocardial contractility. Ventricular arrhythmia induced by quinidine leading to a loss of consciousness has been referred to as quinidine syncope. This devastating side effect is more common in women than in men and may occur at therapeutic or subtherapeutic plasma concentrations. Large doses of quinidine can produce a syndrome known as cinchonism, which is characterized by ringing in the ears, headache, nausea, visual disturbances or blurred vision, disturbed auditory acuity, and vertigo. Larger doses can produce confusion, delirium, hallucinations, or psychoses.Quinidine can decrease blood glucose concentrations, possibly by inducing insulin secretion.

Quinidine can increase the plasma concentrations of digoxin, which may in turn lead to signs and symptoms of digitalis toxicity. Gastrointestinal, central nervous system (CNS), or cardiac toxicity associated with elevated digoxin concentrations may occur.Quinidine and digoxin can be administered concurrently; however, a downward adjustment in the digoxin dose may be required.
Drugs that have been associated with elevations in quinidine concentrations include acetazolamide, the antacids magnesium hydroxide and calcium carbonate, and the H2-receptor antagonist cimetidine. Cimetidine inhibits the hepatic metabolism of quinidine. Phenytoin, rifampin, and barbiturates increase the hepatic metabolism of quinidine and reduce its plasma concentrations.

Quinidine's bioavailability appears to depend on a combination of metabolism and P-gp efflux. The bioavailabilities of quinidine sulfate and gluconate are 80 to 85% and 70 to 75%, respectively. Once absorbed, quinidine is subject to hepatic first-pass metabolism and is approximately 85% plasma protein bound, with an elimination half-life of approximately 6 hours. Quinidine is metabolized mainly in the liver, and renal excretion of unchanged drug also is significant (~10–50%). The metabolites are hydroxylated derivatives at either the quinoline ring through first-pass O-demethylation or at the quinuclidine ring through oxidation of the vinyl group. These metabolites possess only about one-third the activity of quinidine. Their contribution to overall therapeutic effect of quinidine is unclear. Recently, the clinical significance of the well-documented digoxin–quinidine interaction was described previously under digoxin–drug interactions. Apparently, quinidine (a P-gp substrate) inhibits the renal tubular secretion of digoxin via the P-gp efflux pump, resulting in increased plasma concentration for digoxin.

Store at -20°C

Crystallise it from *C6H6 or dry CHCl3/pet ether (b 40-60o), discarding the initial, oily crop of crystals. Dry it under vacuum at 100o over P2O5. It has been used as a chiral catalyst [Wynberg & Staring J Am Chem Soc 104 166 1982, J Org Chem 50 1977 1985]. [Beilstein 23 H 506, 23 I 164, 23 II 414, 23 III/IV 3261, 23/13 V 395.]

One of the few absolute contraindications for quinidine is complete A-V block with an A-V pacemaker or idioventricular pacemaker; this may be suppressed by quinidine, leading to cardiac arrest.
Persons with congenital QT prolongation may develop torsades de pointes tachyarrhythmia and should not be exposed to quinidine.
Owing to the negative inotropic action of quinidine, it is contraindicated in congestive heart failure and hypotension. Digitalis intoxication and hyperkalemia can accentuate the depression of conduction caused by quinidine.
Myasthenia gravis can be aggravated severely by quinidine’s actions at the neuromuscular junction. The use of quinidine and quinine should be avoided in patients who previously showed evidence of quinidine- induced thrombocytopenia.