Quinidine is a stereoisomer of the antimalarial agent quinine and a class Ia antiarrhythmic agent. Quinidine blocks the voltage-gated sodium (Nav) channel Nav1.5 in a use-dependent manner. It decreases the amplitude and duration of action potentials in isolated canine ventricular myocytes. It inhibits KKr, peak INa, and late INa (IC50s = 4.5, 11, and 12 μM, respectively) and can induce torsade de pointes in isolated rabbit hearts when used at a concentration of 1 μM. Quinidine induces QT prolongation in dogs. It also binds to M2 muscarinic acetylcholine receptors (Ki = 7.5 μM for human recombinant receptors expressed in HM2-B10 cells). Formulations containing quinidine have been used in the treatment of atrial fibrillation and ventricular arrhythmias.
Quinidine is a commonly used class I antiarrhythmic drug. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree. It exerts its antiarrhythmic effects on the heart by interacting with the electrophysiology mechanisms that cause arrhythmias to modify the abnormalities in impulse initiation and conduction. Quinidine depresses normal automaticity in cardiac fibers that may act as ectopic pacemakers causing arrhythmias. Quinidine also blocks the slowly inactivating, tetrodotoxin-sensitive Na current, 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.
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 0.05g/100mL (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.
antiarrhythmic, antimalarial
A dextrorotatory stereoisomer of Quinine. Antiarrhythmic (class IA). 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.
Crystals or white powder.
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.
Flash point data for Quinidine are not available. Quinidine is probably combustible.
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.
Poison by ingestion, subcutaneous, intravenous, intramuscular, and intraperitoneal routes. A skin irritant. Implicated in aplastic anemia. When heated to decomposition it emits toxic fumes of NOx.
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.
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.
Wit, Andrew L. "The Effects of Quinidine on the Cellular Electrophysiology of the Heart: A Brief Review." Journal of Cardiovascular Electrophysiology 3.5(2010):316-322.
Alloway, J. A., and M. P. Salata. "Quinidine-induced rheumatic syndromes. " Seminars in Arthritis & Rheumatism 24.5(1995):315-322.
Nakano, J, and M. C. R. Jr. "Effect of quinidine on cardiovascular dynamics." Arch Int Pharmacodyn Ther 168.2(1967):400-416.
