Cytochrome P450db; K+ channel

Quinidine HydroHClone monohydrate has an IC50 of 19.9±1.41 μM and a Hill slope of 1.15±0.15 (n=7), indicating that it inhibits WT mSlo3 (KCa5.1) channels. Similarly, quinidine hydrochloride monohydrate has a stronger inhibitory potency against F304Y mSlo3 (IC50 = 2.42±0.60 μM, n = 9, P<0.005; Hill slope = 0.98±0.12), but a lower inhibitory potency (IC50 = 38.4±6.77 μM, n = 5, P<0.001; Hill slope = 1.05±0.16) against R196Q mSlo3. There is a time dependence detected in the inhibition of F304Y mSlo3 by quinidine hydrochloride monohydrate [1].

When comparing baseline to other time points or comparison experiments, the direct application of quinidine hydrochloride monohydrate to the sciatic nerve produced dose-related decreases in the amplitudes of the descending compound muscle action potential (CMAP) and ascending somatosensory evoked potential (SSEP). Left versus right contralateral limbs treated with glucose. When quinidine hydrochloride monohydrate was applied, the latency of the SSEP and CMAP potentials increased in comparison to the baseline and contralateral side [2].

Mouse (m) Slo3 (KCa 5.1) channels or mutant forms were expressed in Xenopus oocytes and currents recorded with 2-electrode voltage-clamp. Gain-of-function mSlo3 mutations were used to explore the state-dependence of the inhibition. The interaction between quinidine and mSlo3 channels was modelled by in silico docking.
Key results: Several drugs known to block KSper also affected mSlo3 channels with similar levels of inhibition. The inhibition induced by extracellular barium was prevented by increasing the extracellular potassium concentration. R196Q and F304Y mutations in the mSlo3 voltage sensor and pore, respectively, both increased channel activity. The F304Y mutation did not alter the effects of barium, but increased the potency of inhibition by both quinine and quinidine approximately 10-fold; this effect was not observed with the R196Q mutation. Conclusions and implications: Block of mSlo3 channels by quinine, quinidine and barium is not state-dependent. Barium inhibits mSlo3 outside the cell by interacting with the selectivity filter, whereas quinine and quinidine act from the inside, by binding in a hydrophobic pocket formed by the S6 segment of each subunit. Furthermore, we propose that the Slo3 channel activation gate lies deep within the pore between F304 in the S6 segment and the selectivity filter.[1]

Twenty-seven rats were treated with 1, 3, and 5 μmol quinidine in 0.1 ml 5 % glucose. The mixed-nerve somato-sensory evoked potential (M-SSEP), dermatomal-SSEP (D-SSEP), and compound muscle action potentials (CMAP) were evoked and recorded. After positioning Gelfoam strips saturated with quinidine and 5 % glucose around the left and right sciatic nerves, potentials were measured at baseline, immediately after treatment, every 15 min for the 1st hour, and every 30 min for the next 3 h. After 2 weeks, the walking behaviors and potentials were again analyzed and myelinated fibers in the sciatic nerve were counted. Results: Quinidine applied directly to sciatic nerves reduced the amplitude and prolonged the latency in SSEPs and CMAP, compared to baseline and the contralateral right limbs (controls). This persisted for at least 4 h. After 2 weeks, electrophysiological tests and walking behavior showed no significant difference between the controls and experimental limbs. There was also no difference in the number of myelinated fibers in the sciatic nerves. Conclusions: Quinidine decreases amplitude and prolongs latency in the sciatic nerve in a dose-related manner without local neural toxicity.[2]

Absorption
The absolute bioavailability of quinidine sulfate is approximately 70%, but ranges from 45% to 100%. The incomplete bioavailability of quinidine sulfate is due to first-pass metabolism in the liver. In contrast, the absolute bioavailability of quinidine gluconate ranges from 70% to 80%, and the bioavailability of quinidine in gluconate is 1.03 relative to quinidine sulfate. The time to peak concentration (tmax) of quinidine sulfate extended-release tablets is approximately 6 hours, while that of quinidine gluconate is 3 to 5 hours. When taken with food, the peak plasma concentration of immediate-release quinidine sulfate is delayed by approximately 1 hour. Furthermore, drinking grapefruit juice may reduce the absorption rate of quinidine.
Elimination Pathway
Elimination of quinidine is primarily achieved through renal excretion of the unchanged drug (15% to 40% of total clearance) and hepatic biotransformation into various metabolites (60% to 85% of total clearance). When urine pH is below 7, approximately 20% of quinidine is present unchanged in the urine. However, this percentage decreases to about 5% as urine pH increases. Renal clearance of quinidine involves glomerular filtration and active tubular secretion, and is regulated by pH-dependent tubular reabsorption.
Volume of Distribution
The volume of distribution of quinidine in healthy young adults is 2-3 L/kg, in patients with congestive heart failure it is 0.5 L/kg, and in patients with cirrhosis it is 3-5 L/kg.
Clearance
The clearance of quinidine in adults is 3-5 mL/min/kg. In pediatric patients, the clearance of quinidine may be two to three times that of adults.
The volume of distribution of quinidine in healthy young adults is 2-3 L/kg, but may decrease to 0.5 L/kg in patients with congestive heart failure, while increasing to 3-5 L/kg in patients with cirrhosis. At concentrations of 2 to 5 mg/L (6.5 to 16.2 μmol/L), quinidine binds to plasma proteins (primarily α1-acid glycoprotein and albumin) at 80% to 88% in adults and older children, but is lower in pregnant women and may be as low as 50% to 70% in infants and newborns. Because α1-glycoprotein levels increase in stress responses, serum levels of total quinidine may be significantly elevated in cases such as acute myocardial infarction, even if serum levels of the free (active) drug may remain normal. Protein binding is also elevated in chronic renal failure, but it rapidly decreases to near or below normal levels when heparin is used for hemodialysis. It is almost completely absorbed after oral administration; the maximum effect occurs within 1–3 hours and lasts for 6–8 hours. Repeated administration within this interval can result in significant fluctuations in plasma concentrations. Intramuscular gluconate administration reaches peak effect within 30–90 minutes.
All administered compounds are excreted by the kidneys, with approximately 10-50% appearing in the urine as unmetabolized quinidine, which is excreted within 24 hours.
The bioavailability of oral quinidine is 70% to 80%, but varies from individual to individual and from formulation to formulation. Sulfate is rapidly absorbed within 60 to 90 minutes. Polygalacturonate reaches peak quinidine concentrations within 5 to 6 hours; gluconate has moderate gastrointestinal absorption (peak at 3-4 hours).

View More

Approximately 90% of quinidine in plasma is bound to plasma proteins (α/acid glycoproteins and albumin).

The drug enters red blood cells and binds to hemoglobin; under steady state, the concentration of quinidine in plasma and red blood cells is approximately equal. Quinidine accumulates rapidly in most tissues except brain tissue, with a volume of distribution of 2-3 liters/kg. Quinidine metabolites and a portion of the original drug (20%) are excreted in the urine; the elimination half-life is approximately 6 hours. Quinidine is primarily metabolized by the liver and excreted by the kidneys. Enterohepatic circulation does not significantly alter absorption kinetics, which is reflected in blood concentrations. PMID:7264866
Four hours after administration of sustained-release capsules (250 mg quinidine sulfate), the peak plasma concentration of quinidine was measured at 0.29 μg/mL, and it steadily decreased over the next 8 hours; while after administration of sustained-release tablets (300 mg quinidine sulfate), plasma concentrations remained essentially stable for 2-10 hours post-administration. Plasma concentrations in capsules were higher than in tablets in the later stages. Within 12 hours, the bioavailability of quinidine in capsules was 184% of that in tablets. Mean plasma quinidine concentrations were significantly higher at 3, 4, 6, 8, and 10 hours after capsule administration compared to tablet administration.
For more complete data on absorption, distribution, and excretion of quinidine sulfate (24 items), please visit the HSDB record page.

---

Metabolism/Metabolites
Quinidine is primarily metabolized in the liver by cytochrome P450 enzymes, particularly CYP3A4. The major metabolite of quinidine is 3-hydroxyquinidine, which has a larger volume of distribution than quinidine and an elimination half-life of approximately 12 hours. Non-clinical and clinical studies have shown that the antiarrhythmic activity of 3-hydroxyquinidine is approximately half that of quinidine; therefore, this metabolite is responsible for some of the adverse reactions observed with long-term quinidine use.
Lactate conjugates of quinidine and its 3-hydroxy metabolite were detected in a patient who committed suicide by overdose of quinidine. Quinidine is primarily metabolized in the liver, mainly through hydroxylation to produce 3-hydroxyquinidine and 2-quinidineone. Some metabolites possess antiarrhythmic activity. Approximately 10-50% of the dose is excreted unchanged in the urine within 24 hours (possibly via glomerular filtration). Quinidine metabolites include 3-hydroxyquinidine N-oxide, 2'-oxoquinidineone, desmethylquinidine, and quinidine N-oxide. Although there is considerable inter-individual variability in metabolism, at least in cases of quinidine-induced torsades de pointes, the metabolites do not appear to be involved in the formation of arrhythmias. Quinidine undergoes extensive oxidative metabolism in the liver… one of the metabolites, 3-hydroxyquinidine, has an almost equivalent ability to block cardiac sodium channels or prolong action potentials to quinidine. Most quinidine is cleared from the liver by the action of cytochrome P450 IIIA. Quinidine is metabolized in humans as 2'-hydroxyquinidine. /quinidine; from table/
Most urinary metabolites undergo hydroxylation at only one site, either on the quinoline ring or the quinine ring; small amounts of dihydroxy compounds have also been found. The metabolic rate and pathway of quinidine appear to vary from patient to patient.
Quinidine is primarily metabolized in the liver, via hydroxylation to 3-hydroxyquinidine and 2-quinidineone. These metabolites may be pharmacologically active. Approximately 10-50% of the dose is excreted unchanged in the urine over 24 hours (possibly through glomerular filtration). Quinidine
Known metabolites of quinidine include quinidine-N-oxide and 3-hydroxyquinidine.

---

Biological half-life
The elimination half-life of quinidine in adults is 6-8 hours, and in pediatric patients it is 3-4 hours. The plasma half-life of quinidine in healthy individuals is typically 6–8 hours, but can be 3–16 hours or longer. In a study of patients with Plasmodium falciparum malaria, the mean elimination half-life of the drug was 12.8 hours (range: 6.6–24.8 hours). Following intravenous administration, the plasma half-life is typically around 7 hours, but is prolonged in patients with chronic liver disease. The elimination half-life of quinidine in healthy individuals is 4 to 10 hours, with a typical mean of 6 to 7 hours. The half-life is significantly prolonged in older adults, even if they appear healthy. Quinidine is primarily excreted in the urine; the elimination half-life is approximately 6 hours. The plasma half-life of quinidine in healthy individuals is typically 6–8 hours, but can be 3–16 hours or longer. In a study of patients with Plasmodium falciparum malaria, the drug's elimination half-life averaged 12.8 hours (range: 6.6–24.8 hours).

Hepatotoxicity
Long-term use of quinidine is associated with a lower incidence of elevated serum enzymes, which are usually mild, asymptomatic, and resolve spontaneously even without dose changes. However, there have been numerous reports of acute hypersensitivity reactions to quinidine, including liver involvement. These reactions typically occur 1 to 2 weeks after treatment, but can also occur within 24 hours of restarting quinidine or taking it again. Clinical manifestations include fatigue, nausea, vomiting, generalized muscle aches, arthralgia, and high fever. Early blood tests show elevated serum transaminase and alkaline phosphatase levels, as well as mild jaundice, which may persist for several days and worsen even after discontinuation of quinidine. The pattern of elevated serum enzymes is usually cholestatic or mixed. Skin rash is uncommon, and eosinophilia is not a typical symptom, although other signs of hypersensitivity (fever, arthralgia) are present. Autoantibodies are usually not detectable. Liver biopsy typically shows mild damage and small epithelioid granulomas, which are common in many organs in systemic hypersensitivity reactions. Quinine (the optical isomer of quinidine, primarily used as an antimalarial drug) can also cause similar clinical manifestations of liver injury. Reports of quinidine-induced liver injury are rare in recent years, possibly because quinidine is now rarely used.
Probability Score: A (Etiology of clinically confirmed liver injury).

---

Effects during pregnancy and lactation
◉ Overview of use during lactation
Limited information suggests that even with daily administration of up to 1.8 grams of quinidine by the mother, the concentration of quinidine in breast milk is very low and is not expected to have any adverse effects on breastfed infants, especially those older than 2 months. If this drug is used during lactation, exclusively breastfed infants should be closely monitored, and serum drug concentrations may need to be measured to rule out toxicity if there are any concerns.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

---

View More

Adverse Reactions
Occupational Hepatotoxicity - Secondary Hepatotoxicity: Potential toxic effects in occupational environments based on case studies of human ingestion or animal poisoning.
Skin Sensitizers - Substances that can induce allergic skin reactions.

---

Protein Binding
At concentrations of 6.5 to 16.2 µmol/L, 80% to 88% of quinidine is bound to plasma proteins, primarily α1-acid glycoprotein and albumin. Binding rates are lower in pregnant women and may be as low as 50% to 70% in infants and newborns.

---

Toxicity Overview
Identification: Quinidine is a class IIa antiarrhythmic drug. Source: Quinidine is the D-isomer of quinine. Quinidine is an alkaloid, possibly derived from various cinchona trees. Cinchona bark contains 0.25% to 3.0% quinidine. Quinidine can also be prepared from quinine. Quinidine is a powder or white crystal, odorless, and bitter. Quinidine bisulfate is a colorless and odorless crystal with a bitter taste. Quinidine gluconate is a white powder, odorless, and bitter. Quinidine polygalacturonic acid is a powder. Quinidine sulfate is a white powder or odorless crystal with a bitter taste. Indications: Description: Ventricular premature beats and ventricular tachycardia; supraventricular arrhythmias; maintenance of sinus rhythm after cardioversion of atrial fibrillation or atrial flutter. Human Exposure: Major Risks and Target Organs: Cardiotoxicity is the major risk of quinidine poisoning. Quinidine may cause central nervous system symptoms. Clinical Overview: Symptoms of poisoning usually appear within 2–4 hours of ingestion, but the timing may vary depending on the quinidine salt and formulation. Symptoms may include cardiac arrhythmias (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, somnolence, syncope, coma, convulsions, delirium. Respiratory depression. Quinidine concentration may be helpful for diagnosis but is of no clinical significance. Contraindications: Hypersensitivity or idiosyncratic reaction to cinchona alkaloids; atrioventricular block or complete atrioventricular block; intraventricular block; loss of atrial activity; digitalis poisoning; myasthenia gravis and torsades de pointes. Precautions include: congestive heart failure, hypotension, kidney disease, liver failure; concurrent use of other antiarrhythmic drugs; elderly and lactating women. Route of Administration: Oral: Oral absorption is the most common cause of poisoning. Injection Administration: Intravenous toxicity is rare, but has been reported in patients receiving intravenous quinidine for arrhythmia. Absorption Routes: Oral: Quinidine is almost completely absorbed from the gastrointestinal tract. However, due to the first-pass effect in the liver, its absolute bioavailability is approximately 70% to 80% of the ingested dose and may vary depending on the patient and formulation. The peak plasma concentration time for quinidine sulfate is 1 to 3 hours, for quinidine gluconate it is 3 to 6 hours, and for quinidine polygalacturonic acid it is approximately 6 hours. Sustained-release quinidine can be absorbed continuously over 8 to 12 hours. Injection Administration: Absorption of quinidine after intramuscular injection can be unstable and unpredictable; the administered dose may not be completely absorbed, possibly due to drug precipitation at the injection site. Other studies have shown no difference in absorption rates between intramuscular and oral quinidine. Drug Distribution (by Route of Administration): Oral: Protein Binding: Approximately 70%–80% of the drug is bound to plasma proteins. Plasma protein binding is reduced in patients with chronic liver disease. Tissue: Quinidine concentrations in the liver are 10–30 times higher than in plasma. Quinidine levels in skeletal muscle, cardiac muscle, brain, and other tissues fall between these two ranges. The erythrocyte-plasma partition ratio is 0.82. Biological half-life (by route of administration): Elimination half-life: Approximately 6–7 hours. The elimination half-life is prolonged in patients with chronic liver disease and the elderly. Congestive heart failure or renal failure does not appear to alter the elimination half-life. Metabolism: 50%–90% of quinidine is metabolized in the liver to hydroxylated products. Metabolites include 3-hydroxyquinidine, 2-oxoquinidine, O-demethylquinidine, and quinidine-N-oxide. The major metabolite is 3-hydroxyquinidine, which has similar effects to quinidine and may partially explain the observed antiarrhythmic effects. The elimination kinetics of hydroxyquinidine appear similar to those of quinidine. Elimination via exposure: Renal: The amount excreted unchanged in urine varies considerably, but is approximately 17% of the administered dose. Up to 50% of the quinidine dose (original + metabolites) is excreted in the urine within 24 hours after administration. Renal excretion depends on urine pH. Excretion is inversely proportional to urine pH. Renal insufficiency and congestive heart failure reduce excretion. Liver: 50% to 90% of the quinidine dose is metabolized in the liver. Bile: Approximately 1% to 3% of quinidine is excreted in feces via bile. Breast milk: Quinidine is secreted into breast milk. Mechanism of action and toxicology: Quinidine reduces myocardial permeability to electrolytes (membrane stabilizer) and is a systemic cardiac depressant. It has negative inotropic effects; inhibits spontaneous diastolic depolarization; slows conduction; prolongs the effective refractory period; and increases the electrical threshold. This leads to decreased myocardial contractility, impaired conduction (atrioventricular and intraventricular conduction), and decreased excitability, but may be accompanied by anomalous reentry mechanisms. Quinidine has anticholinergic and peripheral vasodilatory effects. In experimental studies, the following progressive changes were observed: Electrocardiogram: bradycardia, prolonged PR interval, prolonged QT interval, widened QRS complex, and the appearance of ventricular voluntary rhythms, eventually developing into ventricular arrest. Sometimes, the terminal event is ventricular fibrillation. Blood pressure gradually decreases. Blood pressure drops significantly when QRS widening occurs; blood pressure approaches zero when slow ventricular voluntary rhythms appear. Electrolyte abnormalities: decreased plasma potassium, sodium, and magnesium concentrations, accompanied by acidosis. Electrolytes: hypokalemia may occur, possibly related to the drug's direct effect on cell membrane permeability, leading to intracellular potassium ion transport. Neurological symptoms: syncope and seizures may represent the drug's direct toxic effects on the central nervous system, or may be related to cerebral ischemia caused by circulatory or respiratory failure. Pharmacodynamics: Quinidine can slow the firing rate of normal and ectopic rhythmic pacemakers; increase the threshold for electrically induced arrhythmias; prevent ventricular arrhythmias; and prevent or terminate cyclonic flutter. Teratogenicity: Quinidine has been shown to cause minor cranial nerve damage in fetuses, even at doses far exceeding those required for treating arrhythmias. Drug Interactions: Several drug interactions have been reported. Quinidine has a synergistic effect with warfarin (lowering prothrombin levels). Quinidine can enhance the effects of both non-depolarizing and depolarizing neuromuscular blocking agents. The cardiac depressant effect of quinidine is enhanced when used in combination with other antiarrhythmic drugs; amiodarone can increase blood quinidine concentrations. Rifampin, anticonvulsants, nifedipine, and acetazolamide can decrease quinidine concentrations. Antacids, cimetidine, verapamil, and amiodarone can increase quinidine concentrations; terfenadine, astemizole, as well as thiazide diuretics and loop diuretics increase the risk of quinidine toxicity. Quinidine can increase plasma concentrations of propafenone and digoxin. Major Adverse Reactions: Several adverse reactions have been reported during quinidine treatment. Cardiovascular system: Hypotension; syncope may occur after intravenous administration; arrhythmic effects: torsades de pointes ventricular tachycardia; ECG: widened QRS interval; prolonged PR and QT intervals. Central nervous system: Cinchona poisoning: headache, fever, visual disturbances, mydriasis, tinnitus, nausea, vomiting, and rash. Gastrointestinal tract: Nausea, vomiting, diarrhea, and colic have been reported. Liver: Granulomatous hepatitis or hepatitis with centrilobular necrosis. Skin: Drug fever and photosensitive rash may occur. Hematologic system: Thrombocytopenia (immune reaction) has been observed. Clinical manifestations: Acute poisoning: Ingestion: The severity of quinidine poisoning is related to cardiotoxicity. Symptoms usually appear within 2 to 4 hours and may include: Cardiovascular symptoms: hypotension, cardiogenic shock, cardiac arrest. Electrocardiogram (ECG) may show: decreased T waves; prolonged QT and QRS intervals; atrioventricular block; ventricular arrhythmias (torsades de pointes). Neurological symptoms: tinnitus, drowsiness, syncope, coma, seizures, blurred vision, and diplopia. Respiratory symptoms: hypoventilation and apnea. Cardiotoxicity may be enhanced if other cardiotoxic drugs (antiarrhythmic drugs, tricyclic antidepressants) are ingested concurrently. Parenteral exposure: Symptoms appear more quickly after intravenous administration. Chronic poisoning: Ingestion: The most relevant symptoms of chronic poisoning are: ECG abnormalities; syncope (caused by ventricular arrhythmias such as torsades de pointes) and gastrointestinal disturbances caused by cinchona poisoning. Course, prognosis, and cause of death: The typical course of quinidine poisoning is dominated by cardiovascular disturbances, usually appearing within 2 to 4 hours after exposure, but may not appear until 12 hours after exposure (even later with extended-release formulations). Symptoms can last 24 to 36 hours. Patients who survive 48 hours after acute poisoning are likely to recover. Death may be due to cardiac arrest caused by cardiac cessation or electromechanical dissociation, and in rare cases, ventricular fibrillation. Systematic description of clinical manifestations: Cardiovascular: Acute: Cardiovascular symptoms are the main feature of quinidine poisoning. Tachycardia caused by anticholinergic effects usually occurs in the early or moderate stages of poisoning. In severe poisoning, bradycardia caused by atrioventricular block may occur. Hypotension and shock: Hypotension caused by peripheral vasodilation is common. In severe poisoning, cardiogenic shock is usually observed, accompanied by elevated central venous pressure, which is related to decreased myocardial contractility. Cardiac arrest may occur, which may be related to electromechanical dissociation, ventricular arrhythmias, or cardiac cessation. Arrhythmias are common and may include: atrioventricular block, ventricular voluntary rhythms, ventricular tachycardia and ventricular fibrillation, and torsades de pointes. Symptomatic poisoning patients invariably exhibit ECG changes: repolarization abnormalities, T-wave depression, U-wave elevation, QT and PR interval prolongation, QRS complex widening (>0.08 seconds), and atrioventricular block. Torsades de pointes (TDPT) may cause syncope. Chronic: ECG changes (including repolarization abnormalities, T-wave depression, and QT interval prolongation) are common features during quinidine treatment. Syncope is associated with transient TDPT, occurring in 1% to 8% of quinidine-treated patients. The occurrence of TDPT is not related to plasma quinidine concentration, but QT interval prolongation increases its incidence. Respiratory system: Acute: Respiratory depression or apnea is primarily associated with severe cardiac disturbances such as shock or ventricular arrhythmias. Pulmonary edema with normal pulmonary capillary wedge pressure has been reported after suicide attempts. Nervous System: Central Nervous System: Acute: Drowsiness, delirium, coma, and seizures may occur without cardiac symptoms. However, heart failure should always be considered when central nervous system symptoms are present. Cinchona poisoning may occur occasionally. Chronic: Cinchona poisoning. Delirium has been reported. Peripheral Nervous System: Chronic: Quinidine can enhance the neuromuscular blocking effects of certain skeletal muscle relaxants; administration of quinidine shortly after the neuromuscular blockade has been lifted may lead to a relapse of respiratory paralysis. Autonomic Nervous System: Acute: Quinidine has anticholinergic effects. However, this effect is usually limited to the vagus nerve. Skeletal and Smooth Muscles: Chronic: An elevated serum skeletal muscle enzyme level has been reported in a male patient treated with quinidine. Gastrointestinal Tract: Acute: Nausea and vomiting may occur. Chronic: Gastrointestinal toxicity (nausea, vomiting, diarrhea, and colic) is the most common side effect of quinidine. Liver: Chronic: Quinidine has been reported to cause hepatotoxicity, manifested by elevated serum transaminase, lactate dehydrogenase, and alkaline phosphatase levels, and cholestasis. Kidneys: Acute: No direct nephrotoxicity has been reported. Acute renal failure associated with cardiogenic shock may occur. Dermatology: Chronic: Quinidine use can cause skin lesions, including rash, photosensitivity, and lichen planus. Eyes, Ears, Nose, and Throat: Local Effects: Acute: Cinchona poisoning is rare in acute poisoning. Toxic doses may cause toxic amblyopia, scotomas, and color vision impairment. Chronic: Chronic cumulative overdose may lead to cinchona poisoning: A patient who took quinidine for two years has been reported to experience headache, tinnitus, dizziness, mydriasis, blurred vision, diplopia, photophobia, deafness, and corneal deposits. Hematologic System: Chronic: Immune thrombocytopenic purpura and hemolytic anemia have been reported. Immune System: Chronic: Quinidine may cause a variety of immune-mediated reactions: thrombocytopenia, hemolytic anemia, angioedema, rash, fever. Metabolism: Acid-base imbalance: Acute: Metabolic acidosis may occur in severe poisoning with shock. Fluid and electrolyte imbalance: Acute: Hypokalemia is common. Special Risks: Pregnancy: Long-term use of quinidine may cause cranial nerve damage in the fetus, even at doses much higher than those required to treat arrhythmias. A newborn of a pregnant woman who took quinidine throughout her pregnancy had the same serum quinidine concentration as the mother. The infant's electrocardiogram was normal, and there was no evidence of teratogenicity. Lactation: Long-term use of quinidine: Quinidine concentrations in breast milk are slightly lower than serum concentrations. The dose of quinidine ingested by an infant per liter of breast milk is lower than the therapeutic dose. However, breastfeeding is not recommended because quinidine may accumulate in the immature liver of newborns. Identification: Quinidine is a class II antiarrhythmic drug. Source: Quinidine is the D-isomer of quinine. Quinidine is an alkaloid that may be derived from various cinchona species. Cinchona bark contains 0.25% to 3.0% quinidine. Quinidine is also derived from quinine. Quinidine is a white powder or crystal, odorless, and bitter. Quinidine sulfate is a colorless crystal, odorless, and bitter. Quinidine gluconate is a white powder, odorless, and bitter. Quinidine polygalacturonic acid is a powder. Quinidine sulfate is a white powder or odorless crystal, bitter. Indications: Description: Ventricular premature beats and ventricular tachycardia; supraventricular arrhythmias; maintenance of sinus rhythm after cardioversion of atrial fibrillation or atrial flutter. Human Exposure: Major Risks and Target Organs: Cardiotoxicity is the major risk of quinidine poisoning. Quinidine may cause central nervous system symptoms. Clinical Manifestations Overview: Symptoms of poisoning usually appear within 2–4 hours after ingestion, but the time of onset may vary depending on the quinidine salt and formulation. Symptoms may include cardiac arrhythmias (especially in patients with coexisting cardiovascular disease), neurotoxicity, and respiratory depression. Diagnosis: Cardiac disturbances: circulatory arrest, shock, conduction disturbances, ventricular arrhythmias, ECG changes; Neurological symptoms: tinnitus, somnolence, syncope, coma, seizures, delirium. Respiratory depression. Quinidine concentration may be helpful for diagnosis but is of no clinical benefit. Contraindications: Hypersensitivity or idiosyncratic reaction to cinchona alkaloids; atrioventricular block or complete atrioventricular block; intraventricular block; loss of atrial activity; digitalis poisoning; myasthenia gravis and torsades de pointes. Precautions include: congestive heart failure, hypotension, kidney disease, liver failure; concomitant use of other antiarrhythmic drugs. Use with caution in the elderly and breastfeeding women. Route of administration: Oral: Oral absorption is the most common cause of poisoning. Parenteral administration: Poisoning after intravenous injection is rare, but has been reported in patients receiving intravenous quinidine for arrhythmias. Absorption route: Oral: Quinidine is almost completely absorbed from the gastrointestinal tract. However, due to the first-pass effect of the liver, its absolute bioavailability is approximately 70% to 80% of the ingested dose and may vary depending on the patient and formulation. The time to peak plasma concentration for quinidine sulfate is 1 to 3 hours, for quinidine gluconate it is 3 to 6 hours, and for quinidine polygalacturonic acid it is approximately 6 hours. Sustained-release quinidine is continuously absorbed over 8 to 12 hours. Parenteral administration: After intramuscular injection, quinidine absorption may be unstable and unpredictable; the administered dose may not be completely absorbed, possibly due to drug precipitation at the injection site. Other studies have shown no difference in absorption rates between intramuscular and oral quinidine. Drug distribution (by route of exposure): Oral: Protein binding: Approximately 70%–80% of the drug is bound to plasma proteins. Plasma protein binding is reduced in patients with chronic liver disease. Tissues: Quinidine concentrations in the liver are 10–30 times higher than in plasma. Concentrations in skeletal muscle, myocardium, brain, and other tissues fall between these levels. The erythrocyte-plasma partition ratio is 0.82. Biological half-life (by route of exposure): Elimination half-life: The half-life is approximately 6–7 hours. The elimination half-life is prolonged in patients with chronic liver disease and the elderly. Congestive heart failure or renal failure does not appear to alter the elimination half-life. Metabolism: 50%–90% of quinidine is metabolized in the liver to hydroxylated products. Metabolites include 3-hydroxyquinidine, 2-oxoquinidine, O-demethylquinidine, and quinidine-N-oxide. The major metabolite is 3-hydroxyquinidine, which has similar effects to quinidine and may partially explain the observed antiarrhythmic effects. The elimination kinetics of hydroxyquinidine appear to be similar to those of quinidine. Elimination via exposure: Kidneys: The amount excreted unchanged in urine varies considerably, but is approximately 17% of the administered dose. Up to 50% of the quinidine dose (unchanged + metabolites) is excreted in the urine within 24 hours after administration. Renal excretion depends on urine pH. Excretion is inversely proportional to urine pH. Renal insufficiency and congestive heart failure reduce excretion. Liver: 50% to 90% of the quinidine dose is metabolized in the liver. Bile: Approximately 1% to 3% of quinidine is excreted in feces via bile. Breast milk: Quinidine is secreted into breast milk. Mechanism of Action and Toxicology: Quinidine reduces myocardial permeability to electrolytes (membrane stabilizer) and is a systemic cardiac depressant. It has negative inotropic effects; inhibits spontaneous diastolic depolarization; slows conduction; prolongs the effective refractory period; and increases the electrical threshold. This leads to decreased myocardial contractility, impaired conduction (atrioventricular and intraventricular conduction), and decreased excitability, but may be accompanied by anomalous reentry mechanisms. Quinidine has anticholinergic and peripheral vasodilatory effects. The following progressive changes have been observed in experimental studies: Electrocardiogram: bradycardia, prolonged PR interval, prolonged QT interval, widened QRS complex, and the appearance of ventricular voluntary rhythms, eventually developing into ventricular arrest. Sometimes, the terminal event is ventricular fibrillation. Blood pressure gradually decreases. Blood pressure drops significantly when QRS widening occurs, and approaches zero when slow ventricular voluntary rhythms appear. Electrolyte abnormalities: decreased plasma potassium, sodium, and magnesium concentrations, and acidosis. Electrolytes: Hypokalemia may occur, possibly due to the drug's direct effect on cell membrane permeability, leading to intracellular potassium transport. Neurological symptoms: Syncope and seizures may represent direct toxicity of the drug to the central nervous system, or may be related to cerebral ischemia caused by circulatory or respiratory failure. Pharmacodynamics: Quinidine slows the firing rate of normal and ectopic pacemakers; it increases the threshold for electrically induced arrhythmias; it prevents ventricular arrhythmias; and it can prevent or terminate vortex fibrillation. Teratogenicity: Quinidine has been shown to cause minor cranial nerve damage in fetuses, even at doses far exceeding those required for treating arrhythmias. Drug interactions: Several drug interactions have been reported. Quinidine has a synergistic effect with warfarin (lowering prothrombin levels). Quinidine can enhance the effects of non-depolarizing and depolarizing neuromuscular blocking agents. The cardiac depressant effect of quinidine is enhanced when used in combination with other antiarrhythmic drugs; amiodarone can increase the concentration of quinidine in the blood. Rifampin, anticonvulsants, nifedipine, and acetazolamide can decrease quinidine concentrations. Antacids, cimetidine, verapamil, and amiodarone can increase quinidine concentrations. Terfenadine, astemizole, thiazides, and loop diuretics increase the risk of quinidine poisoning. Quinidine can increase plasma concentrations of propafenone and digoxin. Major adverse reactions: Several adverse reactions have been reported during quinidine treatment. Cardiovascular system: Hypotension after intravenous administration; syncope; arrhythmogenic effects: torsades de pointes; ECG: widened QRS interval; prolonged PR and QT intervals. Central nervous system: Cinchona poisoning: headache, fever, visual disturbances, mydriasis, tinnitus, nausea, vomiting, and rash. Gastrointestinal tract: Nausea, vomiting, diarrhea, and colic have been reported. Liver: Granulomatous hepatitis or hepatitis with centrilobular necrosis. Skin: Drug fever and photosensitive rashes may occur. Hematologic system: Thrombocytopenia (immune response) has been observed. Clinical manifestations: Acute poisoning: Ingestion: The severity of quinidine poisoning is related to cardiotoxicity. Symptoms usually appear within 2 to 4 hours and may include: Cardiovascular symptoms: hypotension, cardiogenic shock, cardiac arrest. Electrocardiogram may show: decreased T waves; prolonged QT and QRS intervals; atrioventricular block; ventricular arrhythmias (torsades de pointes). Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsions, blurred vision, and diplopia. Respiratory symptoms: hypoventilation and apnea. Cardiotoxicity may be enhanced if other cardiotoxic drugs (antiarrhythmic drugs, tricyclic antidepressants) are ingested concurrently. Parenteral exposure: Symptoms appear more rapidly after intravenous administration. Chronic Poisoning: Ingestion: The most relevant symptoms of chronic poisoning include: ECG abnormalities; syncope due to ventricular arrhythmias (torsades de pointes) and cinchona poisoning; gastrointestinal disturbances. Course, Prognosis, and Causes of Death: The typical course of quinidine poisoning is dominated by cardiovascular disturbances, usually appearing within 2 to 4 hours of exposure, but may occur as late as 12 hours (even later with sustained-release formulations). Symptoms can last 24 to 36 hours. Patients who survive 48 hours after acute poisoning are likely to recover. Death may be due to cardiac arrest or electromechanical dissociation, and in rare cases, ventricular fibrillation. Systematic Description of Clinical Effects: Cardiovascular: Acute: Cardiovascular symptoms are the main feature of quinidine poisoning. Tachycardia caused by anticholinergic effects usually occurs in the early or moderate stages of poisoning. In severe poisoning, bradycardia due to atrioventricular block may occur. Hypotension and Shock: Hypotension due to peripheral vasodilation is common. In severe poisoning, cardiogenic shock often occurs, accompanied by elevated central venous pressure, which is related to decreased myocardial contractility. Cardiac arrest may occur, possibly related to electromechanical dissociation, ventricular arrhythmias, or cardiac arrest. Arrhythmias are common and may include: atrioventricular block, ventricular voluntary rhythms, ventricular tachycardia and ventricular fibrillation, and torsades de pointes. In symptomatic poisoning, ECG changes are consistently present: repolarization abnormalities, T-wave depression, U-wave elevation, QT and PR interval prolongation, QRS complex widening (>0.08 seconds), and atrioventricular block. Syncope caused by torsades de pointes may occur. Chronic: ECG changes (including repolarization abnormalities, T-wave depression, and QT interval prolongation) are common features during quinidine treatment. Syncope is associated with transient torsades de pointes and occurs in 1% to 8% of patients treated with quinidine. The occurrence of torsades de pointes ventricular tachycardia is not related to plasma quinidine concentration, but QT interval prolongation increases its likelihood. Respiratory System: Acute: Respiratory depression or apnea is mostly associated with severe cardiac disturbances, such as shock or ventricular arrhythmias. Cases of pulmonary edema with normal pulmonary capillary wedge pressure following suicide attempts have been documented. Nervous System: Central Nervous System: Acute: Drowsiness, delirium, coma, and seizures may occur without cardiac symptoms. However, heart failure should always be considered when central nervous system symptoms are present. Cinchona poisoning may sometimes occur. Chronic: Cinchona poisoning. Delirium has been reported. Peripheral Nervous System: Chronic: Quinidine can enhance the neuromuscular blocking effects of certain skeletal muscle relaxants; administration of quinidine shortly after the recovery of neuromuscular blockade may lead to relapse of respiratory paralysis. Autonomic Nervous System: Acute: Quinidine has anticholinergic effects. However, this effect is usually limited to the vagus nerve. Skeletal and smooth muscle: Chronic: An elevated serum skeletal muscle enzyme level has been reported in a male patient treated with quinidine. Gastrointestinal tract: Acute: Nausea and vomiting may occur. Chronic: Gastrointestinal toxicity (nausea, vomiting, diarrhea, and colic) is the most common side effect of quinidine. Liver: Chronic: Hepatotoxicity has been reported, manifested as elevated serum transaminase, lactate dehydrogenase (LDH), alkaline phosphatase levels, and cholestasis. Kidney: Acute: No direct nephrotoxicity has been reported. Acute renal failure associated with cardiogenic shock may occur. Skin: Chronic: Skin lesions associated with quinidine use include rash, photosensitivity, and lichen planus. Eyes, ears, nose, and throat: Local effects: Acute: Cinchona poisoning is rare in acute cases. Toxic doses may cause toxic amblyopia, scotomas, and color vision impairment. Chronic: Long-term cumulative overdose may lead to cinchona poisoning: A patient who took quinidine for two years has been reported to experience symptoms such as headache, tinnitus, dizziness, dilated pupils, blurred vision, double vision, photophobia, deafness, and corneal deposits. Hematologic system: Chronic: Immune thrombocytopenic purpura and hemolytic anemia have been reported. Immune system: Chronic: Quinidine may cause various immune-mediated reactions: thrombocytopenia, hemolytic anemia, angioedema, rash, and fever. Metabolism: Acid-base imbalance: Acute: Metabolic acidosis may occur in severe poisoning with shock. Fluid and electrolyte imbalance: Acute: Hypokalemia is commonly observed. Special risks: Pregnancy: Chronic: Quinidine doses far exceeding those required for treating arrhythmias have been shown to cause fetal cranial nerve damage. A pregnant woman took quinidine throughout her pregnancy, and her newborn had the same serum quinidine concentration as the mother. The infant's electrocardiogram was normal, and no evidence of teratogenicity was found. Breastfeeding: Long-term breastfeeding: Quinidine concentrations in breast milk are slightly lower than serum concentrations. The dose of quinidine ingested by an infant drinking 1 liter of breast milk is lower than the therapeutic dose. However, breastfeeding is not recommended because quinidine may accumulate in the immature liver of newborns. /Quinidine/ International Programme for Chemical Safety; Toxic Information Monograph: Quinidine (PIM 463) (1990) Available as of April 7, 2009 at: https://www.inchem.org/pages/pims.html

[1]. Wrighton DC, et al. Mechanism of inhibition of mouse Slo3 (KCa 5.1) potassium channels by quinine, quinidine and barium. Br J Pharmacol. 2015 Sep;172(17):4355-63.
[2]. Cheng KI, et al. Application of quinidine on rat sciatic nerve decreases the amplitude and increases the latency of evoked responses. J Anesth. 2014 Aug;28(4):559-68

Quinidine is a cinchona alkaloid composed of cinchonaine, in which the hydrogen at the 6-position of the quinoline ring is replaced by a methoxy group. It possesses a variety of pharmacological activities, including alpha-adrenergic antagonist, antimalarial drug, antiarrhythmic drug, sodium channel blocker, muscarinic receptor antagonist, potassium channel blocker, P450 inhibitor, EC 1.14.13.181 (13-deoxydaunorubicin hydroxylase) inhibitor, EC 3.6.3.44 (xenobiotic transporter ATPase) inhibitor, and drug allergen. It is derived from the hydride of cinchonaine. Quinidine is the D-isomer of quinine, found in cinchona bark and similar plants. This alkaloid was first described in 1848 and has a long history of use as an antiarrhythmic drug. Quinidine is considered the first antiarrhythmic drug (Class Ia) and has moderate efficacy in converting acute atrial fibrillation to normal sinus rhythm. It prolongs cellular action potentials by blocking sodium-potassium currents. A phenomenon known as "quinidine syncope" was first described in the 1950s, characterized by syncope and ventricular fibrillation in patients taking the drug. Quinidine use declined in the following decades due to its side effects and increased risk of death. However, it is still used to treat Brugada syndrome, short QT syndrome, and idiopathic ventricular fibrillation. Quinidine is an antiarrhythmic drug and a cytochrome P450 2D6 inhibitor. Quinidine's mechanism of action is as a cytochrome P450 2D6 inhibitor. Quinidine is a natural cinchonas alkaloid with potent antiarrhythmic activity and has been used for decades to treat atrial and ventricular arrhythmias. Quinidine is associated with fever, mild jaundice, and clinically significant liver damage in up to 2% of treated patients. Quinidex has been reported in cinchona calisaya, ciliosemina pedunculata, and other organisms with relevant data. Quinidex sulfate is the sulfate form of quinidex, an alkaloid with antimalarial and antiarrhythmic (class Ia) properties. Quinidex sulfate exerts its antimalarial activity primarily by binding to heme polymers (heme crystals) in the acidic food vacuoles of Plasmodium, thereby inhibiting further polymerization of heme polymerase, ultimately leading to the accumulation of toxic heme and the death of the Plasmodium. Quinidex sulfate also exerts its antiarrhythmic effect by inhibiting the influx of sodium ions into cells during phase 0 of the myocardial action potential, thus slowing impulse conduction through the atrioventricular node, reducing the rate of phase 0 depolarization, and prolonging the refractory period. Quinidex sulfate can also reduce the slope of phase 4 depolarization of Purkinje fibers, thereby slowing cardiac conduction velocity and reducing cardiac automaticity.

---

View More

Quinidine is an alkaloid extracted from cinchona bark, possessing class 1A antiarrhythmic and antimalarial effects. Quinidine stabilizes neuronal membranes by binding to and inhibiting the activity of voltage-gated sodium channels, thereby suppressing the sodium ion influx required for impulse initiation and conduction, leading to an increased excitation threshold and reduced depolarization during phase 0 of the action potential. Furthermore, the effective refractory period (ERP), action potential duration (APD), and ERP/APD ratio are all prolonged, resulting in decreased nerve impulse conduction velocity.

Quinidine exerts its antimalarial activity primarily by binding to heme polymers (heme crystals) in the acidic food vacuoles of Plasmodium, thereby inhibiting further polymerization of heme polymerase, ultimately leading to the accumulation of toxic heme and the death of the Plasmodium. Quinine is an optical isomer of quinine, extracted from cinchona bark and similar plants. This alkaloid reduces the excitability of cardiac and skeletal muscle, prolongs cellular action potentials, and decreases automaticity by blocking sodium-potassium currents on cell membranes. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission. Indications: Quinidine is indicated for the treatment and prevention of atrial fibrillation/atrial flutter, and for the suppression of recurrent, documented ventricular arrhythmias. It is also used to treat Brugada syndrome, short QT syndrome, and idiopathic ventricular fibrillation.

---

Therapeutic Uses
Adrenergic alpha receptor antagonist; antiarrhythmic drug; antimalarial drug; enzyme inhibitor; muscarinic receptor antagonist
Quinidine is indicated for the treatment of recurrent, documented, life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Quinidine should not be used to treat milder ventricular arrhythmias, such as asymptomatic premature ventricular contractions. /US Product Label/
Quinidine is indicated for the treatment of symptomatic atrial fibrillation or atrial flutter, especially in patients whose symptoms cannot be controlled by measures to lower the ventricular rate. /US Product Label/
For certain patients at high risk of developing symptomatic atrial fibrillation or atrial flutter, such as those with a history of frequent episodes and poor tolerance, for whom the risk of prophylactic quinidine treatment outweighs the risk, long-term use of quinidine is recommended.

---

Drug Warnings
Quinidine may cause rare skin reactions, including measles-like and scarlet fever-like rashes, urticaria, rash, pruritus, exfoliative dermatitis, eczema, severe exacerbation of psoriasis, lichenification, flushing, pigmentary abnormalities, photosensitive dermatitis, and contact dermatitis.
Adverse reactions are not related to plasma concentrations and may include drug fever, cholestatic hepatitis, systemic lupus erythematosus, asthma, allergic reactions, thrombocytopenia, hemolytic anemia (especially in glucose-6-phosphate dehydrogenase deficiency), and hypoprothrombinemia. Skin changes include maculopapular rash, thrombocytopenic purpura, cutaneous vasculitis, photosensitivity, and bullous lesions.
Drug-induced agranulocytosis is a clinical condition characterized by a selective reduction in circulating neutrophils, typically decreasing to below 0.2 × 10⁹/L after administration. Quinidine is a widely used antiarrhythmic drug in outpatient settings and has some known hematological side effects. Mid-term use of quinidine has been associated with a small number of cases of agranulocytosis. This article describes a case of a 60-year-old male patient with atrial fibrillation who developed sudden agranulocytosis 3 days after starting quinidine, and whose neutrophil levels returned to normal on the third day of hospitalization.

---

Pharmacodynamics
Quinidine is an antimalarial schizotoxic agent and a class Ia antiarrhythmic drug used to terminate or prevent reentrant arrhythmias and arrhythmias caused by increased automaticity, such as atrial flutter, atrial fibrillation, and paroxysmal supraventricular tachycardia. In most patients, quinidine causes an increase in sinus rate. Quinidine also significantly prolongs the QT interval in a dose-dependent manner, acts as an alpha-adrenergic antagonist in the periphery, and has anticholinergic and negative inotropic effects. Quinidine-induced QT interval prolongation can lead to increased ventricular automaticity and polymorphic ventricular tachycardias, such as torsades de pointes. Bradycardia, hypokalemia, hypomagnesemia, or elevated serum quinidine concentrations increase the risk of torsades de pointes ventricular tachycardia. However, this arrhythmia can occur even in the absence of any of these conditions. Patients receiving quinidine may also experience paradoxical increases in ventricular rate during atrial flutter/fibrillation, while patients with sick sinus syndrome receiving quinidine may experience significant sinoatrial node suppression and bradycardia. Mechanism of Action
Quinidine has complex electrophysiological properties that are not fully elucidated. The antiarrhythmic effect of this drug is achieved by affecting sodium channels in Purkinje fibers. Quinidine blocks fast sodium channels (INa), thereby reducing the zero phase of the rapid depolarization of the action potential. Quinidine also reduces repolarizing potassium currents (IKr, IKs), inward rectified potassium currents (IK1), and transient outward potassium currents (Ito), as well as L-type calcium currents (ICa) and late inward sodium currents (INa). The reduction of these currents leads to a prolongation of the action potential duration. Quinidine promotes early after-depolarization (EAD) by shortening the plateau phase and prolonging late depolarization. Furthermore, in malaria patients, quinidine primarily functions as an intraerythrocyte schizonticide, exhibiting gametophyte-killing activity against Plasmodium vivax and Plasmodium malariae, but ineffective against Plasmodium falciparum. The exact mechanism of quinidine's antiarrhythmic effect is not fully elucidated, but it is considered a class I (membrane-stable) antiarrhythmic drug. Like other class I antiarrhythmic drugs, quinidine is thought to bind to inactive fast sodium channels, thereby inhibiting post-repolarization recovery in a time- and voltage-dependent manner, which is related to the subsequent dissociation of the drug from the sodium channel. Quinidine exhibits the characteristic electrophysiological effects of class IA antiarrhythmic drugs. The electrophysiological characteristics of different subgroups of class I antiarrhythmic drugs may be related to the quantitative differences in their binding and dissociation rates with transmembrane sodium channels, with class IA drugs exhibiting binding and dissociation rates intermediate between the two. Like lidocaine and procainamide, quinidine inhibits the automaticity of the His-Purkinje system. Commonly used doses of quinidine reduce the automaticity of ectopic pacemakers, but the extent of this effect depends on the drug's anticholinergic effects on the sinoatrial node, atria, and atrioventricular node. Very high concentrations of quinidine may increase myocardial automaticity. This drug reduces conduction velocity in the atria, ventricles, and His-Purkinje system, and may reduce or not affect the conduction velocity of the atrioventricular node. Quinidine may inhibit atrial fibrillation or flutter by prolonging the effective refractory period and increasing the action potential duration in the atria, ventricles, and His-Purkinje system. Because the prolongation of the effective refractory period is greater than the increase in action potential duration, myocardial tissue remains in a refractory state even after the resting membrane potential recovers. Quinidine can shorten the effective refractory period of the atrioventricular node, and its anticholinergic effects may also increase the conductivity of the atrioventricular node. The effects of quinidine on the atrial fiber refractory period and action potential duration may be regulated by its anticholinergic effects. Quinidine reduces cardiac excitability during diastole and relative refractory periods by increasing the electrical excitation threshold. At therapeutic plasma concentrations, quinidine prolongs the QRS complex and QT interval. Quinidine also has some antipyretic and oxytocin-inducing effects. Quinidine has a very weak curare-like effect on the neuromuscular junction and can inhibit skeletal muscle action potentials. Intravenous quinidine primarily inhibits myocardial contractility and reduces systemic vascular resistance by blocking α-adrenergic receptors. High plasma concentrations of quinidine can increase left ventricular end-diastolic pressure through its negative inotropic effect. Inhibition of myocardial contractility can lead to cardiovascular failure. Quinidine primarily kills the schizonts in the asexual erythrocytes of Plasmodium falciparum during the cell cycle. Quinidine can also kill the gametophyte stages of Plasmodium (including Plasmodium malariae, Plasmodium vivax, and Plasmodium ovale).

C20H24N2O2.HCL.H2O

378.89298

378.171

6151-40-2

Quinidine (15% dihydroquinidine);56-54-2;Quinidine sulfate;50-54-4;Quinidine sulfate dihydrate;6591-63-5;Quinidine polygalacturonate;27555-34-6;Quinidine gluconic acid;7054-25-3

16219921

Typically exists as White to off-white solid at room temperature

495.9ºC at 760 mmHg

258-259ºC

253.7ºC

3.848

3

5

4

26

457

4

C=C[C@H]1C[N@](CC[C@H]1C2)[C@@]2([H])[C@@H](O)C3=CC=NC4=CC=C(OC)C=C34.[H]Cl.[H]O[H]

SGVZDMWHXVXUBY-KAIFKDDSSA-N

InChI=1S/C20H24N2O2.ClH.H2O/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18;;/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3;1H;1H2/t13-,14-,19+,20-;;/m0../s1

(S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol;hydrate;hydrochloride

Quinidine hydrochloride monohydrate; 6151-40-2; Quinidine, monohydrochloride, monohydrate; Z1PDY5DB92; 6'-Methoxycinchonan-9-ol hydrochloride monohydrate; Cinchonan-9-ol, 6'-methoxy-, hydrochloride, hydrate (1:1:1), (9S)-; Cinchonan-9-ol, 6'-methoxy-, monohydrochloride, monohydrate, (9S)-; (S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol;hydrate;hydrochloride;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~263.93 mM)
H2O : ~2.5 mg/mL (~6.60 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (6.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (6.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)