What Is Quinidine?

Quinidine, also known as isoquinine, is a chemical (alkaloid) with white to pale yellow crystalline powder. The chemical name is (9 S ) -6-methoxy-deoxycinconine-9-ol, the molecular formula is C ₂₀ H ₂₅ N ₂ O ₂ and the molecular weight is 325.4242. Quinidine is used clinically for maintenance treatment of atrial fibrillation or atrial flutter after electrical conversion.

Chinese name: Quinidine
Foreign name: Quinidine
CAS number: 56-54-2

Molecular formula: C20H25N2O2
Molecular weight: 325.4242
Melting point: 168-172

Introduction to quinidine compounds

Quinidine

Chinese name: Quinidine

Chinese alias: Isoquinine; Heterophylline Sodium; (+)-Quinidine

English name: Quinidine

English alias: Quinidine free base; (+)-Quindine; (9S) -6'-methoxycinchonan-9-ol; (9S) -6'-methoxycinchonan-1-ium-9-ol; (4beta, 8alpha, 9S) -9-hydroxy-6'-methoxycinchonan-1-ium; (4beta, 9S) -9-hydroxy-6'-methoxycinchonan-1-ium; (8alpha, 9S) -9-hydroxy-6'-methoxycinchonan-1- ium

CAS: 56-54-2

Molecular formula: C ₂₀ H ₂₅ N ₂ O ₂

Molecular weight: 325.4242 ^[1]

Chemical structure:

Quinidine physical and chemical properties

Appearance and properties: white to light yellow crystal powder

Density: 0.05 g / 100 mL (20ºC)

Melting point: 168-172 ° C (lit.)

Boiling point: 495.9ºC at 760 mmHg

Flash point: 253.7ºC

Water solubility: 0.05 g / 100 mL (20 ºC)

Stability: Stable. Incompatible with strong oxidizing agents.

Storage conditions: Keep containers tightly closed. Store protected from light. Store in a cool, dry area away from incompatible substances. ^[1]

Overview of basic information about quinidine drugs

Quinidine source

Cinchona contains alkaloids and is an isomer of quinine. Properties: Its sulfate is commonly used as white fine needle-like crystals; it is odorless; its taste is extremely bitter; it gradually changes color when exposed to light; its solution is dextral and exhibits neutral or alkaline reactions. Easily soluble in boiling water or ethanol, soluble in chloroform, slightly soluble in water, and almost insoluble in ether ^[2] .

Quinidine preparation

1. Tablets: 0.2g each;

2. Quinidine gluconate injection: 0.5g (10ml) each. ^[2]

Quinidine indications

Oral for premature atrial beat, atrial fibrillation, paroxysmal supraventricular tachycardia, preexcitation syndrome with supraventricular arrhythmia, ventricular premature beat, ventricular tachycardia and fibrillation or atrial flutter after electroconversion. Maintenance treatment. Intramuscular and intravenous injections are no longer used ^[2] .

Quinidine dosage

1. Oral: 0.2g each time, 1 time every 2 hours, 5 times in a row; if it is not effective without obvious toxicity, increase to 0.3g each time on the second day, and 0.4g each time on the 3rd day, Once every 2 hours, 5 times in a row. The daily total should not exceed 2g. After returning to normal heart rhythm, change the maintenance amount to 0.2-0.4g per day. If it is not effective for 3 to 4 days or has a toxic reaction, the drug should be discontinued.

2. Intravenous injection: used when necessary, and must be performed under ECG observation. 0.25g each time, diluted with 5% glucose solution to 50ml slowly intravenously. Pediatric 2mg / kg each time ^[2] .

Quinidine adverse reactions

If you feel unwell during taking this product, tell your doctor or pharmacist as soon as possible. In case of emergency, you can stop taking the medicine first. About one-third of patients with this product have adverse reactions. The following are possible adverse reactions, but not everyone is sure to happen, you may not encounter any of them, don't be nervous.

Extracting quinidine plants

1. Cardiovascular system: This product has an arrhythmogenic effect and produces cardiac arrest and conduction block. It is more common in patients with existing heart disease. Ventricular premature beats, ventricular tachycardia and ventricular fibrillation can also occur. Induced ventricular tachycardia (torsional ventricular tachycardia) or ventricular fibrillation, repeated spontaneous spontaneous stop, with syncope during the onset, this effect has nothing to do with the dose, and can occur when the blood concentration is still within the treatment range Time. This product can cause vasodilation to produce hypotension, and individual vasculitis can occur.

2, gastrointestinal adverse reactions: very common. Includes nausea, vomiting, painful cramps, diarrhea, decreased appetite, lobular hepatitis, and esophagitis.

3. Cinchonism: can produce tinnitus, gastrointestinal disorders, palpitations, convulsions, headaches and flushing. Visual impairments such as blurred vision, photophobia, diplopia, color vision disorders, dilated pupils, dark spots, and night blindness. Hearing impairment, fever, local edema, dizziness, tremor, excitement, coma, anxiety, and even death. Generally associated with an increase in plasma quinidine concentration, which can be prevented and treated by reducing the dose.

4. Atypical reactions: dizziness, nausea, vomiting, cold sweat, shock, bruising, respiratory depression or stop. It has nothing to do with the dose.

5, allergic reactions: various rashes, especially urticaria, pruritus, fever, asthma, hepatitis and collapse. It has nothing to do with the dose.

6, muscle: make myasthenia gravis worse.

7, blood system: thrombocytopenia, acute hemolytic anemia, granulocytopenia, leukocyte classification left shift, neutropenia.

8, immune response: the most common is thrombocytopenia, rare hepatitis, bone marrow suppression, lupus erythematosus. (Note: The above response is not related to the plasma concentration of quinidine, but is determined by the body's specific immune constitution) ^[3]

Treatment of quinidine adverse reactions

1. For adverse cardiac reactions, one is ventricular arrest and conduction block. Isoproterenol or norepinephrine can be dripped intravenously. If it is still ineffective, a ventricular pacemaker is used, but it is not easy to succeed because the pacing threshold is increased. Antifibrillating drugs should not be used, including potassium salts, unless severe hypokalemia.

2. The first is abnormal myocardial agitation. The treatment is to reduce or stop ventricular tachycardia and prevent the development of ventricular fibrillation. Propranolol, lidocaine, phenytoin sodium, or electrocardiographic reversion of ventricular tachycardia and Ventricular fibrillation.

3. Polymorphic ventricular tachycardia can be treated with isoprenaline and sodium bicarbonate (or sodium lactate).

4. Other symptomatic treatments are basically the same as those for general poisoning and allergic reactions. In excess, hemodialysis can be performed to speed up drug clearance. In vitro tests confirmed that activated carbon can adsorb this product. Residual vision impairment may be effective with nitrates and methacholine. Intravenous injection of sodium nitrate can alleviate the toxic blackness in the acute phase ^[3] .

Quinidine contraindications

Cross-allergic reactions:

1. Those who are allergic to quinine may also be allergic to this product.

2. In view of the lack of human data and quinine, a drug closely related to this product, can produce fetal central nervous system and limb deformities, neonatal ototoxicity and oxytocin. Pregnant women should weigh the advantages and disadvantages when using it. This product can be excreted through breast milk and enters the body with breast milk. Although the amount received by the infant is much lower than the therapeutic amount, it may cause drug accumulation due to immature liver development and poor ability to metabolize drugs. Due to the decline in the ability to clear the elderly, it should be appropriately reduced in time.

3. The following conditions should be disabled: digitalis poisoning; degree II to III atrioventricular block (unless a pacemaker is already available); sick sinus node syndrome; cardiogenic shock; severe liver or kidney damage; Ning or its derivatives are allergic; thrombocytopenia (including those with previous history).

4. The following conditions should be used topically; allergic patients; liver or kidney damage; untreated heart failure; first degree atrioventricular block; extreme bradycardia; hypotension (not included due to arrhythmia); low Blood potassium. Severe myocardial damage and pregnant women are contraindicated. Quinidine can affect the fetal heart function through the placenta ^[3] ^[2] .

Quinidine drug interactions

1. When combined with other antiarrhythmic drugs, the effects can be added.

2. Combining with anticoagulants can further reduce prothrombin, and can also reduce the combination of this product and protein. Therefore, it is necessary to pay attention to adjusting the combined dose and the dose after discontinuation.

3. Phenobarbital and phenytoin can increase the intrahepatic metabolism of this product and reduce the serum drug concentration. The dosage should be adjusted as appropriate.

4, digitalis drugs, this product can aggravate arrhythmia when digitalis is excessive. This product can increase the serum concentration of digoxin to toxic levels, and it can also increase the serum concentration of digoxigenin. Therefore, the blood concentration should be monitored and the dosage should be adjusted.

5. Combination with anticholinergic drugs can increase anticholinergic effect.

6, can reduce the effect of choline-like drugs, the dose should be adjusted as needed.

7. This product can enhance and prolong the respiratory depression of neuromuscular blocking drugs, especially cyproterine, succincholine and pancuronium bromide.

8. This product can enhance the effect when combined with potassium preparations, and vice versa when hypokalemia occurs.

9, urine alkalizing drugs such as acetazolamide, a large amount of lemon juice, antacids or bicarbonate, etc., can increase the reabsorption of this product by the renal tubules, so that the common amount of toxic reactions.

10. Combined with antihypertensive drugs, vasodilators and beta blockers, this product can aggravate the antihypertensive and vasodilator effects; combined with beta blockers can also increase the inhibitory effect on the sinoatrial node and atrioventricular node.

11. Rifampicin can increase the metabolism of this product and reduce the blood concentration.

12. Isoprenaline may aggravate the arrhythmia caused by this product overdose, but it is beneficial to the polymorphic ventricular tachycardia on the T wave caused by the prolongation of the QT interval.

Any drug that can increase the activity of liver microsomal metabolic enzymes can promote quinidine metabolism and reduce the effect of quinidine. The combination of quinidine and rifampicin reduces the plasma quinidine concentration and its antiarrhythmic effect. Cimetidine slows the metabolism of quinidine in the liver, causing T1 / 2 of quinidine to prolong, resulting in quinidine accumulation and poisoning. Quinidine has a neuromuscular blocking effect that strengthens some muscle relaxants. Quinidine reinforces the role of warfarin. It is used in combination with other anticholinergics for an additive effect. 10% quinidine sulfate solution is weakly acidic and cannot be used together with alkaline drugs or injections, tannic acid and iodide. Quinidine has a cross-allergic reaction with propanone.

Quinidine notes

1. When used to correct atrial fibrillation and atrial flutter, digitalis saturation should be given first to prevent the heartbeat from speeding up after the heart rhythm changes, leading to heart failure.

2. When combined with quinidine and digoxin, quinidine can reduce the renal excretion of digoxin and increase the blood concentration of digoxin. Therefore, the amount of digoxin should be reduced when combined.

3. Carefully observe changes in heart rhythm and blood pressure before each administration, and avoid dosing at night. When the dose is large during the day, the heart rhythm and blood pressure should also be paid attention at night.

4. In patients with atrial fibrillation, when the heart rhythm returns to normal during the medication, it may induce the thrombus in the atrium to fall off and produce embolic disease, such as cerebral embolism, mesenteric artery embolism, etc., which should be closely observed.

5. For patients who have indications for quinidine but have low blood pressure or are in shock, they should first increase blood pressure, correct shock, and then use it. If the low blood pressure is caused by tachycardia and small cardiac output, quinidine should be used while increasing blood pressure ^[2] .

6, patients with severe myocardial damage and pregnant women are contraindicated.

7. Intravenous injection often causes severe hypotension, which has a greater risk, so please pay attention. Disabled for severe myocardial disease. or degree atrioventricular block, digitalis poisoning, prolonged QT interval, pregnancy, severe liver and kidney function impairment and allergic reactions to this product, be used with caution for degree atrioventricular block and significant heartbeat Those with slowness, hypotension, and myasthenia gravis. Check blood pressure, heart rate, and rhythm before each medication, and record the electrocardiogram to avoid hypokalemia ^[4] .

Quinidine pharmacodynamics

The mechanism of action is mainly to inhibit the transmembrane movement of sodium ions, and secondly to inhibit the inflow of calcium ions. In addition, it has a local anesthetic effect and an indirect block through anticholinergic effects. Receptor produces hypotension (especially more easily produced by parenteral administration); and block vagus nerve can accelerate atrioventricular conduction, for patients with atrial fibrillation or flutter and paroxysmal tachycardia, heart rate can be further accelerated after administration , Aggravating circulatory disorders, therefore, quinidine must be applied on the basis of applying a sufficient amount of cardiac glycosides ^[2] .

Quinidine pharmacokinetics

1. Fast and complete absorption after oral administration. Individual bioavailability varies widely, about 44-98%. Intramuscular absorption is irregular. Due to the strong affinity of the protein, it is widely distributed throughout the body, with an apparent volume of distribution of 0.47 L / kg and a protein binding rate of 70-80%. The effect begins 30 minutes after oral administration and reaches the maximum effect in 1-3 hours, lasting about 6 hours. The effective blood concentration is 3-6 g / ml, and the toxic blood concentration is 8 g / ml. The half-life is 6-8 hours and 2.5-6.7 hours in children ^[2] .

2. Liver dysfunction is prolonged, mainly metabolized by the liver, and some metabolites are pharmacologically active. Liver drug enzyme inducer can increase the metabolism of this product. It is excreted by the kidney, and it is excreted in the original form with about 18.4% (10-20) of the amount consumed. It is mainly filtered through the glomerulus, and the excretion in acid urine is increased. Hemodialysis can promote the elimination of the original drug and metabolism. Feces can be excreted in about 5% of the original form, and a small amount of milk and saliva are also excreted ^[2] .