How Effective Is Digoxin for Atrial Fibrillation?

Digoxin is a medium-effect cardiac glycoside drug, which is white crystal or crystalline powder; odorless; bitter. During treatment, the effect on the heart appears as a positive inotropic effect, which slows down the heart rate and inhibits cardiac conduction. It is suitable for low-volume congestive heart failure, atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. Among the digitalis drugs, digoxin is excreted faster and less accumulatively, the oral absorption is incomplete and irregular, the human poisoning blood concentration is 2.73 ~ 3.9nmol / L, and the adult lethal dose is 10mg.

On October 27, 2017, the list of carcinogens released by the International Agency for Research on Cancer of the World Health Organization initially compiled and referenced digoxin in the list of 2B carcinogens. ^[1]

Drug type: Essential medicines
Drug name: Digoxin

English name: Digoxin
Chinese alias: Isohydroxydigoxigenin; cardiotonin
English alias: Cardiox; Cardoxin; Cedoxin

Digoxin compounds

Digoxin Basic Information

Chinese name

Chinese alias: isoxodigoxigenin; digoxin; cardiotonin; isoxodigoxigenin

Chemical name: 3-[[O-2,6-dideoxy--D-nuclear-hexapyranosyl- (1 4) -O-2,6-dideoxy--D-nuclear-hexane Pyranosyl- (1 4) -2,6-dideoxy--D-nucleo-hexylpyranosyl] oxo] -12, 14-dihydroxy-5-cardiosteroid-20 (22) Lactone

English name: digoxin

English alias: digonix; dynamos; dixina; Digon; davoxin; 12-Hydroxydigitoxin

CAS number: 20830-75-5

Molecular formula: C ₄₁ H ₆₄ O ₁₄

Structural formula:

Molecular weight: 780.93800

Exact mass: 780.43000

PSA: 203.06000

LogP: 2.21810

Digoxin Regulation Information

China

Hazardous Chemicals

Digoxin physical and chemical properties

Appearance and properties: white crystal or crystalline powder; odorless, bitter taste. Melting point is 235 to 245 ° C (decomposed). Soluble in pyridine, slightly soluble in dilute alcohol, very slightly soluble in chloroform, insoluble in water or ether ^[2] .

Density: 1.36 g / cm ³

Melting point: 248-250ºC

Boiling point: 931.6ºC at 760 mmHg

Flash point: 278.5ºC

Storage conditions: Store in a low-temperature, ventilated and dry place, separate from food ingredients

Vapor pressure: 0mmHg at 25 ° C

Digoxin safety information

Packing level: II

Danger category: 6.1

Dangerous Goods Transport Code: UN 3462 6

WGK Germany: 3

Danger category code: R25

Safety instructions: S28-S45

RTECS number: IH6125000

Dangerous goods mark: T ^[2]

Digoxin production method

The dried leaves of purple digitalis or foxglove digitalis were fermented, extracted with ethanol and chloroform, and finally recrystallized from a 70% ethanol solution ^[2] .

Digoxin use

Cholesterol reagent, biochemical research, clinically used as a cardiotonic agent.

Digoxin Pharmacopoeia Standard

[Identification] (1) Take about 1mg of this product, put it in a small test tube, add glacial acetic acid containing ferric trichloride (take 10ml of glacial acetic acid, and add 1 drop of ferric chloride test solution). Slowly add 1ml of sulfuric acid to the wall to form two liquid layers, and the junction will be brown; after being placed, the upper layer will be indigo blue. (2) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution. (3) The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 139).

[Check] The clarity of the solution is to take an appropriate amount of this product, add methanol-trichloromethane (1: 1) to make a 0.5% solution, and it should be clarified. Take the appropriate amount of this substance, weigh it accurately, add dilute ethanol to dissolve and dilute it to make a solution containing about 1mg per lml as the test solution; take 2ml of precise amount, place it in a 100ml volumetric flask, and dilute with diluted ethanol to Scale and shake well as control solution. Another digitalisin reference substance was weighed precisely, dissolved in dilute ethanol and quantitatively diluted to make a solution containing about 0.02 mg per 1 ml as a reference substance solution. According to the chromatographic conditions under the content determination item, take 20 l of the control solution, inject it into the liquid chromatograph, and adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full range; and then accurately measure the test solution and the control. 20 l each of the solution and the reference solution were injected into the liquid chromatograph, and the chromatogram was recorded to 3 times the peak retention time of the main component. If the chromatogram of the test solution has a chromatographic peak consistent with the retention time of digoxigenin peak, the peak area is calculated according to the external standard method. The amount of digoxigenin must not exceed 2.0%; if there are other impurity peaks ( Except for the solvent peak), the area of a single impurity peak must not be greater than the main peak area of the control solution (2.0%), and the sum of the area of each impurity peak must not be greater than 2 times (4.0%) the main peak area of the control solution. Take this product after losing weight and dry it under reduced pressure at 105 for 1 hour. The weight loss should not exceed 1.0% (Appendix L).

[Content determination] Determination according to high performance liquid chromatography (Appendix VD). Chromatographic conditions and system suitability tests use octadecylsilane bonded silica as a filler; acetonitrile-water (10:90) as mobile phase A; acetonitrile-water (60:40) as mobile phase B; as shown in the table below Gradient elution was performed; the detection wavelength was 230 nm; the flow rate was 1.5 ml per minute. The number of theoretical plates is calculated to be not less than 2000 according to the digoxin peak.

Take the appropriate amount of the product by measurement, accurately weigh it, add dilute ethanol to dissolve and quantitatively dilute to make a solution containing about 0.1 mg per 1 ml. As a test solution, take a precise amount of 20 l, inject it into a liquid chromatograph, and record the chromatography Figure; another appropriate amount of digoxin reference substance, measured in the same way. Calculate the peak area according to the external standard method, and get ^[3] .

[Category] Heart-strengthening medicine.

[Storage] Keep sealed.

Digoxin drug description

Digoxin classification

Circulatory System Drugs> Anti-cardiac Insufficiency Drugs> Cardiac Glycosides

Digoxin dosage form

1. Tablet: 0.25mg;

2. Injection: 0.25mg (1ml), 0.5mg (2ml).

Pharmacological effects of digoxin

During treatment, the effect on the heart is shown as a positive inotropic effect, which is a direct effect, not achieved through a neural mechanism. Enhance myocardial contractility, improve pump function, slow heart rate, inhibit myocardial conduction system, increase cardiac output and output, improve pulmonary circulation and systemic circulation. Shrinks an enlarged heart, but does not improve myocardial diastolic function.

Digoxin pharmacokinetics

Oral absorption is rapid and complete, bioavailability is as high as 90% or more, plasma drug concentration peaks at 1h after taking the drug, and the effect is significant after 4h, peak effect is achieved at 6-12h, serum therapeutic concentration is 15-25ng / ml, and plasma protein binding rate is 97 %. It is mainly metabolized by liver microsomal enzymes, and the elimination half-life is generally 4-7 days. It is excreted by bile and excreted by urine after recycling.

Digoxin indication

For a variety of acute and chronic cardiac insufficiency and supraventricular tachycardia, atrial fibrillation and flutter. It is usually taken orally, and intravenously in patients with severe heart failure.

Digoxin usage and dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Digoxin adverse reactions

(1) Common reactions include: new arrhythmia, poor appetite or nausea, vomiting (stimulation of the medulla oblongata center), lower abdominal pain, abnormal weakness (electrolyte disorders). (2) Rare reactions include blurred vision or "yellow vision" (symptoms of poisoning), diarrhea (electrolyte imbalance), and central nervous system reactions such as depression or disturbance. (3) Rare reactions include: lethargy, headache, rash, urticaria (allergic reaction). (4) Arrhythmia is the most important factor in digitalis poisoning, and the most common is premature ventricular contraction; it accounts for about 33% of cardiac responses. Followed by atrioventricular block, paroxysmal or non-paroxysmal junction tachycardia, paroxysmal atrial tachycardia with atrioventricular block, ventricular tachycardia, sinus arrest, ventricular fibrillation Wait. Arrhythmias are more common in children than other reactions, but ventricular arrhythmias are less common than in adults. Newborns may have prolonged PR intervals.

Digoxin contraindications

Prohibited in: For those who are poisoned by cardiac glycoside preparations; Patients with ventricular tachycardia and ventricular fibrillation; Obstructive hypertrophic cardiomyopathy (those with systolic dysfunction or atrial fibrillation can still be considered); Preexcitation Signs associated with atrial fibrillation or flutter.

Digoxin notes

(1) Digitalis is excreted slowly, and it is easy to accumulate poisoning. Therefore, you should check the medication history in detail before taking the drug. In principle, those who have not used slow-acting digitalis in two weeks can be given as usual. Otherwise, the dosage should be adjusted according to specific conditions. . (2) The difference between the amount of cardiac glycoside treated and poisoned is small, and the tolerance and elimination rate of each patient are very different. Most of the listed doses are average doses, so it depends on the condition, Formulation, efficacy and other factors to explore the optimal dose for different patients. (3) Cardiotonin poisoning, generally including nausea, vomiting, anorexia, headache, dizziness, etc., should first be identified whether it is due to increased cardiac insufficiency or excessive cardiac glycosides. The former needs to be increased, and the latter should be stopped. medicine. Once the poisoning is diagnosed, the drug must be discontinued immediately, and the following drugs should be applied according to the specific situation: mild, oral potassium chloride, 1g each time, 3 times a day; if the illness is urgent, such as mental disorders and severe arrhythmia, then Use 1.5 to 3 g of potassium chloride, dissolved in 500 ml of 5% glucose, and slowly instilled intravenously; at the same time, magnesium salts need to be added. Magnesium sulfate or L-aspartate potassium magnesium can be used. However, potassium salts should not be used in patients with renal insufficiency, hyperkalemia, or severe atrioventricular block. Atrioventricular block, sinus bradycardia, sinus arrest, etc. caused by cardiac glycoside, atropine 1 to 5 mg can be injected intravenously and repeated once every 2 to 3 hours. Ventricular arrhythmia caused by digitalis, the effect is better with sodium phenytoin. For emergency cases, 250mg is usually given intravenously, and then 100mg intravenously or 100mg intramuscularly can be continued according to the condition. After that, it can be taken orally and taken daily in 400mg portions. For non-emergency cases, oral administration is sufficient. Lidocaine can also be used for digital arrhythmia and ventricular fibrillation caused by digitalis. Avoid using calcium injection during medication.

Digoxin drug interactions

(1) When used equally with amphotericin B, corticosteroids, or potassium-deficient diuretics such as bumetanide and itanilic acid, it can cause hypokalemia and cause digitalis poisoning. (2) When used with antacids (especially magnesium trisilicate) or antidiarrheal adsorbents such as white clay and pectin, cholestyramine and other anion exchange resins, sulfasalazine or neomycin, it can inhibit foreign Rehmannia glycoside absorption leads to weakened effect of cardioside. (3) When used in combination with antiarrhythmic drugs, calcium salt injection, cocaine, pancuronium bromide, rapamine, succincholine, or pseudoadrenaline drugs, arrhythmia may be caused by the additive effect. (4) -receptor antagonist and this product can lead to atrioventricular block and severe bradycardia, but it cannot be ruled out that supraventricular rapid heart rate cannot be controlled by digitalis alone. (5) With the use of quinidine, the blood concentration of this product can be doubled, and even the poisoning concentration is reached. The degree of increase is related to the amount of quinidine. Even after digoxin is discontinued, the blood concentration will continue. The rise is caused by quinidine displacing digoxin from the tissue junction and reducing its distribution volume. Generally, the dosage of digoxin should be reduced when the two drugs are combined. (6) Used together with verapamil, diltiazem or amiodarone, it can cause severe bradycardia due to lowering the clearance of digoxin by the kidney and the whole body and increasing its blood concentration. (7) Ethanol chloride can cause significant bradycardia when used with this product. (8) Angiotensin-converting enzyme inhibitors, their receptor antagonists, and spironolactone can increase the blood concentration of this product. (9) Indomethacin can reduce the renal clearance of this product, prolong the half-life of this product, and there is a danger of digitalis poisoning. Monitor blood concentration and electrocardiogram. (10) When used with liver and kidney, as this product may partially offset the anticoagulant effect of heparin, the amount of heparin needs to be adjusted. (11) Intravenous magnesium sulphate should be used with extreme caution when digitalis is infused, especially when calcium salts are injected intravenously, changes in cardiac conduction and blockage can occur. (12) Erythromycin can increase the absorption of this product in the gastrointestinal tract due to changes in the gastrointestinal flora. (13) Metoclopramide reduces the bioavailability of digoxin by promoting bowel movement by about 25%. Probencin improves the bioavailability of digoxin by inhibiting intestinal peristalsis by about 25%.

^[3-6]

Digoxin poisoning

Digoxin (Digoxin, isohydroxydigoxigenin) is a medium-effect cardiac glycoside drug, whose main function is to increase myocardial contractility, slow down heart rate, and inhibit cardiac conduction. Among the digitalis drugs, digoxin is excreted faster and has less accumulation, oral absorption is incomplete and irregular, the absorption rate is about 50% to 70%, the onset time is 1 to 2 hours, and the maximum effect is 3 to 6 hours. The effect is maintained for 4 to 7 days; the intravenous injection is effective after 10 to 30 minutes, the maximum effect is reached in 2 to 4 hours, and the effect disappears after 3 to 6 days. The drug is excreted from the urine in its original form without metabolism, with a half-life of 33 to 34 hours. The general oral dose is 0.125 0.5mg, 1 2 / d. The total effective dose is 1 1.5mg, and it is taken in divided portions every 24h, once every 6 8h. The concentration of human poisoning blood drug is 2.73 3.9nmol / L, and the adult lethal dose is 10mg.

This medicine mainly damages the digestive system, heart, vision and nervous system.

Clinical manifestation

1. Early manifestations of poisoning include gastrointestinal reactions such as nausea, vomiting, diarrhea, anorexia, and systemic symptoms such as headache, dizziness, fatigue, and insomnia.

2. Cardiotoxicity, which can occur a variety of arrhythmias, slowing heart rate, pre-ventricular contraction, multi-source multi-phase pre-contraction contraction, triplet, causing supraventricular tachycardia, atrioventricular block Atrioventricular node suppression, sinus arrest, severe cases may occur ventricular tachycardia, ventricular fibrillation, and even sudden cardiac arrest and sudden death.

3. Visual changes, yellow vision, green vision, blurred vision may appear.

4. Nervous system manifestations, headache, insomnia in the early stage, disorientation, delirium, insanity, epileptic seizures, etc. may occur.

treatment

The main points of treatment for digoxin poisoning are:

1. If the pre-frequent contraction, doublet, ventricular bradycardia, less than 60 beats / min, and chromo-visual impairment, etc., stop taking the drug in time, and the symptoms of poisoning will alleviate and disappear.

2. For hypertachyarrhythmias and ventricular premature contractions, potassium salts can be used for treatment, potassium chloride 1.0-2.0 g, dissolved in 5% glucose solution 500ml intravenously for 24 hours.

3. Ventricular contraction, ventricular fibrillation can use lidocaine 100 ~ 800mg, dissolved in 5% glucose solution 500ml, intravenous drip. Supraventricular tachycardia can be given to verapamil (Vapadidine), propafenone (Routine) and so on.

4. Conduction block, sinus bradycardia, sinus arrest, atropine 1 ~ 5mg, intravenous drip, repeated once every 2 ~ 3h.

5. Ion exchange resins (such as cholestyramine) can multiply complex cardiac glycosides in the intestinal cavity, preventing them from being absorbed and excreted with feces.

6. Dialysis therapy: dialysis treatment is feasible within 36 hours after poisoning. Patients with severe acute conditions can perform plasma exchange therapy.

7. Digoxin specific antibodies can be used to quickly and effectively remove digoxin ^[7] .

Digoxin preparation

Tablet: 0.25mg

Digoxin Expert Reviews

Among the cardiotonics, digitalis' most unique effect is to slow down heart rate while enhancing myocardial contractility, without drug resistance, easy to take, low price, and withstanding more than 200 years of clinical practice. In particular, the recently completed DIG trials have affirmed the efficacy of digitalis, which can not only increase the stroke volume and cardiac output, upgrade cardiac function, increase exercise tolerance, reduce the number of hospitalizations, combined with diuretics and ACF inhibitors, there are The combined effect, therefore, digitalis is currently the only long-term oral cardiotonic agent approved by the US FDA ^[8] .

Digoxin tablets

Indications: 1. For acute and chronic cardiac insufficiency such as hypertension, valvular heart disease, and congenital heart disease. Particularly suitable for cardiac insufficiency in atrial fibrillation with rapid ventricular rate; cardiac function for pulmonary heart disease, severe myocardial ischemia, active myocarditis and extracardiac factors such as severe anemia, hypothyroidism and vitamin B1 deficiency Incomplete efficacy is poor.

2. Used to control atrial fibrillation with rapid ventricular rate, ventricular rate in patients with atrial flutter, and supraventricular tachycardia.

Dosage:

1. Usual dose for adults. Oral: commonly used 0.125 0.5mg (half tablet-2 tablets), once a day, 7 days to reach steady-state blood drug concentration; if the rapid load is reached, 0.25mg (1 tablet) can be administered every 6-8 hours, The total dose is 0.75 1.25mg / day (3-5 tablets / day); the maintenance amount is 0.125 0.5mg per day (half tablets-2 tablets).

2. Commonly used in children. Oral: the total amount of this product, 0.02 to 0.03 mg / kg for premature infants; 0.03 to 0.04 mg / kg for newborns under 1 month; 0.05 to 0.06 mg / kg for January to 2 years old; 0.03 to 0.04 mg for 2 to 5 years old / kg; 5 to 10 years old, 0.02 to 0.035 / kg; 10 years old or older, according to the usual dosage for adults; the total amount of this product is divided into 3 times or every 6 to 8 hours. The maintenance amount is 1/5 to 1/3 of the total, divided into 2 times, once every 12 hours or once a day. In infants and young children (especially premature infants), careful titration of doses and close monitoring of plasma concentrations and electrocardiograms are needed. In recent years, studies have shown that digoxin is given daily at a fixed dose and can reach a stable concentration in the body after 6 to 7 days to exert its full effect. Therefore, those who are not ill and are susceptible to poisoning can use 5.5 g / kg daily. Administration can also obtain satisfactory therapeutic effects and reduce the incidence of poisoning.

Dosage form: tablet

Adverse reactions:

1. Common adverse reactions include: arrhythmia, poor appetite or nausea, vomiting (stimulation of the medulla oblongata), lower abdominal pain, abnormal weakness, and weakness.

2. Rare reactions include blurred vision or "color vision," such as yellow vision, green vision, diarrhea, and central nervous system reactions such as depression or confusion.

3. Rare reactions include: lethargy, headache and rash, and measles (allergic reaction).

4. Among the manifestations of digitalis poisoning, arrhythmia is the most important. The most common one is ventricular premature beats, accounting for about 33% of the adverse reactions to arrhythmia. Followed by atrioventricular block, paroxysmal or accelerated border tachycardia, paroxysmal atrial tachycardia with atrioventricular block, ventricular tachycardia, sinus arrest, ventricular fibrillation, etc. Central arrhythmias are more common in children than in other reactions, but ventricular arrhythmias are less common than in adults. Newborns may have prolonged PR intervals.

Contraindications: 1. Combined with calcium injection.

2. Poisoning from any digitalis preparation.

3. Ventricular tachycardia, ventricular fibrillation.

4. Obstructive hypertrophic cardiomyopathy (those with systolic insufficiency or atrial fibrillation can still be considered).

5. Preexcitation syndrome with atrial fibrillation or flutter.

Precautions:

1. Not compatible with acids and bases.

2. Use with caution: hypokalemia; incomplete atrioventricular block; hypercalcemia; hypothyroidism; ischemic heart disease; myocardial infarction; myocarditis; impaired renal function.

3. Follow-up inspections should be taken during medication: blood pressure, heart rate and heart rhythm; electrocardiogram; cardiac function monitoring; electrolytes especially potassium, calcium, magnesium; renal function; when digitalis poisoning is suspected, blood concentration of digoxin should be determined. When overdose, due to the small accumulation,-the symptoms of poisoning usually disappear 1 to 2 days after stopping the drug.

4. Monitor digoxin blood concentration during application.

5. The dosage of this product should be individualized.

Ingredients: Chemical name: 3-[[O-2,6-dideoxy--D-core-hexapyranosyl- (1 4) -O-2,6-dideoxy--D-core -Hexopyranosyl- (1 4) -2,6-dideoxy--D-nucleo-hexopyranosyl] oxo] -12, 14-dihydroxy-5-cardiosteroid-20 ( 22) lactone.

Molecular formula: C41H64O14

Molecular weight: 780.95

Medication for pregnant and lactating women: This product can pass through the placenta, so the amount of mother's body may increase in the second trimester, and it should be reduced 6 weeks after delivery. This product can be excreted into breast milk. The application of breastfeeding women must be weighed against the pros and cons.

Medication for children: The neonatal tolerance to this product is uncertain, and its renal clearance is reduced; premature and immature babies are sensitive to this product, and the dose is reduced according to their immaturity. According to body weight or body surface area, infants over 1 month are slightly larger than adults.

Drugs for the elderly: elderly patients with liver and kidney dysfunction, reduced apparent distribution volume or electrolyte imbalance, the tolerance to this product is low, the dose must be reduced.

Drug Interactions: 1. When used in the same manner as amphotericin B, corticosteroids, or potassium-deficient diuretics such as Bumetanide (products are bupropionate) and Ethacrynic Acid (diuretic acid), it can cause Digitalis poisoning caused by hypokalemia.

2. With antacids (especially magnesium trisilicate) or antidiarrheal adsorbents such as white clay, pectin, colestyramine (cholestyramine) and other anion exchange resins, sulfasalazine (Sulfasalazine) or When neomycin and p-salicylic acid are used together, it can inhibit the absorption of digitalis and cardiac glycosides, resulting in a weakened effect of cardiac glycosides.

3. With antiarrhythmic drugs, calcium injections, cocaine, pancuronium bromide (Pancoron, Pawrowang), rapifine, succinylcholine (Scoline, Suxamethonium Chloride)

Or when used together with pseudoadrenaline drugs, arrhythmia may be caused by the additive effect.

4. Patients with severe or complete atrioventricular block with normal blood potassium should not use potassium salts at the same time. However, when thiazide diuretics are used together with this product, potassium salts must be given to prevent Hypokalemia.

5. Beta blockers used with this product may cause severe bradycardia in the atrioventricular block, which should be taken seriously. However, it is not ruled out that -blockers are used for digital ventricular tachyarrhythmias that cannot control ventricular rate.

6. With the use of quinidine, the blood concentration of this product can be doubled. The increase is related to the amount of quinidine. It can even reach the toxic concentration. Even if digoxin is stopped, its blood concentration will continue to rise. This is because quinidine replaces digoxin from the tissue junction and reduces its distribution volume. The dosage of digoxin should be reduced by 1/2 to 1/3 when the two drugs are combined.

7. Combined with verapamil, diltiazem, and amiodarone, it can cause severe bradycardia due to lowering the clearance of digoxin by the kidney and the whole body and increasing its blood concentration.

8. Spironolactone can prolong the half-life of this product. You need to adjust the dose or the interval between administrations. Follow-up monitoring of the blood concentration of this product.

9. Angiotensin-converting enzyme inhibitor and its receptor antagonist can increase the blood concentration of this product.

10. Ephedrine chloramine (E (# dro #) honium Chloride, Tensilon) can cause significant bradycardia in combination with this product.

11. Indometacin (Indomethacin) can reduce the renal clearance of this product, prolong the half-life of this product, and there is a danger of poisoning. It is necessary to monitor blood concentration and electrocardiogram.

12. With the use of heparin, as this product may partially offset the anticoagulant effect of heparin, the amount of heparin needs to be adjusted.

13. Intravenous magnesium sulphate should be used with extreme caution when digitalis is present, especially when calcium salts are also given intravenously, cardiac block can occur.

14. Erythromycin can increase the absorption of this product in the gastrointestinal tract due to changes in the gastrointestinal flora.

15. Metoclopramide (Metoclopramide, Maxolon) has reduced the bioavailability of digoxin by promoting intestinal movement by about 25%. Probencin improves the bioavailability of digoxin by inhibiting intestinal peristalsis by about 25%.

Pharmacological effects: at the therapeutic dose

1. Positive inotropic effect: This product selectively binds to the Na + -K + ATPase of the cardiac cell membrane and inhibits the enzyme activity, impairs the active coupling transport of Na + K + inside and outside the myocardial cell membrane, and increases the Na + concentration in the myocardial cell, thereby Make the Na + Ca2 + exchange on the muscle membrane become active, increase the Ca2 + in the cytoplasm, increase the Ca2 + storage in the sarcoplasmic network, and release more Ca2 + when the myocardium is excited; the Ca2 + concentration in the myocardial cells increases, and the myocardial contraction protein is stimulated Thereby increasing myocardial contractility.

2. Negative frequency effect: Due to its positive inotropic effect, the cardiac output of the failing heart is increased, the hemodynamic state is improved, the reflexivity of eliminating sympathetic nerve tension is increased, and the vagus nerve tension is increased, thereby slowing the heart rate. In addition, increasing the sensitivity of the sinoatrial node to vagus nerve impulses at low doses can enhance its heart rate slowing effect. Large doses (usually close to the amount of poisoning) can directly inhibit the sinoatrial node, atrioventricular node, and the His bundle and show sinus bradycardia and atrioventricular block of varying degrees.

3 Cardiac electrophysiological effects: through direct effects on myocardial electrical activity and indirect effects on vagus nerves, reduce sinus node self-discipline; improve Purkinje fiber self-discipline; slow atrioventricular node conduction velocity and extend its effective refractory period , Leading to increased atrioventricular node occult conduction, which can slow the ventricular rate of atrial fibrillation or atrial flutter; because this drug shortens the effective refractory period of atrial, when used in atrial tachycardia and atrial flutter, it may lead to atrial Accelerated rate and atrial flutter turned into atrial fibrillation; shortened effective refractory period of Purkinje fibers.

Drug overdose: 1. If the blood concentration of digoxin is 2.0 ~ 2.5ng / ml, the digoxin drug should be alert for overdose or toxic reaction.

2. Patients have taken any digitalis preparations 2 to 3 weeks ago, and should be given in small doses to avoid poisoning.

3 Cardiac glycoside dose calculation should be based on standard body weight, because adipose tissue does not take up cardioside.

4 The recommended dose is only an average dose, and each dose must be adjusted according to the needs of the patient.

5. For patients with liver dysfunction, digitalis preparations that do not focus on liver metabolism should be selected.

6. Digitalis is used in patients with renal insufficiency, because most of the metabolites excreted in urine are inactive and do not affect the half-life of this product.

7. Digitalis patients are extremely sensitive to cardioversion and should be highly vigilant.

8. Dialysis cannot remove this product quickly from the body.

9. When this product causes severe or complete atrioventricular block, potassium supplementation is not recommended.

10 Renal insufficiency, the elderly and the weak can have poisoning reactions at the usual dose and blood concentration. Infants and young children, especially premature and stunted infants, should adjust the dose under the blood drug concentration and ECG monitoring.

11. When the patient changed from cardiac glycoside injection to this product, the dose needs to be adjusted in order to compensate for the pharmacokinetic differences between drugs.

12. It should be administered intravenously because intramuscular injection has a marked local response, and has a slow effect and poor bioavailability.

13. Treatment of this product overdose and toxic reaction: Those with mild poisoning should stop using this product and diuretic treatment. If there is hypokalemia and renal function is good, potassium salt can be given. Available for those with arrhythmia:

(1) Intravenous infusion of potassium chloride is often effective in eliminating ectopic rhythms.

(2) Sodium phenytoin, which can compete with cardiac glycosides for Na + -K + -ATPase, and thus has a detoxifying effect. For adults, take a slow intravenous injection of 100 200 plus 20ml of water for injection. If the situation is not urgent, it can be taken orally, 0.1 each time, 3 ~ 4 times a day.

(3) Lidocaine is effective for eliminating ventricular arrhythmias. Adults use 50 to 100% of glucose injection to intravenously inject, which can be repeated if necessary.

(4) Atropine is available for those with bradycardia. Adults use 0.5 ~ 2 subcutaneously or intravenously.

(5) Temporary pacemaker can be implanted when bradycardia or complete atrioventricular block may cause Asthma Syndrome. Application of isoproterenol can increase slow heart rate.

(6) Calcium Disodium Edetate, with its chelation effect on calcium, can also be used to treat arrhythmias caused by digitalis.

(7) Digoxin-immunized Fab fragments can be administered intravenously through membrane filters to potentially life-threatening digitalis poisoning. Each 40 g of digoxin-immunized Fab fragments binds approximately 0.6 g of digoxin or digoxigenin.

Pharmacokinetics: This product is cardiac glycoside, which is purified from foxglove digitalis, and is characterized by faster excretion and less accumulation. Oral absorption is mainly through the upper small intestine, absorption is incomplete and irregular, oral absorption rate is about 75%, bioavailability: 60% to 80% for tablets, oral onset time 0.5 to 2 hours, and plasma concentration peak time 2 ~ 3 hours, the maximum effect time is 4 ~ 6 hours. Digoxin elimination half-life averaged 36 hours. Distribution: It is widely distributed to various tissues after absorption, and partly absorbed into the blood through the biliary tract, forming the liver-gut circulation. The plasma protein binding rate is low, 20% to 25%, and the apparent volume of distribution is 6 to 10 L / . Metabolism and excretion: Digoxin is rarely transformed and metabolized in the body, and is mainly eliminated by the kidneys in the original form. The urine excretion is 50% to 70% of the amount.

Storage: sealed.

Drug validity: 36 months.

Implementation standard: "Chinese Pharmacopoeia" 2010 edition two ^[9] .