Generic name: Deacetylphlorin C Injection
Old name: Cediran D, Hairy Flower Strong Heart C, Deacetylphlorin
Trade name:
English name:
Hanyu Pinyin:
This product's main ingredient is deacetylphlorin C. It is a white crystalline powder, no crystal powder, with the name of "Deacetylphlorin C".
Properties
White crystalline powder, odorless, bitter taste, hygroscopic. Several insoluble in water, slightly soluble in ethanol.
Pharmacology and toxicology
This product is the deacetyl derivative of Trichoside C. The product is a non-acetyl derivative of Trichoside C. It is also used as an antioxidant in the treatment of cancer. When the therapeutic dose of this product ① Positive inotropic effect: this product selectively binds with the cardiac machine cell membrane Na+--K++ATPase and inhibits the activity of this enzyme, so that the Na+-K+ active coupling transport inside and outside the cardiac muscle cell membrane is impaired, and the concentration of Na+ inside the cardiac muscle cell is elevated, which makes the exchange of Na+Ca2+ on the myocardial membrane tends to be active, and makes the intracellular cytoplasmic Ca2+ increase. Ca2+ storage in the sarcoplasmic reticulum also increases, and when the myocardium is excited, more Ca2+ is released; the increased concentration of Ca2+ in the cardiomyocyte agitates the myocardial contractile proteins and thus increases the myocardial contractility. ② Negative frequency effect: Due to its positive inotropic effect, it increases the cardiac output of the failing heart, improves the hemodynamic status, eliminates the reflex increase of sympathetic tone, and enhances the vagal tone, thus slowing down the heart rate and delaying the atrioventricular conduction. In addition, increased sensitivity of the sinus node to vagal impulses in small doses enhances its rate-slowing effect. Due to its negative frequency effect, the diastolic period is relatively prolonged, which is conducive to increasing myocardial blood supply; large doses (usually close to the amount of toxicity) can directly inhibit the sinoatrial node, atrioventricular node and Hirschsprung's bundle, which presents sinus bradycardia and atrioventricular block of different degrees. Cardiac electrophysiological effects: through the direct effect on myocardial electrical activity and the indirect effect on the vagus nerve, reduce the sinus node autoregulation; increase the autonomy of Purkinje fibers; slow down the atrioventricular node conduction velocity, prolong the effective response period, leading to an increase in the atrioventricular node occult conduction, which can slow down the ventricular rate of atrial fibrillation or atrial flutter; due to the drug to shorten the effective response period of the atrium, when used for atrial tachycardia and atrial flutter When used in atrial tachycardia and atrial flutter, it may result in acceleration of the atrial rate and conversion of atrial flutter to atrial fibrillation; shortens the Purkinje fiber effective refractory period. (lack of toxicology, needs to be supplemented).
Pharmacokinetics
It is a cardiac glycoside naturally occurring in digitalis, in the process of extraction, it can be hydrolyzed to lose glucose and acetic acid and become digitoxin, a fast-acting cardiac glycoside, and its action is faster than digitalis and digitoxin, but a little slower than the poisonous hairy glycoside K. It can be distributed rapidly to all tissues. Intravenous injection can be rapidly distributed to the tissues, 10-30 minutes onset of action, 1-3 hours to reach the peak effect, the duration of action 2-5 hours. The protein binding rate is low, 25%. The half-life is 33-36 hours. 3-6 days the effect is completely disappeared in the body into digoxin, excreted by the kidneys. Due to faster excretion, accumulation is small.
Indications
(1) Mainly used in heart failure. Due to its faster action, it is suitable for patients with acute cardiac insufficiency or acute exacerbation of chronic cardiac insufficiency. (2) It can also be used to control the ventricular rate in patients with atrial fibrillation and atrial flutter accompanied by rapid ventricular rate. (3) Termination of supraventricular tachycardia has a slow onset of action and has been used sparingly.
Use and dosage
Intravenous injection Adults: diluted with 5% dextrose injection and injected slowly, the first dose of 0.4-0.6 p.m., and then 0.2-0.4 p.m. can be given every 2-4 hours, the total amount of 1-1.6 p.m.. 1.6㎎. Usual dosage for pediatrics: give in 2-3 doses at 3-4 hours intervals according to the following dosage. For preterm and full-term newborns or children with renal hypoplasia or myocarditis, 0.022 p.p.m./kg of body weight is given intramuscularly or intravenously, and 0.025 p.p.m./kg of body weight is given from 2 weeks to 3 years of age. After satisfactory efficacy of this product by intravenous injection, the usual maintenance dose of digoxin can be changed to maintain the efficacy.
Adverse Reactions
(1) Common adverse reactions include: new onset of cardiac arrhythmia, poor appetite or nausea, vomiting (stimulation of medullary centers), lower abdominal pain, and unusual weakness and tenderness. (2) Less common reactions include: blurred or "yellow vision" (toxic symptoms), diarrhea, and central nervous system reactions such as depression or confusion. (3) Rare reactions include drowsiness, headache and rash, and measles (allergic reactions). (4) Among the toxic manifestations of digitalis, cardiac arrhythmias are the most important, the most common being premature ventricular contractions, which account for about 33% of cardiac reactions. This is followed by atrioventricular block, paroxysmal or accelerated junctional tachycardia, paroxysmal atrial tachycardia with atrioventricular block, ventricular tachycardia, sinus arrest, and ventricular fibrillation. Arrhythmias are more common than other responses in children, but ventricular arrhythmias are less common than in adults. Prolongation of the P-R interval may be seen in neonates.
Contraindications
Prohibited: ① combined with calcium injection; ② any cardiac glycoside preparation poisoning; ③ ventricular tachycardia, ventricular fibrillation; ④ obstructive hypertrophic cardiomyopathy (if with systolic insufficiency or atrial fibrillation can still be considered); ⑤ preexcitation syndrome with atrial fibrillation or flutter.
Precautions
(1) It is not suitable to be paired with acids and bases. (2) Use with caution: (1) hypokalemia; (2) incomplete atrioventricular block; (3) hypercalcemia; (4) hypothyroidism; (5) ischemic heart disease; (6) early acute myocardial infarction (AMI); (7) myocarditis in the active stage; (8) renal impairment. (3) During the use of the drug, attention should be paid to the follow-up examination: (1) blood pressure, heart rate and rhythm; (2) electrocardiogram; (3) cardiac function monitoring; (4) electrolytes, especially potassium, calcium and magnesium; (5) renal function; (6) suspected digitalis toxicity, digoxin blood concentration should be measured. In case of overdose, due to the small accumulation, the toxicity can subside 1-2 days after stopping the drug.
Pregnant and lactating women
This product can pass through the placenta, so the maternal dosage may be appropriately increased in the second trimester of pregnancy, and the dosage is reduced 6 weeks after delivery. This product can be excreted into breast milk, the application of lactating women must weigh the advantages and disadvantages.
Children
Newborns have variable tolerance to the product, with reduced renal clearance; premature and immature infants are sensitive to the product, and the dose is reduced according to their degree of immaturity. Infants over 1 month of age are given a slightly larger dosage than adults by weight or body surface area.
Medication in Elderly Patients
Elderly patients with hepatic or renal insufficiency, reduced apparent volume of distribution, or electrolyte balance disorders have low tolerance for this product and must have their dosage reduced.
Drug interactions
(1) with amphotericin B, corticosteroids, or potassium-losing diuretics such as bumetanide (product of butyramide), ethacrynic acid (Ethacrynic Acid, diuretic acid), when used together, can cause hypokalemia resulting in digitalis toxicity. (2) and acid-making drugs (especially magnesium trisilicate) or antidiarrheal adsorbents such as white clay, pectin, Kaolai enamine (Cholestyramine, cholestyramine) and other anion-exchange resins, Liuzasalazine (Sulfasalazine) or neomycin, p-amino-salicylic acid, can inhibit the absorption of cardiac glycosides of digitalis and lead to cardiac glycoside effect of the weakening. (3) With antiarrhythmic drugs, calcium injections, cocaine, Pancuronium Bromide (Pancuronium Bromide, Pancuronium Bromide, Bavulan), Rovuline, Succinylcholine (Scoline; Suxamethonium Chloride) or adrenergics, can lead to arrhythmia due to the effect of the combination. (4) Potassium salts should not be used concomitantly in digitalisized patients with severe or complete atrioventricular block with normokalemia; however, potassium salts must often be given to prevent hypokalemia when thiazide diuretics are used in conjunction with this product. (5) The possibility of severe bradycardia resulting from atrioventricular block should be emphasized when β-blockers are used with this product. However, it does not exclude the use of beta blockers for supraventricular tachyarrhythmias in which digitalis fails to control the ventricular rate. (6) With quinidine, can make the product blood concentration increased about double, the degree of increase is related to the dosage of quinidine, and can even reach the concentration of poisoning, even if the discontinuation of digoxin, its blood concentration continues to rise, this is quinidine from the tissue binding to replace the digoxin, reduce its distribution volume. The dosage of digoxin should be reduced by 1/2-1/3 when the two drugs are used together. (7) Combined with verapamil, diltiazem, and amiodarone, the blood concentration of digoxin is increased due to the reduction of renal and systemic clearance of digoxin, which may cause severe bradycardia. (8) Spironolactone may prolong the half-life of this product, requiring dose adjustments or intervals between administrations, and follow-up monitoring of blood concentrations of this product. (9) Angiotensin-converting enzyme inhibitors and their receptor antagonists may increase blood concentrations of this product. (10) Edrophonium Chloride (Edrophonium Chloride, Tensilon) can cause significant bradycardia when combined with this product. (11) Indometacin (Anti-inflammatory pain) can reduce the renal clearance of this product, so that the half-life of this product is prolonged, and there is a risk of toxicity, and it is necessary to monitor the blood concentration of the drug and electrocardiogram. (12) When used with heparin, the dosage of heparin needs to be adjusted because this product may partially counteract the anticoagulant effect of heparin. (13) Intravenous magnesium sulfate should be used with extreme caution when digitalisating, especially when calcium salts are also administered intravenously, as cardiac conduction block may occur. (14) Erythromycin may increase the absorption of this product in the gastrointestinal tract due to changes in gastrointestinal flora. (15) Metoclopramide (Maxolon) reduces the bioavailability of digoxin by approximately 25% by promoting intestinal motility. Probenecid increases digoxin bioavailability by about 25% by inhibiting intestinal motility.
Overdose
Cediran acts by releasing digoxin from the body, so poisoning is measured as digoxin poisoning. (1) The concentration of digoxin poisoning is ﹥2.0ng/ml. (2) If a loading dose is given, it is necessary to know whether the patient has taken any digitalis preparations before 2-3 weeks, and if there is a residual effect of digitalis, it is necessary to reduce the dosage of digoxin in order to avoid poisoning. (3) Cardiac glycoside dose calculations should be based on standard body weight, as adipose tissue does not take up cardiac glycosides. (4) The recommended dose is only the average dose, and each dose must be adjusted according to the patient's needs. (5) In patients with hepatic insufficiency, digoxin, which is not metabolized by the liver, should be used. (6) In renal insufficiency, digoxin should not be used, and digitalis toxicoside should be chosen. (7) Digitalisized patients are often extremely sensitive to electrical resuscitation and should be highly alert. (8) Dialysis does not rapidly remove this product from the body. (9) Potassium supplementation is contraindicated in cases of severe or complete atrioventricular block caused by this product. (10) Renal insufficiency, the elderly and the frail can have toxic reactions at commonly used doses and blood levels. In infants and children, especially premature and underdeveloped children, the dose should be adjusted with blood concentration and cardiac monitoring. (11) Traditionally, the treatment of heart failure has been to give a larger dose (loading dose) of the drug over several days (1-3 days) to achieve digitalization, and then to give a maintenance dose day by day to compensate for elimination. It is now believed that the shorter half-life of the drug (average half-life 36 hours), 0.25 p.p.m. orally per day, can also achieve 96% of the final blood concentration (digitalisations) after 5 half-lives (about 6-8 days), which achieves the therapeutic effect and avoids digitalis toxicity. If the therapeutic effect cannot be achieved, the dose can be increased appropriately. If the condition is more acute, in order to reach the effective concentration faster, it is still necessary to give a loading dose, but the dose needs to be individualized. (12) When patients are changed from cardiac glycoside injection to this product, the dose needs to be adjusted to compensate for the pharmacokinetic differences between drugs. (13) It should be administered intravenously because intramuscular injections have significant local reactions and are slow acting and poorly bioavailable. (14) Treatment of overdose and toxic reactions to the product: in mild poisoning, discontinue the product and diuretic therapy, and if there is hypokalemia and renal function is still good, potassium salts can be given. Arrhythmia can be used: ① potassium chloride intravenous drip, often effective in eliminating ectopic rhythm. ② Phenytoinna, which can compete with cardiac glycosides for Na-K-ATPase and thus has a detoxifying effect. Adults with 100-200 p.p.m. plus 20 ml of water for injection slowly injected, if the situation is not urgent, can also be taken orally, 0.1 p.p.m. each time, 3-4 times a day. ③ Lidocaine, effective in eliminating ventricular arrhythmia, adults use 50-100㎎ added to glucose injection intravenously, can be repeated if necessary. ④ Atropine, available for those with bradyarrhythmia. Adults can use 0.5-2㎎ subcutaneously or intravenously. ⑤ Temporary pacemakers may be placed when bradycardia or complete atrioventricular block has the potential for Asperger's syndrome. Isoproterenol, which increases the slow heart rate. (vi) Calcium Disodium Edetate, for its chelation with calcium, is also used to treat arrhythmias caused by digitalis. (vii) In potentially life-threatening digitalis poisoning, digoxin-immune Fab fragments may be administered intravenously via a membrane filter, binding approximately 0.6 p.p. of digoxin or digitalis glycosides for every 40 p.p. of digoxin-immune Fab fragments. ⑧ Note that the dosage should be reduced in case of poor hepatic function. Concomitant administration of phenytoinna, phenobarbital, prednisone, and rifampicin decreases blood digitalis toxicoside concentrations by 50%.