Is It Safe to Take Beta Blockers During Pregnancy?

Beta-blockers are a type of drug that selectively bind to beta-adrenergic receptors, thereby antagonizing the agonistic effects of neurotransmitters and catecholamines on beta-receptors. Epinephrine receptors are distributed on most of the effector cell membranes dominated by the sympathetic ganglion fibers. The receptors are divided into 3 types, which can stimulate the increase of heart rate and myocardial contractility, bronchiectasis, vasodilation, relaxation of visceral smooth muscle, etc. And lipolysis. These effects can be blocked and antagonized by beta blockers.

Chinese name: beta blockers
Foreign name: -receptor blocker

Features: Selectively binds to -adrenergic receptors
Efficacy: Beta receptor agonism
Application range: medicine

Main categories of beta blockers

Epinephrine receptors are distributed on the effector cell membranes dominated by most of the sympathetic ganglion fibers. The receptors are divided into 3 types, namely 1 receptor, 2 receptor, and 3 receptor. 1 receptors are mainly distributed in the myocardium, which can stimulate the increase of heart rate and myocardial contractility; 2 receptors are present in the bronchus and vascular smooth muscle, which can cause bronchodilation, vasodilation, and visceral smooth muscle relaxation; 3 receptors are mainly present in fat cells On, can cause lipolysis. These effects can be blocked and antagonized by beta blockers.

-blockers can be divided into 3 categories: non-selective -blockers, which simultaneously block 1 and 2 receptors, such as propranolol; selective -blockers Has little or no effect on 2 receptors, such as bisoprolol; Blocks 1 and receptors, such as carvedilol.

Beta blockers Pharmacology of beta blockers

Beta blocker mechanism:

Beta-blockers have cardiovascular protective effects. The main mechanism is anti-catecholamine adrenergic transmitter toxicity, especially the cardiotoxicity mediated by beta1 receptors. Other mechanisms include anti-hypertension, anti-myocardial ischemia, blocking renin angiotensin aldosterone system by inhibiting renin release, improving cardiac function and increasing left ventricular ejection fraction, and antiarrhythmia.

Beta blockers adverse reactions:

-blockers can cause some serious adverse reactions when used in large doses: The cardiovascular system: it can slow heart rate, and even cause severe bradycardia and atrioventricular block, mainly seen in sinus node and atrioventricular node function. Damaged patients; Metabolic system: The use of non-selective beta blockers in type 1 diabetes can mask some of the alert symptoms of hypoglycemia such as tremor and tachycardia; Respiratory system: it can lead to increased airway resistance, so it is disabled For asthma or bronchospasm chronic obstructive pulmonary disease; Central nervous system: can produce fatigue, headache, sleep disorders, insomnia, dreaminess and depression; withdrawal syndrome: sudden withdrawal after long-term treatment can occur, manifested as Hypertension, arrhythmia, and angina pectoris worsened.

Beta blockers are disabled or used with caution

Beta-blockers are contraindicated or used with caution in the following cases: bronchospasm asthma, symptomatic hypotension, bradycardia or second-degree atrioventricular block, heart failure with significant sodium retention requiring substantial diuresis, And hemodynamic instability requires intravenous application of positive inotropic drugs. However, for the majority of patients with cardiovascular disease, -blocker therapy has more advantages than disadvantages, and cardiovascular patients with chronic obstructive pulmonary disease or peripheral vascular disease without bronchospasm can still be treated with -blockers. Significant benefit; diabetes and intermittent claudication of the lower limbs are not absolute contraindications.

Clinical effects of beta-blockers beta-blockers

Application of beta blockers in hypertension

Beta blockers exert their antihypertensive effect by antagonizing the excessive activation of the sympathetic nervous system.The main antihypertensive mechanisms involve reducing cardiac output, improving the blood pressure regulating function of the baroreceptor, and inhibiting the renin angiotensin aldosterone system. ; It also prevents the cardiotoxic effects of catecholamines by reducing sympathetic tone.

Beta blockers are one of the initial and long-term antihypertensive drugs for patients with hypertension, and can be used alone or in combination with other antihypertensive drugs. Beta-blockers may be considered for middle-aged and young patients with hypertension without complications. Beta blockers should be given priority in patients with hypertension who have: arrhythmia (e.g. sinus tachycardia, atrial fibrillation), coronary atherosclerotic heart disease (coronary heart disease, e.g. angina pectoris, myocardial infarction) After), chronic heart failure, and increased sympathetic nerve activity such as anxiety, tension and other mental stress, perioperative hypertension, high circulation dynamics such as hyperthyroidism. -blockers such as bisoprolol, metoprolol, and carvedilol are recommended for those with no intrinsic sympathomimetic activity, high selectivity for 1 receptors, or a combination of -blocker vasodilator action. These drugs have little effect on metabolism and few adverse reactions, and can be safely used in patients with hypertension with diabetes, chronic obstructive pulmonary disease and peripheral vascular disease.

The combination of beta blockers and long-acting dihydropyridine calcium antagonists is one of the currently recommended antihypertensive drug combinations; beta blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists The combination of agents is suitable for patients with hypertension and coronary heart disease.

Application of -blockers in coronary heart disease

Beta blockers are beneficial for patients with various types of coronary heart disease. The first is to reduce myocardial oxygen consumption by reducing myocardial contractility, heart rate and blood pressure; at the same time, prolonging the diastolic period and increasing blood supply and perfusion of the coronary arteries and their collaterals, thereby reducing and alleviating myocardial deficiency in daily activities or exercise states Blood attacks that improve quality of life. The second is to reduce the scope of infarction, reduce fatal arrhythmia, and reduce the mortality rate of acute phase including sudden cardiac death and the incidence of various cardiovascular events. Third, long-term application can improve the long-term prognosis and survival rate of patients, which is beneficial to the secondary prevention of coronary heart disease.

All patients with coronary heart disease should use -blockers for long-term use as secondary prevention. Patients with ST-elevated myocardial infarction or non-ST-elevated acute coronary syndrome cannot be applied due to contraindications during the acute phase, and should be re-evaluated before discharge, and -blockers should be used as much as possible to improve the prognosis. .

Application of beta blockers in heart failure

Beta-blockers block the sympathetic nervous system, renin angiotensin aldosterone system, and over-activated neurohumoral factors by effectively antagonizing the malignant circulation chain of cardiovascular disease, thereby delaying or reversing myocardial remodeling Play the "biological effect" of improving endogenous myocardial function.

Beta Blockers in Arrhythmia Beta Blockers are the only antiarrhythmic drugs that can reduce sudden cardiac death and reduce overall mortality. Its application indications are recommended as Class I: partial sinus tachycardia, perioperative arrhythmia, atrial fibrillation with rapid ventricular response, ventricular tachycardia storm, tachyarrhythmia caused by sympathetic nerve excitement, and some Some types of long QT syndrome.

Beta blockers in other cardiovascular diseases

1 In the early stage of dilated cardiomyopathy, patients with only enlarged heart and no clinical manifestations of heart failure can apply -blockers to reduce myocardial damage and delay the progression of the disease, especially suitable for fast heart rate and ventricular arrhythmia , And beta-positive antibody-positive patients. Patients who have developed symptoms and signs of heart failure in the middle and late stages should also be treated with -blockers according to the treatment of chronic heart failure.

2 Patients with a clear diagnosis of hypertrophic cardiomyopathy, including early and mild patients, are suitable for -blockers; patients with obstructive hypertrophic cardiomyopathy can improve symptoms by using larger doses.

3 Mitral valve prolapse is suitable for symptomatic patients.

4 Hyperthyroidism blockers can quickly relieve symptoms such as tachycardia, tremor, and anxiety.

5. Aortic dissection

Medical treatment often uses a combination of beta blockers and sodium nitroprusside to reduce the impact of blood flow on the aorta and reduce the contraction rate of the left ventricle to slow the progress of the disease.

6 LQTS

LQTS (hereditary QT extension syndrome): Unless there are serious contraindications, beta blockers are the treatment of choice for patients with symptomatic LQTS today. If there is no absolute contraindication, it is recommended to take the maximum tolerated dose of -blocker for life, which can significantly reduce the occurrence of cardiovascular events. As of 2015, it is believed that beta-blockers are also recommended for asymptomatic LQTS patients.

7 left atrial valve prolapse

For patients with symptomatic left atrial valve prolapse, beta-blockers are often the drug of choice. ^[1]

Beta blockers commonly used

(1) Atenolol (also known as aminoacid-an-an) is a cardiac-selective beta-blocker that has no endogenous inhibition of sympathetic nerve activity, and has a half-life of 6 to 9 hours. Most clinical studies show that One medication can continuously lower blood pressure for 24 hours, especially for patients with tachycardia and hypertension. Combined with vasodilators, calcium antagonists or diuretics, the effect of lowering blood pressure is better. Some people are used to treat severe hypertension crisis. After oral administration of 10mg, blood pressure gradually decreases within 12 hours, the average systolic blood pressure decreases by 7.5kPa (56mmHg), and the diastolic blood pressure decreases by 5.3kPa (40mmHg). It is considered a safe and effective drug.

(2) Metoprolol (Betaloc) is a selective beta-blocker. After its introduction in 1975, it has achieved certain effects in the treatment of hypertension, angina pectoris, myocardial infarction, and arrhythmia. For the treatment of hypertension, 100 mg orally for 4 weeks, the total effective rate is 82.4%. After 2 weeks of treatment, the blood pressure gradually decreases, and the heart rate does not decrease. Symptoms apply to patients with stage I or II hypertension. Its side effects include slow heart rate, fatigue, dry mouth, chest tightness, etc. Most can be reduced or disappeared after a period of treatment, but those with bronchial asthma or bradycardia are disabled. ^[2]

(3) Sotalol hydrochloride

[Product name] Shi Taike

[Drug name] Sotalol hydrochloride

[Indications] Suitable for life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Because of its arrhythmogenic effect, it is generally not recommended for non-sustained ventricular tachycardia and supraventricular arrhythmia.

[Pharmacology] (1) Pharmacodynamics: This product has both -blocking effect and class III antiarrhythmic drug properties. This product is a racemate, and both isomers have a class III effect, but only the L-isomer has a -blocker effect. Its effect is non-cardioselective and has no intrinsic sympathomimetic effect. This product prolongs the action potential platform phase and reduces the sinus rhythm. Delay atrioventricular node conduction. Prolong the refractory period of the atrium, ventricular muscle and conduction system (including bypass). ECG jumping produces a dose-dependent prolongation of QTc, which has the effect of slightly reducing cardiac output and lowering blood pressure.

(2) Pharmacokinetics: Bioavailability is 90% to 100%. Oral peak time is 2.5 to 4 hours. Steady-state concentration can be achieved by taking it orally twice a day for 2 to 3 days. In the range of 160 to 640 mg per day, the blood concentration and the dose are in phase with each other. Does not bind to plasma proteins and has no liver metabolism. Difficult to cross the blood-brain barrier. All excreted from the kidneys in their original form. t _1/2 is 12 hours, and half-life is prolonged in renal dysfunction. But liver dysfunction has no effect on the metabolism of this product.

[Adverse reactions] (1) The most important adverse reaction is arrhythmia, which causes torsional ventricular tachycardia and new severe ventricular arrhythmias. Can also produce bradycardia, syncope, hypotension, dyspnea, exacerbation of heart failure, and edema. (2) Nervous system: fatigue, dizziness. (3) Digestive system: nausea and vomiting. (4) Others: asthma. Rash, limb pain, etc.

[Contraindications] This product is contraindicated in the following cases: bronchial asthma, sinus bradycardia, or degree atrioventricular block (unless there is a pacemaker), congenital or acquired prolonged QT syndrome, cardiogenic shock, Uncontrolled heart failure and history of allergies.

[Precautions] (1) Patients with renal dysfunction can cause accumulation of this product, and the interval between medications should be extended according to creatinine clearance. (2) This product can be passed through the placenta and into the milk. Pregnant women and lactating women should be used with caution. (3) Same as other beta blockers. Do not stop the medicine suddenly. (4) The following situations should be used with caution: heart failure controlled with digitalis, hypokalemia, hypomagnesemia, and first degree atrioventricular block. (5) Pay attention to monitoring during application: changes in ECG, especially QT interval; blood pressure; electrolytes; renal function.

[Drug Interactions] (1) There is a synergistic effect when used together with other antiarrhythmic drugs of type a, and . (2) When used with calcium antagonists, it can aggravate cardiac conduction disorder, further inhibit ventricular function, and lower blood pressure. (3) With the use of catecholamines (such as lisepine, guanethidine) can produce hypotension and severe bradycardia. (4) There have been reports of increased blood sugar and the need to increase insulin and hypoglycemic agents.

[Dosing instructions] (1) When the ECG QTc is greater than 500ms, the arrhythmia effect should be paid attention to, and the QTc should be discontinued when the QTc exceeds 550ms. (2) When the medicine needs to be discontinued, it should be gradually reduced to the minimum and used within 1 to 2 weeks. (3) When switching to this product from other antiarrhythmic drugs, the previous drug should be discontinued for 2 to 3 half-lives under close monitoring before using this product. When changing this product from amiodarone, wait until QT returns to normal before you can start using it.

[Usage and Dosage] (1) Commonly used amount for adults: oral administration starts from 80mg twice a day, and the dosage is increased to 120 to 160mg twice a day according to the response, twice a day. 640mg a day. (2) Pediatric usage and safety: not yet determined.

[Formulations and specifications] Sotalol hydrochloride tablets: (1) 80mg * 28 tablets; (2) 160mg; (3) 240mg.

(4) Propranolol hydrochloride

[Trade name] Good night

[Drug Name] Propranolol Hydrochloride

[Indications] For: hypertension, alone or in combination with other drugs. Angina pectoris (typical angina pectoris, that is, labor-type angina pectoris). Arrhythmia, control of supraventricular tachyarrhythmias, ventricular arrhythmias, especially those related to catecholamines and digitalis-induced arrhythmias, can be used to control the ventricular rate of atrial flutter and atrial fibrillation with digitalis unsatisfactory efficacy, and can also be used for refractory Premature beats improve patient symptoms. Hypertrophic cardiomyopathy is used to reduce the pressure difference in the outflow tract and reduce the symptoms of angina pectoris, palpitations and syncope. Pheochromocytoma, combined with alpha blockers for controlling tachycardia. Hyperthyroidism, used to control excessive heart rate, but also used to treat thyroid crisis. Myocardial infarction as a secondary prevention to reduce mortality. Mitral valve prolapse syndrome. It is also used for migraines and primary tremors.

[Pharmacology] (1) Pharmacodynamics: This product has a non-selective and competitive inhibition of adrenaline beta receptors. By weakening or preventing receptor excitement, the contractile force and contraction speed of the heart are reduced, and the conduction speed of the conduction system is slowed, so that the heart's response to exercise or stress is weakened. Therefore, it is used in the treatment of angina pectoris to reduce myocardial oxygen consumption and increase exercise tolerance. Adrenaline is used to treat cardiac arrhythmias because it blocks excitatory adrenaline. It is possible that this product is suitable for the treatment of hypertension through the effects of central, adrenergic neuron block, inhibition of renin release, and reduced cardiac output. Because this product can antagonize the catecholamine effect, it is also used to treat pheochromocytoma and hyperthyroidism, so that the activities of 1 and 2 receptors are in an inhibited state.

(2) Pharmacokinetics: The gastrointestinal absorption is relatively complete (90%) after oral administration, and the blood drug concentration reaches a peak within 1 to 1.5 hours, but it is inactivated by the liver by a large amount before entering the systemic circulation. The bioavailability is 30 %. The binding rate to plasma proteins is very high, at 93%. t _1/2 is 2 to 3 hours. Excreted by the kidney, mainly metabolites, a small part (<l%) of the original. Can not be discharged on dialysis. [Adverse reactions] (1) More common are dizziness or dizziness (caused by hypotension) and slow heart rate (<50 beats / minute). (2) Rarely have bronchospasm and dyspnea, congestive heart failure, confusion (especially in the elderly), mental depression, and unresponsiveness. (3) Less common are fever and sore throat (granulocytosis), rash (allergic reaction), and bleeding tendency (thrombocytopenia).
(4) When adverse reactions persist, special attention must be paid to the coldness of Raynaud's limbs, diarrhea, burnout, dry eyes and skin, nausea, numbness of fingers and toes, and abnormal fatigue.

[Contraindications] Bronchial asthma; Cardiogenic shock; Cardiac block (II to degree atrioventricular block); Severe or acute heart failure; Sinus bradycardia; Allergy to this product By.

[Precautions] (1) This product can enter the fetus through the placenta. It has been reported that those with pregnancy-induced hypertension can cause intrauterine fetal growth retardation, inability to cause dystocia during delivery, and neonates can produce hypotension, hypoglycemia, and respiratory depression. And heart rate slowing down, although there have been reports of no effect on the mother and fetus, it must be used with caution and should not be used as a first-line treatment for pregnant women. (2) A small amount can be secreted from milk, so it must be used with caution in lactating women. (3) Elderly people have low metabolism and excretion ability of this product, and they should wither the proper dose. (4) Interference to diagnosis: When using this product, blood urea nitrogen, lipoprotein, creatinine, potassium, triglyceride, uric acid, etc. may be increased; blood sugar is reduced, but it may be increased in patients with diabetes. During renal insufficiency, metabolites of propranolol can accumulate in the blood, interfere with the diazonium response to the determination of serum bilirubin, and can produce false positives. (5) The following conditions should be used with caution: history of allergies; congestive heart failure; diabetes; emphysema or non-allergic bronchitis; liver insufficiency; hypothyroidism; Raynaud's disease or other peripheral blood vessels Disease; renal function. (6) The blood routine, blood pressure, heart function, liver function and kidney function should be checked regularly during the application of this product. Diabetics should check blood glucose regularly. (7) The dosage must emphasize individualization. Different individuals and diseases have different dosages, and small amounts are used for patients with liver and kidney dysfunction; (8) Note that the blood drug concentration cannot fully predict the pharmacological effect, so it should also be based on heart rate and blood pressure, etc. Clinical signs guide clinical medication; (9) Coronary heart disease patients should not use this product for sudden stop, otherwise angina pectoris, myocardial infarction or ventricular tachycardia may occur; (10) Hyperthyroid patients should not use this product for sudden arrest, otherwise it will cause hyperthyroidism symptoms Aggravated; (11) Long-term application can cause heart failure in a small number of patients. If it occurs, it can be corrected with digitalis and / or diuretics. (12) Overdose: Give atropine or isoprenaline to bradycardia, install a pacemaker if necessary, and give lidocaine or phenytoin sodium to the ventricular premature beat. Heart failure is given oxygen, digitalis or diuretics. Infusion and hypotension during hypotension. Convulsions to diazepam or phenytoin. Bronchial spasm is given to isoprenaline and aminophylline.

[Drug Interactions] (1) Interaction with antihypertensive drugs: When coadministered with clonidine and need to be discontinued, this product must be stopped first, and then clonidine can be gradually stopped after a few days to avoid blood pressure fluctuations. With the use of monoamine oxidase inhibitors can cause extreme hypotension, it is banned. Used with reserpine. When the two effects are added together, -blocking effect is enhanced, and bradycardia and hypotension may occur. (2) Used with digitalis. Atrial rate block may occur and the heart rate is too slow, so it must be closely observed. (3) With the use of calcium antagonists, especially the intravenous administration of verapamil, be very vigilant against the inhibition of the myocardium and the conduction system. (4) Used with epinephrine, phenylephrine, or sympathomimetic amines, it can cause significant hypertension, slow heart rate, and atrioventricular block may occur, so it must be closely observed. (5) It can make non-depolarizing muscle relaxants such as cyproteronide and galiodomide, etc., and the aging time is prolonged. (6) This product can cause hypoglycemia in diabetic patients, so the dosage of the latter should be adjusted when used with hypoglycemic agents. (7) With the same use of isoproterenol or xanthine, the latter can weaken the curative effect. (8) With the use of chlorpromazine, the blood concentration of both can be increased. (9) Sodium phenytoin, phenobarbital, and rifampicin accelerate the elimination of this product. (1O) Antipyrine, lidocaine, and theophylline slow down the elimination of this product.

[Dosing instructions] (1) Oral can be taken on an empty stomach or with food, which can slow down the metabolism of this product in the liver and increase the bioavailability. (2) Withdrawal from long-term use of this product should gradually reduce the dose, at least after 3 days, usually 2 weeks. This product is gradually decremented and finally discontinued.

[Usage and Dosage] (1) Angina pectoris, myocardial infarction: start at 10mg orally, 3 to 4 times a day, 10 to 20mg can be added every 3 days, and can be gradually increased to 200mg a day, divided into doses. (2) Hypertension: Start at 10 mg orally, 3 to 4 times a day, and gradually adjust as needed and tolerated until the blood pressure is controlled. (3) Anti-arrhythmia: Orally, 10 to 30 mg once, 3 to 4 times a day, the dosage should be adjusted according to needs and tolerance. Severe arrhythmia can be injected intravenously at a rate of 1 to 3 mg at a rate of no more than 1 mg per minute, and can be repeated every 2 minutes if necessary, and every 4 hours thereafter. (4) Hypertrophic cardiomyopathy: Orally, 10-20 mg once, 3 to 4 times a day, adjusted as needed and tolerated. (5) Pheochromocytoma: Oral, 10-20 mg once, 3 to 4 times a day, 3 days before surgery, often used with alpha blockers, generally alpha blockers should be used first, Add this product after the effect appears and stabilizes. (6) Sustained-release tablets are used for the treatment of hypertension and angina pectoris. If necessary, it can be increased to 80mg. Prevention after myocardial infarction is available to 160mg per day. (7) The dosage of children has not yet been determined. Generally, oral administration is divided into 0.5 to 1.0 mg / kg per day, and divided into doses; intravenous injection is to be carried out slowly according to body weight of 0.01 to 0.1 mg / kg.

[Formulations and specifications] propranolol hydrochloride tablets: 10 mg * 100 tablets.

Propranolol hydrochloride sustained-release tablet: 40 mg. Propranolol hydrochloride sustained-release capsules: 40mg. ^[3]

(5) Carvedilol

[Product Name] Dali Full Lot

[Drug Name] Carvedilol

[Indications] Essential hypertension, used alone or in combination with other antihypertensive drugs such as diuretics. Symptoms of chronic congestive heart failure.

[Pharmacology] (1) Pharmacodynamics: This product is an epinephrine alpha and beta receptor blocker, and its beta receptor blocking effect is strong. 33 times for Laberol and 3 times for Putzalol. This product blocks the post-synaptic membrane alpha receptor, dilates blood vessels and reduces peripheral vascular resistance. At the same time, it blocks beta receptors, inhibits renin secretion, blocks the renin angiotensin-aldosterone system, and produces a hypotensive effect. This product has no intrinsic sympathetic activity and has membrane stability. This product has little effect on cardiac output and heart rate, and rarely produces water and sodium retention. Animal tests and various human cell tests in vitro confirm. This medicine also has antioxidant properties. This medicine has an antagonistic effect at high concentrations.

(2) Pharmacokinetics: The drug is easy to be absorbed by oral administration, and the first pass effect is about 60% to 75%. Bioavailability is 25%. Take with food to slow absorption. However, there was no significant effect on bioavailability. The plasma protein binding rate in plasma was 98%. The drug is completely metabolized, with a metabolic half-life of about 2 hours. Metabolites are mainly excreted from the feces through the bile, and about 16% are excreted by the kidneys. This medicine has high lipophilicity, and its distribution volume is about 2L / kg, so it may be secreted with milk. Elimination half-life is about 6 to 10 hours. Cannot be cleared by hemodialysis.

[Adverse reactions] (1) Central nervous system: occasional mild dizziness, headache, fatigue, especially early in the treatment. Rare depression, sleep disturbances, and paresthesias. (2) Cardiovascular system: bradycardia, orthostatic hypotension occasionally in the early stage of treatment, rarely syncope; peripheral circulation disorders (cold limbs) are not common, which can cause symptoms of patients with intermittent intermittent claudication or Raynaud Heavier. Edema and angina are uncommon. Individual patients develop atrioventricular block and increased heart failure. (3) Respiratory system: I can induce the onset of asthma or dyspnea in patients. Rare nasal congestion. (4) Digestive system: occasional gastrointestinal discomfort (such as abdominal pain, diarrhea, nausea, etc.), constipation and vomiting are not common. (5) The genitourinary system: dysuria, sexual dysfunction; patients with heart failure and diffuse vascular disease and / or renal insufficiency may further aggravate renal damage, and renal failure may occur in individual cases. (6) Skin: Allergic rash is rare, and individual patients may have urticaria, pruritus, and lichen planus-like skin reactions. Psoriasis-like skin damage may occur or exacerbate the original condition. (7) Eye: May have dry eye symptoms; rare visual impairment and eye irritation. (8) Others: Occasionally pain in the extremities and dry mouth.

[Contraindications] (1) Those who are allergic to this product. (2) Pregnant and lactating women. (3) Those with low liver function. (4) Patients with bronchospasm or asthma or chronic obstructive pulmonary disease. (5) Severe bradycardia (heart rate <50 beats / min), sick sinus syndrome (including sinoatrial block), and - degree AV block (6) Cardiogenic shock. (7) Severe hypotension (systolic blood pressure <85mmHg). (8) Patients with grade IV decompensated heart failure who require intravenous positive inotropic drugs.

[Precautions] (1) Use with caution: surgery patients. Hyperthyroidism. Patients with peripheral vascular disease (such as intermittent claudication). Patients with pheochromocytoma. Orthostatic hypotension. Patients with unstable or secondary hypertension. Variable angina pectoris. Diabetics. (2) Impact of the drug on children: There is no research data on the safety and efficacy of this drug in patients under 18 years of age. (3) The effect of the drug on the test value or diagnosis: occasionally elevated serum aminotransferase, thrombocytopenia, and leukopenia. (4) This medicine may affect the ability to drive and operate machines. It is more pronounced at the beginning of the medication, a change in dose or drinking. (5) When patients use this medicine during anesthesia, they should closely observe the adverse effects of negative muscle strength and hypotension. (6) Patients receiving digoxin, diuretics, and angiotensin-converting enzyme inhibitors must use these drugs to stabilize their condition before using carvedilol. (7) If transient heart failure or sodium retention occurs during the use of this product, the dose of diuretics must be increased. Sometimes it is necessary to reduce or discontinue treatment of this medicine. (8) Management of drug overdose: The patient should be in a supine position, if necessary, keep observation and take special care and treatment. Gastric lavage or drugs can be used to induce vomiting shortly after ingestion of the drug. For those with excessive bradycardia, atropine 2mg can be injected intravenously. (9) Because the half-life of this drug is 7 to 10 hours, in the case of severe poisoning (with shock symptoms), the treatment of detoxification must be continued for a sufficient time. ^[1]

[Drug interaction] (1) This product can strengthen other antihypertensive drugs (such as: reserpine, methyldopa, clonidine, calcium antagonists, alpha receptor antagonists, etc.) and drugs with side effects of hypotensive ( The antihypertensive effect of barbiturate), phenothiazine, and bicyclic antidepressants also increased the corresponding side effects. (2) Hepatic enzyme inhibitors such as cimetidine can weaken the decomposition of the drug in the body, so it may cause the blood concentration of the drug to increase. (3) When this medicine is combined with amiodarone, the effect on the heart is enhanced, and hypotension, bradycardia, or cardiac arrest may occur. (4) Cardiac block may occur when used with diltiazem or verapamil. (5) This medicine may enhance the effect of islets or oral hypoglycemic agents. (6) When this drug is combined with methacholine, it can synergistically contract bronchial smooth muscle. Prolong bronchial contraction time. (7) This medicine can inhibit the metabolism of cyclosporine and increase the toxicity of the latter. (8) This medicine can increase the bioavailability and trough concentration of digoxin. It enhances its effect on the heart, and it can cause atrioventricular block and cause toxic symptoms of digoxin. The clinical measurement of digoxin blood concentration should be strengthened. (9) Non-steroidal anti-inflammatory drugs can reduce the hypotensive effect of this drug. (10) Rifampin. Hepatic enzyme-inducing drugs such as rifabutin can induce the metabolism of this drug, thereby reducing its effect. (11) This medicine can block the beta effect of the adrenal cord, thereby causing bradycardia and antagonizing the allergic response to adrenaline. (12) Combined with fentanyl, it can produce severe hypotension. The mechanism is unknown. (13) Moxidine combined with this drug may cause rebound hypertension, and its mechanism of action is unclear. ^[2]

[Dosing instructions] (1) This medicine generally requires long-term use, and at the same time to avoid sudden withdrawal, it should be taken gradually for more than 1 to 2 weeks. Physical activity should be minimized within 2 to 3 weeks after discontinuation to avoid worsening angina or other serious cardiovascular diseases. (2) When the combined application of this drug and clonidine is discontinued, the drug should be stopped first, and then clonidine will be gradually reduced in a few days. (3) Before taking carvedilol in patients with pheochromocytoma, alpha receptor blockers should be used first. (4) Carvedilol must be reduced for bradycardia with a heart rate <55 beats / min. (5) Although the time of taking this medicine is not related to meals, it must be taken at meals for patients with congestive heart failure to slow absorption and reduce the occurrence of orthostatic hypotension.

[Usage and Dosage] (1) Usual doses for adults: oral, primary hypertension and angina pectoris, the initial dose is 12.5mg, once a day, orally; 25mg two times a day orally once a day, and the dose can be gradually increased later as needed Take 50mg a day, taking 1 or 2 times. For chronic congestive heart failure, the dose must be individualized. Increasing the dose requires close observation. The recommended dose for the first 2 weeks is 3.125 mg, twice daily. If it is well tolerated, the dose can be increased to 6.25 mg twice a day, then 12.5 mg each time, twice a day, and then to 25 mg twice a day. The dose must be increased to the highest limit that the patient can tolerate. For patients weighing <85 kg, the maximum recommended dose is 25 mg twice daily; for patients weighing 85 kg, the maximum recommended dose is 50 mg twice daily. When Carvedilol is discontinued for more than 2 weeks, re-administration should start at 3.125 mg once a day, twice a day, and then increase the dose as recommended above. (2) Dose for the elderly: The initial dose for patients with essential hypertension is 12.5 mg once a day. If the effect is not good, the dose can be increased to the recommended maximum dose of 50 mg a day at least 2 weeks later, once a day or in divided doses.

[Formulation specifications] Carvedilol tablets: Daliquan (1) 6.25mg * 10 tablets; (2) 25mg * 10 tablets. Lot (3) 10mg * 20 tablets; ^[3-4]