What Is Isoproterenol?

Isoprenaline, a beta-receptor agonist, is used for bronchial asthma and cardiac atrioventricular block. Widely used in clinical applications

Drug Name: Isoprenaline
Alias: ISOprenaline
Foreign name: Astigmatine, isoprenaline sulfate

Whether prescription drugs: prescription
Main indications: Bronchial asthma and cardiac atrioventricular block
Pharmacology: Agonist beta receptor
Shape: White or off-white crystalline powder

Introduction to isoprenaline compounds

Isoprenaline Basic Information

Chinese name: isoprenaline

Chinese aliases: isoproterenol, (-)-N-isopropyl-L-norepinephrine, asthidine, isoprenaline sulfate, isoprenaline hydrochloride, isopropyl norepinephrine, Zhichuanling

English name: isoprenaline

English alias: asmalar, A 21, isoprel, (+/-)-isoproterenol, Aludrine, Isonorin, Isoprenaline Hydrochloride, Isopreterenol, Isoproterenol, Isoproterenol Hydrochloride, Isuprel, Medihaler-Iso, Norisodrine

CAS number: 7683-59-2

Molecular formula: C ₁₁ H ₁₇ NO ₃

Structural formula:

Molecular weight: 211.25800

Exact mass: 211.12100

PSA: 72.72000

LogP: 1.52010 ^[1]

Isoprenaline physicochemical properties

Appearance and properties: White crystalline powder, commonly used as its hydrochloride salt, is white or almost white crystalline powder; odorless, slightly bitter taste, gradual discoloration when exposed to light and air, more easily discolored in alkaline solution Soluble in water, slightly soluble in ethanol, insoluble in chloroform or ether.

Melting point: 165-170ºC

Isoprenaline Drug Description

Isoprenaline Classification

Circulatory Drugs> Antiarrhythmic Drugs> Treatment of Bradycardia

Isoproterenol traits

The hydrochloride is commonly used as a white or off-white crystalline powder; it is odorless, has a slightly bitter taste, and gradually changes color when exposed to light and air. It is more likely to change color in alkaline solutions. Soluble in water, slightly soluble in ethanol, insoluble in chloroform or ether.

Isoprenaline dosage form

1. Injection: 0.5mg (0.5ml), 1mg (1ml);

2. Tablet: 10mg; 3. Aerosol: 0.25% (20ml).

Pharmacological effects of isoprenaline

Isoprenaline

1. Exciting the cardiac 1 receptors, which can increase myocardial contractility, increase heart rate, accelerate conduction, increase cardiac output and myocardial oxygen consumption. Can expand the coronary arteries and increase coronary flow, but excessive doses can cause strong dilation of blood vessels, which will reduce the perfusion volume. The effect of accelerating heart rate and conduction is strong. It has a stronger effect on orthotopic pacing points than on ectopic pacing points, and is less likely to cause arrhythmia than adrenaline.

2. Isoproterenol excites 2 receptors, which mainly causes skeletal muscle blood vessels to dilate, and also has a weaker dilating effect on kidney and mesenteric blood vessels. Its cardiovascular effects increase systolic blood pressure, diastolic blood pressure, and increase pulse pressure.

3. It acts on 2 receptors of bronchial smooth muscle, which has a strong relaxing effect on bronchial smooth muscle, relieves bronchospasm and has a stronger effect than epinephrine. But unlike epinephrine, isoproterenol does not constrict bronchial mucosal blood vessels and eliminate bronchial mucosal edema.

4. Other effects include promoting glycogen decomposition and release of free fatty acids, increasing tissue oxygen consumption.

Isoprenaline pharmacokinetics

Nebulization is completely absorbed by inhalation. It takes effect after inhalation for 2 to 5 minutes, and the effect can be maintained for 0.5 to 2 hours. Intravenous effect is maintained for less than 1 hour; sublingual administration is effective for 15 to 30 minutes, and the effect is maintained for 1 to 2 hours. After intravenous injection, the 1 adrenergic receptor has a half-life of only 1 minute and a half-life of 4 minutes. It is mainly metabolized in the liver and excreted through the kidneys. About 5 to 10% is discharged in the original form after inhalation; about 40 to 50% is discharged in the original form after intravenous injection.

Isoprenaline indication

Treatment of bronchial asthma; Treatment of cardiogenic or septic shock; Treatment of complete atrioventricular block and cardiac arrest.

Isoprenaline contraindications

1. Coronary heart disease, myocarditis, hyperthyroidism and heart rate greater than 120 beats / min, children with heart rate greater than 160 beats per minute are contraindicated.

2. Allergic to isoproterenol or other components in the product.

3. Tachycardia.

4. Ventricular arrhythmias need to improve myocardial contractility.

5. Patients with angina pectoris, myocardial infarction, pheochromocytoma and atrial fibrillation are contraindicated.

Isoprenaline dosage

The product is not effective by mouth. Sublingual medicine, can be quickly absorbed from the sublingual venous plexus. The aerosol is quickly absorbed by inhalation, and its bioavailability is about 80% -100%. The effective blood concentration was 0.5-2.5 mg / ml, and Vd was 0.7 L / kg. It binds with sulfuric acid in the liver and is inactivated by catechol oxygen methyltransferase methylation in other tissues. After intravenous administration, the urine excreted the original drug and methylated metabolites each accounted for 50%. After aerosol inhalation, all urine excretions are methylated metabolites

1. Bronchial asthma: sublingual, adult, commonly used, 10-15mg once a day, 3 times a day; extreme, 20mg once a day, 60mg a day. Pediatrics, over 5 years old, 2.5 to 10 mg each time, 2 or 3 times a day. Aerosol inhalation, commonly used amount, 0.1 ~ 0.4mg once; Extreme amount, 0.4mg once, 2.4mg a day. The interval between repeated use should not be less than 2 hours.

2, cardiac arrest: intracardiac injection of 0.5-lmg.

3. Atrioventricular block: those with degree take sublingual lozenge, 10mg each time, once every 4 hours degree, heart rate is lower than 40 times / min, 0.5 1mg can be dissolved in 5% glucose The solution was dripped slowly 200-300 ml.

4. Anti-shock: 0.5-lmg is added to 200ml of 5% glucose solution, and the drip rate is 0.5 2g / min. Adjust the drip rate according to the heart rate to maintain the systolic pressure at 12kPa (90mmHg). The pressure is above 2.7kPa (20mmHg) and the heart rate is below 120 beats / min.

Isoprenaline precautions

1. (1) insufficient coronary blood supply; (2) diabetes; (3) angina; (4) hypertension; (5) convulsions.

2. The effects of drugs on pregnancy: The US FDA believes that isoproterenol should be a class C pregnancy.

3. Check or monitor before, after and during medication: Monitor blood potassium levels when using isoprenaline.

4. Excessive and repeated application of aerosol can produce tolerance. At this time, not only there is cross-tolerance between adrenaline beta receptor agonists, but also tolerance to endogenous adrenergic transmitters. , Make bronchospasm worse, reduce efficacy, and even increase mortality.

5. When taking under the tongue, the tablets should be chewed up and contained under the tongue, otherwise the quick effect cannot be achieved.

6. Asthma patients who have obvious hypoxia, if the dosage is too large, it will easily lead to increased myocardial oxygen consumption, cause arrhythmia, and even cause ventricular tachycardia and ventricular fibrillation.

7. When inhaling aerosols, the number and quantity of inhalations should be limited.

8. When the inhalation spray has been sprayed 3 to 5 times within 12 hours and the effect is not obvious, the medicine should be changed.

9. Isoproterenol can be used interchangeably with epinephrine, but cannot be used at the same time. When used alternately, the prodrug can only be used after the prodrug effect disappears.

10. Isoproterenol is destroyed by acid and alkali, and it is not compatible with oxides and alkaline substances, otherwise the curative effect is reduced.

11. Use with caution in patients with obstructive hypertrophic cardiomyopathy, ventricular arrhythmia, mechanical obstruction after myocardial infarction, and hypovolemia. Bronchial asthma patients have obvious hypoxia. Excessive dosage can increase myocardial oxygen consumption, easily cause arrhythmia, and even ventricular tachycardia and atrial fibrillation. It should be used with caution when the heart rate of adults exceeds 120 beats per minute and the heart rate of children exceeds 140 beats per minute.

12. Blood volume and acidosis should be corrected before use; blood pressure, cardiac output, electrocardiogram, and pulmonary wedge pressure should be regularly or continuously monitored during medication ^[2] .

Isoprenaline adverse reactions

Common adverse reactions are: dryness of the oropharynx and palpitations; rare adverse reactions include: dizziness, dizziness, facial flushing, nausea, heart rate increase, tremor, sweating, fatigue, etc.

Have arrhythmia, myocardial damage, palpitations, induced angina pectoris, headache, tremor, dizziness, prolapse, bronchoconstriction (spasm) in individual cases, sublingual administration can cause oral ulcers, tooth damage. Repeatedly aerosol excessive tolerance Sex, make bronchospasm worse, reduce efficacy, and even increase mortality.

When this drug is used to treat respiratory diseases, its adverse reactions include tachycardia, arrhythmia, palpitations, flushing and angina pectoris. The use of this medicine has a tendency to gradually increase the dose, thereby increasing the toxic effect on the heart. This medicine can cause a waveform of myocardial infarction on the ECG, or if the medicine is injected intravenously, it can cause ventricular fibrillation or even myocardial necrosis.

It relaxes the bronchial smooth muscle and reduces the airway resistance, but makes the ventilation perfusion ratio abnormal and aggravates hypoxemia. The patient feels better and the condition is worsening. In addition, it can sometimes induce strange bronchospasm.

Headaches, tremors, anxiety, dizziness, and collapse are common.

Sublingual use of this drug can also cause a whole body reaction, and often has oral ulcers.

Isoprenaline drug interactions

1. Cross-allergy with other sympathomimetic amines.

2. Combined with general anesthesia, it can increase the possibility of ventricular arrhythmia.

3, -blockers can antagonize the effect of the product on island receptors, so that the -receptor effect is dominant, and total peripheral vascular resistance is increased.

4. With the use of sodium nitroprusside, the cardiac output can be slightly increased, and the pulmonary wedge pressure is slightly reduced.

5. Combined with phenylephrine, it has a synergistic effect on the control of asthma and can further improve the ventilation function.

6. It is forbidden to use with halothane anesthetics such as cyclopropane and halothane, otherwise it may cause severe arrhythmia.

7. Potassium chloride and various drugs that can cause high or low blood potassium can increase the excitability of the product to the heart and easily cause arrhythmia.

8, can not be compatible with drugs with a pH value of 6.0, such as calcium preparations, aminophylline, lidocaine, sulfadiazine sodium and so on.

9, combined with oral anticoagulants, can increase anticoagulant effect.

10. Combination with other epinephrine drugs can increase the efficacy, but the adverse reactions also increase.

11. The effect of this product is antagonized when combined with propranolol.

12. Simultaneous application with epinephrine drugs, theophylline and thyroid preparations will increase the toxicity of this drug

Isoprenaline poisoning

Toxicology

Isoproterenol has a strong effect on beta receptors; in excess, it can cause cardiac arrhythmia and myocardial ischemia due to increased myocardial contractility and oxygen consumption; it can penetrate the blood-brain barrier and cause central excitement symptoms. A small number of asthma patients inhaled isoproterenol excessively or caused exacerbation of asthma symptoms at conventional doses, called "paradoxical bronchial response", which may be due to its intermediate metabolite 3-methoxyisoproterenol having beta receptor Body block effect, resulting in bronchial smooth muscle spasm.

Clinical manifestation

Nausea, palpitations, angina pectoris, and various arrhythmias; central nervous system symptoms include headache, dizziness, anxiety, insomnia, and tremor.

Poisoning emergency treatment

1. Stop the medicine immediately. A tourniquet is ligated at the proximal end of the subcutaneous injection site to limit rapid drug absorption.

2. Give epinephrine blocking drugs, such as alpha receptor blocker phentolamine 10 mg, and dilute with 5% glucose solution or saline 100 ml slowly; intravenous infusion of propranolol After 5mg dilution, it was slowly injected intravenously. It can also be taken with 0.5 mg of nitroglycerin, repeated 15 to 30 minutes if necessary; inhalation of isoamyl nitrite is also effective. Monitor the patient's blood pressure and heart rate during medication to prevent accidents.

3. Patients with ventricular fibrillation prefer non-synchronous DC shock defibrillation with energy of 200 ~ 300 joules. If there is no defibrillator at one time, 100-150 mg of lidocaine can be injected intravenously; then intravenous infusion is continued at a rate of 1 to 4 mg / min; if the rhythm is not converted, another 100 mg of intravenous injection can be performed 5 to 10 minutes later, and one heart can be used Intraluminal injection of 200 ~ 250mg. Multiple electrical defibrillation failures are an indication of the use of other antiarrhythmic drugs, such as intravenous injection of procainamide 100 mg, once every 5 minutes, the total amount is 500 to 1000 mg; then continued at 2 to 4 mg / min Intravenous drip. Or take the first dose of 3mg / kg bromobenzylamine intravenously; then shock again. This medicine can then be used again every 15 minutes until the maximum dose is 25 mg / kg. Can also be used amiodarone 150 ~ 500mg, intravenous injection, or 10 mg / (kg · d) intravenous drip.

4. Symptomatic treatment, oxygen inhalation, etc. ^[3] .

Isoprenaline Expert Review

The commonly used inhaled dose of isoproterenol is effective 1 minute after inhalation, and the effect is maintained for 2.5 hours. It is mainly used in the rescue of bronchial acute attacks and rarely used for routine treatment. Isoprenaline has both 1 and 2 receptor excitatory effects. Exciting high cardiac pacing points. It can also expand peripheral blood vessels, reducing peripheral resistance. Applicable to septic shock and cardiogenic shock. It is also the first choice for sinus bradycardia and cardiac arrest. Its aerosol can be used for bronchial asthma ^[2] .

Isoprenaline aerosol

Isoprenaline hydrochloride aerosol

Indications: Treatment of bronchial asthma.

Dosage: 1. Commonly used for adults: 0.25% aerosol inhalation 1-2 times a day, 2-4 times a day, the interval between spraying and inhalation should not be less than 2 hours. Inhale deeply when spraying, close the mouth for 8 seconds, and exhale slowly.

2, commonly used in children (except infants and young children): 0.25% spray inhalation.

3. Extreme amount: 0.4mg once a day, 2.4mg a day.

Dosage form: aerosol

Adverse reactions: Common adverse reactions are: dry oropharynx and palpitations; rare adverse reactions are: dizziness, dizziness, flushing, nausea, heart rate increase, tremor, sweating, fatigue, etc.

Contraindications: Patients with angina pectoris, myocardial infarction, hyperthyroidism, and pheochromocytoma are contraindicated.

Precautions: 1. Arrhythmia accompanied by tachycardia; Cardiovascular diseases, including angina pectoris and insufficient coronary blood supply; diabetes; hypertension; hyperthyroidism;

2. Pay attention to chest pain and arrhythmia early.

3. Cross-allergies. Patients who are allergic to other epinephrine agonists are often allergic to this product.

Ingredients: [chemical name] The main ingredient of this product is isoproterenol hydrochloride, and the chemical name is 4-[(2-isopropylamino-1-hydroxy) ethyl] -1,2-benzenediol hydrochloride.

Properties: The liquid medicine in the pressure-resistant container is a colorless or yellowish clear liquid; when the valve is pressed, the liquid medicine is sprayed out as mist.

Medication for pregnant and lactating women: It is not clear.

Pediatric use: Unclear.

Elderly medication: Not clear.

Drug interactions: 1. Combination with other epinephrine-based drugs can increase the efficacy, but the adverse reactions also increase.

2. The effect of this product is antagonized when combined with propranolol.

Pharmacological effects: This product is a beta receptor agonist, which has a strong agonizing effect on the beta 1 and beta 2 receptors, and has little effect on the alpha receptors. Main effects: It acts on cardiac 1 receptors, which can increase cardiac contractility, accelerate heart rate, accelerate conduction, increase cardiac output and myocardial oxygen consumption. It acts on vascular smooth muscle 2 receptors, which significantly relaxes skeletal muscle blood vessels. The renal, mesenteric blood vessels and coronary arteries also relax to varying degrees, and the total peripheral resistance of blood vessels is reduced. Its cardiovascular effects lead to an increase in systolic blood pressure, a decrease in diastolic blood pressure, and a large pulse pressure difference. It acts on 2 receptors of bronchial smooth muscle, and relaxes the bronchial smooth muscle. Promote glycogen and lipolysis, increase tissue oxygen consumption.

Drug overdose: excessive, repeated application of aerosol can produce tolerance, at this time, not only cross-tolerance between receptor agonists, but also tolerance to endogenous adrenergic transmitters Make bronchospasm deeper, reduce efficacy, and even increase mortality. Therefore, the number and quantity of inhalation should be limited.

Pharmacokinetics: Inhalation is completely absorbed by inhalation, it will take effect after 2-5 minutes, and the effect can be maintained for 0.5-2 hours. After inhalation, about 5% to 15% are discharged in the original form.

Storage: shading, sealed, and stored in a cool and dark place (not more than 20 ) ^[4] .