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Background
Isoprenaline (also known as Isoproterenol) is a non-selective beta-adrenergic receptor agonist indicated to treat heart block, Adams-Stokes attacks, bronchospasm in anesthesia, cadiac arrest, hypovolemic shocks, septic shock, hypoperfusion, congestive heart failure, and cardiogenic shock.
Isoprenaline research in the 1940s found that this isopropyl analog of epinephrine dilated the bronchi, as well as raising the heart rate and cardiac output, without vasoconstriction. The US patent from 1943 states that this compound had a wider therapeutic index and a stronger action than adrenaline. Isoprenaline was granted FDA approval on 19 February 1948.
Properties and characteristics of Isoprenaline
| Drug class | Adrenergic agonists |
| Brand Names | Isuprel |
| Synonyms | Isoprenalina, Isoprenaline, Isoprénaline, Isoprenalinum, Isopropyl noradrenaline, Isoproterenol, N-Isopropylnoradrenaline, N-Isopropylnorepinephrine |
| Molecular Formula | C11H17NO3 |
| Molecular Weight | 211.26 g/mol |
| IUPAC Name | 4-{1-hydroxy-2-[(propan-2-yl)amino]ethyl}benzene-1,2-diol |
| Structural formula of main components |  |
| Pure active ingredient | Isoproterenol Hydrochloride |
| Appearance | Solid |
| Melting point | 170.5 °C |
| Solubility | 5.86e+00 g/L |
| Excretion | Excretion occurs via urine in the form of sulfate conjugates |
| Storage | Store below 25 degrees Celsius |
| Available Forms | Tablet, Aerosol, Injection, Liquid |
| Prescription | Do not consume without the doctors’ advice |
Isoprenaline uses
Isoprenaline is used to treat heart block and episodes of Adams–Stokes syndrome that are not caused by ventricular tachycardia or fibrillation, in emergencies for cardiac arrest until electric shock can be administered, for bronchospasm occurring during anesthesia, and as an adjunct in the treatment of hypovolemic shock, septic shock, low cardiac output (hypoperfusion) states, congestive heart failure, and cardiogenic shock. It is also used to prevent Torsades de Pointes in patients with long QT refractory to magnesium and to treat patients with intermittent Torsades de Pointes refractory to treatment with magnesium.
Historically, it was used to treat asthma via metered aerosol or nebulizing devices; it was also available in sublingual, oral, intravenous, and intramuscular formulations. The U.S. National Asthma Education and Prevention Program Expert Panel recommends against its use as a nebulizer for acute bronchoconstriction.
Isoprenaline can also ameliorate the impairment of intestinal stem cells mediated by β2-adrenoreceptors after chemotherapy.
What are side effects of Isoprenaline?
Isoprenaline may cause serious side effects including:
- Worsening symptoms,
- Chest pain,
- Racing or pounding heartbeats,
- Loss of consciousness,
- Paleness,
- Abnormal movements,
- Coldness of the skin,
- Anxiety,
- Fast heartrate,
- Coughing up blood or bloody froth,
- Fatigue,
- High or low blood pressure,
- Weakness,
- Dizziness,
- Fainting,
- Lightheadedness, and
- Shortness of breath
Get medical help right away, if you have any of the symptoms listed above.
Common side effects of Isoprenaline include:
- Tremor,
- Nervousness,
- Shakiness,
- Headache,
- Nausea,
- Vomiting,
- Diarrhea,
- Heartburn,
- Lightheadedness,
- Dizziness,
- Difficulty sleeping (insomnia),
- Unusual taste in mouth,
- Sweating,
- Hoarseness,
- Flushing,
- Shortness of breath,
- Blurred vision, or
- Dry mouth or throat as your body adjusts to the medication.
Seek medical care once if you have the following serious side effects:
- Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, light-headedness, or passing out;
- Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.
Mechanism of action
Isoprenaline is a non-selective beta-adrenergic receptor agonist. Agonism of beta-1 and beta-2 adrenergic receptors causes the alpha subunit of G-protein coupled receptors to exchange GMP for GTP, activating them, and allowing the alpha subunit to dissociate from the beta and gamma subunits. Dissociation of the alpha subunit activates adenylate cyclase, converting ATP to cyclic AMP. Cyclic AMP activates protein kinase A (PKA), which phosphorylates cardiac L-type calcium channels such as Cav1.2. These channels depolarize cells by inward active transport of calcium ions.
Agonism of beta-1 adrenergic receptors lead to increased strength of contractility, conduction of nerve impulses, speed of relaxation, and rate in the heart.
Agonism of beta-2 adrenergic receptors leads to glycogenolysis in the liver, glucagon release from the pancreas, and activation of the renin-angiotensin-aldosterone system.
In the alveoli, agonism of beta-2 adrenergic receptors, activates similar pathways to the heart, however the end result is regulation of sodium channels, the cystic fibrosis transmembrane conductance regulator (CFTR), and sodium potassium ATPase. PKA phosphorylates scaffolding proteins and sodium channels, increasing the number of sodium channels on the apical side of alveolar cells and increasing active transport of sodium ions into cells. Agonism of beta-2 adrenergic receptors can also increase chloride ion transport across CFTR. Together, these actions lead to passive transport of water out of the alveoli, and the clearance of alveolar fluid.
What other drugs interact with Isoproterenol?
If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first
- Isoproterenol has severe interactions with the following drugs:
- Isocarboxazid
- Linezolid
- Phenelzine
- Procarbazine
- Selegiline transdermal
- Tranylcypromine
- Isoproterenol has serious interactions with at least 26 other drugs.
- Isoproterenol has moderate interactions with at least 238 other drugs.
- Isoproterenol has minor interactions with at least 29 other drugs.
This information does not contain all possible interactions or adverse effects. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.
Isoproterenol Dosage
Applies to the following strengths: 0.2 mg/mL; 0.5%; 1%; 0.131 mg/inh; 0.02 mg/mL; 0.08%; 0.25%; hydrochloride; sulfate
Usual adult dose for Adams-Stokes Syndrome
IV Bolus:
- Initial dose: 0.02 to 0.06 mg IV bolus
- Subsequent dose range: 0.01 to 0.2 mg
IV Infusion:
Initial dose: 5 mcg/min via IV infusion
IM:
- Initial dose: 0.2 mg IM
- Subsequent dose range: 0.02 to 1 mg IM
Subcutaneous:
- Initial dose: 0.2 mg subcutaneously
- Subsequent dose range: 0.15 to 0.2 mg subcutaneously
Intracardiac:
- Initial dose: 0.02 mg via intracardiac route
Comments:
- Subcutaneous, intracardiac, and IM doses should be administered using undiluted solution.
- Bolus IV doses should be administered after diluting 1 mL (0.2 mg) in 9 mL of sodium chloride or 5% dextrose injection.
- IV infusion doses should be administered after diluting 10 mL (2 mg) in 500 mL of 5% dextrose injection.
- Subsequent doses and method of administration depend on ventricular rate and rapidity with which the cardiac pacemaker can take over when the drug is gradually withdrawn.
Uses: For mild or transient episodes of heart block that do not require electric shock or pacemaker therapy; for serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation); and for use in cardiac arrest until electric shock or pacemaker therapy is available
Usual adult dose for AV Heart Block
IV Bolus:
- Initial dose: 0.02 to 0.06 mg IV bolus
- Subsequent dose range: 0.01 to 0.2 mg
IV Infusion:
- Initial dose: 5 mcg/min via IV infusion
IM:
- Initial dose: 0.2 mg IM
- Subsequent dose range: 0.02 to 1 mg IM
Subcutaneous:
Initial dose: 0.2 mg subcutaneously
- Subsequent dose range: 0.15 to 0.2 mg subcutaneously
Intracardiac:
- Initial dose: 0.02 mg via intracardiac route
Comments:
- Subcutaneous, intracardiac, and IM doses should be administered using undiluted solution.
- Bolus IV doses should be administered after diluting 1 mL (0.2 mg) in 9 mL of sodium chloride or 5% dextrose injection.
- IV infusion doses should be administered after diluting 10 mL (2 mg) in 500 mL of 5% dextrose injection.
- Subsequent doses and method of administration depend on ventricular rate and rapidity with which the cardiac pacemaker can take over when the drug is gradually withdrawn.
Uses: For mild or transient episodes of heart block that do not require electric shock or pacemaker therapy; for serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation); and for use in cardiac arrest until electric shock or pacemaker therapy is available
Usual Adult Dose for Cardiac Arrest
IV Bolus:
- Initial dose: 0.02 to 0.06 mg IV bolus
- Subsequent dose range: 0.01 to 0.2 mg
IV Infusion:
- Initial dose: 5 mcg/min via IV infusion
IM:
- Initial dose: 0.2 mg IM
Subsequent dose range: 0.02 to 1 mg IM
Subcutaneous:
- Initial dose: 0.2 mg subcutaneously
- Subsequent dose range: 0.15 to 0.2 mg subcutaneously
Intracardiac:
- Initial dose: 0.02 mg via intracardiac route
Comments:
- Subcutaneous, intracardiac, and IM doses should be administered using undiluted solution.
- Bolus IV doses should be administered after diluting 1 mL (0.2 mg) in 9 mL of sodium chloride or 5% dextrose injection.
- IV infusion doses should be administered after diluting 10 mL (2 mg) in 500 mL of 5% dextrose injection.
- Subsequent doses and method of administration depend on ventricular rate and rapidity with which the cardiac pacemaker can take over when the drug is gradually withdrawn.
Uses: For mild or transient episodes of heart block that do not require electric shock or pacemaker therapy; for serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation); and for use in cardiac arrest until electric shock or pacemaker therapy is available.
Usual Adult Dose for Shock
- Initial dose: 0.5 to 5 mcg/min via IV infusion
Comments:
- Dilute 5 mL (1 mg) in 500 mL of 5% dextrose injection prior to administration.
- Consider decreasing or temporarily stopping the infusion if the heart rate exceeds 100 beats per minute.
- Concentrations up to 10 times greater have been used when limitation of volume is essential.
- Rates over 30 mcg per minute have been used in advanced stages of shock.
- The rate of infusion should be adjusted based on heart rate, central venous pressure, systemic blood pressure, and urine flow.
Uses: As an adjunct to fluid and electrolyte replacement therapy and the use of other drugs and procedures in the treatment of hypovolemic and septic shock, low cardiac output (hypoperfusion) states, congestive heart failure, and cardiogenic shock
Usual Adult Dose for Bronchospasm During Anesthesia
- Initial dose: 0.01 to 0.02 mg IV bolus; may be repeated when necessary
Comments:
- Dilute 1 mL (0.2 mg) in 9 mL of sodium chloride or 5% dextrose injection.
Use: For the treatment of bronchospasm during anesthesia
What are Warnings and Precautions for Isoprenaline?
Contraindications
- Hypersensitivity, digitalis intoxication, angina pectoris, preexisting cardiac arrhythmias (particularly ventricular arrhythmias that require inotropic treatment and tachyarrhythmias).
Effects of drug abuse
- None
Short-Term Effects
- See “What Are Side Effects Associated with Using Isoproterenol?”
Long-Term Effects
- See “What Are Side Effects Associated with Using Isoproterenol?”
Cautions
- Use caution in patients with convulsive disorders, renal disease, CAD, coronary insufficiency, DM, HTN, hyperthyroidism, hyperresponsiveness to sympathomimetic amines, elderly
- May cause thyroid storm in susceptible patients with hyperthyroidism
- May transiently increase blood glucose levels
Cardiac effects
- Isoproterenol hydrochloride injection should be started at the lowest recommended dose and gradually increased if necessary while carefully monitoring the patient; doses sufficient to increase heart rate to more than 130 beats per minute may increase the likelihood of inducing ventricular arrhythmias such increases in heart rate will also tend to increase cardiac work and oxygen requirements which may adversely affect failing heart or heart with a significant degree of arteriosclerosis
- Adequate filling of the intravascular compartment by suitable volume expanders is of primary importance in most cases of shock and should precede administration of vasoactive drugs; in patients with normal cardiac function, determination of central venous pressure is a reliable guide during volume replacement; if evidence of hypoperfusion persists after adequate volume replacement, isoproterenol hydrochloride injection may be given
- In addition to routine monitoring of systemic blood pressure, heart rate, urine flow, and electrocardiograph, monitor response to therapy by frequent determination of central venous pressure and blood gases
- Closely observe patients in shock during isoproterenol hydrochloride injection administration; if the heart rate exceeds 110 beats per minute, it may be advisable to decrease infusion rate or temporarily discontinue infusion
- Determinations of cardiac output and circulation time may also be helpful; take appropriate measures to ensure adequate ventilation; pay attention to acid-base balance and correction of electrolyte disturbances
- By increasing myocardial oxygen requirements while decreasing effective coronary perfusion isoproterenol hydrochloride injection may have a deleterious effect on the injured or failing heart
- Most experts discourage the use of the drug as an initial agent in treating cardiogenic shock following myocardial infarction; however, when low arterial pressure has been elevated by other means, isoproterenol hydrochloride injection may produce beneficial hemodynamic and metabolic effects
- In a few patients, presumably with organic disease of AV node and branches, the drug has paradoxically been reported to worsen heart block or to precipitate Adams-Stokes attacks during normal sinus rhythm or transient heart block
- The drug is no longer recommended for cardiac arrest
Pregnancy and Lactation
- Use with caution if the benefits outweigh the risks during pregnancy.
Lactation
- Not known if excreted into breast milk, avoid.