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Pronunciation:

(eye soe proe TER e nole)

U.S. Brand Names:

Isuprel®

Synonyms:

Isoproterenol Hydrochloride

Generic Available:

Yes

Use:

Ventricular arrhythmias due to AV nodal block; hemodynamically compromised bradyarrhythmias or atropine- and dopamine-resistant bradyarrhythmias (when transcutaneous/venous pacing is not available); temporary use in third-degree AV block until pacemaker insertion

Use - Unlabeled/Investigational:

Temporizing measure before transvenous pacing for torsade de pointes; diagnostic aid (vasovagal syncope)

Pregnancy Risk Factor:

Lactation:

Excretion in breast milk unknown

Contraindications:

Hypersensitivity to sulfites or isoproterenol, any component of the formulation, or other sympathomimetic amines; angina, pre-existing cardiac arrhythmias (ventricular); tachycardia or AV block caused by cardiac glycoside intoxication

Warnings/Precautions:

Use with extreme caution; not currently a treatment of choice; use with caution in elderly patients, diabetics, renal or cardiovascular disease, seizure disorder, or hyperthyroidism; excessive or prolonged use may result in decreased effectiveness.

Adverse Reactions:

Frequency not defined.

Cardiovascular: Premature ventricular beats, bradycardia, hyper-/hypotension, chest pain, palpitation, tachycardia, ventricular arrhythmia, MI size increased

Central nervous system: Headache, nervousness or restlessness

Endocrine & metabolic: Serum glucose increased, serum potassium decreased, hypokalemia

Gastrointestinal: Nausea, vomiting

Respiratory: Dyspnea

Overdosage/Toxicology:

Symptoms of overdose include tachycardia, tremor, hypertension or hypotension, angina, and seizures. Hypokalemia also may occur. Cardiac arrest and death may be associated with abuse of beta-agonist bronchodilators. Treatment includes immediate discontinuation and symptomatic and supportive therapies. Cautious use of beta-adrenergic blocking agents may be considered in severe cases.

Drug Interactions:

Increased toxicity: Sympathomimetic agents may cause headaches and elevate blood pressure; general anesthetics may cause arrhythmias

Ethanol/Nutrition/Herb Interactions:

Herb/Nutraceutical: Avoid ephedra, yohimbe (may cause CNS stimulation).

Stability:

Isoproterenol solution should be stored at room temperature; it should not be used if a color or precipitate is present. Exposure to air, light, or increased temperature may cause a pink to brownish pink color to develop. Stability of parenteral admixture at room temperature (25°C) or at refrigeration (4°C) is 24 hours.

Standard diluent: 2 mg/500 mL D5W; 4 mg/500 mL D5W

Minimum volume: 1 mg/100 mL D5W

Incompatible with alkaline solutions, aminophylline and furosemide

Compatibility:

Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D5¹/4 NS, D5¹/2NS, D5NS, D5W, D10W, LR, ¹/2NS, NS; not stable in sodium bicarbonate 5%

Y-site administration: Compatible: Amiodarone, atracurium, bretylium, cisatracurium, famotidine, heparin, hydrocortisone sodium succinate, inamrinone, levofloxacin, milrinone, pancuronium, potassium chloride, propofol, remifentanil, tacrolimus, vecuronium, vitamin B complex with C

Compatibility in syringe: Compatible: Ranitidine.

Compatibility when admixed: Compatible: Atracurium, calcium chloride, cimetidine, dobutamine, floxacillin, heparin, magnesium sulfate, multivitamins, potassium chloride, ranitidine, succinylcholine, verapamil, vitamin B complex with C. Incompatible: Aminophylline, furosemide, sodium bicarbonate

Mechanism of Action:

Stimulates beta1- and beta2-receptors resulting in relaxation of bronchial, GI, and uterine smooth muscle, increased heart rate and contractility, vasodilation of peripheral vasculature

Pharmacodynamics/Kinetics:

Onset of action: Bronchodilation: I.V.: Immediate

Duration: I.V.: 10-15 minutes

Metabolism: Via conjugation in many tissues including hepatic and pulmonary

Half-life elimination: 2.5-5 minutes

Excretion: Urine (primarily as sulfate conjugates)

Dosage:

I.V.: Cardiac arrhythmias:

Children: Initial: 0.1 mcg/kg/minute (usual effective dose 0.2-2 mcg/kg/minute)

Adults: Initial: 2 mcg/minute; titrate to patient response (2-10 mcg/minute)

Administration:

I.V. infusion administration requires the use of an infusion pump. To prepare for infusion: 1 mg isoproterenol to 500 mL D5W, final concentration 2 mcg/mL

Monitoring Parameters:

ECG, heart rate, respiratory rate, arterial blood gas, arterial blood pressure, CVP; serum glucose, serum potassium, serum magnesium

Patient Education:

You may experience nervousness, dizziness, or fatigue (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or dry mouth, nausea, or vomiting (small, frequent meals may reduce the incidence of nausea or vomiting). If you have diabetes, check blood sugar; blood glucose level may be increased. Report chest pain, rapid heartbeat or palpitations, unresolved/persistent GI upset, dizziness, fatigue, trembling, increased anxiety, sleeplessness, or respiratory difficulty. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Consult prescriber if breast-feeding.

Anesthesia and Critical Care Concerns/Other Considerations:

An important use for isoproterenol is in the intensive care setting in the treatment of torsade de pointes. In patients with recurrent torsade de pointes, treatment consists of correcting underlying cause (eg, electrolyte abnormalities or drug ingestion). Supportive therapy consists of increasing heart rate so as to decrease the QT interval.

Cardiovascular Considerations:

Isoproterenol is being increasingly used for provoking vasovagal syncope during tilt table testing. Incremental doses of isoproterenol are used in patients with a history suggestive of vasovagal syncope but in whom upright tilt alone does not induce symptoms. Another important use for isoproterenol is in the intensive care setting in the treatment of torsade de pointes. In patients with recurrent torsade de pointes, treatment consists of correcting underlying cause (eg, electrolyte abnormalities or drug ingestion). Supportive therapy consists of increasing heart rate so as to decrease the QT interval. This can be achieved by either placement of a temporary external pacemaker or by incremental isoproterenol infusion to achieve a resting heart rate of approximately 100 beats per minute or a resting heart rate that is not conducive to the occurrence of torsade de pointes.

Isoproterenol may be used together with atropine as a temporizing measure in treating patients with hemodynamically significant bradycardia.

Study data suggest that elderly healthy or hypertensive patients are less responsive to beta-adrenergic stimulation compared to younger subjects. Use caution in elderly patients; start dosing at the lower end of the dosing range.

Dental Health: Effects on Dental Treatment:

Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Isoproterenol is selective for beta-adrenergic receptors and not alpha receptors; therefore, there is no precaution in the use of vasoconstrictor such as epinephrine

Mental Health: Effects on Mental Status:

Insomnia and restlessness are common

Mental Health: Effects on Psychiatric Treatment:

None reported

Dosage Forms:

Injection, solution, as hydrochloride: 0.02 mg/mL (10 mL); 0.2 mg/mL (1:5000) (1 mL, 5 mL) [contains sodium metabisulfite]

International Brand Names:

Aleudrina® (ES); Autohaler® (IN); Bronhodilatin® (RO); Ciapar® (AR); Euspiran® (CZ); Imuprel® (ZA); Ingelan® (AT); Isolin® (IN); Isomenyl® (JP); Isoprenalina Cloridrato® (IT); Isoprenalin Hydrochlorid® (AU); Isoprenalinhydrochlorid-Braun® (LU); Isoprenalin SAD® (DK); Isoproterenol® (AR); Isoproterenol Clorhidrato® (CL); Isuprel® (AU, BE, CY, EG, FR, HU, ID, IL, JO, KW, LB, LU, NZ, SG, TH); Isuprel Mistometer® (HK); Izoprenalin® (RO); Lenoprel® (ZA); Medihaler-Iso® (HK); Min-I-Jet Isoprenaline® (GB); Proterenal® (AR); Saventrine® (CY, GB, HK, JO, KW, MT)

References

Almquist A, Goldenberg IF, Milstein S, et al, "Provocation of Bradycardia and Hypotension by Isoproterenol and Upright Posture in Patients With Unexplained Syncope,"N Engl J Med, 1989, 320(6):346-51.

"Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science,"Circulation, 2000, 102(8):I-123.

Hemstreet MP, Miles MV, and Rutland RO, "Effect of Intravenous Isoproterenol on Theophylline Kinetics,"J Allergy Clin Immunol, 1982, 69(4):360-4.

Illi A, Sundberg S, Ojala-Karlsson P, et al, "The Effect of Entacapone on the Disposition and Hemodynamic Effects of Intravenous Isoproterenol and Epinephrine,"Clin Pharmacol Ther, 1995, 58(2):221-7.

Lang CC, Stein CM, Brown RM, et al, "Attenuation of Isoproterenol-Mediated Vasodilatation in Blacks,"N Engl J Med, 1995, 333(3):155-60.

"Practice Parameters for Hemodynamic Support of Sepsis in Adult Patients in Sepsis. Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine,"Crit Care Med, 1999, 27(3):639-60.

Rachelefsky GS and Siegel SC, "Asthma in Infants and Children - Treatment of Childhood Asthma: Part 1l,"J Allergy Clin Immunol, 1985, 76(3):409-25.

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