Isoproterenol is indicated for the following:
Isoproterenol is a beta-1 and beta-2 adrenergic receptor agonist resulting in the following:
Both beta-1 and beta-2 adrenergic receptors exert their effects through a G-alpha stimulatory second messenger system. G-protein coupled receptors are structurally composed of a seven-transmembrane-spanning protein. The extracellular domain serves as the ligand binding site. In the inactivated state, the intracellular domain is linked to a G-alpha stimulatory protein bound to a GDP molecule. Upon binding of a ligand to the extracellular domain of a beta-1 receptor, the alpha subunit exchanges a GDP molecule for a GTP and becomes activated. The (now active) G-alpha protein dissociates from the intracellular domain and activates adenylate cyclase. Activated adenylate cyclase subsequently converts intracellular ATP to cAMP. The major second messenger in this pathway, cAMP, activates protein kinase A (PKA). Activated PKA phosphorylates L-type calcium channels in cardiac myocytes, resulting in an increase in intracellular calcium. PKA also causes an increase in calcium release from ryanodine receptors on the sarcoplasmic reticulum.
Beta-1 adrenergic receptors are primarily concentrated on the heart. The terminal effects of activation of beta-1 adrenergic receptors are an increase in intracellular calcium. In cardiac pacemaker cells, increased calcium causes an increase in the slope of phase 4 of the cardiac pacemaker action potential. By increasing the slope of phase 4, pacemaker cells reach the threshold at a faster rate, resulting in the characteristic increased heart rate seen in patients on an isoproterenol infusion. In non-pacemaker cardiac myocytes, an increase in intracellular calcium causes the increased contractility characteristic of isoproterenol infusion.
The result of beta-1 agonism on the heart can be summarized as follows:
Beta-2 adrenergic receptors function similarly to beta-1 receptors. Activation of the G-protein coupled receptor results in an increase in intracellular cAMP. The second messenger cAMP then activates protein kinase A (PKA). PKA phosphorylates myosin light chain kinase (MLCK) thus inactivating it. In smooth muscle cells, MLCK is responsible for the phosphorylation of myosin, leading to myosin-actin cross-bridge formation and muscle contraction. As stated, agonism of beta-2 receptors leads to inactivation of MLCK and subsequent relaxation of smooth muscle, bronchial dilation, peripheral vasodilation, and gastrointestinal and uterine smooth muscle relaxation.
Other effects of isoproterenol:
Isoproterenol is administered intravenously via an infusion pump.
Brand and generic: 0.2 mg/mL (1 mL, 5mL)
Bradydysrhythmias, AV nodal block
2 to 10 mcg/minute titrated to desired effect
Brugada syndrome (off-label)
Bolus 1 to 2 mcg followed by 0.15 to 0.3 mcg/minute for 24 hours
2 to 20mcg/minute continuous infusion
Provocation of syncope during tilt table testing (off-label)
1mcg/minute, initially, then increase based on the desired response; max dose of 5 mcg/minute
Provocation of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (off-label)
45 mcg/minute for 3 minutes, then evaluate rhythm
Refractory torsades de pointes (off-label)
2-10 mcg/minute continuous infusion titrated to patient response
Bradycardia, AV nodal block
0.05-0.5 mcg/kg/minute, adjusted to desired effect; max dosage of 2 mcg/kg/minute
0.05 to 1 mcg/kg/minute continuous infusion titrated to effect
Isoproterenol is immediately active upon infusion. Its half-life is 2.5 to 5 minutes. Conjugation in hepatic and pulmonary tissues is the major method of metabolism. Excretion occurs via urine in the form of sulfate conjugates.
The use of isoproterenol during pregnancy has not been evaluated. The presence of isoproterenol in breast milk is presently unknown.
Central Nervous System
Endocrine & Metabolic
Use with caution in patients with the following:
Isoproterenol is a Pregnancy Risk Factor C. It may interfere with uterine contractions due to its beta-2 agonist properties. Animal reproduction studies have not been conducted at this time. It is currently unknown if isoproterenol is present in breast milk; breastfeeding mothers are advised to exercise caution when taking isoproterenol.
Risk C: Monitor Therapy
Risk D: Consider modifying therapy
Risk X: Avoid
Vitals (i.e., heart rate, respiratory rate, blood pressure) in addition to ECG, arterial blood gas, blood glucose levels, and serum potassium and magnesium levels should be monitored continuously in patients who are administered isoproterenol.
Isoproterenol is used by a multidisciplinary team that consists of ICU nurses, intensivist, cardiologist, cardiac surgeon, and critical care specialists. The drug is only used as an intravenous drip for severe bradycardia and cardiac arrest. It is sometimes used to manage hypovolemic shock and bronchospasm. Isoproterenol can cause tachyarrhythmias and hypertension at high doses. When used in the ICU, the patient must be closely monitored. Because of the availability of pacemakers and other chronotropic drugs, the use of isoproterenol has diminished today.
|||Field JM,Hazinski MF,Sayre MR,Chameides L,Schexnayder SM,Hemphill R,Samson RA,Kattwinkel J,Berg RA,Bhanji F,Cave DM,Jauch EC,Kudenchuk PJ,Neumar RW,Peberdy MA,Perlman JM,Sinz E,Travers AH,Berg MD,Billi JE,Eigel B,Hickey RW,Kleinman ME,Link MS,Morrison LJ,O'Connor RE,Shuster M,Callaway CW,Cucchiara B,Ferguson JD,Rea TD,Vanden Hoek TL, Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010 Nov 2 [PubMed PMID: 20956217]|
|||Neumar RW,Otto CW,Link MS,Kronick SL,Shuster M,Callaway CW,Kudenchuk PJ,Ornato JP,McNally B,Silvers SM,Passman RS,White RD,Hess EP,Tang W,Davis D,Sinz E,Morrison LJ, Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010 Nov 2 [PubMed PMID: 20956224]|
|||van Diepen S,Katz JN,Albert NM,Henry TD,Jacobs AK,Kapur NK,Kilic A,Menon V,Ohman EM,Sweitzer NK,Thiele H,Washam JB,Cohen MG, Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017 Oct 17 [PubMed PMID: 28923988]|
|||Denis A,Sacher F,Derval N,Lim HS,Cochet H,Shah AJ,Daly M,Pillois X,Ramoul K,Komatsu Y,Zemmoura A,Amraoui S,Ritter P,Ploux S,Bordachar P,Hocini M,Jaïs P,Haïssaguerre M, Diagnostic value of isoproterenol testing in arrhythmogenic right ventricular cardiomyopathy. Circulation. Arrhythmia and electrophysiology. 2014 Aug [PubMed PMID: 24970294]|
|||Benditt DG,Ferguson DW,Grubb BP,Kapoor WN,Kugler J,Lerman BB,Maloney JD,Raviele A,Ross B,Sutton R,Wolk MJ,Wood DL, Tilt table testing for assessing syncope. American College of Cardiology. Journal of the American College of Cardiology. 1996 Jul [PubMed PMID: 8752825]|
|||Al-Khatib SM,Stevenson WG,Ackerman MJ,Bryant WJ,Callans DJ,Curtis AB,Deal BJ,Dickfeld T,Field ME,Fonarow GC,Gillis AM,Hlatky MA,Granger CB,Hammill SC,Joglar JA,Kay GN,Matlock DD,Myerburg RJ,Page RL, 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2017 Oct 30 [PubMed PMID: 29084731]|
|||Watanabe A,Fukushima Kusano K,Morita H,Miura D,Sumida W,Hiramatsu S,Banba K,Nishii N,Nagase S,Nakamura K,Sakuragi S,Ohe T, Low-dose isoproterenol for repetitive ventricular arrhythmia in patients with Brugada syndrome. European heart journal. 2006 Jul [PubMed PMID: 16760208]|
|||Desimine VL,McCrink KA,Parker BM,Wertz SL,Maning J,Lymperopoulos A, Biased Agonism/Antagonism of Cardiovascular GPCRs for Heart Failure Therapy. International review of cell and molecular biology. 2018 [PubMed PMID: 29776604]|
|||Matera MG,Page C,Rinaldi B, β2-Adrenoceptor signalling bias in asthma and COPD and the potential impact on the comorbidities associated with these diseases. Current opinion in pharmacology. 2018 Jun [PubMed PMID: 29763833]|
|||Biazi GR,Frasson IG,Miksza DR,de Morais H,de Fatima Silva F,Bertolini GL,de Souza HM, Decreased hepatic response to glucagon, adrenergic agonists, and cAMP in glycogenolysis, gluconeogenesis, and glycolysis in tumor-bearing rats. Journal of cellular biochemistry. 2018 May 15 [PubMed PMID: 29761924]|
|||Matsubara S,Morimatsu Y,Shiraishi H,Kuwata T,Ohkuchi A,Izumi A,Takeda S,Suzuki M, Fetus with heart failure due to congenital atrioventricular block treated by maternally administered ritodrine. Archives of gynecology and obstetrics. 2008 Jul [PubMed PMID: 18066569]|
|||Mahon WA,Reid DW,Day RA, The in vivo effects of beta adrenergic stimulation and blockade on the human uterus at term. The Journal of pharmacology and experimental therapeutics. 1967 Apr [PubMed PMID: 6023594]|
|||Kislitsina ON,Rich JD,Wilcox JE,Pham DT,Churyla A,Vorovich EB,Ghafourian K,Yancy CW, Shock - Classification and Pathophysiological Principles of Therapeutics. Current cardiology reviews. 2018 Dec 12; [PubMed PMID: 30543176]|