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Continuing Education Activity

Isoproterenol is a beta-1 and beta-2 adrenergic receptor agonist indicated primarily for bradydysrhythmias. The administration and subsequent post-administration monitoring of this medication are complex and necessitate an interprofessional approach to its usage. This activity covers isoproterenol, including mechanism of action, pharmacology, adverse event profiles, eligible patient populations, contraindications, monitoring, and highlights the role of the interprofessional team in the management of isoproterenol therapy.


  • Identify indications for the use of isoproterenol.
  • Describe the mechanism of action of isoproterenol.
  • Review potential complications arising from the use of isoproterenol.
  • Summarize the importance of an interprofessional team approach to the use of isoproterenol.


Isoproterenol Indications[1]

  • Heart block not requiring pacing 
  • Cardiac arrest from heart block when pacemaker therapy is unavailable

Off-label Uses[2][3][4][5][6][7]

  • Bradycardia
  • Bronchospasm during anesthesia 
  • Cardiogenic shock
  • Hypovolemic shock (adjunctive treatment) 
  • Provocation of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy: used during electrophysiological studies to induce ventricular arrhythmias in patients with a history of arrhythmogenic right ventricular cardiomyopathy
  • Provocation of syncope during tilt table testing
  • Torsades de pointes
  • Beta-blocker overdose 
  • Ventricular arrhythmias secondary to AV block 
  • Short QT syndrome 
  • Electrical storm in patients with Brugada syndrome
  • Bradycardia in a cardiac transplant patient

Mechanism of Action

Isoproterenol is a beta-1 and beta-2 adrenergic receptor agonist resulting in the following: 

  • Increased heart rate 
  • Increased heart contractility 
  • Relaxation of bronchial, gastrointestinal, and uterine smooth muscle 
  • Peripheral vasodilation 

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 links 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 principal second messenger in this pathway, cAMP, activates protein kinase A (PKA). Activated PKA phosphorylates L-type calcium channels in cardiac myocytes, resulting in increased intracellular calcium. PKA also causes an increase in calcium release from ryanodine receptors on the sarcoplasmic reticulum.

Beta-1 adrenergic receptors are primarily concentrated in heart tissue. 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.[8]

The result of beta-1 agonism on the heart can be summarized as follows:

  • Positive inotropy (contractility)
  • Positive lusitropy (relaxation)
  • Positive chronotropy (heart rate)
  • Positive dromotropy (conduction velocity) 

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.[9]

Other effects of isoproterenol:[10]

  • Hepatic glycogenolysis (beta-2)
  • Release of glucagon from the pancreas (beta-2)
  • Activation of the renin-angiotensin-aldosterone system in the kidney (beta-1)


Isoproterenol is administered intravenously via an infusion pump.

Available Forms

Brand and generic: 0.2 mg/mL (1 mL, 5mL) 

Adult Dosage

Bradydysrhythmias, AV Nodal Block

2 to 10 mcg/minute titrated to desired effect[2] 

Brugada Syndrome (off-label)

Bolus 1 to 2 mcg followed by 0.15 to 0.3 mcg/minute for 24 hours[7]

Cardiogenic Shock (off-label)

2 to 20mcg/minute continuous infusion[3]

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[4]

Refractory Torsades de Pointes (off-label)

2 to 10 mcg/minute continuous infusion titrated to patient response[6] 

Pediatric Dosage

Bradycardia, AV Nodal Block

0.05 to 0.5 mcg/kg/minute IV, adjusted to desired effect; max dosage of 2 mcg/kg/minute[2] 

Neonatal Dosage


0.05 to 1 mcg/kg/minute continuous infusion titrated to effect[11]


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.[12]

Adverse Effects


  • Headache
  • Dizziness
  • Upset stomach
  • Flushing
  • Fatigue
  • Nervousness


  • Angina 
  • Flushing 
  • Hypotension 
  • Hypertension 
  • Palpitations 
  • Ventricular arrhythmia 
  • Premature ventricular contractions 
  • Adams-stokes syndrome 
  • Bradycardia (with tilt table testing) 


  • Dyspnea 
  • Edema 


  • Blurred vision 

Central Nervous System

  • Headache
  • Dizziness
  • Nervousness
  • Restlessness
  • Seizures 


  • Nausea
  • Vomiting 

Endocrine & Metabolic

  • Hypokalemia
  • Increased serum glucose 


  •  Tremor
  • Weakness 


Absolute Contraindications

  • Angina
  • Tachydysrhythmias
  • Preexisting ventricular arrhythmias
  • Digoxin intoxication
  • Sulfa allergy: Contains sulfites

Isoproterenol requires caution in patients with the following:

  • Cardiovascular disease: Isoproterenol causes an increase in myocardial oxygen demand
  • Diabetes: May cause an increase in blood glucose levels
  • Distributive shock: Beta-2 agonism will further decrease total peripheral resistance
  • Hyperthyroidism: May induce thyroid storm
  • Contains sulfites which may provoke an allergic reaction in patients with a sulfa allergy
  • Elderly


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.[12] 

Drug Interactions

Risk C: Monitor Therapy

  • Atomoxetine: Propensity to increase heart rate
  • Cannabinoid-containing products: Propensity to increase heart rate
  • COMT Inhibitors: Isoproterenol is degraded by catechol O-methyltransferase (COMT) and may rise to dangerous levels in the presence of a COMT inhibitor
  • Doxofylline: Increased risk of doxofylline toxicity
  • Tedizolid: Increased risk of a hypertensive episode

Risk D: Consider Modifying Therapy

  • Topical Cocaine: Heightened risk of hypertension, tachycardia, and increased oxygen demand
  • Linezolid: Increased risk of hypertension due to COMT inhibitor-like action of linezolid
  • Mifepristone: QTc prolongation
  • QTc prolonging agents: Avoid giving isoproterenol in combination with other QTc prolonging agents.

Risk X: Avoid

  • Inhaled Anesthetics: Increased risk of arrhythmia


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 require continuous monitoring in patients receiving isoproterenol.

Enhancing Healthcare Team Outcomes

Isoproterenol use is through a team that consists of ICU nurses, intensivists, cardiologists, cardiac surgeons, and critical care specialists. The drug only has an application 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 requires close monitoring. Because of the availability of pacemakers and other chronotropic drugs, the use of isoproterenol has diminished today.[13]

Isoproterenol requires interprofessional collaboration for effective use. The ordering clinician decides to use the drug, but the entire team is involved. This team includes specialists, as listed above, as well as pharmacists and other nursing staff. The pharmacist needs to verify dosing and perform thorough medication reconciliation. Nursing is at the front lines for entering patient medication history and also conducting the monitoring necessary when administering isoproterenol. Any abnormal results or concerns require communication to the team, both physicians and the pharmacy, for dosing or drug changes. Only with this type of collaborative effort and interprofessional communication can the team optimize isoproterenol therapy. [Level 5]

Article Details

Article Author

Michael Szymanski

Article Editor:

Davinder Singh


5/1/2021 4:18:04 PM

PubMed Link:




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 Sep     [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]