Catecholamine · Inotrope

Isoproterenol (Isuprel)

Also called Isuprel

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

Indications

• Bradycardia or AV block unresponsive to atropine, as a bridge to pacing (older labels; off-label in current ones)
• Pause-dependent torsades de pointes: raises the rate and shortens QT until pacing (off-label)
• Bradycardia in the denervated heart after transplant, where atropine fails (off-label)
• Electrical storm in Brugada syndrome (off-label)
• Distributive or low-output shock, and bronchospasm during anesthesia (current label)
• Electrophysiology studies and tilt-table testing (off-label)

Dosing

Mechanism of action

Isoproterenol is a synthetic catecholamine and a nonselective β1 and β2 agonist with very low α affinity. Both receptors couple to Gs: adenylyl cyclase raises cAMP, which speeds sinus and escape pacemakers and AV conduction and, through protein kinase A, strengthens contraction. In bronchial and arteriolar smooth muscle the same cAMP rise causes relaxation, and with no α1 constriction to oppose it, SVR falls.

Pharmacology

• Cardiovascular: raises heart rate, AV conduction, contractility and cardiac output; shortens QT by speeding the rate
• Cardiovascular: β2 vasodilation lowers SVR and diastolic pressure; systolic may hold or rise, and MAP often falls
• Cardiovascular: higher O₂ demand with lower coronary perfusion pressure, so ischemia and arrhythmias, worst in coronary disease
• Respiratory: potent β2 bronchodilator; also dilates pulmonary vessels
• Metabolic: less hyperglycemia than epinephrine and more free fatty acid release (label); β2 shifts K⁺ into cells

Pharmacokinetics

Chemistry

• Synthetic catecholamine: norepinephrine with an isopropyl group on the amine; the bigger the N-substituent (norepinephrine, then epinephrine, then isoproterenol), the less α and the more β activity
• Racemic hydrochloride (label); the (R)-(−) isomer carries most of the activity
• Amine pKa about 8.6 (PubChem): ionized and hydrophilic at pH 7.4
• 0.2 mg/mL vials, pH 2.5–4.5; some products contain sodium metabisulfite, others edetate and citrate; protect from light, discard if pinkish or darker than slightly yellow, and keep away from alkali such as bicarbonate

Adverse effects and cautions

In the one-pagers

• Heart FailureAdvanced HF: shock bridge, MCS, transplant and palliative care: A peak VO₂ ≤12 mL/kg/min on a β-blocker supports transplant listing (ISHLT 2016), and median survival after transplant is about 12.5 years (ISHLT registry, 2002–2009 era). The denervated heart rests at 90–110 bpm, does not respond to atropine (use isoproterenol, epinephrine or pacing), needs a reduced adenosine dose, and develops allo
• Rhythm GalleryVentricular rhythms and wide-complex tachycardia: Torsades is polymorphic VT twisting around the baseline on a long QT, typically started by a short–long–short sequence. Risk rises with QTc over 500 ms, female sex, bradycardia, low K⁺ or Mg²⁺, heart failure and QT drugs (class IA and III antiarrhythmics, haloperidol, ondansetron, macrolides, fluoroquinolones, methadone). Sustained polymorphic VT g
• Temporary PacingIndications and the 2018 ACC/AHA/HRS guideline: Drugs: atropine IIa for SND and AV-nodal block, including in acute MI; beta agonists (isoproterenol, dopamine, dobutamine, epinephrine) IIb when ischemia is unlikely; aminophylline IIb in inferior MI, IIa after heart transplant or spinal cord injury; atropine after heart transplant III: Harm.

In the algorithms

• VT Storm

Sources

1. FDA label: isoproterenol, Amphastar (2022)
2. FDA label: Isuprel, Hospira (2018)
3. PubChem: isoproterenol

For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.