Isoproterenol indications include 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 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 primarily concentrate in 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
Cardiogenic shock (off-label)
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 to 10 mcg/minute continuous infusion titrated to patient response
Bradycardia, AV nodal block
0.05 to 0.5 mcg/kg/minute IV, 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
Isoproterenol requires 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 require continuous monitoring in patients receiving isoproterenol.
Isoproterenol use is through a team that consists of ICU nurses, intensivist, cardiologist, cardiac surgeon, 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.
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. Pharmacy 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]
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