Difference between revisions of "Isoprenaline"
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Isoprenaline (also known as | '''Isoprenaline''' (also known as '''isoproterenol''') is a direct-acting synthetic catecholamine. It has agonist activity at both beta-1 and beta-2 adrenergic receptors. Its approved uses are in the treatment of AV block and cardiac arrest secondary to heart block, when pacemaker therapy is not available or ineffective. However, it is also used clinically in the treatment of symptomatic bradycardia, bronchospasm, shock, arrhythmia secondary to conduction abnormalities, and to induce arrhythmia or syncope. | ||
==Uses<!-- Describe uses of the drug. If appropriate, add subsections for each indication. -->== | ==Uses<!-- Describe uses of the drug. If appropriate, add subsections for each indication. -->== | ||
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*Short QT syndrome | *Short QT syndrome | ||
*Torsades de pointes | *Torsades de pointes | ||
*Electrical storm in patients with Brugada syndrome | *Electrical storm in patients with [[Brugada syndrome]] | ||
==Contraindications<!-- List contraindications and precautions for use of the drug. -->== | ==Contraindications<!-- List contraindications and precautions for use of the drug. -->== | ||
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*Digitalis toxicity-induced AV block | *Digitalis toxicity-induced AV block | ||
*Tachycardia | *Tachycardia | ||
*Pheochromocytoma | *[[Pheochromocytoma]] | ||
===Precautions<!-- List precautions for use of the drug. If none, this section may be removed. -->=== | ===Precautions<!-- List precautions for use of the drug. If none, this section may be removed. -->=== | ||
*Diabetes mellitus, as it induces glycogenolysis and insulin resistance | *Diabetes mellitus, as it induces glycogenolysis and insulin resistance | ||
*Hyperthyroidism, as it can induce thyroid storm<ref>{{Citation|last=Cannon|first=Ayana|title=Isoproterenol (Isuprel, Medihaler-ISO)|date=2011|url=http://dx.doi.org/10.1016/b978-1-4377-1720-4.00535-5|work=Essence of Anesthesia Practice|pages=613|publisher=Elsevier|access-date=2024-01-09|last2=Bernstein|first2=Wendy K.}}</ref> | *[[Hyperthyroidism]], as it can induce thyroid storm<ref>{{Citation|last=Cannon|first=Ayana|title=Isoproterenol (Isuprel, Medihaler-ISO)|date=2011|url=http://dx.doi.org/10.1016/b978-1-4377-1720-4.00535-5|work=Essence of Anesthesia Practice|pages=613|publisher=Elsevier|access-date=2024-01-09|last2=Bernstein|first2=Wendy K.}}</ref> | ||
*Children with refractory asthma, as its use in this population can result in clinical deterioration, myocardial necrosis, congestive heart failure, and death<ref>{{Cite journal|last=Boniol|first=Scott|last2=Slatkin|first2=Neal E.|last3=Stambler|first3=Nancy|last4=Israel|first4=Robert J.|date=2021-05-20|title=Rescue-free laxation response with methylnaltrexone treatment in cancer patients with opioid-induced constipation: The impact of baseline ECOG status.|url=http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e24083|journal=Journal of Clinical Oncology|volume=39|issue=15_suppl|pages=e24083–e24083|doi=10.1200/jco.2021.39.15_suppl.e24083|issn=0732-183X}}</ref> | *Children with refractory asthma, as its use in this population can result in clinical deterioration, myocardial necrosis, congestive heart failure, and death<ref>{{Cite journal|last=Boniol|first=Scott|last2=Slatkin|first2=Neal E.|last3=Stambler|first3=Nancy|last4=Israel|first4=Robert J.|date=2021-05-20|title=Rescue-free laxation response with methylnaltrexone treatment in cancer patients with opioid-induced constipation: The impact of baseline ECOG status.|url=http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e24083|journal=Journal of Clinical Oncology|volume=39|issue=15_suppl|pages=e24083–e24083|doi=10.1200/jco.2021.39.15_suppl.e24083|issn=0732-183X}}</ref> | ||
*Recent myocardial infarction, ischemic heart disease | *Recent myocardial infarction, ischemic heart disease | ||
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====Mechanism of action<!-- Describe the mechanism of action for the primary uses of the drug. -->==== | ====Mechanism of action<!-- Describe the mechanism of action for the primary uses of the drug. -->==== | ||
Isoprenaline is a potent nonselective beta agonist. Upon binding beta-1 adrenergic receptors, it increases intracellular calcium in cardiac myocytes, with positive | Isoprenaline is a potent nonselective beta agonist. Upon binding beta-1 adrenergic receptors, it increases intracellular calcium in cardiac myocytes, with positive inotropic, lusitropic, chronotropic, and dromotropic effects. Beta-1 activation also activates the RAAS system in the kidney.<ref>{{Cite journal|last=Biazi|first=Giuliana R.|last2=Frasson|first2=Isabele G.|last3=Miksza|first3=Daniele R.|last4=de Morais|first4=Hely|last5=de Fatima Silva|first5=Flaviane|last6=Bertolini|first6=Gisele L.|last7=de Souza|first7=Helenir M.|date=2018-05-15|title=Decreased hepatic response to glucagon, adrenergic agonists, and cAMP in glycogenolysis, gluconeogenesis, and glycolysis in tumor‐bearing rats|url=http://dx.doi.org/10.1002/jcb.27027|journal=Journal of Cellular Biochemistry|volume=119|issue=9|pages=7300–7309|doi=10.1002/jcb.27027|issn=0730-2312}}</ref> Upon binding beta-2 adrenergic receptors, it increases intracellular cAMP and PKA, inactivating myosin light chain kinase. Thus, agonism of these beta-2 receptors results in the relaxation of smooth muscle, peripheral vasodilation, bronchial dilation, and uterine smooth muscle relaxation. Isoprenaline also induces hepatic glycogenolysis and release of glucagon from the pancreas via beta-2 adrenergic activity.<ref>{{Cite journal|last=Matera|first=Maria Gabriella|last2=Page|first2=Clive|last3=Rinaldi|first3=Barbara|date=2018-06|title=β2-Adrenoceptor signalling bias in asthma and COPD and the potential impact on the comorbidities associated with these diseases|url=http://dx.doi.org/10.1016/j.coph.2018.04.012|journal=Current Opinion in Pharmacology|volume=40|pages=142–146|doi=10.1016/j.coph.2018.04.012|issn=1471-4892}}</ref> | ||
====Adverse effects<!-- Describe any potential adverse effects of the drug. -->==== | ====Adverse effects<!-- Describe any potential adverse effects of the drug. -->==== | ||
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===Pharmacokinetics<!-- Describe the pharmacokinetics of the drug. -->=== | ===Pharmacokinetics<!-- Describe the pharmacokinetics of the drug. -->=== | ||
*Poor substrate for MAO | *Poor substrate for MAO and not taken up by neurons to the same extent as epinephrine and norepinephine, leading to a longer duration of action | ||
* | *Metabolized in the liver and other tissues by catechol-O-methyltransferase (COMT) to the 3-O-methyl isoproterenol metabolite, which is subsequently conjugated with sulfate | ||
*Excretion occurs via the urine | *Excretion occurs via the urine | ||
*Onset of action: immediate | *Onset of action: immediate | ||
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==Chemistry and formulation<!-- Describe the chemistry and formulation of the drug. -->== | ==Chemistry and formulation<!-- Describe the chemistry and formulation of the drug. -->== | ||
Isoprenaline hydrochloride | Isoprenaline hydrochloride is 3,4-Dihydroxy-alpha-(isopropylamino) methyl benzyl alcohol hydrochloride, a synthetic sympathomimetic amine that is structurally related to epinephrine but acts almost exclusively on beta adrenergic receptors. | ||
==History<!-- Describe the historical development of the drug. -->== | ==History<!-- Describe the historical development of the drug. -->== | ||
Revision as of 17:27, 10 January 2024
Isoprenaline
| Trade names |
Isuprel |
|---|---|
| Clinical data | |
| Drug class |
Synthetic catecholamine |
| Contraindications |
Tachyarrhythmia, tachycardia |
| Routes of administration |
IV, IM, subcutaneous, inhalation |
| Dosage |
Treatment of AV block or cardiac arrest: IV - 0.02-0.06 mg, then 0.01-0.2 mg depending on ventricular rate IM - 0.2 mg, then 0.02-1 mg depending on ventricular rate Subcutaneous - 0.2 mg, then 0.15-0.2 mg depending on ventricular rate Treatment of hypovolemic and septic shock, low cardiac output, CHF: IV - 0.5-5 mcg/min continuous infusion, titrate to goal HR, CVP, SBP, or urine output Treatment of cardiogenic shock: IV - 0.5-20 mcg/min continuous infusion Treatment of bronchospasm: IV - 0.01-0.02 mg PRN Treatment of symptomatic bradycardia: IV - 20-60 mcg initial bolus, then 10-20 mcg as needed until goal HR and rhythm response met Treatment of ventricular tachyarrhythmia in patients with short QT or Brugada syndrome: IV - 2-10 mcg/min continuous infusion |
| Dosage | |
| Pharmacodynamics | |
| Mechanism of action |
Beta agonism |
| Adverse effects |
Tachycardia, hypertension, hypotension, ventricular arrhythmia, Adam-stokes syndrome, angina, skin necrosis |
| Pharmacokinetics | |
| Onset of action |
Immediate |
| Duration of action |
10-15 minutes |
| Metabolism |
Liver metabolism by COMT |
| Physical and chemical data | |
| Formula |
C11H17NO3 |
| Molar mass |
211.258 g/mol |
| Article quality | |
| Editor rating | |
| User likes | 0 |
Isoprenaline (also known as isoproterenol) is a direct-acting synthetic catecholamine. It has agonist activity at both beta-1 and beta-2 adrenergic receptors. Its approved uses are in the treatment of AV block and cardiac arrest secondary to heart block, when pacemaker therapy is not available or ineffective. However, it is also used clinically in the treatment of symptomatic bradycardia, bronchospasm, shock, arrhythmia secondary to conduction abnormalities, and to induce arrhythmia or syncope.
Uses
- AV block not requiring pacing
- Cardiac arrest from heart block when pacemaker therapy is unavailable
- Bradycardia, especially in cardiac transplant patients
- Acute bronchospasm
- Cardiogenic shock
- Hypovolemic and septic shock, congestive heart failure
- For electrophysiological procedures: to provoke ventricular arrhythmias
- For tilt table testing: to provoke syncope
- Treatment of beta-blocker overdose
- Short QT syndrome
- Torsades de pointes
- Electrical storm in patients with Brugada syndrome
Contraindications
Absolute contraindications
- Tachyarrhythmias, including atrial fibrillation, atrial flutter, ventricular fibrillation
- Digitalis toxicity-induced AV block
- Tachycardia
- Pheochromocytoma
Precautions
- Diabetes mellitus, as it induces glycogenolysis and insulin resistance
- Hyperthyroidism, as it can induce thyroid storm[1]
- Children with refractory asthma, as its use in this population can result in clinical deterioration, myocardial necrosis, congestive heart failure, and death[2]
- Recent myocardial infarction, ischemic heart disease
- Hypovolemia causing hypotension
- Hypertension
- Sulfite hypersensitivity
Pharmacology
Pharmacodynamics
Mechanism of action
Isoprenaline is a potent nonselective beta agonist. Upon binding beta-1 adrenergic receptors, it increases intracellular calcium in cardiac myocytes, with positive inotropic, lusitropic, chronotropic, and dromotropic effects. Beta-1 activation also activates the RAAS system in the kidney.[3] Upon binding beta-2 adrenergic receptors, it increases intracellular cAMP and PKA, inactivating myosin light chain kinase. Thus, agonism of these beta-2 receptors results in the relaxation of smooth muscle, peripheral vasodilation, bronchial dilation, and uterine smooth muscle relaxation. Isoprenaline also induces hepatic glycogenolysis and release of glucagon from the pancreas via beta-2 adrenergic activity.[4]
Adverse effects
- Headache
- Dizziness
- Nausea
- Flushing
- Fatigue
- Diaphoresis
- Mild tremor
- Weakness
- Blurred Vision
- Tachycardia
- Hypertension
- Hypotension
- Ventricular arrhythmia or PVCs
- Adams-Stokes syndrome
- Dyspnea
- Hypokalemia
- Hyperglycemia
- Angina
- Skin necrosis
Pharmacokinetics
- Poor substrate for MAO and not taken up by neurons to the same extent as epinephrine and norepinephine, leading to a longer duration of action
- Metabolized in the liver and other tissues by catechol-O-methyltransferase (COMT) to the 3-O-methyl isoproterenol metabolite, which is subsequently conjugated with sulfate
- Excretion occurs via the urine
- Onset of action: immediate
- Duration of action 10-15 minutes
- Plasma half-life: 2.5-5 minutes
Chemistry and formulation
Isoprenaline hydrochloride is 3,4-Dihydroxy-alpha-(isopropylamino) methyl benzyl alcohol hydrochloride, a synthetic sympathomimetic amine that is structurally related to epinephrine but acts almost exclusively on beta adrenergic receptors.
History
References
- ↑ Cannon, Ayana; Bernstein, Wendy K. (2011), "Isoproterenol (Isuprel, Medihaler-ISO)", Essence of Anesthesia Practice, Elsevier, p. 613, retrieved 2024-01-09
- ↑ Boniol, Scott; Slatkin, Neal E.; Stambler, Nancy; Israel, Robert J. (2021-05-20). "Rescue-free laxation response with methylnaltrexone treatment in cancer patients with opioid-induced constipation: The impact of baseline ECOG status". Journal of Clinical Oncology. 39 (15_suppl): e24083–e24083. doi:10.1200/jco.2021.39.15_suppl.e24083. ISSN 0732-183X.
- ↑ Biazi, Giuliana R.; Frasson, Isabele G.; Miksza, Daniele R.; de Morais, Hely; de Fatima Silva, Flaviane; Bertolini, Gisele L.; de Souza, Helenir M. (2018-05-15). "Decreased hepatic response to glucagon, adrenergic agonists, and cAMP in glycogenolysis, gluconeogenesis, and glycolysis in tumor‐bearing rats". Journal of Cellular Biochemistry. 119 (9): 7300–7309. doi:10.1002/jcb.27027. ISSN 0730-2312.
- ↑ Matera, Maria Gabriella; Page, Clive; Rinaldi, Barbara (2018-06). "β2-Adrenoceptor signalling bias in asthma and COPD and the potential impact on the comorbidities associated with these diseases". Current Opinion in Pharmacology. 40: 142–146. doi:10.1016/j.coph.2018.04.012. ISSN 1471-4892. Check date values in:
|date=(help)
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