Isoprenaline

Last updated

Isoprenaline
Isoprenaline.svg
Clinical data
Trade names Isuprel, many others [1] [2]
Other namesIsoproterenol; Isopropylnorepinephrine; Isopropylnoradrenaline; Isopropydine; WIN-5162
AHFS/Drugs.com Monograph
MedlinePlus a601236
Pregnancy
category
  • AU:A
Routes of
administration 		Intravenous, intramuscular injection, subcutaneous injection, intracardiac injection, inhalation, sublingual administration, rectal administration [3] [4]
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability Oral: Very low [5] [6]
Protein binding 69% (mostly to albumin) [3]
Metabolism Methylation (COMT Tooltip Catechol O-methyltransferase), conjugation (sulfation) [7] [3]
Metabolites • 3-O-Methylisoprenaline [3]
• Sulfate conjugates [7]
Onset of action Inhalation: 2–5 min [8]
Elimination half-life IV Tooltip Intravenous infusion: 2.5–5 min [3]
Oral: 40 min [3]
Duration of action Inhalation: 0.5–2 hours [8]
Excretion Urine: 59–107% [3]
Feces: 12–27% [3]
Identifiers
  • 4-[1-hydroxy-2-(isopropylamino)ethyl]benzene-1,2-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.028.807 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C11H17NO3
Molar mass 211.261 g·mol−1
3D model (JSmol)
  • CC(C)NCC(O)c1cc(O)c(O)cc1
  • InChI=1S/C11H17NO3/c1-7(2)12-6-11(15)8-3-4-9(13)10(14)5-8/h3-5,7,11-15H,6H2,1-2H3 Yes check.svgY
  • Key:JWZZKOKVBUJMES-UHFFFAOYSA-N Yes check.svgY
   (verify)

Isoprenaline, also known as isoproterenol and sold under the brand name Isuprel among others, is a sympathomimetic medication which is used in the treatment of acute bradycardia (slow heart rate), heart block, and rarely for asthma, among other indications. [9] It is used by injection into a vein, muscle, fat, or the heart, by inhalation, and in the past under the tongue or into the rectum. [3] [4]

Contents

Side effects of isoprenaline include rapid heart beat, heart palpitations, and arrhythmias, among others. [9] Isoprenaline is a selective agonist of the β-adrenergic receptors, including both the β1- and β2-adrenergic receptors. [9] By activating these receptors, it increases heart rate and the force of heart contractions. [10] Chemically, isoprenaline is a synthetic catecholamine and is the N-isopropyl analogue of norepinephrine (noradrenaline) and epinephrine (adrenaline). [11] [3] [12] [13]

Isoprenaline was one of the first synthetic sympathomimetic amines and was the first selective β-adrenergic receptor agonist. [7] [14] The medication was discovered in 1940 [5] and was introduced for medical use in 1947. [15]

Medical uses

Isoprenaline is used to treat heart block and episodes of Adams–Stokes syndrome that are not caused by ventricular tachycardia or fibrillation, in emergencies for cardiac arrest until electric shock can be administered, for bronchospasm occurring during anesthesia, and as an adjunct in the treatment of hypovolemic shock, septic shock, low cardiac output (hypoperfusion) states, congestive heart failure, and cardiogenic shock. [9] It is also used to prevent Torsades de Pointes in patients with long QT refractory to magnesium and to treat patients with intermittent Torsades de Pointes refractory to treatment with magnesium. [16] Isoprenaline is used in the acute management of bradycardia, though not in the chronic treatment of bradycardia. [17]

Historically, it was used to treat asthma via metered aerosol or nebulizing devices; it was also available in sublingual, oral, intravenous, and intramuscular formulations. [15] The U.S. National Asthma Education and Prevention Program Expert Panel recommends against its use as a nebulizer for acute bronchoconstriction. [18]

Available forms

Many formulations of isoprenaline appear to have been discontinued in the United States and many other countries. [4] [1] [2] [3] In the United States, it remains available only as an injectable solution. [4] It was previously also available in the United States as a solution, metered aerosol, powder, or disc for inhalation and as a tablet for sublingual and rectal administration, but these formulations were discontinued. [4]

Contraindications

It should not be used in people with tachyarrhythmias (except in special circumstances), [19] tachycardia or heart block caused by digitalis poisoning, ventricular arrhythmias which require inotropic therapy, or with angina. [9]

Side effects

Side effects of isoprenaline may include nervousness, headache, dizziness, nausea, blurred vision, tachycardia, palpitations, angina, Adams-Stokes attacks, pulmonary edema, hypertension, hypotension, ventricular arrhythmias, tachyarrhythmias, difficulty breathing, sweating, mild tremors, weakness, flushing, and pallor. [9] Isoprenaline has been reported to cause insulin resistance leading to diabetic ketoacidosis. [20]

Overdose

Overdose of isoprenaline may produce effects including tachycardia, arrhythmias, palpitations, angina, hypotension, hypertension, and myocardial necrosis. [3] [9]

Pharmacology

Pharmacodynamics

Isoprenaline is a β1- and β2-adrenergic receptor full agonist and has almost no activity at the α-adrenergic receptors at lower concentrations. [15] [21] It has similar affinity for the β1- and β2-adrenergic receptors. [21] [8] At higher concentrations, isoprenaline can also evoke responses mediated by α-adrenergic receptors. [8] [22] [23] Its agonist effects at the trace amine-associated receptor 1 (TAAR1) additionally provide it with pharmacodynamic effects that resemble those of the endogenous trace amines, like tyramine. [24]

Isoprenaline's effects on the cardiovascular system (non-selective) relate to its actions on cardiac β1-adrenergic receptors and β2-adrenergic receptors on smooth muscle within the tunica media of arterioles. Isoprenaline has positive inotropic and chronotropic effects on the heart. β2-Adrenergic receptor stimulation in arteriolar smooth muscle induces vasodilation. Its inotropic and chronotropic effects elevate systolic blood pressure, while its vasodilatory effects tend to lower diastolic blood pressure. The overall effect is to decrease mean arterial pressure due to the vasodilation caused by β2-adrenergic receptor activation. [25]

The isopropylamine group in isoprenaline makes it selective for β-adrenergic receptors. [26]

The adverse effects of isoprenaline are also related to the drug's cardiovascular effects. Isoprenaline can produce tachycardia (an elevated heart rate), which predisposes people who take it to cardiac arrhythmias. [15]

Pharmacokinetics

Absorption

Data on the absorption of isoprenaline are limited. [3] Oral isoprenaline is well-absorbed but is subject to strong first-pass metabolism [27] and is approximately 1,000 times less potent than intravenous administration. [6] Hence, its oral bioavailability is very low. [5] [6] Another study suggested that its oral bioavailability, based on pharmacodynamic activity via different routes, was slightly less than 4%. [27] [28]

Distribution

Isoprenaline is minimally able to cross the blood–brain barrier and hence is a peripherally selective drug. [29] [30] This is attributed to its high hydrophilicity. [29] Whereas the extraction of isoprenaline in a single passage of the brain circulation following intravenous injection in humans was 3.8%, the extraction of propranolol, which is a more lipophilic compound and is readily able to cross into the brain, was 63.0%. [29]

The plasma protein binding of isoprenaline is 68.8 ± 1.2%. [3] It is bound mainly to albumin. [3]

Metabolism

Isoprenaline is metabolized by catechol O-methyltransferase (COMT) and conjugation by sulfation. [7] [31] [32] [3] It does not appear to be glucuronidated. [7] There is very large interindividual variability in the sulfation of isoprenaline. [7] The free catechol hydroxyl groups keep it susceptible to enzymatic metabolism. [26] The drug is a poor substrate for monoamine oxidase (MAO) and is not metabolized by this enzyme. [7] [9] This is in contrast to epinephrine and norepinephrine. [7] Isoprenaline is much more strongly metabolized and conjugated with oral administration than with intravenous administration. [6] Its metabolite 3-O-methylisoprenaline, formed by COMT, is active as a weak β-adrenergic receptor antagonist. [7]

Elimination

Isoprenaline is excreted primarily in the urine, as sulfate conjugates. [7] [31] [32] [3] It is excreted 59 to 107% in urine and 12 to 27% in feces. [3] A majority of isoprenaline is excreted in urine in conjugated form, whereas 6.5 to 16.2% is excreted as unchanged isoprenaline and 2.6 to 11.4% is excreted as 3-O-methylisoprenaline and conjugates. [3] [6]

The elimination half-life of isoprenaline by intravenous administration is approximately 2.5 to 5 minutes. [3] Its half-life with oral administration is approximately 40 minutes. [3] [6]

Chemistry

Isoprenaline, also known as N-isopropyl-3,4,β-trihydroxyphenethylamine or as N-isopropylnorepinephrine, is a substituted phenethylamine and synthetic catecholamine derivative. [11] [3] [12] [9] It is the N-isopropyl analogue of norepinephrine (3,4,β-trihydroxyphenethylamine) and epinephrine (3,4,β-trihydroxy-N-methylphenethylamine). [11] [13]

Isoprenaline is a small-molecule compound with the molecular formula C11H17NO3 and a molecular weight of 211.26 g/mol. [11] [3] [12] [9] It is a hydrophilic compound [29] with a predicted log P of -0.6 to 0.25. [11] [3] [12] For comparison, the experimental log P values of epinephrine and norepinephrine are -1.37 and -1.24, respectively. [33] [34]

Isoprenaline is used pharmaceutically as the hydrochloride and sulfate salts. [1] It is also used to a much lesser extent as the free base. [1]

Isoprenaline is a racemic mixture of levorotatory and dextrorotatory enantiomers. [11] [3] [12] The levorotatory or (R)-enantiomer of isoprenaline is known as levisoprenaline (INN Tooltip International Nonproprietary Name) but was never marketed. [35] [36] [37]

Synthetic analogues closely related to isoprenaline include arbutamine, dichloroisoprenaline (dichloroisoproterenol), hexoprenaline, isoetharine (α-ethylisoprenaline), orciprenaline (metaproterenol; a positional isomer of isoprenaline), prenalterol, and soterenol (3-methanesulfonamidylisoprenaline), among others. [5]

History

Isoprenaline was discovered in 1940 [5] and was developed in the 1940s. [7] It was first approved for medical use in 1947 in the United States. [15] Isoprenaline was one of the first synthetic sympathomimetic amines, was the first selective β-adrenergic receptor agonist, and was the first major sympathomimetic agent devoid of pressor effects. [7] [14]

Between 1963 and 1968 in England, Wales, Scotland, Ireland, Australia, and New Zealand there was an increase in deaths among people using isoprenaline to treat asthma. This was attributed to unintentional overdose: the inhalers produced in that area were dispensing five times the dosage dispensed by inhalers produced in the United States and Canada, where the deaths were not observed. [38] [39]

The short duration of action and poor oral activity of isoprenaline led to the development of the much longer-acting and orally active orciprenaline (metaproterenol). [40] [7]

Society and culture

Names

Isoprenaline is the major generic name of the drug and its INN Tooltip International Nonproprietary Name, BAN Tooltip British Approved Name, and DCF Tooltip Dénomination Commune Française. [35] [1] [36] [2] Isoprenalina is its Italian generic name and its DCIT Tooltip Denominazione Comune Italiana. [1] [2] Isoprenaline hydrochloride and isoprenaline sulfate are its BANM Tooltip British Approved Name in the case of the hydrochloride and sulfate salts, respectively. [1] Isoproterenol is another important synonym of the drug. [35] [1] [2] Isoproterenol hydrochloride is its USAN Tooltip United States Adopted Name and JAN Tooltip Japanese Accepted Name in the case of the hydrochloride salt and isoproterenol sulfate is its USAN and JAN in the case of the sulfate salt. [35] [1] [36] [2] Other synonyms of the drug include isopropylnorepinephrine, isopropylnoradrenaline, and isopropydine. [35] [1] [36] [2] It is additionally known by the former developmental code name WIN-5162. [1] [2]

Isoprenaline has been marketed under many brand names worldwide. [1] [2] These include Aleudrina, Asthpul, Iludrin, Iprenol, Isomenyl, Isuprel, Isoprenaline, Isoprenalina, Isoproterenol, Neo-Epinine, Neodrenal, Proternol, and Saventrine, among others. [1] [2] It is also marketed as a combination drug with cromoglicic acid as Frenal Compositum, in combination with pronase as Isopal P, and in combination with atropine as Stmerin D. [2]

Related Research Articles

<span class="mw-page-title-main">Beta blocker</span> Medications for abnormal heart rhythms

Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients.

<span class="mw-page-title-main">Propranolol</span> Beta blocker drug

Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors, as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken orally or by intravenous injection. The formulation that is taken orally comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.

<span class="mw-page-title-main">Adrenergic receptor</span> Class of G protein-coupled receptors

The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example.

<span class="mw-page-title-main">Atenolol</span> Beta blocker medication

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality in those with the condition. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">Sotalol</span> Medication

Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. Evidence does not support a decreased risk of death with long term use. It is taken by mouth or given by injection into a vein.

<span class="mw-page-title-main">Sympathomimetic drug</span> Substance that mimics effects of catecholamines

Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in heart rate, force of cardiac contraction, and blood pressure. The primary endogenous agonists of the sympathetic nervous system are the catecholamines, which function as both neurotransmitters and hormones. Sympathomimetic drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.

<span class="mw-page-title-main">Phenylephrine</span> Decongestant medication

Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among numerous others, is a medication used as a decongestant for uncomplicated nasal congestion, used to dilate the pupil, used to increase blood pressure, and used to relieve hemorrhoids. It can be taken by mouth, as a nasal spray, given by injection into a vein or muscle, applied to the skin, or as a rectal suppository.

An adrenergic agonist is a drug that stimulates a response from the adrenergic receptors. The five main categories of adrenergic receptors are: α1, α2, β1, β2, and β3, although there are more subtypes, and agonists vary in specificity between these receptors, and may be classified respectively. However, there are also other mechanisms of adrenergic agonism. Epinephrine and norepinephrine are endogenous and broad-spectrum. More selective agonists are more useful in pharmacology.

Beta<sub>2</sub>-adrenergic agonist Compounds that bind to and activate adrenergic beta-2 receptors

Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.

<span class="mw-page-title-main">Dobutamine</span> Medication which strengthens heart contractions

Dobutamine is a medication used in the treatment of cardiogenic shock and severe heart failure. It may also be used in certain types of cardiac stress tests. It is given by IV only, as an injection into a vein or intraosseous as a continuous infusion. The amount of medication needs to be adjusted to the desired effect. Onset of effects is generally seen within 2 minutes. It has a half-life of two minutes. This drug is generally only administered short term, although it may be used for longer periods to relieve symptoms of heart failure in patients awaiting heart transplantation.

<span class="mw-page-title-main">Labetalol</span> Medication used to treat high blood pressure

Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.

<span class="mw-page-title-main">Levosalbutamol</span> Chemical compound

Levosalbutamol, also known as levalbuterol, is a short-acting β2 adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Evidence is inconclusive regarding the efficacy of levosalbutamol versus salbutamol or salbutamol-levosalbutamol combinations, though levosalbutamol is believed to have a better safety profile due to its more selective binding to β2 receptors versus β1.

<span class="mw-page-title-main">Ritodrine</span> Chemical compound

Ritodrine, sold under the brand name Yutopar, is a tocolytic drug used to stop premature labor. This drug has been removed from the US market, according to FDA Orange Book. It was available in oral tablets or as an injection and was typically used as the hydrochloride salt.

<span class="mw-page-title-main">Fenoterol</span> Chemical compound

Fenoterol is a β adrenoreceptor agonist. It is classed as sympathomimetic β2 agonist and an inhaled bronchodilator asthma medication.

<span class="mw-page-title-main">Beta-adrenergic agonist</span> Medications that relax muscles of the airways

Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, causing widening of the airways and resulting in easier breathing. They are a class of sympathomimetic agents, each acting upon the beta adrenoceptors. In general, pure beta-adrenergic agonists have the opposite function of beta blockers: beta-adrenoreceptor agonist ligands mimic the actions of both epinephrine- and norepinephrine- signaling, in the heart and lungs, and in smooth muscle tissue; epinephrine expresses the higher affinity. The activation of β1, β2 and β3 activates the enzyme, adenylate cyclase. This, in turn, leads to the activation of the secondary messenger cyclic adenosine monophosphate (cAMP); cAMP then activates protein kinase A (PKA) which phosphorylates target proteins, ultimately inducing smooth muscle relaxation and contraction of the cardiac tissue.

β1-Adrenergic receptor agonists, also known as beta-1 agonists, are a class of drugs that bind selectively to the β1-adrenergic receptor. As a result, they act more selectively upon the heart. β-Adrenoceptors typically bind to norepinephrine release by sympathetic adrenergic nerves and to circulating epinephrine. The effect of β-adrenoceptors is cardiac stimulation, such as increased heart rate, heart contractility, heart conduction velocity, and heart relaxation.

<span class="mw-page-title-main">Phenylethanolamine</span> Chemical compound

Phenylethanolamine, or β-hydroxyphenethylamine, is a trace amine with a structure similar to those of other trace phenethylamines as well as the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine. As an organic compound, phenylethanolamine is a β-hydroxylated phenethylamine that is also structurally related to a number of synthetic drugs in the substituted phenethylamine class. In common with these compounds, phenylethanolamine has strong cardiovascular activity and, under the name Apophedrin, has been used as a drug to produce topical vasoconstriction.

<span class="mw-page-title-main">Olodaterol</span> Chemical compound

Olodaterol is an ultra-long-acting β adrenoreceptor agonist (ultra-LABA) used as an inhalation for treating people with chronic obstructive pulmonary disease (COPD). It is manufactured by Boehringer Ingelheim.

β2-adrenoceptor agonists are a group of drugs that act selectively on β2-receptors in the lungs causing bronchodilation. β2-agonists are used to treat asthma and COPD, diseases that cause obstruction in the airways. Prior to their discovery, the non-selective beta-agonist isoprenaline was used. The aim of the drug development through the years has been to minimise side effects, achieve selectivity and longer duration of action. The mechanism of action is well understood and has facilitated the development. The structure of the binding site and the nature of the binding is also well known, as is the structure activity relationship.

Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest of the body without producing side-effects related to their effects on the brain or spinal cord. For example, most opioids cause sedation when given at a sufficiently high dose, but peripherally selective opioids can act on the rest of the body without entering the brain and are less likely to cause sedation. These peripherally selective opioids can be used as antidiarrheals, for instance loperamide (Imodium).

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 662. ISBN   978-3-88763-101-7 . Retrieved 1 August 2024.
  2. 1 2 3 4 5 6 7 8 9 10 11 "Isoprenaline". drugs.com. 6 August 2017. Archived from the original on 26 June 2019. Retrieved 1 August 2024.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 "Isoprenaline: Uses, Interactions, Mechanism of Action". DrugBank Online. 19 February 1948. Retrieved 31 July 2024.
  4. 1 2 3 4 5 "Drugs@FDA: FDA-Approved Drugs". accessdata.fda.gov. Retrieved 31 July 2024.
  5. 1 2 3 4 5 Waldeck B (June 2002). "Beta-adrenoceptor agonists and asthma--100 years of development". Eur J Pharmacol. 445 (1–2): 1–12. doi:10.1016/s0014-2999(02)01728-4. PMID   12065188.
  6. 1 2 3 4 5 6 Conolly ME, Davies DS, Dollery CT, Morgan CD, Paterson JW, Sandler M (November 1972). "Metabolism of isoprenaline in dog and man". Br J Pharmacol. 46 (3): 458–472. doi:10.1111/j.1476-5381.1972.tb08143.x. PMC   1666503 . PMID   4656607.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 Morgan DJ (April 1990). "Clinical pharmacokinetics of beta-agonists". Clin Pharmacokinet. 18 (4): 270–294. doi:10.2165/00003088-199018040-00002. PMID   1969785.
  8. 1 2 3 4 Sterling LP (May 1995). "Beta adrenergic agonists". AACN Clin Issues. 6 (2): 271–278. doi:10.1097/00044067-199505000-00010. PMID   7743429.
  9. 1 2 3 4 5 6 7 8 9 10 "Label: Isoproterenol hydrochloride injection, solution". NIH DailyMed. September 10, 2013. Retrieved June 21, 2017.
  10. ↑ Motwani SK, Saunders H (2024). "Inotropes". Anaesthesia & Intensive Care Medicine. 25 (3): 185–191. doi:10.1016/j.mpaic.2023.11.019.
  11. 1 2 3 4 5 6 "Isoproterenol". PubChem. Retrieved 31 July 2024.
  12. 1 2 3 4 5 "Isoprenaline". ChemSpider. 21 July 2022. Retrieved 31 July 2024.
  13. 1 2 Konzett H (1981). "On the discovery of isoprenaline". Trends in Pharmacological Sciences. 2: 47–49. doi:10.1016/0165-6147(81)90259-5.
  14. 1 2 Ružena Č, Jindra V, Renáta H (18 June 2020). "Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis". Open Chemistry. 18 (1): 628–647. doi: 10.1515/chem-2020-0056 . ISSN   2391-5420.
  15. 1 2 3 4 5 Mozayani A, Raymon L (2003). Handbook of Drug Interactions: A Clinical and Forensic Guide. Springer Science & Business Media. pp. 541–542. ISBN   978-1-59259-654-6.
  16. ↑ Cohagan B, Brandis D (August 2022). "Torsade de Pointes". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   29083738. NBK459388.
  17. ↑ Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, et al. (August 2019). "2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society". Circulation. 140 (8): e382–e482. doi:10.1161/CIR.0000000000000628. PMID   30586772.
  18. ↑ National Asthma Education and Prevention Program Expert Panel (August 28, 2007). "Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma" (PDF). NIH National Heart, Lung, and Blood Institute.
  19. ↑ Jongman JK, Jepkes-Bruin N, Ramdat Misier AR, Beukema WP, Delnoy PP, Oude Lutttikhuis H, et al. (April 2007). "Electrical storms in Brugada syndrome successfully treated with isoproterenol infusion and quinidine orally". Netherlands Heart Journal. 15 (4): 151–155. doi:10.1007/BF03085972. PMC   1847769 . PMID   17612676.
  20. ↑ Hoff R, Koh CK (2018). "Isoproterenol Induced Insulin Resistance Leading to Diabetic Ketoacidosis in Type 1 Diabetes Mellitus". Case Reports in Endocrinology. 2018: 4328954. doi: 10.1155/2018/4328954 . PMC   6311779 . PMID   30647979.
  21. 1 2 Emilien G, Maloteaux JM (February 1998). "Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists". Eur J Clin Pharmacol. 53 (6): 389–404. doi:10.1007/s002280050399. PMID   9551698.
  22. ↑ Furchgott RF, Bhadrakom S (June 1953). "Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs". The Journal of Pharmacology and Experimental Therapeutics. 108 (2): 129–143. PMID   13062084.
  23. ↑ Copik AJ, Baldys A, Nguyen K, Sahdeo S, Ho H, Kosaka A, et al. (21 January 2015). "Isoproterenol acts as a biased agonist of the alpha-1A-adrenoceptor that selectively activates the MAPK/ERK pathway". PLOS ONE. 10 (1): e0115701. Bibcode:2015PLoSO..1015701C. doi: 10.1371/journal.pone.0115701 . PMC   4301629 . PMID   25606852.
  24. ↑ Kleinau G, Pratzka J, Nürnberg D, Grüters A, Führer-Sakel D, Krude H, et al. (October 2011). "Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists". PLOS ONE. 6 (10): e27073. Bibcode:2011PLoSO...627073K. doi: 10.1371/journal.pone.0027073 . PMC   3205048 . PMID   22073124. Table 1. EC50 values of different agonists at hTAAR1, hADRB1 and hADRB2
  25. ↑ Korbut R (2017). Farmakologia (in Polish). Wydawnictwo Lekarskie PZWL. p. 36. ISBN   978-83-200-5368-5.
  26. 1 2 Mehta A (January 27, 2011). "Notes - Medicinal Chemistry of the Peripheral Nervous System - Adrenergics and Cholinergic". Pharmaxchange. Archived from the original on 4 November 2010. Retrieved June 21, 2017.
  27. 1 2 George CF (1981). "Drug metabolism by the gastrointestinal mucosa". Clin Pharmacokinet. 6 (4): 259–274. doi:10.2165/00003088-198106040-00002. PMID   6113909.
  28. ↑ Redwood D (January 1969). "Conservative treatment of chronic heart block". Br Med J. 1 (5635): 26–29. doi:10.1136/bmj.1.5635.26. PMC   1981820 . PMID   5761891.
  29. 1 2 3 4 Olesen J, Hougård K, Hertz M (1978). "Isoproterenol and propranolol: ability to cross the blood-brain barrier and effects on cerebral circulation in man". Stroke. 9 (4): 344–349. doi:10.1161/01.str.9.4.344. PMID   209581. Mean extraction of isoproterenol in a single passage of the brain circulation was 3.8% and the calculated PS product was 2.0 ml/100g/min. The mean extraction of propranolol was 63.0% and the mean PS product 46.7 ml/100 g/min. [...] Passage of Isoproterenol and Propranolol Across Blood–Brain Barrier: No data are available in the literature concerning the ability of isoproterenol to cross the blood-brain barrier. From the hydrophilic nature of the molecule one might expect diffusion to be very slow, but the possibility of active uptake mechanisms still existed. The extraction of 3.8% found in the present study corresponds to that of sodium or other hydrophilic molecules.12 It is likely that a significant part of this extraction stems from areas known to be devoid of a blood-brain barrier. The extraction is clearly much smaller than that seen for amino acids and other substances that pass the barrier by facilitated diffusion.14
  30. ↑ Crystal GJ, Salem MR (October 2002). "Beta-adrenergic stimulation restores oxygen extraction reserve during acute normovolemic hemodilution". Anesth Analg. 95 (4): 851–857, table of contents. doi:10.1097/00000539-200210000-00011. PMID   12351256. The lack of effect of blood-borne catecholamines, including isoproterenol, on cerebral blood flow has been attributed to their inability to cross the blood-brain barrier (26).
  31. 1 2 Procaccini DE, Sawyer JE, Watt KM (2019). "Pharmacology of Cardiovascular Drugs". Critical Heart Disease in Infants and Children. pp. 192–212.e6. doi:10.1016/B978-1-4557-0760-7.00019-X. ISBN   978-1-4557-0760-7. S2CID   81053428.
  32. 1 2 Szymanski MW, Singh DP (2023). "Isoproterenol". StatPearls. StatPearls Publishing. PMID   30252298. NBK526042.
  33. ↑ "Epinephrine". PubChem. Retrieved 1 August 2024.
  34. ↑ "Norepinephrine". PubChem. Retrieved 1 August 2024.
  35. 1 2 3 4 5 Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 710. ISBN   978-1-4757-2085-3 . Retrieved 1 August 2024.
  36. 1 2 3 4 Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 157. ISBN   978-94-011-4439-1 . Retrieved 1 August 2024.
  37. ↑ Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 164. ISBN   978-94-011-4439-1 . Retrieved 2024-08-01.
  38. ↑ Pearce N, Hensley MJ (1998). "Epidemiologic studies of beta agonists and asthma deaths". Epidemiologic Reviews. 20 (2): 173–186. doi: 10.1093/oxfordjournals.epirev.a017979 . PMID   9919437.
  39. ↑ Jalba MS (2008). "Three generations of ongoing controversies concerning the use of short acting beta-agonist therapy in asthma: a review". The Journal of Asthma. 45 (1): 9–18. doi:10.1080/02770900701495512. PMID   18259990. S2CID   31732029.
  40. ↑ Dserendorf H (1995). Drug Actions: Basic Principles and Theraputic Aspects. CRC-Press. p. 227. ISBN   978-0-8493-7774-7 . Retrieved 1 August 2024.


This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.