Isoprenaline


Isoprenaline
Isoprenaline
Systematic (IUPAC) name
4-[1-hydroxy-2-(isopropylamino)ethyl]benzene-1,2-diol
Clinical data
AHFS/Drugs.com International Drug Names
MedlinePlus a601236
Pregnancy cat. C
Legal status  ?
Routes inhaled 80-120μg
Identifiers
CAS number 7683-59-2
ATC code C01CA02 R03AB02
R03CB01
PubChem CID 3779
IUPHAR ligand 536
DrugBank APRD00182
ChemSpider 3647 YesY
UNII L628TT009W YesY
KEGG D08090 YesY
ChEMBL CHEMBL434 YesY
Chemical data
Formula C11H17NO3 
Mol. mass 211.258 g/mol
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

Isoprenaline (INN) or isoproterenol (USAN, trade names Medihaler-Iso and Isuprel) is a medication used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma. It is a non-selective beta-adrenergic agonist and structurally similar to adrenaline.[1]

Contents

Structure-activity relationship

The isopropyl amine group in isoprenaline makes it selective for β receptors. The free catechol hydroxy groups keeps it susceptible to enzymatic metabolism.[2]

Uses

Its primary use is for bradycardia or heart block. By activating β1-receptors on the heart, it induces positive chronotropic, dromotropic, and inotropic effects.[1]

It can be used as an inhaled aerosol to treat asthma, although this is currently a rare treatment.[1] Although it activates all beta adrenergic receptors, it works in a similar fashion to the more selective β2-adrenergic agonists e.g. salbutamol, by relaxing the airways to increase airflow.

It is also supplied in ampules under the brand name Isuprel for injection and in sublingual pill form for treatment of asthma, chronic bronchitis and emphysema.

Used with caution, it can also be used to treat torsades de pointes by acquired defect, in conjunction with overdrive pacing and magnesium.

Pharmacology

Isoprenaline is a β1- and β2-adrenoreceptor agonist which was commonly used to treat asthma before the more widespread use of salbutamol, which has more selective effects on the airways. Its route of administration is either intravenous, oral, intranasal, subcutaneous, or intramuscular, depending on use. The plasma half-life for isoprenaline is approximately two hours.

Isoprenaline's effects on the cardiovascular system (non-selective) relate to its actions on cardiac β1 receptors and β2 receptors on skeletal muscle arterioles. Isoprenaline has positive inotropic and chronotropic effects on the heart. In skeletal muscle arterioles it produces vasodilatation. Its inotropic and chronotropic effects elevate systolic blood pressure, while its vasodilatory effects tend to lower diastolic blood pressure.

The adverse effects of isoprenaline are also related to the drug's cardiovascular effects. Isoprenaline can produce an elevated heart rate (tachycardia), which predisposes patients to cardiac dysrhythmias.

Warnings and contraindications

Isoprenaline should not be administered to patients with myocardial ischemia.

According to Code of Federal Regulations (CFR) Title 21 Section 201.305; use of isoprenaline has been regulated by mandating the inclusion of the following warning label: "Occasional patients have been reported to develop severe paradoxical airway resistance with repeated, excessive use of isoprenaline inhalation preparations. The cause of this refractory state is unknown. It is advisable that in such instances the use of this preparation be discontinued immediately and alternative therapy instituted, since in the reported cases the patients did not respond to other forms of therapy until the drug was withdrawn. Deaths have been reported following excessive use of isoprenaline inhalation preparations and the exact cause is unknown. Cardiac arrest was noted in several instances"

Chemistry

Isoprenaline, 1-(3,4-dihydroxyphenyl)-2-iso-propylaminoethanol, is synthesized by an analogous scheme of making epinephrine. Interaction of ω-chloro-3,4-dihydroxyacetophenone (chloroacetylpyrocatechol) with isopropylamine gives ω-isopropylamino-3,4-dihydroxyacetophenone, reduction of the carbonyl group of which by hydrogen using a palladium on carbon catalyst gives isoprenaline. Isoproterenol synthesis.png

History

An epidemic of deaths within a group of individuals who were being treated for asthma was detected between 1963 - 1968 in England, Wales, Scotland, Ireland, Australia, and New Zealand; this was latter found to be largely contributed to isoprenaline inhalers which were being used at 5 times the dose USA and Canada were using it at, subsequently, USA and Canada did not add to this epidemic; but quite substantially showed that overuse of the drug was attributed to many deaths. Shortly after realizing the drug was causing many deaths, the medication was removed and the number of asthmatics dying quickly decreased. How the drug passed trials is unknown.

References

  1. ^ a b c Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 5. ISBN 1-59541-101-1. 
  2. ^ Medicinal Chemistry of Adrenergics and Cholinergics