Isoprenaline

From Wikipedia, the free encyclopedia
  (Redirected from Isuprel)
Jump to: navigation, search
Isoprenaline
Isoproterenol.png
Isoprenaline ball-and-stick.png
Systematic (IUPAC) name
(RS)-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 Prescription only
Routes inhaled 80-120μg
Identifiers
CAS number 7683-59-2 YesY
ATC code C01CA02 R03AB02
R03CB01
PubChem CID 3779
IUPHAR ligand 536
DrugBank DB01064
ChemSpider 3647 YesY
UNII L628TT009W YesY
KEGG D08090 YesY
ChEMBL CHEMBL434 YesY
Chemical data
Formula C11H17NO3 
Mol. mass 211.258 g/mol
 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]

Uses[edit]

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 ampoules 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 sulfate.

Pharmacology[edit]

Isoprenaline is a β1- and β2-adrenoreceptor agonist which was commonly used to treat asthma before the more widespread use of albuterol, 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 minutes.

Isoprenaline's effects on the cardiovascular system (non-selective) relate to its actions on cardiac β1 receptors and β2 receptors on smooth muscle within the tunica media of arterioles. Isoprenaline has positive inotropic and chronotropic effects on the heart. β2--adrenoceptor 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 β2 receptor's vasodilation.

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[edit]

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[edit]

Isoprenaline 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.[2][3] Isoproterenol synthesis.png

Structure-activity relationship[edit]

The isopropyl amine group in isoprenaline makes it selective for β receptors. The free catechol hydroxy groups keeps it susceptible to enzymatic metabolism.[4]

History[edit]

An epidemic of deaths within a group of individuals who were being treated for asthma was detected between 1963 and 1968 in England, Wales, Scotland, Ireland, Australia, and New Zealand. This was later found to be largely attributed 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.[5] Shortly after realizing overdose of the drug was causing many deaths, the medication was withdrawn and the number of asthmatics dying quickly decreased.

References[edit]

  1. ^ a b c Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 5. ISBN 1-59541-101-1. 
  2. ^ G. Schening, O. Thomae, US 723278  (1942)
  3. ^ G. Schening, O. Thomae, U.S. Patent 2,308,232 (1943)
  4. ^ Medicinal Chemistry of Adrenergics and Cholinergics
  5. ^ Pierce, Neil and Hensley, Michael J. (1998). "Epidemiologic Studies of Beta Agonists and Asthma Deaths". Epidemiologic Studies 20 (2).