Terbutaline

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Terbutaline
Terbutaline.svg
Terbutaline ball-and-stick model.png
Terbutaline (top),
and (R)-(−)-terbutaline (bottom)
Names
Trade namesBricanyl, Marex, others
  • (RS)-5-[2-(tert-Butylamino)-1-hydroxyethyl]benzene-1,3-diol
Clinical data
Drug classβ2 adrenergic receptor agonist
Main usesAsthma, COPD, preterm labor[1]
Side effectsAnxiety, shakiness, fast heart rate, nausea[1]
Pregnancy
category
  • AU: A
  • C
Routes of
use
bY MOUTH (tablets, solution), inhalational (DPI, nebulizer solution), SQ
External links
AHFS/Drugs.comMonograph
MedlinePlusa682144
Legal
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Pharmacokinetics
Protein binding25%
MetabolismGI tract (oral), liver; CYP450: unknown
Elimination half-life11-16 hours
Excretionurine 90% (60% unchanged), bile/faeces
Chemical and physical data
FormulaC12H19NO3
Molar mass225.288 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • Oc1cc(cc(O)c1)C(O)CNC(C)(C)C
  • InChI=1S/C12H19NO3/c1-12(2,3)13-7-11(16)8-4-9(14)6-10(15)5-8/h4-6,11,13-16H,7H2,1-3H3 ☒N
  • Key:XWTYSIMOBUGWOL-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Terbutaline, sold under the brand names Bricanyl among others, is a medication used for symptoms of asthma or COPD and to temporally delay delivery in preterm labor.[1] The delay in deliver is used to allow time for steroids to speed lung development in the baby or moving a women to a location with more resources.[1] It is generally take by mouth, inhaled, or injected under the skin.[1][2]

Common side effects include anxiety, shakiness, fast heart rate, and nausea.[1] Other side effects may include high blood sugar, low potassium, heart arrhythmia, and insufficient blood flow to the heart.[1] It should not be used to prevent preterm labor or delay labor more than 48–72 hours.[3] It is a β2 adrenergic receptor agonist.[1]

Terbutaline was patented in 1966 and came into medical use in 1970.[4] It is available as a generic medication.[2] In the United Kingdom 100 tablets of 5 mg costs the NHS about 15 pounds.[2] This amount in the United States costs about 135 USD as of 2021.[5]

Medical uses

Terbutaline is used as a fast-acting bronchodilator (often used as a short-term asthma treatment) and as a tocolytic[6] to delay premature labor.

As an asthma treatment, the inhaled form of terbutaline, starts working within 15 minutes and can last up to 6 hours. It is also sold as an injectable solution, an oral tablet, and as a syrup (in combination with guaifenesin).

Terbutaline is a pregnancy category C medication and is prescribed to stop contractions. After successful intravenous tocolysis, little evidence exists that oral terbutaline is effective.[7] Terbutaline as a treatment for premature labor is an off-label use not approved by the US FDA, who have warned that oral terbutaline is not effective and can cause severe heart problems or death, and while injectable terbutaline can be used for premature labor in emergency situations in a hospital setting, it should only be usedfor short periods of time.[8]

Dosage

For asthma it may be used at a dose of 2.5 to 5 mg by mouth up to three times per day; 0.25 to 0.5 mg by injection up to four times per day; or 0.5 mg by inhalation up to four times per day.[2]

For preterm labor it may be given at a dose of 0.25 mg every 20 min to 3 hours.[1] It may also be used as an intravenous infusion at 2.5 to 20 micrograms per minute.[1]

Side effects

Pharmacology

The tertiary butyl group in terbutaline makes it more selective for β2 receptors. Since there is no hydroxy group on position 4 of the benzene ring, the molecule is less susceptible to metabolism by the enzyme catechol-O-methyl transferase.[11]

Chemistry

Terbutaline is synthesized by brominating 3,5-dibenzyloxyacetophenone into 3,5-dibenzyloxybromoacetophenone, which is reacted with N-benzyl-N-tert-butylamine, giving a ketone intermediate. Reduction of this product with H₂ over Pd/C leads to terbutaline.[12][13][14]

Terbutaline synthesis.png

Stereochemistry

Terbutaline contains a stereocenter and consists of two enantiomers. This is a racemate, ie a 1: 1 mixture of (R) - and the (S) - form:[15]

Enantiomers of terbutaline
(R)-Terbutalin Structural Formula V1.svg
(R)-Terbutaline
(S)-Terbutalin Structural Formula V1.svg
(S)-Terbutaline

Society and culture

Athletics

As with all β2-adrenergic receptor agonists, terbutaline is on the World Anti-Doping Agency's list of prohibited drugs, except when administered by inhalation and a Therapeutic Use Exemption (TUE) has been obtained in advance.

Brand names

Brand names include Bronclyn, Brethine, Bricanyl, Brethaire, Marex, and Terbulin.

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 "Terbutaline Monograph for Professionals". Drugs.com. Retrieved 28 September 2021.
  2. 2.0 2.1 2.2 2.3 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 270. ISBN 978-0-85711-369-6.CS1 maint: date format (link)
  3. "Archived copy". Archived from the original on 2015-09-21. Retrieved 2015-09-13.CS1 maint: archived copy as title (link)
  4. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 542. ISBN 9783527607495.
  5. "Terbutaline Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 29 September 2021.
  6. Mohamed Ismail NA, Ibrahim M, Mohd Naim N, Mahdy ZA, Jamil MA, Mohd Razi ZR (September 2008). "Nifedipine versus terbutaline for tocolysis in external cephalic version". Int J Gynaecol Obstet. 102 (3): 263–6. doi:10.1016/j.ijgo.2008.04.010. PMID 18554601. S2CID 20258298.
  7. Goldenberg, RL (November 2002). "High-Risk Pregnancy Series: An Expert's View". Obstetrics & Gynecology. 100 (5): 1020–1037. doi:10.1016/S0029-7844(02)02212-3. PMID 12423870. Archived from the original on 2011-07-20.
  8. "FDA Drug Safety Communication: New warnings against use of terbutaline to treat preterm labor". Center for Drug Evaluation and Research. FDA. 17 February 2011. Retrieved 11 May 2021.
  9. Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 7. ISBN 978-1-59541-101-3.
  10. [1], 5 Minute Consult (Original Source: UpToDate "Terbutaline: Drug information").
  11. "Medicinal Chemistry of Adrenergics and Cholinergics". Archived from the original on 2010-11-04.
  12. Draco Lunds Farmacevtiska Aktiebolag, GB 1199630  (1967)
  13. Draco Lunds Farmacevtiska Aktiebolag, BE 704932  (1968)
  14. L. A. Svensson, I. K. Wetterlin, U.S. Patent 3,937,838 (1976)
  15. F. v. Bruchhausen, G. Dannhardt, S. Ebel, A. W. Frahm, E. Hackenthal, U. Holzgrabe (Hrsg.): Hagers Handbuch der Pharmazeutischen Praxis: Band 9: Stoffe P-Z, Springer Verlag, Berlin, Aufl. 5, 2014, S. 804, ISBN 978-3-642-63389-8.

External links

Identifiers: