Terbutaline

Terbutaline

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Systematic (IUPAC) name
(RS)-5-[2-(tert-butylamino)-1-hydroxyethyl]benzene-1,3-diol
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682144
Pregnancy category	C
Legal status	UK: POM (Prescription only)
Routes of administration	SQ, Oral, Inhaled
Pharmacokinetic data
Protein binding	25%
Metabolism	GI tract (oral), liver; CYP450: unknown
Biological half-life	11-16 hours
Excretion	urine 90% (60% unchanged), bile/faeces
Identifiers
CAS Number	23031-25-6 Y
ATC code	R03AC03 (WHO) R03CC03
PubChem	CID: 5403
IUPHAR/BPS	560
DrugBank	DB00871 Y
ChemSpider	5210 Y
UNII	N8ONU3L3PG Y
KEGG	D08570 Y
ChEBI	CHEBI:9449 N
ChEMBL	CHEMBL1760 Y
Chemical data
Formula	C12H19NO3
Molecular mass	225.284 g/mol
SMILES Oc1cc(cc(O)c1)C(O)CNC(C)(C)C
InChI 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 Y Key:XWTYSIMOBUGWOL-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Terbutaline (trade names Brethine, Bricanyl, Brethaire, or Terbulin) is a β₂-adrenergic receptor agonist, used as a "reliever" inhaler in the management of asthma symptoms and as a tocolytic (anti-contraction medication) to delay preterm labor for up to 48 hours. This time can then be used to administer steroid injections to the mother which help fetal lung maturity and reduce complications of prematurity. It should not be used to prevent preterm labor or delay labor more than 48–72 hours. In February 2011, the Food and Drug Administration has ordered to put a boxed warning on the drug's label. Pregnant women should not be given injections of the drug terbutaline for the prevention of preterm labor or for long-term (beyond 48–72 hours) management of preterm labor, and should not be given oral terbutaline for any type of prevention or treatment of preterm labor "due to the potential for serious internal heart problems and death."

The American College of Obstetricians and Gynecologists also discourages the use of terbutaline for preventing preterm labor.

Terbutaline is currently on the World Anti-Doping Agency's list of prohibited drugs for Olympic athletes, except when administered by inhalation and a Therapeutic Use Exemption (TUE) has been obtained in advance.

Uses

Terbutaline is used as a fast-acting bronchodilator (often used as a short-term asthma treatment) and as a tocolytic to delay premature labor. The inhaled form of terbutaline starts working within 15 minutes and can last up to 6 hours.

Terbutaline as a treatment for premature labor is an off-label use not approved by the FDA. It is a pregnancy category C medication and is routinely prescribed to stop contractions. After successful intravenous tocolysis, little evidence exists that oral terbutaline is effective. However, following uterine inversion in the third stage of labor. Terbutaline (or either Halothane or magnesium sulfate) can be used to relax the uterus if necessary prior to uterine replacement.

Structure activity relationships

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.

Side effects

• Adult - tachycardia, anxiety, nervousness, tremors, headache, hyperglycemia, hypokalemia, hypotension and, rarely, pulmonary edema.
• Fetal - tachycardia and hypoglycemia.

Chemistry

It is synthesized by brominating 3,5-dibenzyloxyacetophenone into the appropriate 3,5-dibenzyloxybromoacetophenone, which is reacted with N-benzyl-N-tert-butylamine, giving the aminoketone. Reduction of this product by hydrogen over a palladium catalyst leads to terbutaline. 800px