Terbutaline, sold under the brand names Bricanyl and Marex among others, is a β₂ adrenergic receptor agonist, used as a "reliever" inhaler in the management of

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...

symptoms and as a tocolytic (anti-

contraction Contraction may refer to: Linguistics * Contraction (grammar), a shortened word * Poetic contraction, omission of letters for poetic reasons * Elision, omission of sounds ** Syncope (phonology), omission of sounds in a word * Synalepha, merged ...

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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

began requiring a black box 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." It was patented in 1966 and came into medical use in 1970. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Terbutaline is used as a fast-acting

bronchodilator A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lung ...

(often used as a short-term asthma treatment) and as a tocolytic to delay

premature labor Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between ...

. 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 Guaifenesin, also known as glyceryl guaiacolate, is an expectorant medication that aids in the elimination of sputum from the respiratory tract. Chemically it is an ether of guaiacol and glycerine. It is often used in combination with other ...

). Terbutaline is a

pregnancy category The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does ''not'' include any risks conferred by pharmaceutical agents or their ...

C medication and is prescribed to stop contractions. After successful intravenous tocolysis, little evidence exists that oral terbutaline is effective. Terbutaline as a treatment for premature labor is an

off-label use Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

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 used for short periods of time.

Side effects

* Adult —

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

nervousness Nervous may refer to: * nervousness * Nervous system, a network of cells in an animal's body that coordinates movement and the senses ** Nervous tissue, the cells of the nervous system that work in aggregate to transmit signals Music * "Nervous" ...

tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, f ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

hyperglycemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...

and, rarely,

pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due ...

. * Fetal —

and

hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...

.
5 Minute Consult (Original Source: UpToDate "Terbutaline: Drug information").

Pharmacology

The tertiary butyl group in terbutaline makes it more selective for Beta-2 adrenergic receptor, 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.

Chemistry

Terbutaline is synthesized by brominating 3,5-dibenzyloxy

acetophenone Acetophenone is the organic compound with the chemical formula, formula C6H5C(O)CH3. It is the simplest aromatic ketone. This colorless, viscous liquid is a precursor to useful resins and fragrances. Production Acetophenone is formed as a byprodu ...

into 3,5-dibenzyloxybromoacetophenone, which is reacted with ''N''-

benzyl In organic chemistry, benzyl is the substituent or molecular fragment possessing the structure . Benzyl features a benzene ring () attached to a methylene group () group. Nomenclature In IUPAC nomenclature, the prefix benzyl refers to a substi ...

-''N''-''tert''-butylamine, giving a ketone intermediate. Reduction of this product with H₂ over Pd/C leads to terbutaline.L. A. Svensson, I. K. Wetterlin, (1976)
: Terbutaline synthesis

Stereochemistry

Terbutaline contains a stereocenter and consists of two enantiomers. This is a

racemate In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

, ie a 1: 1 mixture of (R) - and the (S) - form: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, .

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

{{Adrenergic agonists Beta2-adrenergic agonists Chemical substances for emergency medicine Resorcinols AstraZeneca brands Tocolytics Tert-butyl compounds Phenylethanolamines