Salbutamol

Chhabi AcharyaB. Pharmacy

HOPE Int’l College

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Content:• Introduction• Structure• Synthesis• SAR• Medical uses• Mechanism of action• Pharmacokinetic• Preparation & dosage• Adverse effect & contraindication• References

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Introduction:

• Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease.

• Salbutamol was the first selective β2-receptor agonist to be marketed – in 1968

• It was first sold by Allen & Hanburys under the brand name Ventolin.

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• The drug was an instant success, and has been used for the treatment of asthma ever since.

• Salbutamol sulfate is usually given by the inhaled route for direct effect on bronchial smooth muscle.

• Salbutamol is rapidly absorbed after oral administration and undergoes presystemic metabolism in the gut, oral bioavailability is 50%.

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• Molecular formula : C13H21NO3

• Molecular weight : 239.31• Pka : 5.9• Half life : 1.6 hours• Melting Point : 157-158 °C• Description : White crystalline powder from ethanol ethyl

acetate or ethyl acetate cyclohexane.• Brand name : Aerolin, Airomir, Asmol, Asthalin,

Asthavent, Broncovaleas, Sal – 4, Beta 2

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Structure:

(RS)-4-[2-(tert-butylamino)-1-hydroxyethyl]-2- (hydroxymethyl)phenol

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(R)-Salbutamol

(S)-Salbutamol

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Synthesis:

• Salbutamol can be prepared from an acetophenone derivative which is itself derived from salicylic acid (hence the "sal" in salbutamol).

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SAR:• The tertiary butyl group in salbutamol (or

albuterol) makes it more selective for β₂-receptors.

• The drug is sold as a racemic mixture mainly because the (S)-enantiomer blocks metabolism pathways while the (R)-enantiomer shows activity.

R

S

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Medical uses:

• Salbutamol is typically used to treat bronchospasm (due to either allergen asthma or exercise-induced), as well as chronic obstructive pulmonary disease.

• Salbutamol has been used in treating acute hyperkalemia on account of its potassium-depleting properties by stimulating potassium inflow in cells.

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Mechanism of action:

• Salbutamol stimulate β2 adrenergic receptors which are predominant receptors in bronchial smooth muscle (β2-receptors are present in human heart in a concentration between 10% and 50%).

• Stimulation of β2 receptors leads to the activation of enzyme adenyl cyclase that form cyclic AMP (adenosine-mono-phosphate) from ATP (adenosine-tri-phosphate).

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• This increase of cyclic AMP relaxes bronchial smooth muscle and decrease airway resistance by lowering intracellular ionic calcium concentrations.

• Salbutamol relaxes the smooth muscles of airways, from trachea to terminal bronchioles.

• Increased cyclic AMP concentrations are also inhibits the release of bronchoconstrictor mediators such as histamine, leukotreine from the mast cells in the airway.

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Contd..

• Salbutamol has more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation at recommended doses while producing fewer cardiovascular effects.

• The R-enantiomer is sold in its pure form as Levalbuterol.

• The presence of only the R-enantiomer produces fewer side-effects

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Pharmacokinetic:

• Absorption: Systemic absorption is rapid following aerosol administration.

• Metabolism: Hydrolyzed by esterases in tissue and blood to the active compound colterol. The drug is also conjugatively metabolized to salbutamol 4'-O-sulfate.

• Route of elimination: Approximately 72% of the inhaled dose is excreted in the urine within 24 hours, 28% as unchanged drug and 44% as metabolite.

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Preparations and dosage

• Salbutamol is available as tablet, syrup, metered dose inhaler (MDI), dry powder inhaler (DPI), nebulised solution and intramuscular or intravenous inject able form that may be given as following dosage:

1) The usual dose of oral salbutamol is 2 to 4 mg three times a day in adult and 1 to 2 mg three times a day in children.

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2) One puff (100 mcg) to two puffs (200 mg) of salbutamol metered dose inhaler (MDI) or one capsule (200 mcg) to two capsules (400 > mcg) of salbutamol dry powder inhaler (DPI) is inhaled as need basis.

3)Orally for: Acute bronchospasmAdult: 2-4 mg (up to 8 mg) 3 times dailyChild: 1 mth-2 yr: 100 mcg/kg (max: 2 mg), 2-6 yr: 1-2 mg, >6 yr: 2 mg. Doses to be taken 3-4 times daily.Elderly: Initially, 2 mg 3-4 times daily.

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4) Intravenous: Uncomplicated premature labour

Usual dose: 10-45 mcg/min

5) Respiratory failure, IM/SC: 500 mcg, repeated every 4 hr if necessary.

• Toxicity LD50=1100 mg/kg (orally in mice)

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Adverse effect:• The most common adverse reactions associated with

use of salbutamol inhalation aerosol are palpitations (occurring in less than 10% of patients, anxiety (less than 10%), tremors (less than 15% of patients) and increased blood pressure (approximately 5%), occasionally resulting in hypertension.

• The most common adverse reactions to salbutamol tablets or syrup are tremors (occurring in 10-20% of patients) and anxiety (9-20%).

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Contraindication:• Salbutamol and Pregnancy

• Caution when used during pregnancy.

• Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available.

• Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

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References:• Health Canada• Salbutamol: Ergogenic effects of salbutamol. Retrieved 2010-

10-20.

• Salbutamol, http://salbutamol.org/• British National Formulary (57 ed.). London: BMJ Publishing

Group Ltd and Royal Pharmaceutical Society Publishing. March 2008. ISBN 0-85369-778-7.

• www.medikidz.com/medipedia/salbutamol• http://www.infomed.ch/100drugs/saladre.html• http://www.drugbank.ca/drugs/DB01001

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