3. 3
• Soliris (eculizumab), produced by Alexion
Pharmaceuticals to treat, ahem, paroxysmal nocturnal
hemoglobinuria. PNH is a rare and life-threatening
disease and is the only form of hemolytic anemia—a
deficiency in red blood cells caused by their destruction,
as opposed to low production—that is acquired rather
than inherited.
• Price: Range between $6830 and $27,320 (300
-1200mg)
]
World’s Most Expensive
Medicine
4. 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.
4
5. Contd..
• 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%.
5
6. Contd..
• 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 ,6
9. Synthesis:
• Salbutamol can be prepared from an
acetophenone derivative which is itself derived
from salicylic acid (hence the "sal" in
salbutamol).
9
10. SAR:
• The tertiary butyl group in salbutamol (or
albuterol) makes it more selective for β -₂
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
10
11. 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.
11
12. 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).
12
13. Contd..
• 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.
13
14. 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
14
15. 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.
15
16. 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.
16
17. Contd..
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 bronchospasm
Adult: 2-4 mg (up to 8 mg) 3 times daily
Child: 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.
17
18. 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)
18
19. 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%).
19
20. 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.
20
23. 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 23
