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Pharmacology
b 2 receptors located in the plasma
membranes of virtually all types of cell
receptors consist of a protein that traverses the membrane 7 times. Linked
to a stimulatory guanine-nucleotide-binding protein (Gs). Receptor
occupancy changes the conformation of Gs leading to activation of
adenylate cyclase and conversion of ATP to cAMP
cAMP responsible for the physiological response: differs with type of cell.
In lung causes bronchodilatation. Also causes enhancement of mucociliary
clearance, inhibition of cholinergic transmission, enhances vascular integrity
and inhibits mast cell mediator release. However despite these effects there
is no evidence that b 2 agonists have
any substantial effect on the chronic inflammation characteristic of asthma
receptors desensitized after high-dose or repeated exposure to agonists.
Several mechanisms. After a few minutes of exposure to agonist receptor is
phosphorylated. This interferes with its coupling to Gs. With more
prolonged exposure receptors are internalized to a region of the cell below
the cell surface. Finally with prolonged exposure the number of receptors in
the membrane is reduced because of decreased production of mRNA for the
receptor (down-regulation). Increase in transcription of gene for receptor,
which is stimulated by glucocorticoid and thyroid hormone, results in
up-regulation
Pharmacokinetics
Administration
PO, inhalation, SC, IV.
Inhaled route preferred because side effects are fewer for any given degree
of bronchodilation. As effective as parenteral administration for treating
acute, severe attacks of asthma in most patients although some who have severe
bronchial obstruction may benefit initially from parenteral therapy
Use of nebulizer was formerly standard practice in emergency treatment of
patients with acute severe asthma, however use of metered dose inhaler with
spacer device, under supervision, is as effective in the emergency setting as
therapy with a nebulizer
In general the dose required in a nebulizer is 6-10 times that used in a
metered-dose inhaler to produce the same degree of bronchodilation
Pharmacodynamics
bronchodilator response is log-linear so that a doubled effect is achieved
only by a 10-fold increase in dose
effect on skeletal muscle: tremor
CVS: tachycardia, vasodilation, +ve inotropy. Latter effect also occurs in
lungs where it decreases hypoxic vasoconstriction and therefore worsens VQ
mismatch. Combined with increase in pulmonary blood flow leads to a fall in
PaO2 (may be > 1 kPa)
metabolic: hyperglycaemia, hypokalaemia, hypomagnesaemia
Further reading
Nelson HS. Drug therapy: (beta)-Adrenergic Bronchodilators. NEJM, 1995; 333:
499-506
© Charles Gomersall December 1999
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