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Beta2 agonists

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Beta2 agonists

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

 

©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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