Question 8

Outline the pharmacology of drugs used to treat asthma.

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College Answer

Answers should have included the most important aspects of the pharmacology of the most commonly used drugs e.g. class, mechanism of action, pharmacodynamics and important adverse reactions. More information on beta-agonists and corticosteroids (mainstays of management) was expected than drugs like magnesium, ketamine and other adjunctive treatments.


Drugs used in the Treatment of Asthma
Mechanism of action Examples
β-agonists (Waldeck, 2002)
  • Bind to G-protein coupled receptors
  • Increase the cAMP concentration in bronchial smooth muscle cells
  • cAMP activates Protein Kinase A
  • Active PKA inactivate myosin light-chain kinase and activates myosin light-chain phosphatase, leading to smooth muscle relaxation
  • High potency and efficiacy, but also high toxicity
  • Salbutamol
  • Adrenaline
  • R-enantiomer is usually the more effective one
Antimuscarinic agents (Soler & Ramsdell, 2014)
  • Muscarinic acetylcholine receptors are G-protein coupled receptors
  • Activation of muscarinic (M3) receptors results in a rise in cyclic GMP, increasing the availability of intracellular calcium
  • This leads to clinical effects (for M3 receptors in the lung, bronchoconstriction and increased bronchial secretion)
  • Antimuscarinic drugs act as competitive antagonists of the acetylcholine receptor, and prevent these clinical effects
  • High potency and efficacy, low toxicity
  • Ipratropium bromide
  • Tiotropium
  • Atropine
Corticosteroids (PJ Barnes, 1996)
  • Corticosteroids bind to cytoplasmic glucocorticoid receptors
  • These receptors, when activated, become dimers and are transported to the nucleus, where they regulate gene transcription
  • This downregulates the syhtesis of proinflammatory cytokines and enzymes involved in the synthesis of inflammatory mediators such as cyclooxygenase and phospholipase
  • High potency and efficacy, high long term toxicity
  • Hydrocortisone
  • Prednisolone
  • Methylprednisolone
  • Budesonide
  • Ciclesonide
Methylxanthines (Tilley, 2011)
  • Methylxanithines are nonselective adenosine receptor antagonists, but their main mechanism of action in asthma is by their nonselective inhibition of phosphodiesterase
  • By inhibiting phosphodiesterase, these drugs increase the intracellular concentration of cyclic AMP in airway smooth muscle cells
  • cAMP activates Protein Kinase A
  • Active PKA inactivate myosin light-chain kinase and activates myosin light-chain phosphatase, leading to smooth muscle relaxation
  • Low potency and efficacy, high toxicity
  • Theophylline
  • Aminophylline
Magnesium sulphate (Noppen, 1990Irazuzta et al, 2017)
  • Antagonists of calcium at the NMDA receptor-gated calcium channels, which produces smooth muscle relaxation
  • Also inhibits acetylcholine and histamine release
  • Low potency, low efficacy, low toxicity
  • Magnesium sulphate
Ketamine (Goyal & Agrawal, 2013Sato et al, 1998)
  • NMDA receptor antagonist; blockade of these receptors reduces availability of intracellular calcium
  • Howeverm, ketamine seems to produce bronchodilation by a mechanism which is independent of the NMDA receptor
  • Instead it appears to interfere with a calcium-dependent step in histamine-induced bronchoconstriction
  • Low potency and efficacy, potentially high toxicity
  • Ketamine
Volatile anaesthetics (Mondoñedo et al, 2015Yamakage, 2002)
  • Decrease intracellular calcium concentration by an unknown mechanism, probably by inhibition of IP3- induced calcium release
  • Thought to be also due to decreased calcium sensitivity and inhibition of Protein Kinase C activity
  • High potency, low toxicity
  • Isoflurane
  • Sevoflurane
  • Enflurane
Helium-oxygen mixtures
  • Decrease the density of inspired gases
  • This decreases the Reynolds number, i.e. decreases the likelihood of turbulent flow through narrow airways
  • As laminar flow  is usually associated with lower resistance than turbulent flow at any given flow rate, the use of helium decreases the respiratory resistance in bronchospasm
  • This improves gas exchange and the distal delivery of nebulised medications
  • Low potency, nil toxicity
  • Helium


Zdanowicz, Martin M. "Pharmacotherapy of asthma." American journal of pharmaceutical education 71.5 (2007).