| 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, 1990; Irazuzta 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
|
|
| Ketamine (Goyal & Agrawal, 2013; Sato 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
|
|
| Volatile anaesthetics (Mondoñedo et al, 2015; Yamakage, 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
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