Mechanism of drugs used in the treatment of respiratory disease Flashcards
Aim of bronchodilators
Rescue patient from bronchospasm
Aims of anti-inflammatories
Reduce frequency of attacks
Reduce severity of attacks
Limit structural remodelling
Examples of bronchodilators
B-adrenoceptor agonists Xanthines e.g. caffeine Muscarinic receptor antagonists Leukotriene receptor antagonists Histamine receptor antagonists Methods all involve inhibition of contraction
Anti-inflammatory classes
Glucocorticoids
Cromoglicate and nedocromil
Anti-IgE
Mechanisms all involve inhibition of inflammation
B-adrenoceptor agonists mechanism
cAMP dependent, causes smooth muscle relaxation
Short acting B2-adrenoceptor agonists
E.g. salbutamol, terbutaline
Hydrophilic in nature, short duration of action (4-6 hours)
Long acting B2-adrenoceptor agonists
E.g. salmeterol, formoterol
Lipophilic in nature
Leech out of membrane prolonging duration of action (>12 hours)
Must not be given in the absence of a corticosteroid
(Old) mechanism for xanthines
Phosphodiesterase metabolises cAMP
Methylxanthines inhibit PDE, maintaining high cAMP levels
Achieves bronchial smooth muscle relaxation
Examples of xanthines
Theophyline
Aminophyline
Muscarinic receptor antagonists mechanism
Aim is to block post-synaptic M3 receptors
Effects are limited by lack of selectivity leading to antagonism of M2 autoreceptors (prevents ACh release)
Blocking M2 knocks out benefit of blocking M3 as more ACh released
Muscarinic receptor antagonist examples (best for COPD)
Ipratropium: onset of action 30 mins, lasts 3-5 hours, not selective for M receptor subtypes, may decrease mucus secretion and increase mucociliary clearance
Tiotropium: longer acting, once daily dosing
Adverse effects of muscarinic receptor antagonists
Minimal when inhaled, anti-muscarinic side effects e.g. dry mouth, sedation
Leukotriene receptor antagonists
Cysteinal leukotrienes (very potent) act on CysLT1 receptor in respiratory mucosa, montelukast and zafirlukast antagonise the receptor, prevents bronchiolar contraction mediated by LTs, inhibits early and late phase responses to irritants
Anti-inflammatory drugs
Used to reduce severity and frequency of asthma attacks
Limit progression of disease by inhibiting remodelling
Reduce night-time asthma attacks by preventing late-phase
Glucocorticoids
No immediate effect
Step 1 inhalation therapy when bronchodilator is used more than once daily