1.4 leukotrine receptor antagonist LTRA short acting muscarinic antagonist SAMA long acting muscarine antagonist phosphodiesterase 3 inhibitors PDE-3 inhibitors nedocromil monoclonal antibodies anti-IgE

Leukotriene Receptor Antagonists (LTRA are normally used following persistent symptoms with high dose MART therapy

montelukast the most commonly prescribed LTRA is typically dosed at 10mg a day in adults.

a less used alternative, zafirlukast, typically dosed at 20mg BD in adults.

Leukotriene Receptor Antagonists competitively block the receptors for the potent spasmogens' cysteinyl leukotrienes (CysLT1  Protein-Coupled Receptor and suppress their effects,

resulting in a reduction in both bronchiolar muscle contraction and mucus secretion.

The only short-acting muscarinic antagonist used is 'ipratropium bromide'.

It is sometimes used in place of salbutamol (a SABA), but typically in young children rather than adults.  

how SAMA works?

• Act on M3 muscarinic receptors (G-Protein Couple Receptors)

• Prevent bronchoconstriction by vagal discharge

• Lead to smooth muscle relaxation and bronchodilation

Long-acting Muscarinic Antagonists

These work as per SAMA but present with a longer duration of action.

The specific drug used in respiratory disease - including asthma - is 'tiotropium'.

It tends to be used more often in COPD.

Phosphodiesterase 3 inhibitors (PDE-3 inhibitors)

Theophylline and aminophylline are other drugs that are infrequently used to manage patients with asthma.

Phosphodiesterase 3 inhibitors are methylxanthines (like caffeine), and inhibit Phosphodiesterase 3 (PDE-3), and to a lesser extent PDE-4.

They work by increasing cAMP,

as well as likely competitively antagonising adenosine receptors,

which possibly reduces bronchoconstriction and inflammation. 

Theophylline:

This drug presents with a narrow therapeutic index, whereby the toxic dose is close to therapeutic dose.

measure plasma concentration 5 days after initiating + 3 days after any dose adjustment.

The plasma concentration is decreased in smokers and by alcohol.

• Aminophylline

• this is a mixture of theophylline and ethylenediamine which is added to increase water solubility, enabling intravenous administration

Nedocromil is a mast cell stabiliser.

Please refer to the drug monograph which summarises its mechanism of action.

Monoclonal antibodies (e.g. anti-IgE) are increasingly used for severe asthma and other respiratory and non-respiratory diseases

but require strict criteria to me met before administration, e.g. elevated blood eosinophils)

he first biologic used for the treatment of asthma is Mepolizumab.