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Treatment of asthma

Asthma is an inflammatory disease with bronchconstriction and overproduction of mucous, and can result in remodelling.

To understand how to treat asthma you must look how at the mechanisms by which it works and perpetuates itself.

The Th-2 response leads mast cells basophils and eosinophils to release mediators of inflammation and this will happen in the future due to desensitisation. These are histamine, prostaglandins, leukotrienes and enzymes. Just think about asthma reaction = inflammatory mediators at the moment.

Overview

  1. Primarily manage the inflammation (use inhaled corticosteroids (ICS))
  2. Secondarily reserve bronchodilators for symptomatic relief (prodilators like LABAs and SABAs, anti-constrictors like SAMAs LAMAs)

Proinflammatory cytokines

Both prostaglandins and leukotrienes are both made of arachidonic acid which in turn is made from membrane phospholipids

Leukotrienes

These are “slow reacting substance of anaphylaxis” and cause contraction of respiratory smooth muscle, and increased vascular permability.

Prostanoids (prostaglandins+thromboxanes)

PGE1

PGE1 promotes vasodilation and also down-regulates the lipoxygenase pathway, resulting in less leukotrienes

Drug-induced rhinitis

As NSAIDs inhibit COX enzymes this can lead to an increase in leukotrienes, which can result in “Non-Allergic Rhinitis with Eosinophilia syndrome”. This is charaterised by rhititis( nasal obstruction rhinorrhoea, sneezing) and facial flushing.

Ensuing asthma triggered 1-3 hours within ingestion of aspirin adn other NSAUDS

Prostaglandins (PGD2)

These mediate bronchoconstriction and vasodilation, they increases permeability and therefore inflammatory cells infiltration.

Thromboxanes (TXA2)

These mediate bronchoconstriction

Bronchial tone regulation

Bronchial smooth muscle can either constrict or dilate

Dilation

In Asthma attacks this isnt happening and we want it to happen. cAMP leads to Bronchodilation. Its production is upregulated by b adrenoreceptor activation which we can stimulate with ß2 Adrenoreceptor agonists. (LABA, long acting ß2 agonist, SABA, short acting ß2 agonist)

Constriction

This is upregulated by adenosine and acetylcholine (the big one). We can limit this with muscarinic antagonists, which block neural bronchocontriction. (LAMAs, Long acting muscarinic antagonist, SAMAs, short acting muscarinic antagonist)

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