Asthma is a major public health problem affecting over 150 million people worldwide. It is caused by bronchial hyperreactivity and airway inflammation in response to various stimuli in genetically susceptible individuals. Current drug treatment aims to provide symptomatic relief through bronchodilation and modify the disease through reducing inflammation. Common classes of drugs used include beta-2 agonists, anticholinergics, theophylline, glucocorticoids, and leukotriene receptor antagonists. Management of acute severe asthma involves oxygen supplementation, nebulized bronchodilators, systemic corticosteroids, and hospital admission if inadequate response.

1. Respiratory Drugs (for Asthma & COPD) Phase III/Therapeutics

8. Arachidonic Acid LTC 4 D 4 E 4 (SRSA) bronchoconstrictors PGs TxA 2 Lipoxygenase Cyclo-oxygenase Phospholipid Phospholipase A2 Montelukast NSAIDs Zileuton

11. Drug Delivery by an Inhaled Aerosol Large particles (>10  m) deposit in the mouth and small ones (<0.5  m) fail to deposit in the distal airways - SPACER devices increase the fraction of droplets in the critical 1-5  m range. Effect of first-pass can be dramatic e.g. equiactive doses of oral and pMDI SALBUTAMOL differ 40-fold (4000 vs 100  g) and FLUTICASONE is inactive orally because of 100% first-pass. NB there is no advantage (I.e. a ‘sparing effect’) in delivering a GCC with low first-pass by aerosolisation e.g. hydrocortisone or prednisolone.

14. 2003 BTS Guidelines for Chronic Asthma prn short-acting  2 agonist Step 1 prn (< once daily) short-acting  2 * Step 2 regular short-acting  2 inhaled + anti-inflammatory agent* ( low-dose GCC) Step 3 ADD regular long-acting  2 agonist. If fails or inadequate increase inhaled GCC to 800  g/day± long-acting  2 . If inadequate trial of methylxanthines or leukotriene antagonist Step 4 Inhaled GCC to 800  g/day AND long-acting  2 agonist regularly, plus: increase GCC to 2000  g/day or methylxanthines or leukotriene antagonist or oral  2 agonist Step 5 Best of step 4 plus oral prednisolone * ‘reliever’ or ‘rescue’ medication vs. anti-inflammatory agents as ‘preventers’ Points to note: 1 . Patient treatment should be reviewed/adjusted at least every 3-6 months. 2. Step down rapidly from high dose oral steroids if PEFR responds promptly i.e. within a few days, otherwise need to be stable for 1-3 months before attempting more gradual step down.

17. Immediate management · Oxygen therapy by tight fitting facemask (60%). · Nebulised  2 agonist eg salbutamol 2.5 +/- 0.5mg ipratropium* · Give Prednisolone 30-60mg p.o. or hydrocortisone 300mg i.v. · Urgent chest X-ray to exclude pneumothorax · Urgent blood gas** · Reassess in 15 min or if life-threatening features appear · Consider i.v. aminophylline if life-threatening features or fails to improve after 15-30 mins *** · Discuss all patients with ITU - ventilation needed if PEFR continues to fall despite medical therapy, patient becoming drowsy/confused/exhausted or deteriorating blood gases **. * Alternatively  2 agonist can be given s.c. ** Beware severe hypoxia (p0 2 <8.0 on high inspired O 2 ) or high/rising pCO 2 *** establish if patient on oral theophylline before giving any aminophylline IV. MANAGEMENT OF ACUTE SEVERE ASTHMA