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