1. Respiratory drugs -Surag Khadka

2. Learning outcomes Classes of drugs MoA of the following Beta-2 agonists Anti-cholinergics Leukotriene antagonists Methylxanthines Steroids Corelate MoA with pathophysiology

3. Asthma drugs Smooth muscle dysfunction Rx: Beta-2 agonists Anti-cholinergics Methylxanthines Leukotriene antagonists Airway inflammation Rx: Glucocorticoids Mast cell stabilisers Airway remodelling Rx: ?????

4. Drugs to treat asthma

5. Chronic Asthma (BTS guidelines) SABA + Inhaled steroid + LABA (Consider increasing inhaled steroid if that doesn’t work) + Leukotrine antagonist (Consider further increasing inhaled steroid dose) + Daily steroid TABLET

6. Acute asthma management Oxygen Beta-2 bronchodilators Glucocorticoids Ipratropium Magnesium Sulphate IV aminophylline ABx

7. COPD management Stop smoking! Bronchodilator therapy (SABA/SAAC) Combination therapy (LABA + inhaled steroids + LAAC) Oral theophylline Home O 2

9. Mechanism of Actions Bronchodilators Beta-2-agonists Anti-cholinergics Methylxanthines Leukotriene receptor antagonists Anti-inflammatory agents Glucocorticoids Mast cell stabilisers

10. Beta-2 agonist Binds with Adenyl Cyclase (AC) via GPCR AC leads to ATP  cAMP cAMP activates PKA PKA phosphorylates MCLK leading to its deactivation This leads to ↓smooth muscle contraction

11. Beta-2 agonist desensitisation ↑SABA/LABA ↑ AC ↑ ATP  cAMP ↑ cAMP= ↑PDE ↑PDE = breakdown of cAMP Side effects: Tremor, Tachycardia, Arrythmia Headache Hypokalaemia

12. SABA v LABA

13. Anti-cholinergics Blocks M3 receptor  ↓PLC  ↓Calcium release from ER  ↓ Smooth muscle contraction  Bronchodilation Side effects: Dry Mouth, Nausea, Headache, Cough Bronchospasm (Paradoxical)

14. Methylxanthines Eg: Theophylline, Aminophylline Full mechanism NOT clear Thought to inhibit PDE  ↑ cAMP  Bronchodilation Side effects: Insomnia, Vomitting, Cardiac arrhythmias, seizures

15. Leukotriene receptor antagonists Leukotriene  Airway inflammation and bronchospasm Leukotreine receptor antagonists  Prevents this Used as a preventer Side effects: Abdominal Pain Headache, Thirst and restlessness

16. Glucocorticoids Activates GR  interaction with nuclear DNA  Influences gene expression Inhibition of pro-inflammatory products Expression of anti-inflammatory products Side effects: Think of Cushings

17. Any questions?