1. Drugs Used to Treat Asthma Dr. Najlaa Saadi Ismael Department of Pharmacology Mosul college of Medicine University of Mosul

2. Asthma is an inflammatory disease of the airways characterized by acute bronchoconstriction causing shortness of breath, cough, wheezing, and rapid respiration.

3. Airflow obstruction in asthma is due to bronchoconstriction that results from: Contraction of bronchial smooth muscle Inflammation of the bronchial wall Increased mucous secretion

5. Approaches to Treatment  Prevention of exposure to allergen(s)  Reduction of the bronchial inflammation and hyperreactivity.  Dilatation of narrowed bronchi

6. Reduction of the bronchial inflammation and hyperreactivity. 1.Glucocorticoids 2.Mast Cell Stabilizers: Sodium cromoglicate 3.Other drugs. Ketotifen

7. 1.Glucocorticoids Prednisolone (orally) Beclomethasone, budesonide (by inhalation)

8. Glucocorticoids MOA: MOA:  Inhibition of the influx of inflammatory cells into the lung after allergen exposure  Inhibition of the release of mediators from macrophages and eosinophils, and T lymphocytes)  Reversing mucosal edema  Decreasing the permeability of capillaries  Inhibiting the release of leukotrienes.  After several months of regular use reduce the hyperresponsiveness of the airway smooth muscle to stimuli, such as allergens, irritants, cold air, and exercise.  Increase the number of B2 recepters so promote bronchodilatation mediated by B2 receptors

9. Oral/systemic: Patients with severe exacerbation of asthma (status asthmaticus) may require intravenous administration of methylprednisolone or oral prednisone.

10. Inhaled Corticosteroids Side Effects: Pharyngeal irritation Coughing Dry mouth Oral fungal infections Dysphonia

11. 2.Sodium Cromoglicate MOA: Stabilize the cell membranes of inflammatory cells (mast cells, monocytes, macrophages Preventing release of harmful cellular contents (Indirect-acting agents that prevent bronchospasm)

12. PK:  Poorly absorbed from the gastrointestinal tract  Well absorbed from the lung  Eliminated unchanged in the urine and bile.

13. Uses: Chronic asthma Children asthma Pregnant wemon Exercise induced asthma Allergic rhinitis

14. 3.Other drugs: 3.Other drugs: Ketotifen is a histamine H1-receptor blocker which may also have some antiasthma effects.

15. Bronchodilators: 1.Adrenergic agonists 2.Xanthine Derivatives 3.Antimuscarinic bronchodilator

16. 1.Adrenergic agonists  Nonselective adrenergics Example: epinephrine  Nonselective beta-adrenergics Example: isoproterenol  Selective beta 2 drugs Example: albuterol

17. Beta-adrenoceptor Agonists MOA Activation of beta 2 receptors activate cAMP, which relaxes smooth muscles of the airway and results in bronchial dilation and increased airflow. B2- adrenoceptor activation also stabilises mast cells

18. Beta-adrenoceptor Agonists Albuterol, terbutaline, salbutamol Rapid onset of action 15-30 minute Short-acting and provide relief for 4-6 hours Drug of choice for acute asthma

19. Beta-adrenoceptor Agonists Salmeterol and Formoterol Slow onset of action Long-acting,12 h or more Used for prophylaxis

20. Side effect: Cardiac arrythmia Oral and parenteral B2 agonist cause vasodilatation in the skeletal muscle vessels and this may lead to hypotension and tremor.

21. 2.Xanthine Derivatives: Theophylline, a methylxanthine Inhibition of phosphodiesterase (PDE),since this enzyme hydrolyzes cyclic nucleotides and this lead to increase cAMP Cause bronchodilation by relaxing smooth muscles of the airways. Relief of bronchospasm and greater airflow into and out of the lungs. Causes CNS stimulation. Causes cardiovascular stimulation: increased force of contraction and increased HR, resulting in increased cardiac output Increased blood flow to the kidneys (diuretic effect).

22. Pk: Rapid and complete Absorption from GIT. 90% is metabolised by the liver. The t l/2 is 8 h. Tobacco smoking enhances theophylline clearance by inducing hepatic P450 enzymes. Low therapeutic index. Use of theophylline in status asthmaticus.

23. Side Effect of Theophyllin  Nausea and diarrhoea, Vomiting, Gastroesophageal reflux during sleep  The chief dangers are cardiac arrhythmia, hypotension, hypokalaemia and seizures. Drug Interaction of Theophyllin Enzyme inhibition by erythromycin, oral contraceptives increases the plasma concentration of theophylline. Enzyme inducers such phenytoin and rifampicin reduce the concentration.

24. 3.Antimuscarinic Bronchodilators  Blockade of muscarinic (M3) receptors and causes bronchodilation, the preferred antimuscarinics Ipratropium Oxitropium. These synthetic compounds, prevents absorption after inhalation and minimizes antimuscarinic effects outside of the lung. Uses: acute severe asthma when combined with B2-adrenoceptor agonists.

25. Leukotriene Receptor Antagonists Montelukast Zafirlukast MOA: Montelukast, Zafirlukast are competitively prevent the bronchoconstrictor effects of leukotrienes By blocking their receptor Prevent leukotrienes from attaching to receptors on cells in the lungs and in circulation. Blocking the Inflammation in the lungs

26. Montelukast Montelukast (once per day) Zafirlukast Zafirlukast (twice per day) Leukotriene receptor antagonists Uses: Prophylaxis and chronic treatment of asthma