1. Course in the Ward Oxygen saturation was 85-88% despite oxygen per mask at 5-6 lpm. She was nebulized with salbutamol and post-nebulization parameters were as follows: – RR 20 cpm – CR 120 bpm – Fair air entry – Loud wheezes and crackles, both lung fields

2. Workups Workups that can be done in our patient include: – Pulse Oximetry – Pulmonary function Test (Spirometry or Peak flow meter) – Arterial Blood Gas – Chest X-ray

3. Managing Asthma in Acute Exacerbation Source: Global Strategy for Asthma Control and Prevention: GINA Guidelines 2009

8. Drugs for Acute Asthma Bronchodilators – Anticholinergics – Methylxanthines – Sympathomimetics Catecholamines – epinephrine B2 agonists – SABA Anti-inflammatory – Corticosteroids Systemic Inhaled

9. Relievers Quickly reverse bronchoconstriction during acute exacerbation or breakthrough symptoms; taken prn Bronchodilators – SABA, epinephrine, methylxanthines Anti-inflammatory agents – Systemic steroids

10. Controllers Have to be taken continuously on a maintenance basis to control asthma Bronchodilators – LABA Anti-inflammatory agents – Inhaled – Systemic – LT antagonists – Mast cell stabilizers

11. Bronchodilators MOA: activation of B receptors -> activation of Gs coupling proteins -> cAMP -> phosphorylation of target enzymes -> relaxation of bronchial muscles Epinephrine B2 agonists

12. Epinephrine For anaphylaxis Not effective in oral intake Rapidly conjugated and oxidized in GIT and liver a1= a2 ; B1=B2 Triggers sympathetic response, fear, anxiety, tenseness, restlessness, cardiac arrythmias Not used in acute asthma, unless not responsive to B2 agonist or asthma is caused by anaphylaxis

13. SABA Terbutaline Salbutamol After oral inhalation, 10% deposited in bronchial airway where absorption takes place -> systemic circulation. No substantial effect on inflammation

14. B2 Agonists SABA – Oral Peak effect 2 hrs Duration of action 4-8 hrs – Inhaled Peak effect 30-90 mins, 75% of maximum bronchodilation by 5 mins >4 hrs

15. Adverse Effects of B2 agonists Skeletal muscle tremors tachycardia, arrthymias increased bronchial hyperreactivity and deterioration of disease control

16. Anticholinergic Drugs Ipratropium bromide: treatment for asthma Binds M2 and M3 receptors with equal affinity, competitive antagonist to acetylcholine at M3 receptors on smooth muscles -> blocking bronchospasm -> decrease mucus secretion In combination with SABA, provides quick relief for acute asthma attack

17. Combivent contains a microcrystalline suspension of ipratropium bromide and salbutamol in a pressurized metered-dose aerosol unit for oral inhalation administration. The 200 inhalation unit has a net weight of 14.7 grams. Anticholinergic bronchodilator Each actuation meters 21 mcg of ipratropium bromide and 120 mcg of salbutamol from the valve and delivers 18 mcg of ipratropium bromide and 103 mcg of salbutamol from the mouthpiece.

18. Dosage 2 inhalations four times a day. Patients may take additional inhalations as required; however, the total number of inhalations should not exceed 12 in 24 hours. Safety and efficacy of additional doses of COMBIVENT Inhalation Aerosol beyond 12 puffs/24 hours have not been studied.

19. All Adverse Events (in percentages), from Two Large Double-blind, Parallel, 12-Week Studies of Patients with COPD

20. Methylxanthines Theophylline – both bronchodilator and anti- inflammatory actions inhibits PDE -> increases cAMP ->smooth muscle relaxation High level of toxicity; narrow therapeutic index AE: nausea, vomiting, GIT disturbances, headache,

21. Corticosteroids Anti-inflammatory effects due to inhibition of production of pro-inflammatory cytokines -> decreased trafficking of lymphocytes, eosinophils -> decreased bronchial hyperreactivity Potentiates B2 agonist effect by increasing synthesis of B2 receptors Decrease mucus production

22. Corticosteroids Systemic steroids – Oral: prednisone, prednisolone, methylprednisolone – Parenteral: hydrocortisone, methylprednisolone Inhaled steroids – Budesonide, fluticasone

23. Indications of CS Systemic steroids – For relief of acute asthma exacerbations – Control of severe persistent asthma Inhaled steroids – As maintenance therapy for all levels of persistent asthma

24. Adverse Effects of CS Inhaled CS adverse effects: hoarseness/dysphonia, oral candidiasis, throat irritation and cough Systemic CS adverse effects: truncal obesity, moon facies, buffalo hump, osteoporosis