1. Therapy of bronchial asthma

2. Management A. Non drug treatment : Avoid exposure to antigen. Avoid humidity. Avoid drugs which precipitate asthma as (parasymathomimetics- morphine, penicillins, and NSAIDS).

3. B. Drug treatment: 1.Bronchodilators. A.Beta agonists B.Muscarinic antagonist C.Methylxanthens 2.Anti-inflammatory A.Corticosteroids B.Leukotriene antagonists 3.Prophylactic treatment: A.Cromlyn

4. 1. Bronchodilators There are three groups of bronchodilator drugs; A.B-adrenergic agonists. B.Muscarinic receptor anatgonists. C.Methyl xanthines: theophylline derivatives.

5. A.  -Adrenergic agonists They are classified into: I.Non-selective  -stimulants: i.e. stimulate β receptors and other receptors: (Epinephrine, Ephedrine, Isoprenaline) II.Beta 2 agonist: Salbutamol, Terbutaline and Bambuterol.

6. Mechanism of action role of β receptors in the bronchi Binding of adrenergic  -agonist with  receptors activate adenyl cyclase cAMP which will lead to: – Relax the airway muscles. – Inhibit release of mediators from mast cells – Enhances mucociliary function. – Decreases vascular permeability.

7. I. Non selective β agonists Epinephrine (Adrenaline) Mechanism of action It directly stimulate alpha and beta adrenoceptors. Pharmacological Effects Bronchodilatation (  2) Decongestion (vasoconstriction of blood vessels)(  1 ). Anti-allergic effect: It is the physiological antidote to histamine

8. Therapeutic Uses Acute attack of bronchial asthma Treatment of allergic reaction e.g. urticaria, angioedema, anaphylactic shock. Side Effects (due to non selectivity) Tachycardia, palpitation, anxiety, headache, tremors, hypertension. Contraindications Heart diseases. Hypertension. Pulmonary embolism.

9. II. Selective  2 agonists Short acting: Albuterol, terbutaline, metaproterenol (duration of action less than 6hrs ) used in emergency Long acting: salmetrol, formoterol (duration of action more than 12hrs) used for prophylaxis Given by inhalation Adverse effects: Tremors of skeletal muscle. Tachycardia. Hypokalemia Tolerance may occur with prolonged use.

10. B. Muscarinic receptor antagonists Mechanism of action: They competitively block muscarinic receptors in the airways and effectively prevent the braonchoconstriction caused by vagal discharge. Classified into: 1.Non selective (e.g. atropine): has a lot of antimuscarinic side effects???

11. 2.Selective (e.g. Ipratropium, Tiotropium) Ipratropium given by inhalation It has very few systemic antimuscarinic effects because it is a quaternary amine i.e. poorly absorbed Ipratropium is less effective than  2 agonists so it is not administered alone.

12. C. Methylxanthines Classified into: 1.Natural: Three major methylxanthines are found in the plants, caffeine (in coffee) theophylline (in tea) and theobromine (in cocoa). 2.Synthetic: aminophylline Mechanism of action: Block adenosine receptors. They inhibit the enzyme phosphodiestrase (PDE) leading to an increase in the intracellular cAMP level. They stimulate the release of epinephrine from adrenal medulla and inhibit COMT (it metabolizes epinephrine)

13. Pharmacological effects: Respiratory effects: – Bronchodilators. CNS effects: – Reduced fatigue, improved mental performance, increased alertness and power of concentration. – Large doses may produce restlessness, insomnia, headache and convulsions.

14. CVS effects: – Xanthines cause constriction of the cerebral vessels – Peripheral vasodilatation, increase the heart rate – Mild elevation in BP Diuretic action: xanthines cause weak diuresis. GIT: Stimulation of GI motility.

15. Therapeutic Uses: 1.Asthma and COPD 2.Other uses: Headache (caffeine + aspirin), Migraine (Caffeine + ergotamine) Adverse effects: GIT: nausea, vomiting, anorexia, reactivation of peptic ulcer. CVS: tachycardia and arrhythmias. Rapid I.V. injection can cause hypotension, syncope and cardiac arrest. CNS: irritability, insomnia, nervousness & convulsions.

16. 2. Anti-inflammatory drugs A. Corticosteroids Cornerstone in the therapy of asthma. They reduce bronchial hyperactivity and inflammation that accompanies asthma Mechanism of action: Reduce the synthesis of arachidonic acid by phospholipase A2 and inhibit the expression of COX2 which lead to reduction of inflammatory mediators (especially leukotrienes which play an important role in asthma) It is suggested that it increases the responsiveness of beta receptors in the airways

18. Indications Asthma: may be used systemically (hydrocortisone, prednisolone) or by inhalation (beclomethazone, fluticasone and triamcinolone) Adverse effects: Systemic corticosteroids (if used in high doses for long time): hypertension, diabetes mellitus, weight gain, salt and water retention, immunosuppression with flare of infection, depression, psychosis, growth retardation in children, peptic ulcer and cataract. Inhaled steroids: oropharyngeal candidiasis which can be avoided by use of mouth wash and gargle after each inhalation.

19. B. Leukotriene inhibitors 1.Zafirlukast and montelukast, are now available leukotriene receptor antagonists. – They are not recommended acute episodes – Toxicity is generally low – Rarely Churg-Strauss syndrome have been reported 2.Zileuton, a leukotriene synthesis inhibitor. – Selectively inhibit 5-lipoxygenase, a key enzyme in the conversion of arachidonic acid to leukotrienes – The drug is effective in preventing exercise-induced and antigen-induced and aspirin-induced asthma – Toxicity: elevation of liver enzymes

20. C. Anti IgE antibody Omalizumab is murine monoclonal antibody to human IgE It binds to IgE on sensitized mast cells and prevent activation by antigens and subsequent release of inflammatory mediators Approved for prophylactic management of asthma It is very expensive and must be administered parentally

21. 3. Prophylactic treatment Mast cell stabilizers: Disodium Cromoglycate and Ketotifen They inhibits or prevents bronchospasm induced by various stimuli including antigens, exercise, cold or dry air. Used in prevention of asthma (not treatment) Mechanism of action: Inhibit Ca ++ influx across mast cell membrane. Stabilizes mast cells so preventing release of mediators induced by antigens & nonspecific stimuli.

22. PHARMACOLOGY OF OXYGEN Oxygen Adminstrations 1- Mixtures of oxygen: Oxygen can be given in mixture with CO 2 or helium 2- Humidified oxygen: Oxygen can be given under water sealing to prevent irritation of nose, pharynx and trachea 3- Hyperbaric oxygen. Therapeutic uses of oxygen : Correction of hypoxia Methods of administration - O 2 is administrated by inhalation. Devices for inhalation include nasal cannula, masks, and oxygen tents. - Hyperbaric oxygen is given in pressure chamber of O 2 therapy.

23. Dangers, adverse effects and precautions 1-Fire and explosion can occur 2-In case of respiratory depression: CO 2 accumulates leading to CO 2 narcosis and failure of the respiratory center. If pure O 2 was administered, the hypoxia is corrected and the patient enters into apnea.  So those patients are oxygenated with artificial respiration. 3-Rapid withdraw of O 2 may lead to sever hypoxemia. 4-Terry syndrome (retinopathy of prematurity) : O 2 should be used only when needed and its concentration must not exceed 35-40% in premature infants. 5-O 2 under pressure greater than 2 atmospheric can cause toxic effects on CNS

24. Good Luck