RESPIRATORY PHARMACOLOGY Dr A.Shyam Sundar, Associate Professor in Pharmacology, University of Nizwa, Sultanate of Oman

OVERVIEW Asthma is a reversible obstructive disease of the lower airway. With asthma, there is increasing airway obstruction caused by bronchoconstriction, inflammation and edema of the lining of the bronchioles, and the production of thick mucus that can plug the airway.

DRUGS USED IN RESPIRATORY DISORDERS Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

ASTHMA There are three types of Asthma 1. Extrinsic Asthma (also referred to as allergic asthma and caused in response to an allergen such as pollen, dust, and animal dander). 2. Intrinsic asthma (also called non-allergic asthma and caused by chronic or recurrent respiratory infections, emotional upset, and exercise). 3. Mixed asthma (caused by both intrinsic and extrinsic factors). In asthma,there will be Contraction of bronchial smooth muscle, Inflammation of the bronchial wall, Increased mucous secretion. Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

Drugs addressing bronchoconstriction and inflammatory issues Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

Sympathomimetic Agents They work by increasing cAMP which results in bronchodialation. Pirbuterol, Terbutaline, Albuterol and Salmeterol* are four commonly used drugs in this class. Most of these drugs are inhaled, which minimize their systemic side effects. Because of their rapid onset, they are used in acute attacks. Tremor and Tachycardia are the most common side effects. *Salmeterol is long acting and hence cannot be used in acute attacks

Corticosteroids Act by reducing inflammation(reverse mucosal edema, decrease permeability of capillaries, inhibit the release of cytokines and leukotrienes) Acute exacerbations: Systemic steroids are used. IV or PO based on the severity. Maintenance therapy: Inhaled corticosteroids are used. Beclonethasone, Flunisolide, Triamcinolone, Fluticasone are common drugs in this class.

Corticosteroids Cough, Oral thrush and Dysphonia are common side effects of inhaled corticosteroids. Abnormal glucose metabolism, increased weight gain, hypertension, adrenal suppression are the common side effects of systemic corticosteroids such as prednisone.

Anticholinergics Parasympathetic stimulation causes bronchoconstriction and mucus secretion. Anticholinergics block these effects and maintain bronchodialation of the airway. Ipratropium is an example for inhaled anticholinergics. Used in the treatment of asthma and COPD Dry mouth and sedation are the most common side effects. Poor systemic absorption and hence minimal side effects.

LEUKOTRIENE INHIBITORS Given Orally Prevents Bronchoconstriction & Airway Inflammation. Not to be used for acute bronchospasm ADR: Zileuton= Hepatitis Zafirlukast= Drug Allergy Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

Theophylline Theophylline is a Methylxanthine derivative MOA: Increases cAMP levels by inhibiting phosphodiesterase enzyme, which results in bronchodilation. It also has some anti-inflammatory effects. Drug Interactions: Cimetidine and Erythromycin increase plasma levels of theophylline 2. Phenytoin and Quinolones decrease plasma levels Overdose: Results in tremor, insomnia, GI distress and Nausea. Major complications include seizures and arrhythmias

Cromolyn Sodium and Nedocromil Effective Prophylactic agents in Exercise induced asthma and allergen induced asthma MoA: Stabilize mast cells and prevent mediator release by blocking calcium gates. Adverse Effects: Cromolyn rarely causes laryngeal edema, cough, and wheezing

Acute and Long- Term management of Asthma Status Asthmaticus is a life-threatening attack of asthma, which can be treated by IV corticosteroids and bronchodilators followed by theophylline. Patients with mild, persistent symptoms should be started on an inhaled steroid(Fluticasone propionate) for routine use. Acute attacks are treated with Beta2- adrenergic agents. Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

Summary- Anti-Asthmatic Drugs

Antitussives, Mucolytics and Expectorants An antitussive is a drug used to relieve coughing. A mucolytic is a drug that loosens respiratory secretions. An expectorant is a drug that aids in raising thick, tenacious mucus from the respiratory passages. Expectorants are used to help raise respiratory secretions. An expectorant may also be included along with one or more additional drugs, such as an antihistamine, decongestant, or antitussive, in some prescription and nonprescription cough medicines.

Therapeutic Uses of Acetylcysteine (Mucolytic) 1. As part of the treatment of bronchopulmonary diseases(Emphysema). 2. As adjunctive therapy in chronic bronchopulmonary diseases(chronic emphysema, emphysema with bronchitis, chronic asthma, tuberculosis, and bronchiectasis, pneumonia), Tracheobronchitis, cystic fibrosis, 3. Acetaminophen overdosage.

RHINITIS Rhinitis is the inflammation of the mucous membranes of the nose. Most commonly caused by viruses or by airborne allergens. Staying away from the allergens should be the primary measure. If irritant avoidance is not possible, use drugs such as, Nasal Corticosteroids Cromolyn sodium Antihistamines Alpha adrenergic agonists Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

RHINITIS Beclomethasone and flunisolide are commonly used steroids for treating rhinitis. Chronic rhinitis does not show improvement until 2 weeks after the start of therapy. Diphenhydramine, Chlorpheniramine, Cyproheptadine and promethazine are commonly used antihistamines for treating rhinitis. Ephedrine and pseudoephedrine are alpha adrenergic agonists used To treat rhinitis. These drugs reduce airway resistance immediately When given as aerosol. Rebound nasal congestion occurs after discontinuation from prolonged use.

Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer