Respiratory System Drugs Part 2 PDF

Respiratory System Drugs Part 2 Cough Forced expiration against a closed larynx which suddenly opens to expel air and unwanted material from the respiratory tract May be voluntary or involuntary Mucosal surface lining respiratory tract Impulses relayed via vagus nerve Cough center in brain stem High...

Respiratory System Drugs Part 2 Cough Forced expiration against a closed larynx which suddenly opens to expel air and unwanted material from the respiratory tract May be voluntary or involuntary Mucosal surface lining respiratory tract Impulses relayed via vagus nerve Cough center in brain stem Higher cough modulating area of the sensory cortex Efferent stimulation diaphragm glottis muscles of chest and abdomen Drugs Used in Treatment Of Cough Cough reflex- involves both afferent stimulation (sensory NS) mediated by irritation of the smooth muscle of the bronchial tree followed by efferent stimulation (motor NS) Irritation of the bronchial mucosa causes broncho-constriction, which stimulates cough receptors located within the tracheo-bronchial tree So cough may be relieved by use of bronchodilators B2 agonists) Afferent nerves from these receptors via the vagus reach multiple centers within the medulla that are distinct from the respiratory center Drugs acting primarily on the peripheral stimulation (afferent system) or the stimulation at the medulla oblongata may relieve cough symptoms Most effective antitussives have been shown to elevate the threshold for coughing by poorly understood by centrally mediated mechanisms at the BS Cough Suppressants Unproductive distressing cough Central cough depressants, e.g. dextromethorphan Productive cough Use expectorants and mucolytics Expectorants act by increasing the volume of secretions in respiratory tract so that they may be more easily expelled by ciliary action and coughing, e.g., guaiphenesin Mucolytics- considered to break up sputum viscosity, e.g. acetylcysteine No cough suppressants Dextromethorphan MC non-opioid antitussive used Has a central action on cough center at the medulla oblongata MOA for the antitussive effect is unclear Uncompetitive antagonist of NMDA receptors Antagonism is believed to decrease the uptake of central catecholamines Structurally related to morphine, has minimal/no analgesic properties, and a minimal sedative activity Antitussive effects may persist for up to 5 hours Contraindicated in patients: - at risk of developing respiratory failure - on monoamine oxidase inhibitor (severe sympathetic reaction) Mucolytics Determination of pulmonary mucus secretions and viscosity Mainly depends on the concentrations of mucoproteins and deoxyribonucleic acid DNA Mucoprotein is the main determinant of viscosity in normal mucus Concentration of DNA in mucus increases due to increased cellular debris Bronchial inflammation may be associated to large amounts of mucous exudate which firmly attaches to the lining of bronchi and bronchioles – increased bronchial wall thickness Produces - “Lumen narrowing“ - Enhancement - Potentiates persistent coughing Mucolytics Mucolytics reduce viscosity and break mucous by splitting the disulfide bonds in mucoproteins mucous from bronchial walls Most frequently prescribed - Acetylcysteine-probably reduces viscosity - Bromhexine hydrochloride Other forms: - Normal saline, directly administered to the airways by effective nebulization therapy-extremely effective mucolytic and expectorant - 3% and 6% (Nebusal) Opioid Antitussives MC- codeine phosphate and hydrocodone Codeine phosphate - Opioid receptor agonist - High potency with oral administration - Short-acting half-life is around 2 to 4 hours - Metabolized by the liver - Excreted in the urine - inactive metabolites - Combo with guaifenesin in oral solution Hydrocodone - Opioid receptor agonist - Combination with homatropine as both an elixir and tablet formulations for cough - Homatropine (parasympatholytic) is designed to enhance any reduction in respiratory secretions and bronchial constriction Other Antitussives Benzonatate - Derivative of local ester anesthetics (esters of PABA) - Cough suppressant believed to act both centrally and peripherally - In the lungs anesthetizes respiratory passages and pleural receptors – reducing cough reflex Dornosa Alfa - Recombinant human DNase - Acts As A Mucolytic - By Hydrolyzing DNA that has accumulated in the sputum marginal decaying neutrophils suppresses cough - Used as nebulizing solution Other Antitussives Leukotriene Receptor Antagonists Montelukast, Zafirlukast - Binds to cysteinyl leukotriene receptors - Decreases mucous secretion and relaxes bronchial muscle - Also inhibits activity of other inflammatory cells Glucocorticoids - Methylprednisolone (solu-Medrol, Medrol) - By reducing inflammation reduces the irritation of C-receptors and thus neural response that leads to coughing Other Antitussives Antihistamines are also used as Antitussives Diphenhydramine Blocks cholinergic activity that induces neural activity that induces cough Also suppresses cough by sedative action Reduces nasal secretions and therefore the post-nasal drip that causes cough (not related lungs) Drugs Used in Treatment of Allergic Rhinitis Inflammation of mucous membranes of the nose characterized by sneezing, nasal itching, rhinorrhea and congestion after mast cell activation by an allergic response Drugs Used in Treatment of Allergic Rhinitis Antihistamines (H1) Diphenhydramine (Benadril®), chlorphenhydramine (Chlortrimethron®), loratadine (Claritin®) amomg others May be use in combination with decongestants. Adrenergic agonist (nasal decongestants) Phenylephrine (Neosynephrine®), oxymetazoline (Afrin®) ay cause rebound nasal congestion after prolonged use Drugs Used in Treatment of Allergic Rhinitis Corticosteroids Nasal Sprays Beclomethasone (Vancense® , Beconase ®) Fluticasone (Flonase ®) Triamcinolone (Nasacort ®) Most common side effects - Nasal bleeding Mast Cell Stabilizer Nasal Spray - Cromolyn Sodium Drugs Used in Treatment for Chronic Obstructive Pulmonary Disease (COPD) Chronic irreversible airflow obstructive disease Lung damage and inflammation of the air sacs (alveoli). Smoking is a high-risk factor Classification based on spirometry - Mild FEV1 < 80% - Stage I - Moderate FEV1 < 50% - Stage II - Severe FEV1 < 30% - Stage III Treatment Inhaled bronchodilators Inhaled glucocorticoids Xanthine derivatives Anti-leukotrienes Oxygen therapy Drugs Used in Treatment for COPD Chronic Bronchitis Continuous inflammation of the bronchi and bronchioles Often occurs as a result of prolonged exposure to bronchial irritants Characterized by - Hypoxemia - Productive cough “Blue Bloaters” - Patient's skin and lips have a blueish tint - Difficulty expelling (CO2) - Hypoxemia - Overweight Drugs Used in Treatment for COPD Emphysema Air spaces enlarge as a result of the destruction of alveolar walls The surface area where gas exchange takes place is reduced Effective respiration is impaired Characterized by: - Increased paCO2 - respiratory acidosis - Difficulty exhaling – pursed lip breathing “Pink Puffer” - Normal weight - Blood oxygen levels are normal - Patients take short, fast breaths - causes temporary redness or pink coloring on their cheeks and faces Drugs Used in Treatment of COPD Tx: B adrenergic agents Anticholinergic agents (ipratropium) Theophylline Corticosteroids (prednisone) Drugs Used in Treatment for COPD Tx Protocol based on Severity Mild - Short acting bronchodilators Moderate - Bronchodilators and glucocorticoids Severe - Bronchodilators and systemic glucocorticoids Long-term control - Antileukotrienes - Cromolyn - Inhaled steroids - Long-acting β2-agonists Quick relief - Intravenous systemic corticosteroids - Short-acting inhaled β2-agonists Bronchodilators Drugs B2 agonists Salbutamol, terbutaline – Short acting – main choice in acute attack of asthma – Inhalation Salmeterol, formoterol Long acting, Prophylaxis Nocturnal asthma Antimuscarinics Ipratropium (Short) Tiotropium (long) Main drugs For COPD Inhalation Inhalation Xanthine derivatives Theophylline Aminophylline (orally) (parenterally) Adenyl cyclase  cAMP Blocks M receprtors Inhibits phosphodi esterase cAMP Anti-inflammatory Drugs (prophylactic) Corticosteroids (Inhibits phospholipase A2) Dexamethasone, Fluticasone, budesonide Inhalation prednisolone Hydrocortisone Orally parenterally Mast stabilizers Cromoglycate (Cromolyn), Nedocromil Inhalation, prophylaxis in children Cysteinyl antagonists (CyLT1 antagoist) Zafirlukast orally Omalizumab (Anti IgE antibody) Injection, SC