Respiratory Pharmacology 1 PDF

Respiratory Pharmacology 1 Prof LJ Egan Outline of Lecture    Asthma and chronic obstructive pulmonary disease Pathophysiology of bronchospasm and airflow limitation Bronchodilator drugs    β-Adrenoceptor agonists Muscarinic receptor antagonists Xanthine oxidase inhibitors What is asthma?  ...

Respiratory Pharmacology 1 Prof LJ Egan Outline of Lecture    Asthma and chronic obstructive pulmonary disease Pathophysiology of bronchospasm and airflow limitation Bronchodilator drugs    β-Adrenoceptor agonists Muscarinic receptor antagonists Xanthine oxidase inhibitors What is asthma?     Common: up to 10% children wheeze at some time Wheezing due to airflow limitation Episodic bouts reflecting reversibility of airflow limitation Triggers      Allergens Exercise Cold air Virus infections Spectrum of severity  Mild occasional symptoms………….life threatening persistent disease Asthma – basic concept of airflow limitation Airflow obsruction Chest hyperinflation Chronic Obstructive Pulmonary Disease       COPD, COAD, chronic bronchitis, emphysema Almost universally linked with cigarette smoking Irreversible damage to airways Airflow limitation Susceptibility to lower respiratory tract infections Loss of lung function Asthma and COPD Which statement about bronchial airflow is incorrect? 1. 2. 3. 4. 5. Vagal efferent nerves secrete acetylcholine to cause bronchoconstriction The second phase of asthmatic attacks is mediated primarily by histamine Low FEV1 is a useful metric of airflow limitation Lungs become hyperinflated In severe cases the small airways can become plugged with mucous Pharmacological control of bronchial smooth muscle tone Inhalation of drugs for airflow limitation  Minimizes systemic exposure to the drugs    Lower side effects Delivers drugs directly to the site of action Note: lipophilic drugs inhaled do not undergo first pass metabolism Disposition of inhaled drugs Methods of inhaled drug delivery   Pressurized canister (metred dose inhaler) Breath-actuated dry powder (metred dose inhaler)   Use of spacer to maximize drug inhalation Nebulized delivery: aerosol of drug via face mask Pros and Cons of inhalation devices -ADRENOCEPTOR AGONISTS -adrenoceptor agonists e.g. salbutamol 2-adrenoceptor Airway smooth muscle cells Airway smooth muscle Relaxation cAMP Adenylyl cyclase Reversibility effect of salbutamol on flow volume loop and FEV1 Predicted Baseline Post-salbutamol Short acting adrenoceptor agonists: selectivity Alpha Beta1 Beta2 Epinephrine + + + Isoproterenol - + + Salbutamol - - + Salbutamol, terbutaline     Selective Beta1 agonists Most effective medication for relief of acute bronchospasm More than one canister per month suggests inadequate asthma control Regularly scheduled use is not generally recommended    May lower effectiveness May increase airway hyperresponsiveness Side effects: related primarily to Beta1 receptor stimulation Salbutamol, terbutaline  Side effects      Tremor Tachycardia Nausea Light-headedness Mostly related to stimulation of Beta1 receptors in CVS  Lack of first-pass metabolism Long-acting -adrenoceptor agonists  Example: salmeterol  Slower onset of action  Not for acute symptoms or exacerbations  Caution: May decrease responsiveness to shortacting Beta2 agonists by down-regulating receptors Which statement is correct? 1. 2. 3. 4. 5. Salbutamol should be given intravenously Inhaled drugs undergo extensive first pass metabolism Selective Beta2 adrenoceptor agonists have no action on Beta1 receptors Salbutamol lowers cAMP levels in bronchial smooth muscle cells Restoration of FEV1 following bronchodilator therapy is characteristic of asthma MUSCARINIC RECEPTOR ANTAGONISTS Anticholinergic       Target vagally-mediated, acetylcholine-dependent parasympathetic airway smooth muscle tone Inhibit muscarinic receptors Example: ipratropium bromide More useful in COPD than asthma Inhaled Very few side effects Additive effect of ipratropium and albuterol (salbutamol) on change in FEV1 Two drugs targeting different mechanisms of action Methylxanthines   Phosphodiesterase inhibitors Examples     Theophylline (oral) Aminophylline (IV) Cause relaxation of bronchial smooth muscle May have other mechanisms of action  Anti-inflammatory effects Methylxanthines  Side effects      Narrow therapeutic index Nausea Gastro-oesophageal reflux Tachycardia Agitation Next Lecture   Airway inflammation Clinical approach to patients