Med Phys Pharm 552 L13 Respiratory Pharm 2025 PDF

Lecture #13: Respiratory Pharmacology Julia M. Hum, Ph.D. Monday/Wednesday/Friday: 2:00-2:50pm Office Hours: Monday/Wednesday/Friday 11:00am-12:00pm [email protected]  L12: Learning Objectives 1. Identify the key pathoph...

Lecture #13: Respiratory Pharmacology Julia M. Hum, Ph.D. Monday/Wednesday/Friday: 2:00-2:50pm Office Hours: Monday/Wednesday/Friday 11:00am-12:00pm [email protected]  L12: Learning Objectives 1. Identify the key pathophysiological features of asthma 2. Apply the asthma guidelines for treatment 3. Define adrenergic and cholinergic pharmacology 4. Know the adrenergic agonists that impact pulmonary function and relate the pathophysiology of asthma to their pharmacological actions 5. Describe the cholinergic antagonists that impact pulmonary function and relate the pathophysiology of COPD/asthma to their pharmacological actions 6. Recognize the mechanisms by which inhaled corticosteroids are useful in the treatment of asthma/COPD 7. Compare and contrast the clinical presentations and treatment of asthma and COPD 8. Interpret a spirometry reading and identify the changes asthma and COPD would cause from normal readings Unless otherwise noted, figures in today’s lecture are from: Lippincott Illustrated Reviews: Pharmacology 6e Yellepeddi (Ch. 29)  Common Forms of Respiratory Compromise Bronchoconstriction – adrenergic agonists, cholinergic antagonists Inflammation - corticosteroids Loss of lung elasticity – respiratory therapy, supplemental oxygen  Pathophysiology of Asthma ht tps ://www.am erican nurs etoday.com/wp-conten t/u ploads/ 2015/07/ Ho w-br onchosp as m-cons tricts-th e-airway.png http: //sphweb. bum c.bu.e du/otlt/M PH -M odule s/PH/Re spiratoryHe al th /Asthma %20F low%20Cha rt. png LO1  Clinical Identification of Asthma LO8  Lung Volumes & Capacities TLC= Total Lung Capacity (TV+IRV+ERV+RV) ERV= Expiratory Reserve Volume FRC= Functional Residual Capacity (ERV+RV) IC= Inspiratory Capacity (TV+IRV) IRV= Inspiratory Reserve Capacity RV= Residual Volume TV= Tidal Volume VC= Vital Capacity (TV+IRV+ERV) LO8  Guidelines for Treatment of Asthma Classification Episodes Spirometry Quick Relief Long-term Control Intermittent Mild Persistent Moderate Persistent Severe Persistent Lippincott’s Pharmacology: Table 29.3 LO2  Inhaled Corticosteroids - ICS Long-term control in patients with any degree of persistent asthma MOA: Inhibit COX-2 action and prostaglandin biosynthesis = activate endogenous anti-inflammatory pathways Few systemic side effects of ICS  Inhaled Corticosteroids - ICS MOA: Inhibit COX-2 action and prostaglandin biosynthesis = activate endogenous anti-inflammatory pathways Actions on lung: do not directly affect the airway smooth muscle ICS directly targets underlying airway inflammation by decreasing the inflammatory cascade After months of regular use, ICS reduce the hyperresponsiveness of the airway smooth muscle  Inhaled Corticosteroids Bec-lo-meth-a-sone (Qvar) Bu-des-o-nide (Pulmicort) Flu-tic-a-sone (Flovent) Ann Intern Med. 2003;139:359-370.  Adrenergic Pharmacology Study of agents that act on pathways mediated by the endogenous catecholamines Norepinephrine, epinephrine, and dopamine The sympathetic nervous system is the major source of catecholamine production and release Therapies for many major diseases Hypertension, shock, asthma, and angina LO4  Direct-Acting Adrenergic Agonists Direct-acting agonists bind to adrenergic receptors on effector organs without interacting with the presynaptic neuron These agents are widely used clinically Epinephrine Norepinephrine Dopamine Dobutamine Isoproterenol Fenoldopam Oxymetazoline Phenylephrine Clonidine Albuterol and Terbutaline Salmeterol and Formoterol Mirabegron LO4  Direct-Acting Adrenergic Agonists Endogenous Catecholamines: Epinephrine Epinephrine is an agonist at both α- and β-adrenoceptors Cardiovascular Actions: The major actions of epinephrine are on the cardiovascular system strengthens the contractility (β1) increases its rate of contraction (β1) Overall = cardiac output increases Respiratory Actions: causes powerful bronchodilation by acting directly on bronchial smooth muscle (β2) LO4  Direct-Acting Adrenergic Agonists Endogenous Catecholamines: Epinephrine Therapeutic Uses: Bronchospasm: Epinephrine is the primary drug used in the emergency treatment of respiratory conditions when bronchoconstriction has resulted in diminished respiratory function Acute asthma and anaphylactic shock Epinephrine can be life saving After SQ administration respiratory function greatly improves in minutes LO4  Direct-Acting Adrenergic Agonists Al-bu-ter-ol Short-acting β2 agonists used primarily as bronchodilators “SABA” administered by a metered-dose inhaler Albuterol is the short-acting β2 agonist (SABA) of choice for the management of acute asthma symptoms LO4  Direct-Acting Adrenergic Agonists Albuterol Short-acting β2 agonists used primarily as bronchodilators When these drugs are administered orally may cause tachycardia or arrhythmia (due to β1 receptor activation) Most common side effects of these agents is tremor Other side effects include restlessness, apprehension, and anxiety LO4  Direct-Acting Adrenergic Agonists Sal-met-er-ol and For-mot-er-ol Long-acting β agonists (LABA) that are β2 selective A single dose provides sustained bronchodilation over 12 hours less than 3 hours for albuterol Salmeterol has a delayed onset of action Formoterol has no delayed onset Salmeterol and formoterol are the agents of choice for treating nocturnal asthma LO4  Combination Therapy: Budesonide/Formoterol (Symbicort) ICS + LABA ICS works by reducing and preventing respiratory tract inflammation LABA decreases resistance in the respiratory airway and increases ht tps ://i.ytimg.com/ vi/ drC WcLn WG P8/hqd efault.jpg airflow to the lungs LO4,6  Clinical Differences of Asthma and COPD Asthma COPD Onset Symptom Pattern Lung Function History Time course Chest X-ray LO7 Modified from Global Initiative for Asthma, 2018 Clinical Differences of Asthma and COPD  Clinical Identification of COPD LO8  Cholinergic Pharmacology Cholinergic antagonist - agents that bind to muscarinic or nicotinic receptors and prevent the effects of acetylcholine and other cholinergic agonists Clinically useful - selective blockers of muscarinic receptors Effects: parasympathetic innervation interruption, therefor promoting the sympathetic stimulation Muscarinic antagonists LO5  Long-Acting Muscarinic Antagonists (LAMA) I-pra-tro-pium and ti-o-tro-pium are derivatives of atropine Approved bronchodilators for treatment of bronchospasm associated with COPD Ipratropium is also used in the acute management of bronchospasm in asthma Tiotropium is administered once daily, a major advantage over ipratropium, which requires dosing up to four times daily. LO5  Pharmacological Management of COPD Patient Group First Line A B C D Lippincott’s Pharmacology: Table 29.5 LO7