Pulmonary Pharmacology
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1 Pulmonary Pharmacology Jeanne E. Houtchens MS, ARNP April 2, 2016 Pulmonary Pharmacology COPD Pulmonary Fibrosis Pulmonary Hypertension 1
2 Pulmonary Pharmocology COPD Chronic obstruceve pulmonary disease (COPD) is a common condieon with a high and conenually increasing mortality, affeceng men and women equally. It is esemated that approximately 7 percent of all individuals have COPD, including approximately 10 percent of individuals 65 years of age or older 2
3 COPD Diagnosis Daily symptoms Tobacco abuse Enviromental exposures OccupaEonal exposures GeneEc predisposeon Imaging Spirometry FEV1/ FVC<70 Cough, wheeze, SOB, frequent respiratory infeceons Cigare[e, cigars, pipes, vapes, hooka, e cigare[es Second hand smoke, air pollueon Fumes, metals, chemicals Alpha one AnEtrypsin HyperinflaEon/emphysema ObstrucEon on spirometry 3
4 Short AcEng Beta 2 Agonists SABA Indicated for GOLD Class A/Low Risk FVC/FEV1 < 70 FEV1 = > 50% SABA Pharmcology SEmulaEon of beta 2 receptors in the airways decreases unbound intracellular calcium producing: smooth muscle relaxaeon mast cell membrane stabilzaeon skeletal muscle semulaeon 4
5 SABA SelecEvity Albuterol and Levalbuterol Beta 1 receptor semulaeon raeo 1/4 Beta 2 receptor semulaeon raeo 4/4 Pharmacological Response to Beta Agonists Airways: B2 smooth muscle relaxaeon, increased ciliary beat, increased serous secreeon and inhibieons of mast cell degranulaeon. Heart : B1 Inotropic and Chronotropic B2 Chronotrophic semuaeon Skeletal: B2 increased neuromuscular transmission ( tremor and strength of contraceon) 5
6 Pharmacological Response to Beta Agonists Vasculature: B2 vasodilaeon decreased microvascular leak Metabolic: B1 glycogenolysis B2 hypokalemia, increased lactate gluconeogenisis SABA Albuterol is a 50:50 racemic mixture of (R)- albuterol (levalbuterol), the pharmacologically aceve enaneomer, and (S)- albuterol, which has li[le or no bronchodilaeng acevity.[3] (R)- albuterol demonstrates 100- fold more potent binding to beta- 2 receptors than (S)- albuterol. 6
7 SABA Albuterol: Ventolin, ProvenEl, Pro air onset of aceon immediate- 10minutes duraeon/proteceon 2-4 hrs Levalbuterol: Xopenex onset of aceon immediate- 10minutes duraeon/proteceon 2-4 hrs Both medicaeons available for nebilizaeon 7
8 Long AcEng Bronchodilators LABA Indicated for GOLD Class B C D Same selecevity, mechanism of aceon. Side effect profiles includes: BLACK BOX WARNING FOR INCREASE IN ASTHMA RELATED DEATHS Long AcEng Bronchodilators LABA ONSET OF ACTION 2-10 MINUTES DuraEon of aceon/ 12 hrs 8
9 Long AcEng Bronchodilators LABA Salmeterol (Serevent) Formoterol (Foradil) (Performist for nebulizaeon) Aformoterol/nebulizaEon ( Brovava) Indacaterol (Arcapta) Olodatetol ( striverdi) Vilanterol ( combinaeon with fluecasone) Inhaled CorEcosteroids Used in conjunceon with LABA for COPD NOT INDICATED FOR MONO THERAPY USED FOR GOLD CLASS C FVC/FEV1 <0.70 FEV1>50% 9
10 ICS GlucocorEcosteroid: Highly lipophillic, readily cross the cell membrane to combine with glucocorecoid receptor ICS Mechanism of AcEon 1. increasing the number Beta- AR and improves receptor responsiveness to B2 adrenergic semulaeon 2. reduces mucous produceon and hypersecreeon 3. Reduces bronchial hyper responsiveness. 4. PrevenEon and reversing airway remolding 10
11 ICS Beneficial effects 1. Decreased eosinophils 2. decreased mast cells 3. Decreased t lymphocyte produceon 4. Reduced endothelial leak 5. Up regulate B2 receptor produceon 6. Reduce airway epithelial subbasement membrane thickening Chronic bronchius/ emphysema ICS Eme Course COPD symptoms: 1-2 weeks of therapy, Max improvement in 4-8 weeks Improvement in FEV 1 and PEF may require 3 to 6 weeks for maximum improvement 11
12 ICS Side Effect 1. Growth retardaeon 2. Osteoporosis 3. Cataract and glucoma formaeon 4. Adrenal axis suppresion 5. Impaired wound healing 6. Hyperglycemia/hypokalemia/HTN 7. Psychiatric disturbances 8. Oral candidiasis and dysphonia ICS/LABA CombinaEon Symbicort 80/4.5mcg 160/4.5 mcg 2 puffs 2 x day Advair 100/50 250/50 500/50 mcg 2 puffs 2 xday Dulera 100/5 200/5 mcg 2 puffs 2 x day 12
13 AnECholinergics Phosphodiasterase Inhibitors Daliresp/Roflumilast Indicated for treatment to reduce COPD exacerbauon in pauents with Severe COPD associated with Chronic BronchiUs and ExacerbaUons GOLD Class C and D 13
14 PDE 4 Inhibitor Mechanism of AcEon: Unknown Inhibits pde4 ( camp) in the lungs /increases accumulaeon of intracellular c AMP. Reduces sputum neutophils 31% Reduces sputum eosinophils 42% PDE4 Inhibitors 17% reduceon in exacerbaeon with use of Daliresp 500 mg daily 14
15 PDE4 Inhibitors Side Effects Weight Loss Diarrhea Nausea LFT ElevaEon New Products Seebri Neo Inhaler Long AcEng AnECholinergic: Glycopyrrolate, long aceng muscarinic Mechanism of AcEon: Affinity to M1- M5 receptors 15
16 New Products UUbron Neonhaler LABA+ anucholinergic Combo Indacaterol ( LABA) + Glycopyrroloate COPD Non Pharmacologic Treatment Oxygen Therapy Lung ReducUon Surgery Pulmonary Rehab/ Physical AcUvity Smoking cessauon VaccinaUons 16
17 PULMONARY FIBROSIS 17
18 18
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