Pulmonary Disorders-2 PDF

Pulmonary Disorders-2 N112 Pathopharmacology Samuel Merritt University Altered Pulmonary Vasculature Pulmonary hypertension (HTN) † Pulmonary embolism (PE) † Pulmonary HTN Normally, pulmonary circulation is high flow and low pressure Pulmonary HTN: sustained pulmonary artery systolic p...

Pulmonary Disorders-2 N112 Pathopharmacology Samuel Merritt University Altered Pulmonary Vasculature Pulmonary hypertension (HTN) † Pulmonary embolism (PE) † Pulmonary HTN Normally, pulmonary circulation is high flow and low pressure Pulmonary HTN: sustained pulmonary artery systolic pressure > 25 mm Hg Pulmonary HTN: Etiologies Idiopathic: Primary (idiopathic) pulmonary HTN F > M Rapidly progressive Poor prognosis, treatment ineffective Secondary to another disease: Secondary HTN  pulmonary blood flow  resistance to blood flow Pulmonary HTN: Pathogenesis Pulm. artery Walls of  systolic sm. pulm. muscl pressure > 25 vessels e mm Hg thicken Internal layer Formation of of pulm. artery plexiform that wall becomes impedes blood fibrotic flow Pulmonary HTN: Clinical Manif. Exercise intolerance  fatigue Syncope Hemoptysis Chest pain on exertion Increasing dyspnea Cor pulmonale Hoarse voice Pulmonary HTN: Treatment Treat underlying cause Supplemental oxygen Vasodilators Diuretics Prostacyclin In advanced cases lung or heart- lung transplant Left to right shunts (surgery) PE: Etiology Venous stasis/ Sluggish blood flow Virchow ’s triad Thromboembol i formation  PE Intimal injury Hypercoagulabili ty PE: Risk factors Immobility Smoking Trauma Diabetes Pregnancy (comorbidity)  cholesterol Cancer (hyperlipidemia treatments ) Heart failure Genetic factors Estrogen use Factor V Leiden  PE: Pathogenesis Direct trauma Exercis Dislodge Stuck in e d pulmonary thrombu vasculatur Muscle s e action Chang es in PE blood flow PE: Clinical Manif. Depends on size of thrombus Restlessness Apprehension Anxiety Dyspnea Tachycardia Tachypnea Chest pain (on inspiration) Hemoptysis PE: Treatment Impl. Treat underlying problems heparin IV drip Thrombolytics Oxygen Bedrest Umbrella filter Embolectomy Prevention PE: Prevention avoid prolonged bedrest active range of motion (AROM) low-dose heparin or low-molecular weight heparins compression hose w/pneumatic compression Restrictive: Infection & Inflammation Pneumonia † Pulmonary Tuberculosis †  PNA: Classifications Community vs. hospital acquired Viral Bacterial Atypical  PNA: Risk factors Elderly Those with a diminished gag reflex  risk for aspiration Seriously ill Hospitalized patients Hypoxic patients Immune-compromised patients  PNA: Etiologies Aspiration of oropharyngeal secretions composed of normal bacterial flora or gastric contents (25% to 35%) Inhalation of pathogens Contamination from the systemic circulation  PNA: Pathogenesis Pathogen enters lungs & multiply Inflammation process initiated Inflammatory cells invade alveolar septa Alveolar air spaces fill with exudative fluid Fluid filled air spaces consolidate PNA: Clinical Manifestations Severity of disease and patient age cause variation in symptoms Crackles (rales) and bronchial breath sounds over affected lung tissue Fever/chills Cough purulent sputum Dyspnea, SOB PNA: Treatment Implications Cough management Codeine-containing medications Suppressants/expectorants  fluid intake Avoid smoke Use a vaporizer Antibiotic therapy Based on sensitivity of culture Mycobacterium tuberculosis TB 1. Risk Factors Prior infection (90%) Malnourished Immunosuppressed Living in overcrowded condition Incarcerated Immigrant Elderly TB classifications Primary May lie dormant for years/decades Reactivating May occur many years after primary infection Impaired immune system causes reactivation HIV, corticosteroid use, silicosis, and diabetes mellitus have been found to be associated with reactivation TB Pathogenesis Mycobacteria enter lung tissue Ingested/processed by alveolar macrophages Mycobacteria multiply Disseminates through body via blood & lymph Form Ghon tubercle or complex TB: Clinical Manifestations Low-grade fever Chronic cough Later productive with purulent sputum Night sweats Fatigue/malaise Weight loss/anorexia/malnourished Apical crackles Bronchial breath sounds over consolidation TB Diagnosis Sputum culture (1-3 weeks for results) 3 consecutive, morning specimens DNA or RNA amplification techniques Pulmonary function tests Chest x-ray: nodules with infiltrates TB skin test (Mantoux/PPD test) Current or past infection? TB: Treatment Implications Anti-TB medications 9-12 month therapy for active disease Shorter with no active disease Add agents when regimen is failing Nonadherence is a major cause of treatment failure  Antimycobacterial Agents: Drugs for Tuberculosis, Leprosy, and Mycobacterium avium Complex Infection Treatment of Mycobacterial Infections Slow-growing microbes Requires prolonged treatment Drug toxicity and poor patient adherence Promotes emergence of drug-resistant mycobacteria 28 Tuberculosis (TB) Global epidemic Approximately 2 billion infected worldwide Kills approximately 1.3 million people a year New cases in the United States are declining Cases outside United States are increasing  95% occur in developing countries  Increase due to AIDS and emerging multidrug- resistant mycobacteria 29 Tuberculosis (TB) Primary infection Transmitted from person to person Inhalation of infected, aerosolized sputum Coughing, sneezing Initial infection in lung Immunity usually develops within a few weeks 90% with normal immune systems never develop clinical or radiologic evidence of TB 30 Tuberculosis (TB) Diagnosis Indications for testing Definitive diagnosis  Chest x-ray  Sputum culture  Evaluation of drug sensitivity  Treatment regimens  Duration of treatment  Promotion of adherence  Evaluation of treatment 31 Multidrug Resistance in Tuberculosis Multidrug-resistant TB (MDR TB) Resistant to both isoniazid and rifampin Extensively drug-resistant TB (XDR TB) Resistant to:  Isoniazid (INH) and rifampin  All fluoroquinolones  At least one of the injectable second-line drugs 32 Treatment Regimens for Tuberculosis Drug-sensitive tuberculosis Isoniazid- or rifampin-resistant tuberculosis MDR TB and XDR TB Patients with TB and HIV infection Duration of treatment Minimum 6 months for drug-sensitive TB Up to 24 months for MDR TB or HIV/AIDS 33 Diagnosis and Treatment of Latent Tuberculosis 9 million to 14 million people in the United States have latent TB (LTB) 5% to 10% will develop active TB without treatment Targeted TB testing Who should be tested? Testing for latent TB TB skin test (TST) QuantiFERON-TB Gold (QFT-G) blood test 34 Tuberculin Skin Test Intradermal injection of a preparation known as purified protein derivative (PPD), an antigen derived from M. tuberculosis If the individual has an intact immune system and has been exposed to M. tuberculosis in the past, PPD elicits a local immune response Test is read 48 to 72 hours after injection Positive reaction is indicated by a region of induration (hardness) around the injection site 35 Treatment of Latent Tuberculosis Isoniazid alone taken daily for 9 months Isoniazid + rifapentine taken weekly for 3 months Active TB must be ruled out Latent TB is treated with just one or two drugs; if active TB is present, treatment promotes emergence of resistant bacill 36 Isoniazid For over 30 years, the standard treatment for latent TB Effective, relatively safe, and inexpensive Drawbacks  Must be taken for a long time ‒ at least 6 months, preferably 9 months  Poses a risk of liver damage 37 Isoniazid Plus Rifampin The combination of isoniazid and rifapentine ‒ taken just once a week for only 3 months ‒ is just as effective as isoniazid alone taken once a day for 9 months, as shown in the PREVENT TB trial 38 Antituberculosis Drugs First-line drugs Isoniazid, rifampin Rifapentine, rifabutin, pyrazinamide, and ethambutol Second-line drugs Levofloxacin, moxifloxacin, kanamycin, amikacin, capreomycin, streptomycin 39 Isoniazid Primary agent for treatment and prevention of TB Bactericidal Resistance Used to treat active and latent TB Adverse effects Peripheral neuropathy (pyridoxine, vitamin B6) Hepatotoxicity Optic neuritis Anemia 40 Rifampin [Rifadin] Broad-spectrum antibiotic Therapeutic use Tuberculosis Leprosy Meningococcus carriers 41 Rifampin [Rifadin] Adverse effects Hepatotoxic/hepatitis Discoloration of body fluids GI disturbances Others Drug interactions Induces P450; can hasten drug metabolism Oral contraceptives Warfarin Drugs for HIV infection 42 Pyrazinamide Bactericidal to M. tuberculosis Use Tuberculosis Adverse effects Hepatotoxicity Nongouty pararthralgias Hyperuricemia GI disturbances Photosensitivity Others 43 Ethambutol [Myambutol] Active only against mycobacteria; nearly all strains of M. tuberculosis are sensitive Active against tubercle bacilli that are resistant to isoniazid and rifampin Use Initial treatment of TB and treatment of patients who have received therapy previously Always used as part of a multidrug regimen Tuberculosis Adverse effects Optic neuritis Others 44 Second-Line Anti-TB Drugs Fluoroquinolones: Levofloxacin [Levaquin] and moxifloxacin [Avelox] Use in TB: Infection caused by multidrug- resistant organisms Adverse effects Aminoglycosides: Amikacin 45