Pulmonary disease induced by cardiovascular drugs
- Edward D Chan, MD
Edward D Chan, MD
- Professor of Medicine
- National Jewish Health
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
A number of cardiovascular drugs have the potential to cause respiratory impairment, although diffuse parenchymal lung disease is quite rare (table 1A-B). Several different respiratory adverse effects have been identified: upper airway angioedema or hematoma, bronchoconstriction, cough, interstitial pneumonitis, organizing pneumonia, eosinophilic pneumonia, drug-induced lupus, acute respiratory distress syndrome, diffuse alveolar hemorrhage, pleuritis, pleural effusion, methemoglobinemia, and solitary lung mass.
This topic review will provide an overview of the lung diseases induced by various cardiovascular drugs. The clinical manifestations, diagnosis, and management of pulmonary toxicity due to amiodarone and an approach to the diagnosis of interstitial lung disease are discussed separately. (See "Amiodarone pulmonary toxicity" and "Approach to the adult with interstitial lung disease: Clinical evaluation" and "Approach to the adult with interstitial lung disease: Diagnostic testing".)
Pulmonary toxicity is a well-known adverse effect of the antiarrhythmic agent amiodarone. Several forms of pulmonary disease have been described, including interstitial pneumonitis, organizing pneumonia, acute respiratory distress syndrome (ARDS), diffuse alveolar hemorrhage (DAH), pulmonary nodules, solitary masses, and also (rarely) pleural effusion. The clinical presentation, pathogenesis, diagnosis, and treatment of amiodarone pulmonary toxicity are discussed separately. (See "Amiodarone pulmonary toxicity".)
ANGIOTENSIN CONVERTING ENZYME INHIBITORS
Angiotensin converting enzyme (ACE) inhibitors are associated with cough, angioedema, and, rarely, pneumonitis.
●Cough – All of the ACE inhibitors can induce a dry, persistent, and often nocturnal cough (in 5 to 20 percent of patients). The cough may develop within hours of the first dose or weeks to months later. It is more common in women, non-smokers, and persons of Chinese origin. The cough typically resolves one to four weeks after discontinuation of the ACE inhibitor but in a subgroup of coughers, resolution may take several months . One important caveat is that cough may be a symptom of heart failure, and a thorough history and physical examination are needed to ascertain whether the cough is truly related to the ACE inhibitor therapy. An increased incidence of cough does not appear to occur with the angiotensin II receptor antagonists. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers" and "Evaluation of subacute and chronic cough in adults".)
- Dicpinigaitis PV. Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:169S.
- Benard A, Melloni B, Gosselin B, et al. Perindopril-associated pneumonitis. Eur Respir J 1996; 9:1314.
- Kidney JC, O'Halloran DJ, FitzGerald MX. Captopril and lymphocytic alveolitis. BMJ 1989; 299:981.
- Schatz PL, Mesologites D, Hyun J, et al. Captopril-induced hypersensitivity lung disease. An immune-complex-mediated phenomenon. Chest 1989; 95:685.
- Slesnick TC, Mott AR, Fraser CD Jr, Chang AC. Captopril-induced pulmonary infiltrates with eosinophilia in an infant with congenital heart disease. Pediatr Cardiol 2005; 26:690.
- Watanabe K, Nishimura K, Shiode M, et al. Captopril, an angiotensin-converting enzyme inhibitor, induced pulmonary infiltration with eosinophilia. Intern Med 1996; 35:142.
- Awadh N, Ronco JJ, Bernstein V, et al. Spontaneous pulmonary hemorrhage after thrombolytic therapy for acute myocardial infarction. Chest 1994; 106:1622.
- Masip J, Vecilla F, Páez J. Diffuse pulmonary hemorrhage after fibrinolytic therapy for acute myocardial infarction. Int J Cardiol 1998; 63:95.
- Ayyub M, Barlas S, Iqbal M, Khurshid SM. Diffuse alveolar hemorrhages and hemorrhagic pleural effusion after thrombolytic therapy with streptokinase for acute myocardial infarction. Saudi Med J 2003; 24:217.
- Kilaru PK, Schweiger MJ, Kozman HA, Weil TR. Diffuse alveolar hemorrhage after clopidogrel use. J Invasive Cardiol 2001; 13:535.
- Conley M, Patino G, Romick B, et al. Abciximab-induced alveolar hemorrhage after percutaneous coronary intervention. Can J Cardiol 2008; 24:149.
- Mikkilineni H, Bruhl SR, Colyer WR, Pandya U. A retrospective analysis and case series of glycoprotein IIb/IIIa inhibitor associated diffuse alveolar hemorrhage: two case reports. Cases J 2009; 2:8553.
- Waness A, Aldabbagh T, Harakati M. Diffuse alveolar haemorrhage secondary to warfarin therapy for atrial fibrillation: a case report and literature review. BMJ Case Rep 2009; 2009.
- Uysal E, Çevik E, Solak S, et al. A life-threatening complication of warfarin therapy in ED: diffuse alveolar hemorrhage. Am J Emerg Med 2014; 32:690.e3.
- Erdogan D, Kocaman O, Oflaz H, Goren T. Alveolar hemorrhage associated with warfarin therapy: a case report and literature review. Int J Cardiovasc Imaging 2004; 20:155.
- Hanf W, Duntze J, Hida H, et al. [The implication of a direct antithrombine in the appearance of (serious) postoperative acute respiratory distress]. Ann Fr Anesth Reanim 2009; 28:885.
- Kim Y, Lim J, Lim J, et al. Pulmonary Alveolar Hemorrhage after Clopidogrel Use for ST Elevation Myocardial Infarction. Korean Circ J 2013; 43:497.
- Ikeda M, Tanaka H, Sadamatsu K. Diffuse alveolar hemorrhage as a complication of dual antiplatelet therapy for acute coronary syndrome. Cardiovasc Revasc Med 2011; 12:407.
- Guo J, Xu M, Xi Y. Tirofiban-induced diffuse alveolar hemorrhage: after primary angioplasty. Tex Heart Inst J 2012; 39:99.
- Gill DS, Ng K, Ng KS. Massive pulmonary haemorrhage complicating the treatment of acute coronary syndrome. Heart 2004; 90:e15.
- Kalra S, Bell MR, Rihal CS. Alveolar hemorrhage as a complication of treatment with abciximab. Chest 2001; 120:126.
- Iskandar SB, Kasasbeh ES, Mechleb BK, et al. Alveolar hemorrhage: an underdiagnosed complication of treatment with glycoprotein IIb/IIIa inhibitors. J Interv Cardiol 2006; 19:356.
- Akoğlu E, Seyfeli E, Akoğlu S, et al. Retropharyngeal hematoma as a complication of anticoagulation therapy. Ear Nose Throat J 2008; 87:156.
- Sinert R, Scalea T. Retropharyngeal and bowel hematomas in an anticoagulated patient. Acad Emerg Med 1994; 1:67.
- Chiti-Batelli S, Vaz F, Coman S. Traumatic retropharyngeal haematoma in an anticoagulated patient: Case report and proposal for a clinical protocol. Acta Otolaryngol 2005; 125:443.
- Persoz CF, Cornella F, Kaeser P, Rochat T. Ticlopidine-induced interstitial pulmonary disease: a case report. Chest 2001; 119:1963.
- Nakamura R, Imamura T, Onitsuka H, et al. Interstitial pneumonia induced by ticlopidine. Circ J 2002; 66:773.
- Tamagaki G, Matsushita H, Suzumura T, et al. [A case of drug-induced pneumonia caused by clopidogrel]. Nihon Kokyuki Gakkai Zasshi 2010; 48:404.
- Mizuno Y, Shimizu H, Yamashita M, et al. [A case of clopidogrel-induced eosinophilic pneumonia]. Nihon Kokyuki Gakkai Zasshi 2011; 49:838.
- McGavin CR, Williams IP. The effects of oral propranolol and metoprolol on lung function and exercise performance in chronic airways obstruction. Br J Dis Chest 1978; 72:327.
- Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005; :CD003566.
- Cody RJ Jr, Calabrese LH, Clough JD, et al. Development of antinuclear antibodies during acebutolol therapy. Clin Pharmacol Ther 1979; 25:800.
- Record NB Jr. Acebutolol-induced pleuropulmonary lupus syndrome. Ann Intern Med 1981; 95:326.
- Faller M, Quoix E, Popin E, et al. Migratory pulmonary infiltrates in a patient treated with sotalol. Eur Respir J 1997; 10:2159.
- Camus P, Lombard JN, Perrichon M, et al. Bronchiolitis obliterans organising pneumonia in patients taking acebutolol or amiodarone. Thorax 1989; 44:711.
- Markou N, Antzoulatos N, Haniotou A, et al. A case of drug-induced pneumonitis caused by carvedilol. Respiration 2004; 71:650.
- Webb DB, Whale RJ. Pleuropericardial effusion associated with minoxidil administration. Postgrad Med J 1982; 58:319.
- Siddiqui A, Ansari M, Shakil J, Chemitiganti R. Minoxidil-associated exudative pleural effusion. South Med J 2010; 103:458.
- Chan ED, Chan MM, Chan MM. Pulse oximetry: understanding its basic principles facilitates appreciation of its limitations. Respir Med 2013; 107:789.
- Kato K, Fukuda S, Fujimaki T, et al. Paclitaxel-induced interstitial pneumonia after drug-eluting stent implantation: report of a fatal case. Intern Med 2009; 48:911.
- Fujimaki T, Kato K, Fukuda S, et al. Acute interstitial pneumonitis after implantation of paclitaxel-eluting stents: a report of two fatal cases. Int J Cardiol 2011; 148:e21.
- Zitnik, RJ. Drug-induced lung disease: Antiarrhythmic agents. J Respir Dis 1996; 17:254.
- Totoritis MC, Tan EM, McNally EM, Rubin RL. Association of antibody to histone complex H2A-H2B with symptomatic procainamide-induced lupus. N Engl J Med 1988; 318:1431.
- Merrill JT, Shen C, Gugnani M, et al. High prevalence of antiphospholipid antibodies in patients taking procainamide. J Rheumatol 1997; 24:1083.
- Asherson RA, Zulman J, Hughes GR. Pulmonary thromboembolism associated with procainamide induced lupus syndrome and anticardiolipin antibodies. Ann Rheum Dis 1989; 48:232.
- Aldrich TK, Prezant DJ. Adverse effects of drugs on the respiratory muscles. Clin Chest Med 1990; 11:177.
- Godley PJ, Morton TA, Karboski JA, Tami JA. Procainamide-induced myasthenic crisis. Ther Drug Monit 1990; 12:411.
- Alperin JB, deGroot WJ, Cimo PL. Quinidine-induced thrombocytopenia with pulmonary hemorrhage. Arch Intern Med 1980; 140:266.
- Poukkula A, Pääkkö P. Quinidine-induced reversible pneumonitis. Chest 1994; 106:304.
- McCormack GD, Barth WF. Quinidine induced lupus syndrome. Semin Arthritis Rheum 1985; 15:73.
- LeBlanc KE. A second case of quinidine-induced thrombocytopenia with pulmonary hemorrhage. Arch Intern Med 1980; 140:1250.
- Fernández AB, Karas RH, Alsheikh-Ali AA, Thompson PD. Statins and interstitial lung disease: a systematic review of the literature and of food and drug administration adverse event reports. Chest 2008; 134:824.
- Liebhaber MI, Wright RS, Gelberg HJ, et al. Polymyalgia, hypersensitivity pneumonitis and other reactions in patients receiving HMG-CoA reductase inhibitors: a report of ten cases. Chest 1999; 115:886.
- Liscoët-Loheac N, André N, Couturaud F, et al. [Hypersensitivity pneumonitis in a patient taking pravastatin]. Rev Mal Respir 2001; 18:426.
- Ponnuswamy A, Manikandan R, Sabetpour A, et al. Association between ischaemic heart disease and interstitial lung disease: a case-control study. Respir Med 2009; 103:503.
- Feinberg L, Travis WD, Ferrans V, et al. Pulmonary fibrosis associated with tocainide: report of a case with literature review. Am Rev Respir Dis 1990; 141:505.
- Stein MG, Demarco T, Gamsu G, et al. Computed tomography: pathologic correlation in lung disease due to tocainide. Am Rev Respir Dis 1988; 137:458.
- Van Natta B, Lazarus M, Li C. Irreversible interstitial pneumonitis associated with tocainide therapy. West J Med 1988; 149:91.
- ANGIOTENSIN CONVERTING ENZYME INHIBITORS
- ANGIOTENSIN RECEPTOR BLOCKERS
- ANTICOAGULANT MEDICATIONS
- BETA BLOCKERS
- Asthma and COPD
- Portopulmonary hypertension
- Drug-induced lupus
- Interstitial lung disease
- PACLITAXEL-ELUTING STENTS
- SUMMARY AND RECOMMENDATIONS