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Pulmonary Veno-Occlusive Disease Medication

  • Author: Hakim Azfar Ali, MD; Chief Editor: Ryland P Byrd, Jr, MD  more...
 
Updated: Apr 01, 2016
 

Medication Summary

As previously stated, the prostaglandin epoprostenol, a vasodilator, has been reported to have some hemodynamic benefits in patients with pulmonary veno-occlusive disease (PVOD) and has been shown to reverse the increase in pulmonary venule vasomotor tone that occurs in this condition.[51] Nonetheless, the development of acute fulminant pulmonary edema and death have been reported with the infusion of intravenous epoprostenol, even at a very low dose. Therefore, this drug should be used with great caution in patients with suspected PVOD.

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Vasodilators

Class Summary

These agents have vasodilatory effects.

Epoprostenol (Flolan, Veletri)

 

Epoprostenol, an analogue of prostacyclin (PGI2), has potent vasodilatory properties, an immediate onset of action, and a half-life of approximately 5 minutes. In addition to its action as a vasodilator, epoprostenol also contributes to the inhibition of platelet aggregation and plays a role in the inhibition of smooth muscle proliferation.[46]

Long-term infusion of this drug improves the outcome in patients with primary pulmonary hypertension and in selected patients with secondary pulmonary hypertension. A short-term vasodilatory response appears to be unrelated because favorable impact on disease progression occurs with long-term therapy.

The dose is determined during a dose/effect study performed in the catheterization laboratory or the intensive care unit (ICU). The selected dose should produce maximum vasodilation with minimal systemic hypotension.

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Anticoagulants

Class Summary

These agents prevent thromboembolic disorders.

Warfarin (Coumadin)

 

Warfarin interferes with the hepatic synthesis of vitamin K–dependent coagulation factors. It is used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders.

Tailor the dose to maintain an INR in the range of 2-3. The recurrence rate of deep venous thrombosis (DVT) and pulmonary embolism increases dramatically when the INR drops to below 2 and decreases when the INR is kept at 2-3. Serious bleeding risk (including hemorrhagic stroke) is approximately constant when the INR is 2.5-4.5 but rises dramatically when INR is over 5.

Procoagulant vitamin K–dependent proteins are responsible for a transient hypercoagulable state when warfarin is first started and when it is stopped. This phenomenon occasionally causes warfarin-induced necrosis of large areas of skin or of distal appendages. Heparin is always used to protect against this hypercoagulability when warfarin is started; however, when warfarin is stopped, the problem resurfaces, causing an abrupt, temporary rise in the rate of recurrent venous thromboembolism.

At least 186 different foods and drugs have been reported to interact with warfarin. Clinically significant interactions have been verified for a total of 26 common drugs and foods, including 6 antibiotics and 5 cardiac drugs. Every effort should be made to keep the patient adequately anticoagulated at all times because procoagulant factors recover first when warfarin therapy is inadequate.

Patients who have difficulty maintaining adequate anticoagulation while taking warfarin may be asked to limit their intake of foods that contain vitamin K. Foods that have moderate to high amounts of this vitamin include Brussels sprouts, kale, green tea, asparagus, avocado, broccoli, cabbage, cauliflower, collard greens, liver, certain beans, soybean oil, soybeans, mustard greens, peas (black-eyed peas, split peas, chick peas), turnip greens, parsley, green onions, spinach, and lettuce.

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Corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Prednisone

 

Prednisone is an immunosuppressant used for autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. It has some role in the treatment of pulmonary veno-occlusive disease (PVOD), particularly when autoimmune features coexist with it.

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Immunosuppressants

Class Summary

These agents have immunosuppressive properties.

Azathioprine (Imuran, Azasan)

 

Azathioprine is an imidazolyl derivative of 6-mercaptopurine, and many of its biologic effects are similar to those of its parent compound. Both compounds are eliminated rapidly from blood and are oxidized or methylated in erythrocytes and the liver. No azathioprine or mercaptopurine is detectable in urine 8 hours after administration.

Azathioprine antagonizes purine metabolism and inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins. The mechanism through which azathioprine affects autoimmune diseases is unknown. The drug works primarily on T cells. It suppresses hypersensitivities of the cell-mediated type and causes variable alterations in antibody production. Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity test results are suppressed to a greater degree than are antibody responses.

Azathioprine works very slowly; it may require 3-6 months of trial prior to effect. Up to 10% of patients may have an idiosyncratic reaction to the drug, disallowing use. The white blood cell (WBC) count must not be allowed to drop below 3000/µL or the lymphocyte count be allowed to drop below 1000/µL. Azathioprine is available in tablet form for oral administration or in 100mg vials for intravenous injection.

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Contributor Information and Disclosures
Author

Hakim Azfar Ali, MD Consultant in Pulmonary and Critical Care Medicine, Christiana Care Hospital

Hakim Azfar Ali, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Shoaib Alam, MD Staff Clinician, Pulmonary and Vascular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health

Shoaib Alam, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Society of Critical Care Medicine, International Society for Magnetic Resonance in Medicine, European Respiratory Society, Pennsylvania Thoracic Society

Disclosure: Nothing to disclose.

Chief Editor

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP Professor of Genomics and Personalized Medicine Research, Internal Medicine, and Pediatrics, Associate Director, Center for Genomics and Personalized Medicine Research, Director of Research, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, and Sigma Xi

Disclosure: See below for list of all activities None None

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Medium-power photomicrograph (original magnification, X10; hematoxylin and eosin stain) demonstrates a fibrotic interlobular septum containing a vein with an occluded lumen (arrowhead). The occlusion is composed of dense, collagen-rich, fibrous tissue. Image courtesy of Thoracic Imaging Section, Department of Radiologic Pathology, Armed Forces Institute of Pathology.
Pulmonary veno-occlusive disease in a 43-year-old man. An axial computed tomography (CT) scan (lung window level) shows multiple septal lines (arrowhead) and a dilated central pulmonary artery (arrow). Image courtesy of Thoracic Imaging Section, Department of Radiologic Pathology, Armed Forces Institute of Pathology.
Table 1. Distinguishing Pulmonary Edema From PVOD Based on Radiographic, Echocardiographic, and Heart Catheterization Data
Features Pulmonary Edema PVOD
Chest radiograph    
Kerley B lines Present Present
Pleural effusion Usually present May be present
Enlarged cardiac silhouette Present Less prominent
Enlarged pulmonary artery Present Present
Chest CT scan    
Thickened septae Present Present
Pleural effusion Usually present May be present
Enlarged heart Present Less prominent
Enlarged pulmonary artery Present Present
Septal concavity into left ventricle Absent Present
Echocardiogram    
Pulmonary artery systolic pressure Elevated (usually not >80 mm Hg) Elevated (may be >80 mm Hg)
Left atrial enlargement Present Absent
Right atrial enlargement Present Present
Right ventricular hypertrophy Absent Present
Paradoxical septal motion Absent Present
Large pericardial effusion Absent May be present
Right-sided heart catheterization    
Pulmonary vascular resistance Below 3.0 Wood units Above 3.0 Wood units
Pulmonary capillary wedge pressure Above 18 mm Hg Usually below 15 mm Hg



(if catheter is properly wedged)



Mean pulmonary artery pressure Elevated (almost never >50 mm Hg) Elevated (may be >50 mm Hg)
Cardiac output May be normal, low, or high Mostly decreased, may be low normal
Oxyhemoglobin step-up Absent Absent
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