J.M. is 66-year-old man with a history of three myocardial infarctions within the last decade. Over that time, his ejection fraction fell to less than 40% and he demonstrated symptom-limited exercise tests with a decline in sustainable workload of less than 5 metabolic equivalents (METs). J.M. qualified for a heart transplant and was enrolled in an outpatient precardiac transplant rehabilitation program to help prevent further functional decline. Two months ago, J.M. received a heart transplant. His post-transplant immunosuppressant maintenance medication includes oral cyclosporine, mycophenolate mofetil, and prednisone. In addition, J.M. is taking other drugs to maintain cardiovascular hemodynamics and improve his plasma lipid profile. After surgery, J.M. spent 14 days in the hospital: 4 days in the cardiac intensive care unit and 10 days on the cardiac telemetry floor. On post-transplant day 18, a cardiologist performed a symptom-limited stress test to determine J.M.’s readiness for a 12-week Phase II outpatient cardiac rehabilitation program. On day 21, J.M. began a physical therapist-supervised and monitored aerobic training by walking on the treadmill. Five minutes of low intensity warm-up were followed by 20 minutes at a sustained Borg rating of perceived exertion (RPE) of 11, and then 5 minutes of cool-down exercise. By day 28, J.M. had progressed to sustained aerobic exercise for 35 minutes at an RPE of 13. At 42 days post-transplant, resistance training was incorporated into the program with alternating upper and lower body exercises and 2 minutes of walking between exercises to prevent hypotension. One week ago (post-transplant day 48) at his regularly scheduled cardiac rehabilitation session, J.M. complained of chest pain and fatigue. The physical therapist noted that J.M.’s blood pressure was low and also observed that the patient’s feet were swollen. The therapist called the referring cardiologist’s office to report J.M.’s symptoms and vital signs. Shortly after, a medical diagnosis of rejection-induced coronary artery vasculitis was made. Cyclosporine and mycophenolate mofetil were continued and prednisone was discontinued. J.M. was placed on antithymocyte globulin and bolus intravenous methylprednisolone.
Drugs that modulate the immune system can be broadly divided into two major classifications: immunosuppressants and immune enhancers (Figure 32-1). Drugs that suppress the immune system play an important role in preventing tissue or organ transplant rejection and in treating certain diseases that arise from dysregulation of the immune response. Drugs that augment the immune response or selectively alter the balance of various components of the immune system are also important in the management of certain diseases such as cancer and autoimmune or inflammatory diseases.
Initial classification of immune system modulators is based on whether drugs suppress or enhance immune function. Classification of immunosuppressants is based on mechanism of action with five classes of small molecular weight synthetic drugs and larger molecular weight biologic agents. Immune enhancers presented in this chapter include large molecular weight biologic agents divided into check point inhibitors ...