All immunosuppressants have similar mechanisms of action in that they selectively suppress certain T-lymphocyte cell lines. By suppressing the T-lymphocyte cell lines, they prevent their involvement in the immune response. This results in a pharmacologically immunocompromised state similar to that in a cancer patient or in a patient with acquired immunodeficiency syndrome (AIDS). Each drug differs in the exact way in which it suppresses certain cell lines involved in an immune response. The major classes of immunosuppressant drugs used in preventing organ rejection include glucocorticoids, calcineurin inhibitors, antimetabolites, and biologics. Corticosteroids inhibit all stages of T-cell activation and are used for induction, maintenance immunosuppression, and acute rejection. Corticosteroids are discussed in depth in Chapter 33 and are not discussed further in this chapter. Calcineurin inhibitors (e.g., cyclosporine, tacrolimus, sirolimus) inhibit the phosphate required for interleukin 2 production. Siromilus does not inhibit calcineurin but instead inhibits mTOR, which ultimately inhibits interleukin 2 communication. Antimetabolites (e.g., azathioprine, mycophenolate) inhibit cell proliferation. Biologics (e.g., muromonab-CD3, basiliximab, daclizumab) inhibit cytotoxic T killer cell function. Table 48-1 gives the mechanisms of action and indications of the available immunosuppressant drugs.

The therapeutic uses of immunosuppressants vary from drug to drug, as noted in Table 48-1. They are primarily indicated for the prevention of organ rejection. Three of the immunosuppressants are indicated for both prevention of rejection and treatment of organ rejection; they include muromonab-CD3, mycophenolate, and tacrolimus. Fingolimod and glatiramer acetate are immunosuppressants that are indicated for reduction of the frequency of relapses (exacerbations) in a type of multiple sclerosis known as relapsing-remitting multiple sclerosis.

Immunosuppressant drugs have many significant adverse effects, which are listed in Table 48-2. By virtue of their actions, immunosuppressants place patients at increased risk of opportunistic infections. Immunosuppressant drugs may also increase the risk of certain types of cancers, especially skin cancers. Other serious adverse effects are limited to the particular drug. For example, cyclosporine and tacrolimus can cause nephrotoxicity, and corticosteroids, cyclosporine, and tacrolimus can cause posttransplant diabetes mellitus. Patients taking immunosuppressant drugs need to avoid live vaccines.

Because transplant patients are on immunosuppressant drugs for their lifetime and are often on combination therapy, they are at increased risk for drug interactions. Immunosuppressants have narrow therapeutic windows, and drug interactions can be significant. Drugs that cause increased levels of immunosuppressant drugs can cause toxicity, whereas drugs that reduce immunosuppressant drug levels may lead to organ rejection. The major drug interactions with immunosuppressant drugs are listed in Table 48-3. Many of the immunosuppressant drugs are metabolized by the cytochrome P-450 enzyme system, thus drug interactions are common and can be significant. Grapefruit can inhibit metabolizing enzymes and thus can increase the activity of cyclosporine, tacrolimus, and sirolimus. Grapefruit juice may increase the bioavailability of cyclosporine by 20% to 200% and should be avoided. Foods that are high in potassium, such as bananas and tomatoes, can increase cyclosporine nephrotoxicity. Meals that have high fat content can increase sirolimus levels.

TABLE 48-3

IMMUNOSUPPRESSANT DRUGS: SELECTED DRUG INTERACTIONS

DRUG	MECHANISM	RESULT
Cyclosporine
clarithromycin fluconazole amiodarone Estrogens verapamil allopurinol Protease inhibitors HMG-CoA reductase inhibitors	Inhibit metabolism of cyclosporine	Increased levels of cyclosporine and toxicity
phenytoin phenobarbital carbamazepine rifampin St. John’s wort	Induce metabolism of cyclosporine	Decreased levels of cyclosporine and reduced effect
NSAIDs	Inhibit synthesis of renal prostaglandin	Increased nephrotoxic effects of cyclosporine; renal failure
Grapefruit juice	Increases absorption of cyclosporine	Cyclosporine toxicity
Sirolimus
cyclosporine	Unknown	Increased concentration of sirolimus
fluconazole ketoconazole clarithromycin erythromycin Protease inhibitors verapamil Grapefruit juice	Inhibit metabolism of sirolimus	Increased concentration and effect of sirolimus
rifampin phenytoin phenobarbital carbamazepine St. John’s wort	Induce metabolism of sirolimus	Decreased concentration and effect of sirolimus
Tacrolimus
amphotericin gentamicin tobramycin	Increase nephrotoxicity of tacrolimus	Renal failure
clarithromycin fluconazole ketoconazole voriconazole Protease inhibitors verapamil diltiazem Grapefruit juice	Inhibit metabolism of tacrolimus	Increased effect of tacrolimus
rifampin phenytoin phenobarbital carbamazepine St. John’s wort Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related Related posts: Pituitary Drugs Cholinergic-Blocking Drugs Biologic Response–Modifying and Antirheumatic Drugs Analgesic Drugs Stay updated, free articles. Join our Telegram channel Join Tags: Pharmacology and the Nursing Process May 9, 2017 | Posted by admin in NURSING | Comments Off on Immunosuppressant Drugs Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access