Lehne Chapter 69

Question 1

Immunosuppressants

Answer 1

Inhibit immune response​

Uses ​

Prevention of organ rejection​

Treatment of autoimmune diseases​

Toxicity​

Increased risk of infection​

Increased risk of neoplasms

Question 2

Calcineurin Inhibitors

Answer 2

Principal use: Prevention of organ rejection in transplant recipients​

Cyclosporine, tacrolimus, pimecrolimus: Most effective immunosuppressants available​

Differ in structure, but share the same mechanism​

Inhibition of calcineurin suppresses production of interleukin (IL-2)​

IL-2 needed for T-cell proliferation​

Cyclosporine was developed first and is used more than tacrolimus

Question 3

Cyclosporine [Sandimmune]

Answer 3

Mechanism​

Suppresses the production of IL-2, interferon gamma, and other cytokines​

Therapeutic uses​

Drug of choice for organ rejection (kidney, liver, and heart) of an allogenic transplant​

Some autoimmune diseases​

Pharmacokinetics
Adverse effects​

Nephrotoxicity​

Infection​

Hepatotoxicity​

Lymphoma​

Hypertension​

Tremor​

Hirsutism​

Leukopenia, gingival hyperplasia, gynecomastia, sinusitis, hyperkalemia​

Anaphylactic reactions
Drug and food interactions​

Drugs that can decrease cyclosporine levels​

Drugs that can increase cyclosporine levels​

Nephrotoxic drugs​

Grapefruit juice​

Repaglinide

Question 4

Neoral or Gengraf

Answer 4

Rheumatoid arthritis​

Psoriasis​

​

Question 5

Tacrolimus [Prograf]

Answer 5

An alternative to cyclosporine​

Somewhat more effective, but also more toxic​

Narrow therapeutic index​

Concurrent use with glucocorticoids​

Therapeutic use​

Prophylaxis of organ rejection (liver, kidney, or heart) ​

Mechanism of action​

Adverse effects​

Nephrotoxicity is the major concern​

Neurotoxicity​

Gastrointestinal (GI) effects​

Hypertension​

Hyperkalemia
Adverse effects (Cont.)​

Hyperglycemia​

Hirsutism​

Gum hyperplasia​

Anaphylaxis with IV administration​

Drug and food interactions​

Agents that inhibit CYP3A (isozyme of cytochrome P450)​

Grapefruit juice​

Nonsteroidal antiinflammatory drugs (NSAIDs) should be avoided

Question 6

mTOR Inhibitors

Answer 6

Enzyme known as mammalian target of rapamycin (mTOR) ​

Protein kinase that helps regulate cell growth, proliferation, and survival​

Structurally similar to tacrolimus ​

Somewhat different mechanism​

Does not involve inhibition of calcineurin

Question 7

Sirolimus [Rapamune]

Answer 7

Actions and therapeutic use​

Only for prevention of renal transplant rejection​

Used in conjunction with cyclosporine and glucocorticoids​

Adverse effects​

Increased risk of infection​

Raises levels of cholesterol and triglycerides​

Risk of renal injury​

Severe complications in the liver and lung​

Rash, acne, anemia, thrombocytopenia, joint pain, diarrhea, hypokalemia
Drug and food interactions​

Drugs that inhibit or induce CYP3A4​

High-fat foods​

Grapefruit juice

Question 8

Everolimus [Zortress]

Answer 8

Therapeutic use​

Mechanism of action​

Adverse effects​

Peripheral edema ​

Constipation ​

Hypertension ​

Nausea ​

Anemia ​

Urinary tract infection ​

Hyperlipidemia
Effects in pregnancy and lactation​

Drug and food interactions​

Drugs that inhibit or induce CYP3A4​

High-fat foods​

Grapefruit juice

Question 9

Glucocorticoids

Answer 9

Used to widely suppress immune response​

Suppression of allograft rejection, treatment of asthma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and multiple sclerosis​

Large doses used to prevent rejection​

Increased risk of infection, thinning of skin, bone dissolution with fracture, impaired growth in children, and suppression of hypothalamic-pituitary-adrenal axis

Question 10

Cytotoxic Drugs

Answer 10

Suppress immune response by killing B and T lymphocytes undergoing proliferation​

Nonspecific: Toxic to all proliferating cells​

Adverse effects​

Bone marrow suppression​

Neutropenia​

Thrombocytopenia ​

GI disturbances​

Reduced fertility​

Alopecia

Question 11

Azathioprine [Imuran]

Answer 11

Suppresses cell-mediated and humoral immune responses​

Therapeutic uses​

Adjuvant treatment with transplants​

Autoimmune disorders​

Adverse effects​

Blood dyscrasias​

Nausea and vomiting ​

Mutagenic and teratogenic​

Neoplasms​

Pancreatitis

Question 12

Cyclophosphamide

Answer 12

Anticancer drug

Question 13

Methotrexate [Rheumatrex, Trexall]

Answer 13

Rheumatoid arthritis​

Psoriasis​

Suppression of B and T lymphocytes by interfering with folate metabolism

Question 14

Mitoxantrone [Novantrone]

Answer 14

Anticancer agent​

Reduction of neurologic disability and clinical relapse for multiple sclerosis (MS) patients​

Hazardous drug reserved for patients who are not responsive to safer drugs

Question 15

Mycophenolate mofetil

Answer 15

Approved for prophylaxis of organ rejection​

Acts on B and T lymphocytes to inhibit inosine monophosphate dehydrogenase​

Selective inhibition of B- and T-lymphocyte proliferation

Question 16

Basiliximab

Answer 16

Monoclonal antibodies​

Blocks activation of T cells by IL-2​

Prophylaxis of acute organ rejection after renal transplantation​

Adverse effects: Generally well tolerated, does not increase the risk of opportunistic infections, and no cancers have been observed 1 year after treatment.

Question 17

Lymphocyte immune globulin [Atgam], antithymocyte [equine]

Answer 17

Prepared by extraction from the serum of horses that have been inoculated with human T lymphocytes​

Therapeutic effects: Decrease in the number and activity of thymus-derived lymphocytes​

Uses: Prevent rejection of renal transplants, treating aplastic anemia​

Adverse effects: Hypersensitivity, anaphylaxis