Immunosuppressant drugs adverse effects

Orally administered glucocorticoids have substantial adverse effects, including immunosuppression, suppression of the synthesis of endogenous glucocorticoids themselves (that can be a problem when glucocorticoid therapy is stopped), resorption of bone, and retention of water. Nonetheless, they are important drugs for control of inflammation. They also augment resistance to stress. 

The adverse effects of atazanavir include fever, jaundice/scleral icterus, myalgia and diarrhea. Its coadministration is not recommended with the drugs that induce cytochrome P-450 isoenzyme CYP3A4. Ritonavir increases plasma concentrations of atazanavir. It is an inhibitor of isoenzymes CYP3A4, CYP2C8 and UGT1A1. The coadministration of atazanavir with calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressants and phosphodiesterase 5 inhibitors should be carefully monitored. 

This chapter addresses immunosuppressive drugs, or immunosuppressants, that are currently available to prevent the rejection of transplants or to treat specific diseases caused by an autoimmune response. Clearly, these drugs must be used very cautiously because too much suppression of the immune system will increase a patient s susceptibility to infection from foreign pathogens. Likewise, these drugs are rather toxic and often cause a number of adverse effects to the kidneys, lungs, musculoskeletal system, and other tissues. Nonetheless, immunosuppressive agents are often life-... 

Adverse effects The major dose-limiting toxicity is bone marrow depression, and the drug is immunosuppressive. Other adverse reactions include nausea, vomiting, diarrhea, stomatitis, and alopecia. Extravasation during injection produces serious problems. Dactinomycin sensitizes to radiation inflammation at sites of prior radiation therapy may occur. 

Adverse effects Its adverse effects include severe nausea and vomiting (centrally mediated). [Note These effects can be diminished by pretreatment with cannabinoids (see p. 243) or pheno-thiazine (see p. 242).] Severe bone marrow depression limits extensive use. Latent viral infections (for example, Herpes zoster] may appear because of immunosuppression. Extravasation is a serious problem. If it occurs, the area should be infiltrated with isotonic sodium thiosulfite to inactivate the drug. 

Adverse effects Long-term use of infliximab is associated with development of anti-infliximab antibodies unless the drug is used in combination with methotrexate. Infusion reactions such as fever, chill, pruritus, or urticaria have occurred. Infections leading to pneumonia, cellulitis, and other conditions have also been reported. Whether treatment with infliximab predisposes to lymphoma, a condition that occurs with immunosuppressive or immune-altering drugs, remains to be established. 

Azathioprine [a zah THIO preen] has been the cornerstone of immunosuppressive therapy over the last several decades. It has a nitroimidazoloyl side chain attached to the sulfur of 6-mercap-topurine, which is removed by non-enzymatic reduction in the body by glutathione to yield 6-mercaptopurine (6-MP). The latter is then converted to the corresponding nucleotide, thioinosinic acid (TIMP), by the salvage pathway enzyme, hypoxanthine-gua-nine phosphoribosyl transferase. The immunosuppressant effects of azathioprine are due to this fraudulent nucleotide. (See pp. 380-381 for a discussion of 6-MP s mechanism of action, resistance, pharmacokinetics, and adverse effects.) Because of their rapid proliferation in the immune response, and their dependence on de novo synthesis of purines required for cell division, lymphocytes are predominantly affected by the cytotoxic effects of azathioprine. The drug has little effect on suppressing a secondary immune response. 

MYCOPHENOLATE ANTIVIRALS -ACICLOVIR, GANCICLOVIR t plasma concentrations of both drugs. Toxic effects of both drugs likely Attributed to competition for renal tubular excretion Monitor blood counts - For signs and symptoms of immunosuppression, see Oinical Features of Some Adverse Drug Interactions, Immunosuppression and blood dyscrasias... 

Very few adverse effects, generally of minor importance, have been reported (4). In immunosuppressed patients abnormal liver function, encephalopathy, and myelosuppression have been observed however, it is unclear at present whether these adverse effects are related to the drug itself or to the underlying disorder (5-7). 

Adverse effects usually occur during the first two months of treatment, do not correlate with the daily dose, and result in treatment withdrawal in 14—18% of patients, mainly because of bone marrow suppression, gastrointestinal symptoms, hypersensitivity reactions, and infections (1-3). Immediate or long-term adverse effects are of particular concern outside the field of immunosuppression where other treatment options are frequently available, but in any field of use the adverse effects of these drugs weigh heavily. 

Philip AT, Gerson B. Toxicology and adverse effects of drugs used for immunosuppression in organ transplantation. Clin Lab Med 1998 18(4) 755-65. 

Busulfan is a potent cytotoxic drug. Early in development of the compound, in vivo experiments indicated that busulfan caused severe depression in the bone marrow. The most prevalent acute toxic effects associated with busulfan in animals are severe pancytopenia from bone marrow failure. Associated in vivo experiments show bone marrow aplasia, stromal cell damage, immunosuppression (impaired T-lymph-ocyte function), and pronounced adverse effects on reproductive glands, germ cells, and fertility in animals (lowest effective dose tested was 2 mg kg... 

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