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Pharmacology

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Cancer Chemotherapy

Question
68 out of 100
 

Which of the following is false about mycophenolate mofetil (AIIMS May 2009)



A It’s a pro drug

B It causes nephrotoxicity

C Gastrointestinal toxicity is common

D The drug is used in refractory patients

Ans. B It causes nephrotoxicity

a. Mycophenolate mofetil is a prodrug and is given as prodrug to improve oral bioavailability of drug. Mycophenolic acid is also available. The drug is derived from Penicillium stoloniferum.

b. Immunosuppressive properties of this drug make it very useful for treatment of organ transplant rejection prevention. It is particularly indicated when other drugs are ineffective. It is an important substitute of azathioprine specially in autoimmune hepatitis (CMDT’2010, pp-883).

c. The drug is also used as a ‘steroid sparing’ agent in patients with psoriasis, vasculitides, and certain immune mediated disorders such as IgA nephropathy.

d. The drug acts by blocking immunophilin and does not act upon calcineurin pathway. It also has powerful anti-chemotactic properties and inhibits proliferation of both B & T lymphocytes. It has poor oral bioavailability owing to its irritant nature. Most common side effect therefore are gastrointestinal in nature. Bone marrow suppression can also occur. Increased frequency of infections can occur in line with other immunosuppressive drugs.

e. Mycophenolate has drastically decreased the incidence of acute rejection in solid transplant recipients, the drug is increasingly utilized as a steroid sparing treatment in immune-mediated disorders including immunoglobulin A nephropathy, small vessel vasculitides, and psoriasis

Clinical Uses:

Indications

a. In general, mycophenolate is used for the prevention of organ transplant rejection. Mycophenolate mofetil is indicated for the prevention of organ transplant rejection in adults and renal transplant rejection in children over 2 years; whereas mycophenolate sodium is indicated for the prevention of renal transplant rejection in adults. Mycophenolate sodium has also been used for the prevention of rejection in liver, heart, and/or lung transplants in children >2 years.

b. An immunosuppressant that has drastically decreased the incidence of acute rejection in solid transplant recipients, mycophenolate is increasingly utilized as a steroid sparing treatment in immune-mediated disorders including immunoglobulin A nephropathy, small vessel vasculitides, and psoriasis.

c. Its increasing application in treating lupus nephritis has demonstrated more frequent complete response and less frequent complications compared to cyclophosphamide bolus therapy, a regimen with risk of bone marrow suppression, infertility, and malignancy. Further work addressing maintenance therapy demonstrated mycophenolate superior to cyclophosphamide, again in terms of response and side effects. Walsh et al. even propose that mycophenolate should be considered as a first-line induction therapy for treatment of lupus nephritis in patients without renal dysfunction, suggesting that mycophenolate will be encountered more frequently in medical practice.

Potential future uses

· Mycophenolate mofetil is beginning to be used in the management of auto-immune disorders such as idiopathic thrombocytopenic purpura(ITP), systemic lupus erythematosus (SLE), and pemphigus vulgaris (PV) with success for some patients.

· It is also currently being used as a long-term therapy for maintaining remission of C-ANCA positive (Wegener's) granulomatosis. A combination of mycophenolate and ribavirin has been found to stop infection by and replication of dengue virus in vitro.

(Mnemonics: Most of immunosuppressive drug are nephrotoxic with few exception e.g. Mycophenolate mofetil.

Cancer Chemotherapy Flashcard List

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