Cerebellar toxicity is seen with:

Pyrimidine antagonists Pyrimidine analogues have varied applications as antineoplastic, antifungal and antipsoriatic agents. Cytarabine It is phosphorylated in the body to the corresponding nucleotide which inhibits DNA synthesis. The triphosphate of cytarabine is an inhibitor of DNA polymerase and blocks generation of cytidilic acid. However, it is now believed that its incorporation into DNA is more impoant for the expression of cellular toxicity. It also interferes with DNA repair. Cytarabine is cell cycle specific and acts primarily during S phase. Its main use is to induce remission in acute leukaemia in children, also in adults. Other uses are-Hodgkin&;s disease and non-Hodgkin lymphoma. Both 5-FU and cytarabine exe primary toxicity on bone marrow and g.i.t. Genetic deficiency of dihydropyrimidine dehydrogenase (DPD) predisposes to severe 5-FU toxicity. High-dose therapy (2,000-3,000 mg/m2) has been associated with severe and potentially fatal toxicities which differ from those seen with usual low doses. Ocular toxicities may include vision loss, reversible corneal toxicity (keratitis), and hemorrhagic conjunctivitis (<80%).2,3,6 Ocular toxicities have been repoed 1-2 weeks after initiating therapy.Symptoms may include tearing, eye pain, foreign body sensation, photophobia, and blurred vision. Conjunctivitis may occur with rash. Toxicity can be minimized by prophylactic use of ophthalmic coicosteroids.2Use prednisolone 0.12% - 1% or dexamethasone 0.1%, 2 drops in each eye every 4 hours, beginning before the first dose of cytarabine and continuing until 48 hours after the last one. NS may also help relieve symptoms. Neurotoxicity (8-10%) typically occurs 3-8 days after initiating therapy. Cerebellar dysfunction is characterized by difficulty with speech, trouble standing or walking, and tremors. Cerebral dysfunction may be seen concomitantly and is characterized by somnolence, confusion, personality changes, cognitive dysfunction, memory loss, psychosis, or seizures. Seizures are usually self-limited. In most patients, neurologic dysfunction resolves in 5-10 days. There is a high incidence (~60%) of recurrent cerebellar toxicity in patients who have already experienced toxicity. It is not conclusively known if cytarabine therapy should be discontinued if neurological toxicity develops. ESSENTIALS OF MEDICAL PHARMACOLOGY, bccancer.bc.ca K.D.TRIPATHI SIXTH EDITION PAGE NO:824