Adverse bone marrow toxicity

Hydroxyurea inhibits cell synthesis in the S phase of the DNA cycle. It is used selectively in the treatment of psoriasis, especially in those with liver disease who would be at risk of adverse effects with other agents. However, it is less effective than methotrexate. The typical dose is 1 g/day, with a gradual increase to 2 g/day as needed and as tolerated. Adverse effects include bone marrow toxicity with leukopenia or thrombocytopenia, cutaneous reactions, leg ulcers, and megaloblastic anemia. 

B. Amphotericin B remains the drug of choice in the treatment of disseminated or invasive fungal infections in immunocompromised hosts bone marrow transplant recipients are the most heavily immunocompromised patients encountered in the hospital setting. 5-Flucytosine has no significant activity against Aspergillus spp., and it has bone marrow toxicity as a common adverse effect it should... 

Adverse effects include drowsiness, restlessness, anaemia, leucopenia, thrombocytopenia, bone marrow toxicity and disulfiram like reaction with alcohol. 

Adverse effects in patients include bone marrow toxicity, skin toxicity, renal toxicity, and pulmonary toxicity, as well as vomiting, nausea, fever, anemia, anorexia, stomatitis, hypoglycemia, mucositis, and diarrhea.2 LD50 (i.v., mice) 5-9 mg/kg.1... 

Hematological toxicity is the most commonly reported severe adverse effect of azathioprine, and is marked by predominant leukopenia, thrombocytopenia, and pancytopenia (SED-13, 1120). In a 27-year survey of 739 patients treated with azathioprine 2 mg/kg for inflammatory bowel disease, dosage reduction or withdrawal of the drug because of bone marrow toxicity was necessary in 37 patients (5%) (11). There was moderate or severe leukopenia in 3.8% of patients in three patients pancytopenia resulted in severe sepsis or death. 

Bone marrow toxicity that leads to leukopenia, anemia, and thrombocytopenia has been shown to be induced by methotrexate. A serious long-term adverse effect is hepatotoxicity. Consequently, methotrexate should typically be avoided in patients with liver disease. Risk factors for hepatotoxicity include a history of excessive alcohol consumption, hepatitis, persistent elevated liver function tests, and family history of inheritable liver disease. ... 

Adverse effects of hydroxyurea are bone marrow toxicity with leukopenia or thrombocytopenia, cutaneous reactions, leg ulcers, and megaloblastic anemia. 

Adverse reactions of idoxuridine include such local reactions as pain, pruritus, edema, burning, and hypersensitivity. Systemic administration of idoxuridine by IV injection may be given in an emergency, but this leads to bone marrow toxicities, such as leukopenia, thrombocytopenia, and anemia. It also may induce stomatitis, nausea, vomiting, abnormalities of liver functions, and alopecia. Idoxuridine has a plasma half-life of 30 minutes and is rapidly metabolized in the blood to idoxuracil and uracil. 

Trifluridine 15-30 mg/kg IV Reversible bone marrow toxicity reported atter 3-5 courses of IV treatment. Systemic absorption is negligible after ophthalmic instillation. Ingestion of contents ot one bottle (7.5 mL, 75 mg) unlikely to cause any adverse effects. 

The combined use of flucytosine and amphotericin B is more effective than flucytosine alone in the treatment of cryptococcal meningitis, as demonstrated in an early study, and is still the recommended treatment. However, amphotericin B can cause deterioration in renal function, which reduces flucytosine elimination, and may result in raised flucytosine blood levels. In addition, amphotericin may increase the cellular uptake of flucytosine. Whatever the exact mechanism, combined use increases flucytosine bone marrow toxicity. A study of 194 patients randomised to either a 4 or 6-week course of low-dose amphotericin B (initially 0.3 mg/kg daily) and maximal dose flucytosine (150 mg/kg daily, adjusted for renal function) found that severe adverse effects were common. These included azotaemia (51 patients), blood dyscrasias (52 patients), and hepatitis (13 patients). ... 

Adverse effects can also be classified as chronic, subchronic, snbacnte, or acute. Chronic toxicity refers to cumulative damage after months or years of exposure to a toxicant. Subchronic usually describes an incidence of exposnre that lasts several weeks or months. Subacute indicates an exposnre event that is limited, bnt repeated more than once. Acute toxicity is the term for an immediate and often severe effect that is apparent after a single dose. A single compound may exert different effects at different exposure levels. For example, one acnte effect of benzene is central nervous system depression, while chronic benzene exposnre may canse bone marrow toxicity. 

Adverse side effects of gold treatments include stomatitis, rash, and proteinuria. Complete blood counts and urinalysis should be performed before each or every other injection of gold compounds. Pmritic skin rash and stomatitis are more common adverse effects that may resolve, if therapy is withheld for a few weeks and then restarted cautiously at a lower dose. Oral gold causes less mucocutaneous, bone marrow, and renal toxicity than injectable gold, but more diarrhea and other gastrointestinal reactions appear. 

The adverse reactions seen with penicillamine include pruritus, rash, anorexia, nausea, vomiting, epigastric pain, bone marrow depression, proteinuria, hematuria, increased skin friability, and tinnitus. Penicillamine is capable of causing severe toxic reactions. 

The answer is c. (Hardman, pp 1134-1135.) Hematologic toxicity is by far the most important adverse effect of chloramphenicol The toxicity consists of two types (1) bone marrow depression (common) and (2) aplastic anemia (rare) Chloramphenicol can produce a potentially fatal toxic reaction, the gray baby syndrome, caused by diminished ability of neonates to conjugate chloramphenicol with resultant high serum concentrations. Tetracyclines produce staining of the teeth and phototoxicity... 

IV colchicine should be avoided because it is associated with serious adverse effects (e.g., bone marrow suppression, tissue necrosis from local extravasation, disseminated intravascular coagulation, hepatocellular toxicity, and renal failure). If considered necessary, the recommended initial IV dose is 2 mg (if renal function is normal) diluted in 10 to 20 mL of normal saline administered slowly over 10 to 20 minutes in a secure, free-flowing IV line to avoid extravasation. This may be followed by two additional doses of 1 mg each at 6-hour intervals, with the total dose not exceeding 4 mg. After a full IV course, patients should not receive colchicine by any route for at least 7 days. 

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