Bone marrow suppression

Both chloramphenicol and thiamphenicol cause reversible bone marrow suppression (9). The irreversible, often fatal, aplastic anemia, however, is only seen for chloramphenicol (9). This rare (1 in 10,000—45,000) chloramphenicol toxicity has been linked to the nitroaromatic function (1,9). Thiamphenicol, which is less toxic than chloramphenicol in regard to aplastic anemia, lacks potency as can be seen in Table 1, and thiamphenicol has never found much usage in the United States. An analogue of thiamphenicol having antimicrobial potencies equivalent to chloramphenicol was sought. Florfenicol (2) was selected for further development from a number of closely related stmctures. 

The usual dose consists of 1000 mg/m2 i.v. It is the most active single agent for treating pancreatic cancer, and it is used as a fust-line treatment for both pancreatic and small cell lung cancers. The dose-limiting toxicity is bone marrow suppression. 

Decitabine is specifically indicated for the treatment of multiple types of myelodysplastic syndromes and chronic myelomonocytic leukemia. As anticipated, use of decitabine is associated with bone marrow suppression including neutropenia and thrombocytopenia which are the most frequently observed serious adverse effects. 

Taxanes (paclitaxel, docetaxel) are derivatives of yew tree bark (Taxus brevifolia). They stabilize microtubules in the polymerized state leading to nonfunctional microtubular bundles in the cell. Inhibition occurs during G2- and M-phases. Taxanes are also radiosensitizers. Unwanted effects include bone marrow suppression and cumulative neurotoxicity. 

The folate antagonists, pyrimethamine and sulfadiazine, inhibit the parasite s DHFR/TS synthase enzyme complex and the DHPS, respectively (Fig. 4) (see antimalarial drugs). To avoid deficiency of folic acid in patients treated with antifolate antagonists, folinic acid supplementation is recommended to reduce bone-marrow suppression. 

When a sulfonamide is administered with an oral anticoagulant, the action of the anticoagulant may be enhanced. The risk of bone marrow suppression may be increased when a sulfonamide is administered with methotrexate When a sulfonamide is administered with a hydantoin, the serum hydantoin level may be increased. 

Hypotension, headache, dizziness, rash, bone marrow suppression, fever, chills, asthenia, nausea, vomiting, diarrhea, stomatitis, fatigue... 

There is an increased risk for bone marrow suppression when levamisole or hydroxyurea are administered witii other antineoplastic dni. Use of levamisole witii phenytoin increases die risk of phenytoin toxicity. Pegaspargase may alter drug response of the anticoagulants. When procarbazine is administered with other central nervous system (CNS) depressants, such as alcohol, antidepressants, antihistamines, opiates, or the sedatives, an additive CNS effect may be seen. Procarbazine may potentiate hypoglycemia when administered witii insulin or oral antidiabetic dru . ... 

Q Risk for Infection related to adverse drug reactions of antineoplastic drugs (eg, bone marrow suppression)... 

MANAGING HONE MARROW SUPPRESSION. Bone marrow suppression is a potentially dangerous adverse reaction resulting in decreased production of blood cells. Bone marrow suppression is manifested by abnormal laboratory test results and clinical evidence of leukopenia, thrombocytopenia, or anemia For example, there is a decrease in the white blood cells or leukocytes (leukopenia), a decrease in the thrombocytes (thrombocytopenia), and a decrease in the red blood cells, resulting in anemia Fhtients with leukopenia have a decreased resistance to infection, and the nurse must monitor them closely for any signs of infection. 

Depending on the nature of the compound, the ddN analogues have been associated with varying toxic side effects such as bone marrow suppression (AZT), pancreatitis (ddl), hypersensitivity reactions (ABC), and neurologic complications consequently to mitochondrial toxicity (ddC), while others, such as 3TC and (-)FTC, have few, if any, side effects. 

Ticlopidine is slightly more beneficial in stroke prevention than aspirin in both men and women.31,32 The usual recommended dosage is 250 mg orally twice daily. Ticlopidine is costly, and side effects include bone marrow suppression, rash, diarrhea, and an increased cholesterol level. Neutropenia is seen in approximately 2% of patients. Thrombotic thrombocytopenic... 

Sulfasalazine is associated with various adverse effects, most of which are thought to be due to the sulfapyridine component. Common adverse effects that may be dose related include headache, dyspepsia, nausea, vomiting, and fatigue.19 Idiosyncratic effects include bone marrow suppression, reduction in sperm counts in males, hepatitis, and pulmonitis. Hypersensitivity reactions may occur in patients allergic to sulfonamide-containing medications. 

Current NKF guidelines define anemia as a hemoglobin (Hgb) level less than 11 g/dL (6.8 mmol/L).31 A number of factors can contribute to the development of anemia, including deficiencies in vitamin B12 or folate, hemolysis, bleeding, or bone marrow suppression. Many of these can be detected by alterations in RBC indices, which should be included in the evaluation for anemia. A complete blood cell count is also helpful in evaluating anemia to determine overall bone marrow function. 

Carbamazepine Manufacturer recommends CBC and platelets (and possibly reticulocyte counts and serum iron) at baseline, and that subsequent monitoring be individualized by the clinician (e.g., CBC, platelet counts, and liver function tests every 2 weeks during the first 2 months of treatment, then every 3 months if normal). Monitor more closely if patient exhibits hematologic or hepatic abnormalities or if the patient is receiving a myelotoxic drug discontinue if platelets are less than 100,000/mm3, if white blood cell (WBC) count is less than 3,000/mm3 or if there is evidence of bone marrow suppression or liver dysfunction. Serum electrolyte levels should be monitored in the elderly or those at risk for hyponatremia. Carbamazepine interferes with some pregnancy tests. 

Hydroxychloroquine may cause retinal toxicity, and patients must have their eyes examined at least annually to detect this abnormality. It is not associated with renal, hepatic, or bone marrow suppression and therefore may be an acceptable treatment option for patients with contraindications to other DMARDs because of their toxicities. 

Streptococcus gentamicin (5 mg/kg per day, dosing based on serum levels) Alternative Therapies Trimethoprim-sulfamethoxazole (TMP-SMX) 10-20 mg/kgTMP IV per day in divided doses every 6-8 hours or meropenem Standard Therapy TMP-SMX Rash, Stevens-Johnson syndrome, bone marrow suppression, nausea/vomiting, hepatotoxicity 14-21... 

Zidovudine (AZT, ZDV) Retrovi r 1 00-mg caps, 300-mg tabs, 1 0 mg/mF intravenous solution, 1 0 mg/mF oral solution 300 mg bid 1 00 mg tid in severe renal impairment or HD None Bone marrow suppression macrocytic anemia or neutropenia gastrointestinal intolerance, headache, insomnia, asthenia Glucuronyl transferase and renal... 

Bone marrow suppression ZDV Onset Few weeks to months Symptoms Fatigue, risk of T bacterial infections due to neutropenia anemia, neutropenia 1. Advanced HIV 2. High dose ZDV 3. Preexisting anemia or neutropenia 4. Concomitant use of bone marrow suppressants Avoid in patients with high risk for bone marrow suppression avoid other suppressing agents monitor CBC with differential at least every 3 months Switch to another NRTI D/C concomitant bone marrow suppressant, if possible for anemia Identify and treat other causes consider erythropoietin treatment or blood transfusion, if indicated for neutropenia Identify and treat other causes consider filgrastim treatment, if indicated... 

Idarubicin inhibits both DNA and RNA polymerase, as well as topoisomerase II. The pharmacokinetics of idarubicin can best be described by a three-compartment model, with an a half-life of 13 minutes, a (3 half-life of 2.4 hours, and a terminal half-life of 16 hours.22 Idarubicin is metabolized to an active metabolite, idarubicinol, which has a half-life of 41 to 69 hours. Idarubicin and idarubicinol are eliminated by the liver and through the bile. Idarubicin has shown clinical activity in the treatment of acute leukemias, chronic myelogenous leukemia, and myelodysplastic syndromes. Idarubicin causes cardiomyopathy at cumulative doses of greater than 150 mg/m2 and produces cumulative cardiotoxic effects with other anthracyclines. Idarubicin is a vesicant and causes red-orange urine, mucositis, mild to moderate nausea and vomiting, and bone marrow suppression. 

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