Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zidovudine (azidothymidine, Retrovir) and ddI (di-deoxy-inosine, Videx) interfere with the multiplication of HIV by incorporation into nascent DNA chains and interruption of the further linking of nucleotides. Zidovudine lowers early mortality in patients with Aids and pneumocystis carinii pneumonia. However, much of the effectiveness of zidovudine is lost later on; the average prolongation of life in treated patients is estimated to be about 1 year. About two thirds of patients with Aids can be treated with zidovudine; in the others, the drug is ineffective or contraindicated. Frequent blood counts are necessary to monitor myelotoxicity, even at relatively low doses of 500 mg/day. In contrast, zidovudine is well tolerated by asymptomatic patients with 200 to 500 CD4 lymphocytes/mm3, in whom it diminishes the incidence of Aids from about 7 to 3% during the first year of treatment, with less than 2% severe anemia or leukopenia. For patients who do not tolerate zidovudine, ddI is an alternative. It is not myelotoxic but can cause neuritis and pancreatitis, especially at doses in excess of 10 mg/kg/day. Although its antiviral effect is excellent both in vitro and in vivo, there is still a lack of firm data on its clinical value, such as the decrease in opportunistic infections and increase in survival.
 ...
PMID:[Antiretroviral therapy in Switzerland 1991]. 192 47

The safety and activity of several antiretroviral agents are being evaluated for treatment of acquired immunodeficiency syndrome (AIDS) in infants and children. Intermittent oral and intravenous regimens and continuous intravenous infusion of the dideoxynucleoside, 3'-azido-3'-deoxythymidine (zidovudine, AZT), have been shown to be beneficial in improving neuro-developmental function and growth velocity in pediatric patients with AIDS. AZT, however, is limited by the associated development of neutropenia and anemia, which frequently necessitates transfusions. Another dideoxynucleoside, 2',3'-dideoxycytidine (ddC), also shows theoretical promise in the treatment of the pediatric AIDS population. This agent is not associated with the hematologic toxicity induced by AZT but does produce a painful sensory peripheral neuropathy. Sequential therapy with AZT and ddC may limit the toxic effects associated with the use of these drugs individually. Dideoxyinosine and soluble recombinant CD4 are two newer antiretroviral agents that are under investigation for the management of AIDS in infants and children. The activity of recombinant CD4 in preventing the transplacental transmission of human immunodeficiency virus is also being evaluated.
 ...
PMID:Treatment of human immunodeficiency virus-infected infants and young children with dideoxynucleosides. 215 4

Ganciclovir is one of only two drugs licensed by the U.S. Food and Drug Administration for the treatment of opportunistic cytomegalovirus (CMV) disease. The combination of ganciclovir and zidovudine has been reported to be poorly tolerated because of dose-limiting hematologic toxicity; thus we retrospectively examined the tolerability of combination therapy with ganciclovir and didanosine in 32 patients with AIDS. These patients were receiving ganciclovir for CMV disease in addition to didanosine in the Videx U.S. Expanded Access Program. During the period of combined therapy, dose-limiting hematologic toxicity (absolute neutrophil count, < 500 cells/microL) developed in only 9.4% of patients and severe anemia (hemoglobin level, < 8.0 g/dL) in only 12.5%. Rates of dose-limiting intolerance to didanosine were similar to those previously reported in the Expanded Access Program. Overall, 15 of 32 patients in the current study tolerated therapeutic doses of didanosine in combination with ganciclovir; in contrast, only 5 of 29 patients tolerated zidovudine (600 mg/d) in combination with ganciclovir in the largest trial of therapy with this combination whose results have been published to date (P = .02, Fisher's exact test). Since recent data suggest that the administration of some form of antiretroviral therapy prolongs survival in patients with CMV retinitis, coadministration of didanosine with ganciclovir should be considered for such patients who do not tolerate other regimens with activity against both retroviruses and CMV.
 ...
PMID:Tolerability of combined ganciclovir and didanosine for the treatment of cytomegalovirus disease associated with AIDS. 838 Oct 32

Dideoxynucleosides currently in use for anti-HIV therapy have been found to be inefficient in passing through the blood-brain barrier to enter and maintain therapeutic drug levels in brain, a very significant reservoir of HIV. The low bioavailability of these drugs combined with the bone marrow toxicity of AZT (3'-azido, 3'-deoxythymidine, Zidovudine), resulting in anemia and leukopenia, pancreatitis with ddI (2',3'-dideoxyinosine, Didanosine) and painful peripheral neuropathy in case of ddC (2',3-dideoxycytosine, Zalcitabine) are the limiting factors in their use. In addition, the emergence of strains of HIV resistant to AZT, the most commonly used drug, further restricts its use. Thus the control of AIDS and its complications, needs special therapeutic approaches to combat the disease. In order to overcome these limitations, AZT and ddI have been synthesized as ester-linked ceramide- and phosphatidylcholine-linked prodrugs possessing therapeutic attributes lacking in the parent compounds. There is greater uptake and longer retention of these prodrugs in NIH/3T3 cells in vitro. Pretreatment with our prodrugs blocked infection of these cells by Moloney murine leukemia virus (M-MuLV) for an extended period, which the parent drugs failed to do. When human CD4+ HeLa cells were continuously exposed to the AZT prodrug, subsequent infection of these cells by HIV was blocked. Similar results were obtained with NIH/3T3 cells exposed to M-MuLV. AE(6)C, a prodrug of AZT linked to ceramide via a cleavable ester bond and a six carbon linker, was less toxic to both mouse and human bone marrow progenitor cells than free AZT. Most significantly, the prodrugs concentration was greater and the retention longer, in well known sanctuaries for HIV, such as the brain, testes and thymus.
 ...
PMID:Improved uptake and retention of lipophilic prodrug to improve treatment of HIV. 1083 73

AIDS patients are able to double their life expectancies after diagnosis. Drug treatment, an integral part in creating this improvement in life expectancy, consists of antiretroviral drugs, drugs that treat and prevent opportunistic diseases, and therapies that treat specific symptoms of AIDS, such as wasting or anemia. Five available drugs for treating HIV are AZT (Retrovir), ddI (Videx), ddC (Hivid), d4T (Zerit), and 3TC (lamivudine). Findings from studies for each drug in such areas as the drug's purpose, dosage level, effectiveness, and side effects are examined.
 ...
PMID:What we know about anti-HIV drugs. 1136 92

Hydroxyurea, an inhibitor of ribonucleotide reductase in cells, is among the strategies being used to reduce HIV levels. Hydroxyurea disrupts DNA synthesis in rapidly dividing cells and reduces the number of deoxyribonucleotides available to make functional viral products. The combination of hydroxyurea and ddI have shown a positive synergistic effect in reducing HIV viral load. Side effects are influenced by dosage, and include hair loss and bone marrow suppression, making it an inappropriate therapy for people with anemia. Results from completed clinical studies have left unanswered questions on the most appropriate dose of hydroxyurea, who should take it, and when therapy should begin.
 ...
PMID:Hydroxyurea. 1136 34

Updates are provided for new anti-HIV drugs currently in development. ABT-378, Tipranavir, and DMP-450 are among the new protease inhibitors discussed. Drugs from other classes that are discussed include emivirine (Coactinon, formerly MKC-442), FTC (emtricitabine, Coviracil), adefovir (Preveon), and pentafuside (T-20). A small study has found that women using Ritonavir (Norvir) may be at a greater risk for anemia (a decrease in red blood cells), caused by excessive menstrual bleeding or hypermenorrhea. New formulations of Ritonavir and ddI (Didanosine, Videx) are described.
 ...
PMID:New anti-HIV drugs in development. 1136 65

The aim of this prospective study was to determine the adverse effects of antiretroviral therapy in HIV-1 infected children and factors associated with adverse effects. The study was performed in a pediatric and perinatal HIV clinic in a tertiary general hospital. Forty-three HIV positive children from the age group of 5 months to 14 years were started on antiretroviral therapy ART. Thirteen patients (30%) had adverse effects related to the ART. Seven patients (16%) had hepatotoxicity, 5 patients (12%) had raised serum amylase without symptomatic pancreatitis, 5 patients (12%) had zidovudine AZT induced anemia, 4 patients (9%) had Nevirapine NVP induced rash, 1 patient (2%) had Didanosine ddI induced pain in abdomen, 1 patient (2%) had Stavudine d4T induced angioedema, and 1 patient (2%) had hepatic steatosis. Five patients (71%) with hepatotoxicity responded to dose adjustment of ART whereas in 2 patients (29%), the elevated liver enzymes resolved on its own. Two patients (40%) with AZT induced anemia required omission of AZT and remaining 3 patients (60%) responded to dosage adjustment. ddI induced abdominal pain, d4T induced angioedema and hepatic steatosis resolved on omitting the respective antiretroviral drug. NVP induced rash and raised serum amylase subsided without any intervention. Hepatotoxicity was seen at higher viral load (Mean = 118608 copies/ml) whereas elevated serum amylase was seen at lower viral load (mean = 37631 copies/ml), which was statistically significant (p < 0.0001). NVP induced rash was seen in early weeks of therapy, serum amylase abnormalities were seen at a mean interval of 0.9 years after starting therapy, hepatotoxicity was seen at a mean interval of 1.7 years and AZT induced anemia was seen at a mean interval of 2.0 years after starting therapy. Adverse effects with antiretroviral drugs in HIV-infected children are quite common. Hepatotoxicity is the commonest adverse effect noted followed by elevated serum amylase and zidovudine induced anemia. Hepatotoxicity is seen at higher viral load as compared to other adverse effects. Most of the adverse effects are reversible on dosage modification or omitting the offending drug.
 ...
PMID:Adverse effects of antiretroviral therapy in HIV-1 infected children. 1612 3