Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abacavir (1592U89) is a nucleoside reverse transcriptase inhibitor with potent activity against human immunodeficiency virus type 1 (HIV-1) when used alone or in combination with other antiretroviral agents. The present study was conducted to determine the multiple-dose pharmacokinetics and pharmacodynamics of abacavir in HIV-1-infected subjects following oral administration of daily doses that ranged from 600 to 1,800 mg, with and without zidovudine. Seventy-nine subjects received abacavir monotherapy for 4 weeks (200, 400, or 600 mg every 8 hours [TID] and 300 mg every 12 h [BID]) and thereafter received either zidovudine (200 mg TID or 300 mg BID) or matching placebo with abacavir for 8 additional weeks. Pharmacokinetic parameters were calculated for abacavir after administration of the first dose and at week 4 and for abacavir, zidovudine, and its glucuronide metabolite at week 12. The concentrations of abacavir in cerebrospinal fluid were determined in a subset of subjects. Steady-state plasma abacavir concentrations were achieved by week 4 of monotherapy and persisted to week 12. At steady state, abacavir pharmacokinetic parameters (area under the plasma concentration-time curve for a dosing interval [AUC(tau)] and peak concentration [C(max)]) were generally proportional to dose over the range of a 600- to 1,200-mg total daily dose. Coadministration of zidovudine with abacavir produced a small and inconsistent effect on abacavir pharmacokinetic parameters across the different doses. At the clinical abacavir dose (300 mg BID) zidovudine coadministration had no effect on the abacavir AUC(tau), which is most closely associated with efficacy. Zidovudine pharmacokinetics appeared to be unaffected by abacavir. Statistically significant but weak relationships were found for the change in the log(10) HIV-1 RNA load from the baseline to week 4 versus total daily AUC(tau) and C(tau) (P < 0.05). The incidence of nausea was significantly associated with total daily AUC(tau) and C(max). In conclusion, abacavir has predictable pharmacokinetic characteristics following the administration of multiple doses.
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PMID:Multiple-dose pharmacokinetics and pharmacodynamics of abacavir alone and in combination with zidovudine in human immunodeficiency virus-infected adults. 1089 76

Dr. Leo Hollister's excellent article begins to address the need for better understanding of the effects of cannabis use on health. The last five years in the US have seen an increase in advocacy groups extolling the medicinal utility of cannabis. On 5 November 1996, this culminated in California (proposition 215) joining the list of states permitting the limited use of cannabis for the medicinal treatment of disorders including intractable pain, glaucoma, nausea induced by chemotherapy for cancer or by AZT or Foscavir for the treatment of AIDS, and for spasticity associated with multiple sclerosis (Burstein, 1997; West and Homi, 1996; Grinspoon and Bakalar, 1995; Nahas and Manger, 1995). Of these potential uses for cannabis, the evidence for the treatment of nausea and the stimulation of appetite in cachetic patients appears most promising (for a review see Voth and Schwartz, 1997). Yet not only do doubts remain about the effectiveness of cannabis for the treatment of these conditions, since definitive controlled clinical studies are typically lacking (Voelker, 1997), but there is concern that any therapeutic advantage is more than offset by its harmful effects. Within this context of increased medical sanction for the use of cannabis in specific disease states for which it may have therapeutic potential, evaluating its risks vs. benefits profile is essential to rational prescribing. In addition, evaluating the public health risks associated with reports of increased risks of cannabis use (Robertson et al., Poulton et al., 1997), is of concern to advocates of its widespread legalization, governmental agencies attempting to limit its promulgation, and to planners and providers of health care charged with providing treatment for its consequences.
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PMID:Comment on 'Health aspects of cannabis: revisited' (Hollister). 1128 48

With the identification of HIV-1 as the etiological agent of AIDS, infected people have pursued to varying degrees pharmaceutical treatment to arrest disease progress. This paper evaluates the use of AZT and other antiretroviral agents, as well as access to, and utilization of, medical and social services among intravenous drug users (IDUs) in Miami, Florida. An ongoing prospective study of street-recruited IDUs in Miami-Dade County identified 20 HIV-infected IDUs who had HIV disease (CDC classification IV), and took antiretroviral and other medications after intervention. Participants included 13 active and 7 inactive IDUs. Longitudinal data and in-depth interviews made possible detailed studies of participants during periods when they were taking antiretroviral medications. Those IDUs who are HIV-positive have also received intensive medical and social services. Participants in the study reported nausea, malaise, insomnia, and dysphoria upon initiating AZT therapy. Eleven readily attributed these symptoms to use of antiretroviral medications, primarily AZT. Nevertheless, 9 reported an overall positive impression of the drug's effects; seven despite initial negative reactions to the medication. These results, plus measurement of medication in the blood, indicate that the IDUs studied not only took the antiviral(s), but often were willing to do so in spite of this medication making them feel bad.
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PMID:Medication therapy among intravenous drug users (IDUs) with HIV infection. 1136 86

The nucleoside reverse transcriptase inhibitor 3TC (lamivudine) appears to induce unusually prolonged HIV suppression when used in combination with AZT, according to the results of four randomized clinical trials. The studies showed that 3TC and AZT had similar antiviral effects when used alone. However, investigators observed a substantial, prolonged increase in CD4 counts and a significant decrease in HIV RNA when the drugs were administered simultaneously. These benefits persisted in all study groups for the 24-week study period, and in several for the six-month follow-up period as well. The combination was well-tolerated by nearly 1000 AZT-naive and AZT-experienced subjects enrolled in these trials, with the most common adverse effects being nausea, vomiting and headaches. A possible explanation for the antiviral effect is suggested by the mutation at HIV codon 184 that is frequently observed in virions exposed to 3TC for extended periods of time. In vitro studies have shown that this mutation confers 3TC resistance. It may also counteract other mutations that would normally lead to AZT resistance, therefore enabling virions exposed to both drugs to remain effectively susceptible to AZT.
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PMID:Combination 3TC/AZT therapy shows promise. 1136 92

The Food and Drug Administration (FDA) approved the first protease inhibitor, saquinavir, for combination treatment with approved nucleoside analogs in adults with advanced HIV. However, it denied the use of saquinavir as a monotherapy. Protease inhibitors prevent infected cells from reproducing viral particles. All saquinavir studies have used a dose of 600mg 3 times per day. Another formulation of saquinavir and higher dosages of the present formulation are being tested to increase the bioavailability. In AZT-naive patients, a combination of saquinavir and AZT produces better improvements in CD4 counts and in viral load reduction compared to either of the drugs alone. In patients with extensive prior AZT therapy, saquinavir in combination with ddC provided greater and longer surrogate marker benefits compared to either drug alone. Saquinavir also improved the activity of ddC plus AZT. The most common side effects were diarrhea and nausea. Altogether, only four percent of patients receiving saquinavir had side effects. Toxicity was not increased when saquinavir was added to AZT and ddC. Cross resistance to other PIs has been found, so the use of saquinavir may limit the benefits of future PIs.
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PMID:No tease this time--pros and cons of a long-awaited anti-HIV drug. 1136 18

The Food and Drug Administration's (FDA) Antiviral Drugs Advisory Committee met February 27 to March 1, 1996. At the meeting, the FDA granted full approval of ritonavir for the treatment of advanced AIDS. Ritonavir manufacturer, Abbott Laboratories, characterized the drug as generally well-tolerated, with the most common side effects being nausea, vomiting, and diarrhea. The committee also recommended accelerated approval of Merck's protease inhibitor, indinavir. Results of several clinical studies and protocols are presented. The committee voted against somatropin (Serostim), the recombinant human growth hormone, for treatment of AIDS-related wasting syndrome. They cited too many gaps in the research data. The manufacturer, Serono, is currently negotiating with the FDA on the best way to pursue approval. The committee also unanimously recommended that ddI (Videx) be indicated as a first-line treatment for HIV. The drug appears to be superior to AZT in delaying disease progression and death.
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PMID:Highlights from the FDA antiviral drug advisory committee meetings, February 27-March 1, 1996. 1136 21

Glaxo-Wellcome is developing a nucleoside analogue, 1529U89. The analogue shows potent in vitro activity against HIV, and initial tests of in-vivo efficacy are encouraging. The primary side effects of 1529U89 were nausea, headache, rash, and elevated liver function tests. Since the drug penetrates the central nervous system, participants are asked to allow spinal tips to measure the concentration of the drug in spinal fluid. Trials are being developed for 1529U89's use in AIDS-related dementia, and trials are being designed to test its effectiveness in combination with AZT and 3TC.
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PMID:A surprisingly potent nucleoside analogue. 1136 84

3TC can raise T4 counts and lower HIV levels, and its use may increase the effectiveness of AZT. Studies show that HIV levels decrease by more than 90 percent in people taking the 2 drugs in combination. Side effects are manageable, and few participants drop out of the studies. Another study showed that 3TC also lowered the amount of hepatitis B virus in the blood to a level where it could not be detected. Side effects include headache, nausea, fatigue, diarrhea, neuropathy, and lowered levels of both red and white blood cells. HIV cells can mutate and resist the effects of 3TC within a few weeks of beginning treatment. The manufacturer, Glaxo Wellcome, has a patient assistance program and an expanded access program for the drug.
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PMID:AZT and 3TC. 1136 95

Dosage guidelines and side effects of three currently available protease inhibitors (saquinavir, ritonavir, indinavir) reveal very different patterns. Dosage regimens are as follows: saquinavir, 3 capsules every 8 hours with food; ritonavir, 6 capsules every 12 hours with food; and indinavir, 2 capsules every 8 hours on an empty stomach. Ritonavir has the severest side effects, including nausea, diarrhea, and initially, tingling feeling of the mouth, arms, or legs. The drugs work best when taken with well-studied medicines such as AZT, d4T, and ddI.
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PMID:A patient's guide to protease inhibitors. 1136 88

It is critical to take HIV medications, particularly protease inhibitors, exactly as prescribed to reduce the risks of developing resistance. The Food and Drug Administration (FDA) recently approved a new drug, Combivir, a combination of 3TC (lamivudine) and AZT in one tablet. Combivir works by interfering with the HIV life cycle to prevent it from replicating, and is taken twice a day with or without food. Patients with low body mass, hepatitis, or liver or kidney disease should not take Combivir. Blood counts need to be monitored regularly when taking this drug. Potential side effects include headache, nausea, fatigue, diarrhea, nasal congestion, or flu-like symptoms. A phone number is provided for more information on Combivir.
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PMID:What you need to know about Combivir. 1136 67


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