Reverse transcriptase inhibitors zalcitabine

APV, amprenavir ATV, atazanavir CNS, central nervous system CVD, cardiovascular disease D/C, discontinue ddC, zalcitabine ddl, didanosine DEXA, dual-energy x-ray absorptiometry d4T, stavudine EFV, efavirenz HDL, high-density lipoprotein HIV, human immunodeficiency virus HTN, hypertension IDV, indinavir LDL, low-density lipoprotein LPV/r, lopinavir+ ritonavir MRI, magnetic resonance imaging NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor RTV, ritonavir SQV, saquinavir TDF, tenofovir disoproxil fumarate TG, triglyceride TPV/r, tipranivir + ritonavir ZDV, zidovudine. 

Zidovudine (ZDV or AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) and it was the first anti-HIV agent to be introduced. Other NRTIs include stavudine (d4T), lamivudine (3TC), didano-sine (ddl), abacavir (ABC) and zalcitabine (ddC). Recent additions to this class are emtricitabine (FTC) which has a molecular structure similar to 3TC and tenofovir (TDF) a nucleotide reverse transcriptase inhibitor. 

At the present time, there are at least 14 compounds that have been formally approved for the treatment of human immunodeficiency virus (HIV) infections. There are six nucleoside reverse transcriptase inhibitors (NRTIs) that, after their intracellular conversion to the 5 -triphosphate form, are able to interfere as competitive inhibitors of the normal substrates (dNTPs). These are zidovudine (AZT), didanosine (ddl), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir (ABC). There are three nonnucleoside reverse transcriptase inhibitors (NNRTIs) — nevirapine, delavirdine, and efavirenz — that, as such, directly interact with the reverse transcriptase at a nonsubstrate binding, allosteric site. There are five HIV protease inhibitors (Pis saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir) that block the cleavage of precursor to mature HIV proteins, thus impairing the infectivity of the virus particles produced in the presence of these inhibitors. 

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS ANTI HYPERTENSIVES AND HEART FAILURE DRUGS-VASODILATOR ANTI HYPERTENSIVES Risk of peripheral neuropathy when hydralazine is co-administered with didanosine, stavudine or zalcitabine Additive effect both drugs can cause peripheral neuropathy Warn patients to report early features of peripheral neuropathy if this occurs, the nucleoside reverse transcriptase inhibitor should be stopped... 

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS GANCICLOVIRAfALGANCIC LOVIR 1. T adverse effects with tenofovir, zidovudine and possibly didanosine, lamivudine and zalcitabine 2. Possibly 1 efficacy of ganciclovir 1. Uncertain possibly additive toxicity. Lamivudine may compete for active tubular secretion in the kidneys 2. Uncertain L bioavailability 1. Avoid if possible otherwise monitor FBC and renal function weekly. It has been suggested that the dose of zidovudine should be halved from 600 mg to 300 mg daily. Monitor for peripheral neuropathy, particularly with zalcitabine 2. Uncertain clinical significance if in doubt, consider alternative cytomegalovirus prophylaxis... 

FOSCARNET SODIUM NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS - LAMIVUDINE, TENOFOVIR, ZALCITABINE t adverse effects with tenofovir and possibly lamivudine and zalcitabine Uncertain possibly additive toxicity via competition for renal excretion Avoid if possible otherwise monitor FBC and renal function weekly... 

The nucleoside analogue reverse transcriptase inhibitors (NRTIs) include abacavir, didanosine, lamivudine, stavu-dine, tenofovir, zalcitabine, and zidovudine (all rINNs). The following abbreviations have been used and may still be encountered in published papers ... 

Zalcitabine is a nucleoside analogue reverse transcriptase inhibitor. Because of the high incidence of nervous system adverse effects and the availability of less toxic alternatives, zalcitabine is no longer used. 

Zagreb antivenom is a non-proprietary antivenom preparation that can be used as an injected ANTIDOTE to the poison from an adder s bite. However, the systemic allergic and other effects of the venom are rarely serious enough to warrant the use of the antivenom, zalcitabine [ban, inn, usan] (ddC DDC Hivid ) is a synthetic nucleoside analogue, a REVERSE TRANSCRIPTASE INHIBITOR which acts as an ANTIVIRAL AGENT. It is active orally as an ANTI-HIV AGENT. 

Successful treatment of human immunodeficiency virus (HIV-1) infection has been achieved through successful implementation of highly active antiretroviral therapy, frequently referred to as HAART. This involves simultaneous administration of both nucleoside and nonnucleoside reverse transcriptase inhibitors and one or more protease inliibitors. The common nucleoside reverse transcriptase inhibitors are the thymidine analogs didanosine (ddl), lamivudine (3TC), and zalcitabine (ddC) and the non-thymidine analogs abacavir (Ziazen), stavudine (d4T), and zidovudine (AZT). The nonnucleoside reverse transcriptase inhibitors include delavirdine, efavirenz, and nevirapine. The protease inhibitors include indinavir, nelfinavir, ritonavir, and saquinavir. Response to therapy is monitored by quantification of HIV-RNA copies (viral load) and CD-4+ T-lymphocyte count. Successful therapy is indicated when viral load is reduced to <50 copies/mL and CD-4+ count >500 per mL. 

Nudeoside analogue reverse transcriptase inhibitors (NRTls) were the first drugs developed for treatment of HIV infection. They are structural analogues of nucleic adds. When phosphorylafed intraceUularly to their triphosphate forms, fhey are competitive inhibitors of viral reverse franscripfase. Drugs in this class indude abacavir, adefovir, didanosine, lamivudine, sta-vudine, tenofovir, zalcitabine, and zidovudine. 

Subsequent reports described a syndrome of type B lactic acidosis in patients treated with zidovudine and other nucleoside reverse transcriptase inhibitors, including stavudine, lamivudine, zalcitabine, and didanosine which has also been attribute to mitochondrial DNA toxicity [82-93]. There are five types of DNA polymerase in human cells that catalyze the synthesis of new complementary DNA from the original DNA template (HIV encodes a reverse transcriptase DNA polymerase which uses RNA as the template). The active triphosphate metabolites of zidovudine, didanosine, zalcitabine, and stavudine inhibit DNA polymerase gamma in mitochondria, block the elongation of mitochondrial DNA, and deplete mitochondrial DNA [78-80, 87, 92-94, 94a]. The link between NRH effects on mitochondrial DNA and lactic acidosis is not entirely clear but is most likely related to disturbances of oxidative phosphorylation and impaired pyruvate metabolism leading to lactate accumulation. 

Ritonavir exhibits additive to synergistic effects against HIV when used in combination with reverse-transcriptase inhibitors such as zidovudine or zalcitabine. Ritonavir pro-dnces a large increase in the plasma concentration of amio-darone, astemizole, bepridil, bupropion, cisapride, clozapine, encainide, flecainide, meperidine, peroxicam, propafenone, propoxyphene, quinidine, rifabutin, and terfenadine. 

Zalcitabine is a nucleoside reverse transcriptase inhibitor that inhibits replication of DNA in HIV. It is indicated in combination therapy for the treatment of selected patients with advanced HIV infection. 

Zalcitabine (2, 3 dideoxycytidine ddC) is a synthetic cytosine analog reverse-transcriptase inhibitor. It is active against HIV-I, HIV-2, and hepatitis B virus (HBV). The in vitro ICjo of zalcitabine against HIV-1 ranges from 2 nM in monocytes-macrophage cell lines to 0.5 pM in human peripheral blood mononuclear cells. Zalcitabine has considerably more antiretroviral activity in monocytes-macrophage cell lines than other nucleoside analogs, but the potential clinical utility of this observation is uncertain. 

Anti-HIV drugs Nucleoside reverse transcriptase inhibitors Zidovudine Didanosine, lamivudine, stavudine, zalcitabine... 

Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zalcitabine (production discontinued), and Zidovudine. Non-nucleoside Reverse Transcriptase Inhibitors include Delavirdine, Efavirenz, and Nevirapine. 

Combination of 16 ARVs seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfmavir, ritonavir, and saquinavir), seven nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, and zidovudine), and two nonnucleoside reverse transcriptase inhibitors (efavirenz and nevirapine)... 

Rezk, N.L. Tidwell, R.R. Kashuba, A.D.M. Simultaneous determination of six HIV nucleoside analogue reverse transcriptase inhibitors and nevirapine by hquid chromatography with ultraviolet absorbance detection, J.Chromatogr.B, 2003, 791, 137-147. [plasma LOQ 10 ng/mL zalcitabine lamivudine didanosine stavudine zidovudine abacavir hexobarbital is internal standard SPE]... 

Abacavir is a guanidine analogue that inhibits HIV reverse transcriptase. In vitro, its potency is similar to that of zidovudine, protease inhibitors, and dual nucleoside combinations. There is evidence that abacavir is effective in reducing viral load and increasing the CD4 count in HIV-infected patients. Viral resistance is not rapidly selected for, but cross-resistance has been shown to other analogues of cytosine and guanidine (didanosine, lamivudine, and zalcitabine). 

The sites at which anti-HIV drugs may. in principle, act, are dealt with in detail under a main heading (see ANTIVIRAL agents). In summary, currently, of the drugs actually in use, a number are reverse transcriptase (enzyme) inhibitors (RTIs). Examples of nucleoside RTIs include zidovudine, didanosine and zalcitabine. Some non-nucleoside RTIs include foscarnet sodium, nevirapine, carbovir and TIBO analogues (some of these are at trial stage only). 

Zalcitabine, a potent nucleoside analog inhibitor of reverse transcriptase with antiviral properties, is used in patients with advanced human immunodeficiency virus (HIV) infection (CD4 count below 300 cells/mm ) who have demonstrated significant clinical or immunologic deterioration. It is approximately tenfold more potent than zidovudine (AZT) and causes reversible peripheral nephropathy (see Figure 107). 

Antiviral nucleoside inhibitor of HIV reverse transcriptase (NRTI). Used in combination regimens. Tox peripheral neuropathy, pancreatitis. Other NRTIs latnivudine (3TC), stavudine (d4T), zalcitabine (ddC), and the prototype, zidovudine (see below). 

Zidovudine inhibits HIV and is used orally in the treatment of AIDS. The drug is activated by triple phosphorylation and then binds to reverse transcriptase, for which it has ItX) time.s the affinity that it has for cellular DNA polymerases. The drug is incoiporated into the DNA chain and, because it lacks a 3 hydroxyl, another nucleotide cannot fomi a 3 -5 phosphodicster bond and. so the DNA chain is terminated. Some palisUits cannot tolerate the severe side-effecU>. which include anaemia, neutropenia, myalgia, nausea and headaches. Other nucleoside reverse imnscriptu.se inhibitors include didanosine and zalcitabine. Newer, non-nucleoside inhibitors include nevirapine and efevirenz. 

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