Cytosine Lamivudine

Lamivudine (Epivir-HBV) is an oral synthetic cytosine nucleoside analogue having antiviral effects against HIV and hepatitis B virus. In patients with chronic hepatitis B, lamivudine is effective in suppressing hepatitis B viral replication, normalizing... 

Lamivudine (3TC, Epivir) is a cytosine nucleoside analogue with activity against HIV-1, HIV-2, and hepatitis B virus. It is approved as part of a multidrug regimen for the therapy of HIV infection in adults and children and has been used for HIV postexposure prophylaxis. Combination products contain lamivudine with either zidovudine (Combivir) or zidovudine and abacavir (Trizivir). The use of low-dose lamivudine in the treatment of chronic hepatitis B is described in Chapter 50. 

C) Lamivudine is a cytosine nucleoside analogue efavirenz is an adenosine nucleotide analogue. 

L D. Lamivudine, a cytosine analogue, is a nucleoside reverse transcriptase inhibitor that acts as a competitive inhibitor of reverse transcriptase. Efavirenz is a nonnucleoside reverse transcriptase inhibitor it acts by binding to a site adjacent to the enzyme s active site. Neither drug exhibits significant activity against HIV protease. 

Lamivudine This is a cytosine(cytidine)-nucleoside analogue. Its effect is based on the inhibition of reverse transcriptase in HIV and of DNA polymerase in HBV The daily oral dosage is 1 (-3) x 100 mg/day. After discontinuation of lamivudine, the previous findings recur here, too, efficacy only exists with continued therapy. A combination with famciclovir seems promising. Its clinical application is mainly in combination with IFN. Long-term monotherapy over several years may be necessary. (48,54) (s. p. 704)... 

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). 

FIGURE 50-3 Intracellular activation of nucleoside analog reverse transcriptase inhibitors. Drugs and phosphory-lated anabolites are abbreviated the enzymes responsible for each conversion are spelled out. The active antiretroviral anabolite for each drug is shown in the blue box. Key ZDV, zidovudine d4T, stavudine ddC, dideoxycytidine FTC, emtricitabine 3TC, lamivudine ABC, abacavir ddl, didanosine DF, disoproxil fumarate MP, monophosphate DP, diphosphate TP, triphosphate AMP, adenosine monophosphate CMP, cytosine monophosphate dCMP, deoxycytosine monophosphate IMP, inosine 5 -monophosphate PRPP, phosphoribosyl pyrophosphate NDR, nucleoside diphosphate. 

Lamivudine is a cytosine analog active against HIV-1, HIV-2, and HBV. The molecule is manufactured as the pure cis-(-) enantiomer (Figure 50-2), which is more potent and substantially less toxic. The active species is the intracellular triphosphate derivative, which has low affinity for human DNA polymerases. High-level resistance to lamivudine occurs with single-amino-acid mutations at codon 184 that can reduce in vitro sensitivity to the drug by up to 1000-fold but restore sensitivity to zidovudine. This effect may contribute to the sustained virologic benefits of combination therapy with lamivudine and zidovudine. 

Emtricitabine is a cytosine analog that is chemically related to lamivudine and shares many of its properties. It is active against HIV-1, HIV-2, and HBV... 

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