Drugs Five Years Later: Acyclovir

Abstract

In the 5 years since its release for clinical use, acyclovir (9-[2-hydroxyethoxymethyl]guanine) has proved to be a safe and effective agent for therapy of herpes simplex and varicella-zoster infections. The drug's availability in topical, oral, and intravenous preparations has allowed its use in a range of clinical situations. Acyclovir must be phosphorylated by viral thymidine kinase in infected cells, where it then acts to inhibit viral DNA replication specifically. Epstein-Barr virus and human cytomegalovirus infections do not seem to respond to acyclovir therapy, although in-vitro effects on these viruses may be seen. Acyclovir is well absorbed and distributed, with cerebrospinal fluid levels 50% that of plasma. Clearance is almost entirely by the renal route, with a half-life of 20 hours in the anuric patient. Acyclovir has an excellent safety profile, its major adverse effect being transient serum creatinine elevations during high-dose intravenous use. Major uses include treatment of primary and recurrent genital herpes and herpes encephalitis and prophyllaxis and therapy of mucocutaneous herpes and varicella-zoster infections in immunocompromised patients. Resistance to acyclovir in herpes simplex virus is rarely encountered and does not seem to be due to long-term chronic suppressive therapy.

Inhibition of immune functions by antiviral drugs.

“…The responsiveness ofPBMC isolated from normal, healthy donors was measured for cultures incubated with or without these agents. As expected, our findings showed that acyclovir, an antiviral drug that has been extensively studied in vitro and in vivo (1,17), had little effect on PBMC responsiveness to mitogen (Figs. 1-3, 5).…”

“…Previous studies have shown many synthetic nucleosides to be toxic on in vivo use (2); however, acyclovir (9-[2-hydroxyethoxymethyl]guanine) which has low in vivo and in vitro toxicity, is a notable exception (1). Acyclovir is now widely used in renal and bone marrow transplant recipients for prophylaxis and treatment of herpes simplex virus and varicella zoster virus infections (1).…”

“…Although antiviral activity has been demonstrated in vitro for the nucleoside analogues 3'-azido-3'-deoxythymidine (Zidovudine; Vetrovir) (AZT),' ribavirin (1-beta-D-ribofuranosyl-1,2,4-trizole-3-carboxamide; Virazole), ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl] guanine; DHPG; BIOLF-62; 2NDG), and 2'3'-dideoxyinosine (ddI), neither their full therapeutic potential nor range of toxicity has been evaluated (1)(2)(3)(4)(5)(6). By virtue of their resemblance to thymidine, adenosine, and guanosine, such nucleoside analogues are likely to have adverse effects on mammalian DNA, RNA, and/or 1. Abbreviations used in this paper: ARC, AIDS related complex; AZT, 3'-azido-3'-deoxythymidine; ddI, 2'3'-dideoxyinosine; Fl, fluorescence; HO, Hoechst 33342; PY, pyronin Y; R640, rhodamine 640.…”

Herpes Simplex Type 1 Encephalitis

“…In conclusion, the viral DNA chain is broken, and thus complete viral DNA synthesis is stopped. Due to lesser affinity to host cell DNA polymerases, causing a very little toxic effect in host cell is another important feature of Acyclovir-triphosphate (Dorsky & Crumpacker, 1987;Van Landingham et al, 1988). Acyclovir prevents virus proliferation but has no protective effect on primary and secondary immune-mediated damage that developed in previously virus infected cells.…”

“…Acyclovir prevents virus proliferation but has no protective effect on primary and secondary immune-mediated damage that developed in previously virus infected cells. Therefore, early treatment is mandatory in patients with HSE and prophylactic Acyclovir treatment should be given even if HSE is suspected (Djukic et al, 2003;Dorsky & Crumpacker, 1987;Whitley et al, 1986). When administered intravenously, Acyclovir may crystallize and cause temporary renal failure.…”