Synthetic nucleosides are a group of drugs used to treat many vi-ral syndromes that can occur in an immunocompromised patient,including herpes simplex virus (HSV) and cytomegalovirus (CMV).
Drugs in this class include:
Acyclovir sodium, used to treat HSV, is an effective antiviral drug that causes minimal toxicity to cells. A derivative of acy-clovir, ganciclovir has potent antiviral activity against HSV and CMV.
Famciclovir is used to treat acute herpes zoster, genital herpes, and recurrent HSV infections in the HIV-infected patient. Valacy-clovir is used to treat herpes zoster, genital herpes, and herpes labialis. Valganciclovir is used to treat CMV retinitis in the patient with acquired immunodeficiency syndrome (AIDS).
Each of these antiviral drugs travels its own route through the body.
When given orally, acyclovir absorption is slow and only 10% to 30% complete. It’s distributed throughout the body and metabo-lized primarily inside the infected cells; the majority of the drug is excreted in urine.
Famciclovir is less than 20% bound to plasma proteins. It’s exten-sively metabolized in the liver and excreted in urine.
Ganciclovir is administered I.V. because it’s absorbed poorly from the GI tract. More than 90% of ganciclovir isn’t metabolized and is excreted unchanged by the kidneys.
Valacyclovir is converted to acyclovir during its metabolism and has pharmacokinetic properties similar to those of acyclovir. Val-ganciclovir is metabolized in the intestinal wall and liver to ganci-clovir; however, interchanging the two drugs isn’t effective.
To be effective, acyclovir, famciclovir, and ganciclovir must be me-tabolized to their active form in cells infected by HSV.
Acyclovir enters virus-infected cells, where it’s changed through a series of steps to acyclovir triphosphate. Acyclovir triphosphate inhibits virus-specific DNA polymerase, an enzyme necessary for viral growth, thus disrupting viral replication.
· On entry into CMV-infected cells, ganciclovir is converted to ganciclovir triphosphate, which is thought to produce its antiviral activity by inhibiting viral DNA synthesis.
· Famciclovir enters viral cells (herpes simplex 1 and 2, varicella zoster), where it inhibits DNA polymerase, viral DNA synthesis and, thus, viral replication.
· Valacyclovir rapidly converts to acyclovir; acyclovir then be-comes incorporated into viral DNA and inhibits viral DNA poly-merase, thus inhibiting viral multiplication.
· Valganciclovir is converted to ganciclovir, which inhibits repli-cation of viral DNA synthesis of CMV.
Acyclovir is used to treat infection caused by herpes viruses, in-cluding HSV types 1 and 2 and the varicella-zoster virus. Oral acy-clovir is used primarily to treat initial and recurrent HSV type 2 in-fections.
I.V. acyclovir is used to treat:
§ severe initial HSV type 2 infections in a patient with a normal immune system
§ initial and recurrent skin and mucous membrane HSV type 1 and 2 infections in an immunocompromised patient
§ herpes zoster infections (shingles) caused by the varicella-zoster virus in an immunocompromised patient
§ disseminated varicella-zoster virus in an immunocompromised patient
§ varicella infections (chickenpox) caused by the varicella-zoster virus in an immunocompromised patient.
Ganciclovir is used to treat CMV retinitis in an immunocompro-mised patient, including a patient with AIDS or other CMV infec-tions such as encephalitis.
Famciclovir is used to treat acute herpes zoster, genital herpes, and recurrent HSV infections in a patient with HIV.
Valganciclovir is used to treat CMV retinitis, and valacyclovir is ef-fective against herpes zoster, genital herpes, and herpes labialis.
Synthetic nucleosides may interact with these drugs.
§ Probenecid reduces kidney excretion and increases blood levels of ganciclovir, valganciclovir, valacyclovir, famciclovir, and acy-clovir, increasing the risk of toxicity.
§ Taking ganciclovir with drugs that are damaging to tissue cells, such as dapsone, pentamidine isethionate, flucytosine, vincristine, vinblastine, doxorubicin, amphotericin B, and co-trimoxazole, in-hibits replication of rapidly dividing cells in the bone marrow, GI tract, skin, and sperm-producing cells.
§ Imipenem-cilastatin increases the risk of seizures when taken with ganciclovir or valganciclovir.
§ Zidovudine increases the risk of granulocytopenia (reduced number of granulocytes, a type of white blood cell) when taken with ganciclovir. (See Adverse reactions to synthetic nucleo-sides.)