Anti-virals (Non-retroviral) MCQs

Acyclovir is cleared primarily by glomerular filtration and tubular secretion. The half-life is 2.5–3 hours in patients with normal renal function and 20 hours in patients with anuria. Reference : LANG' Basic & clinical pharmacology by Bertram G. Katzung, Susen B. Masters and Anthony J. Trevor 12 th edition. Chapter 49- Antiviral Agents by Dr. Sharon Safrin,MD. Page no. 862

Although initially and abortively developed for treatment of HIV infection, adefovir dipivoxil gained approval, at lower and less toxic doses, for treatment of HBV infection. Adefovir dipivoxil is the diester prodrug of adefovir, an acyclic phosphonated adenine nucleotide analog . It is phosphorylated by cellular kinases to the active diphosphate metabolite and then competitively inhibits HBV DNA polymerase and causes chain termination after incorporation into viral DNA. Adefovir is active in vitro against a wide range of DNA and RNA viruses, including HBV, HIV and herpesviruses. Reference : LANG’ Basic & clinical pharmacology by Bertram G. Katzung, Susen B. Masters and Anthony J. Trevor 12 th edition. Chapter 49- Antiviral Agents by Dr. Sharon Safrin,MD. Page no. 884

Favipiravir inhibits SARS-CoV-2 viral replication in vitro with evidence of clinical benefit in open label trials.

Three oral nucleoside analogues are licensed for the treatment of HSV and VZV infections: acyclovir, valacyclovir, and famciclovir. They have similar mechanisms of action and comparable indications for clinical use; all are well tolerated. Acyclovir has been the most extensively studied It was licensed first and is the only one of the three that is available for intravenous use in the United States. Comparative trials have demonstrated similar efficacies of these three agents for the treatment of HSV but modest superiority of famciclovir and valacyclovir for the treatment of herpes zoster infections. Reference: LANG' Basic & clinical pharmacology by Bertram G. Katzung, Susen B. Masters and Anthony J. Trevor 12 th edition. Chapter 49- Antiviral Agents by Dr. Sharon Safrin, MD. Page no. 862

Acyclovir ( Figure 49–2 ) is an acyclic guanosine derivative with clinical activity against HSV-1, HSV-2, and VZV, but it is approximately 10 times more potent against HSV-1 and HSV-2 than against VZV. In vitro activity against Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus-6 (HHV-6) is present but weaker. Acyclovir requires three phosphorylation steps for activation. Reference: LANG' Basic & clinical pharmacology by Bertram G. Katzung, Susen B. Masters and Anthony J. Trevor 12 th edition. Chapter 49- Antiviral Agents by Dr. Sharon Safrin, MD. Page no. 862

Acyclovir requires three phosphorylation steps for activation. It is converted first to the monophosphate derivative by the virus specified thymidine kinase and then to the di- and triphosphate compounds by host cell enzymes (Figure 49-3). Because it requires the viral kinase for initial phosphorylation, acyclovir is selectively activated and the active metabolite accumulates only in infected cells. Acyclovir triphosphate inhibits viral DNA synthesis by two mechanisms: competition with deoxyGTP for the viral DNA polymerase, resulting in binding to the DNA template as an irreversible complex. Reference : LANG’ Basic & clinical pharmacology by Bertram G. Katzung, Susen B. Masters and Anthony J. Trevor 12 th edition. Chapter 49- Antiviral Agents by Dr. Sharon Safrin,MD. Page no. 862

Valacyclovir is the L-valyl ester of acyclovir.It is rapidly converted to acyclovir after oral administration via first pass enzymatic hydrolysis in the liver and intestine, resulting in serum levels that are three to five times greater than those achieved with oral acyclovir and approximate those achieved with intravenous acyclovir. Oral bioavailability is 54–70%, and cerebrospinal fluid levels are about 50% of those in serum. Elimination half-life is 2.5–3.3 hours. Reference: LANG' Basic & clinical pharmacology by Bertram G. Katzung, Susen B. Masters and Anthony J. Trevor 12 th edition. Chapter 49- Antiviral Agents by Dr. Sharon Safrin, MD. Page no. 864

Valacyclovir is generally well tolerated, although nausea, headache, vomiting, or rash occasionally occur. At high doses, confusion, hallucinations, and seizures have been reported. AIDS patients who received high-dosage valacyclovir chronically (ie, 8 g/d) had an increased incidence of gastrointestinal intolerance as well as thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome; this dose has also been associated with confusion and hallucinations in transplant patients. In a recent study, there was no evidence of increased birth defects in 181 infants who were exposed to valacyclovir during the first trimester. Reference: LANG' Basic & clinical pharmacology by Bertram G. Katzung, Susen B. Masters and Anthony J. Trevor 12 th edition. Chapter 49- Antiviral Agents by Dr. Sharon Safrin, MD. Page no. 864