Antiviral Drugs
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Direct answer
Antiviral drugs mostly work by inhibiting viral enzymes, and nucleoside analogues such as acyclovir are selective because a viral kinase activates them before they can act. Acyclovir is activated by viral thymidine kinase in herpes simplex and varicella zoster infection, whereas oseltamivir inhibits viral neuraminidase in influenza. Resistance patterns and dose-limiting toxicities, particularly myelosuppression with ganciclovir, drive most NEET-PG antiviral questions.
What you must remember
- Acyclovir: Activated by viral thymidine kinase, with intravenous therapy standard for herpes simplex encephalitis; crystalluria and renal toxicity need adequate hydration.
- Valacyclovir: Oral prodrug of acyclovir with better bioavailability, used for herpes zoster and genital herpes.
- Ganciclovir: Activated by the viral UL97 kinase in cytomegalovirus, with dose-limiting neutropenia and thrombocytopenia that need regular blood counts.
- Foscarnet: Second-line for ganciclovir-resistant CMV, with nephrotoxicity and electrolyte disturbance, particularly hypocalcaemia, hypomagnesaemia and hypokalaemia.
- Oseltamivir: Neuraminidase inhibitor best started within 48 hours of onset, with nausea and vomiting common; the H275Y mutation confers resistance.
- Ribavirin: Haemolytic anaemia is dose-related, and the drug is teratogenic, so it is contraindicated in pregnancy.
- Lamivudine: Resistance in hepatitis B arises through YMDD motif mutations in the polymerase.
A worked pathway: CMV viraemia after renal transplant
Consider a kidney transplant recipient with cytomegalovirus viraemia and a rising viral load while on immunosuppression. Treatment begins with valganciclovir, the oral prodrug of ganciclovir, after the full blood count and renal function are checked. Two weeks later the blood count shows neutropenia, the expected dose-limiting toxicity. The team reduces the dose or adds growth factor support. If the viral load keeps rising despite adherence, resistance testing looks for UL97 or UL54 mutations, and foscarnet is then used, with careful monitoring of creatinine, calcium and magnesium. Ganciclovir is teratogenic and handled with precautions, so staff preparing doses follow safety procedures throughout. Within a week the team reviews the blood count, creatinine and electrolytes, and documents the dose changes made. Patients are also counselled to report fever, mouth ulcers or bleeding promptly, because neutropenia can evolve between scheduled blood tests. Each agent in the sequence is chosen for its toxicity profile as much as its activity, which is the reasoning examiners want to see in a written answer. Once the viral load falls, the transplant team plans regular monitoring, because relapse can occur after immunosuppression changes.
Where the exam tries to catch you
Examiners exploit the difference between acyclovir and ganciclovir. Acyclovir does not treat cytomegalovirus, and ganciclovir is not the drug of choice for herpes simplex encephalitis. Timing is another favourite, because oseltamivir loses most of its benefit when started late, although severe or high-risk patients may still be treated. Students also miss that ribavirin is teratogenic and that its haemolysis is dose-related rather than immune. Resistance is specific to each drug-target pair: lamivudine resistance in hepatitis B arises through YMDD motif mutations and is not automatically shared by tenofovir or entecavir.
Frequently asked questions
Which antiviral is the drug of choice for herpes simplex encephalitis?
Intravenous acyclovir is the standard drug of choice for herpes simplex encephalitis, and it should begin empirically before CSF PCR results return. It is given at high dose for a prolonged course, with renal function and hydration monitored throughout.
When should oseltamivir be started in influenza?
Oseltamivir works best when started within 48 hours of symptom onset, because viral replication has not yet peaked. Guidelines still support its use in severe or high-risk patients beyond that window, based on clinical judgement.
Why is ganciclovir associated with neutropenia?
Ganciclovir suppresses bone marrow, causing dose-related neutropenia and thrombocytopenia, which is why full blood counts are monitored during treatment. Valganciclovir, the oral prodrug, carries the same haematological toxicity and is handled with precautions because ganciclovir is teratogenic.
Which antiviral is contraindicated in pregnancy because of teratogenicity?
Ribavirin is teratogenic and embryotoxic, so it is contraindicated in pregnancy, and both partners are advised to avoid conception during and after treatment. Its haemolytic anaemia is dose-related and needs haemoglobin monitoring.