Antivirals Flashcards
Why is antiviral therapy difficult?
At what point in illness are antivirals most effective?
Most viruses have intracellular phases, use host enzymes, and can go latent.
Like many drugs, antivirals are more effective in relieving illness early on–before viral replication occurs.
Are antivirals broad or narrow spectrum?
Are antivirals virustatic or virucidal?
Most antivirals are quite narrow-spectrum. Many can only target one phase of a virus’s replication cycle.
Most antivirals are virustatic, relying on the immune system to do the clearing.
How does immunization compare to antiviral treatment in terms of efficacy?
Distinguish between active and passive immunization (from a therapeutic perspective).
Immunization provides much better defense, especially since it is “always-on”.
Active immunization eg Vaccination, immune system recognizes and produces antibodies against the virus.
Passive immunization eg IVIG, protective and lasts for weeks, but expensive and potentially immunogenic.
Amantadine
What is its mechanism of action?
What are its indications?
What are its side effects?
Amantadine
Blocks the M2 influenza protein, stopping acidification and activation (uncoating).
For prophylaxis and treatment of Influenza A.
Low incidence of CNS effects (anxiety, confusion, headache…)
Amantadine
What is the current status of its resistance?
Compare it with rimantadine.
Amantadine
Some strains of Influenza A (especially H3N2) exhibit resistance, which took only a few years to develop…
Rimantadine has milder side effects and it metabolized by the liver. It is also more expensive.
Oseltamivir
What is its mechanism of action?
What are its indications?
What are its side effects?
Oseltamivir
It is an orally-administered prodrug, which is activated by esterases to oseltamivir carboxylate and inhibits viral neuraminidase, blocking release/penetration.
For treatment and prophylaxis of Influenza A & B. Recipients should be at least 1 year old and receive it within 48 hours of symptoms.
N/V/D, bronchitis/cough.
What mechanism of treatment is best for treating Herpesvirus? Why?
Since herpes encodes many of its own DNA enzymes, inhibiting nucleic acid synthesis is an effective method to block it.
Trifluridine
What is its mechanism of action?
What are its indications?
What are its side effects?
Trifluridine
It is a thymidine analog that interferes with DNA synthesis (doesn’t require activation).
As an ophthalmic solution, it treats ocular herpes simplex infections.
Burning, stinging, hypersensitivity.
Acyclovir
What is its mechanism of action?
What are its indications?
What are its side effects?
Acyclovir
Upon phosphorylation by viral & host enzymes, it forms a dGTP analog that blocks DNA chain elongation (no 3’-OH; affects mostly viral DNA pol).
IV (serious HSV; encephalitis & neonatal), Oral (primary genital herpes and gingivostomatitis), topical (primary genital herpes).
Although it is well-tolerated, some experience rash/itching, N/V, headache, fatigue.
Famciclovir
What is its mechanism of action?
What are its indications?
What are its side effects?
Famciclovir
Same as acyclovir: triphosphorylation >> block DNA chain elongation.
For shingles, latent chickenpox, and treatment/suppression of recurrent genital herpes.
Same as acyclovir: Rash, N/V, etc. Note that it is better absorbed.
Penciclovir
What is its mechanism of action?
What are its indications?
What are its side effects?
Penciclovir
Same as acyclovir: triphosphorylation >> block DNA chain elongation.
For recurrent herpes of face and lips (topical).
Same as acyclovir: Rash/irritation (no N/V since not ingested).
How widespread are CMV infections?
Who is especially at risk?
How effective are CMV antivirals in treating them?
Hugely; 50-85% of US popuilation is seropositive and/or latently infected.
Reactivation can occur in the immunocompromised; the infection is generally serious in HIV patients and transplant recipients on immunosuppression.
They slow the progression of CMV, but do not cure it.
Ganciclovir
What is its mechanism of action?
What are its indications?
What are its side effects?
Ganciclovir
SIMILAR to acyclovir. However, mono-phosphorylated by a CMV kinase (not a host kinase!)
For CMV retinitis and CMV prophylaxis in transplant recipients.
Bone marrow suppression (causing leukopenia, thrombocytopenia, anemia), made worse with AZT.
Foscarnet
What is its mechanism of action?
What are its indications?
What are its side effects?
Foscarnet
It is a pyrophosphate analog that inhibits CMV DNA pol. Doesn’t require activation.
Used for CMV retinitis, and for HSV that resists acyclovir.
Renal damage, electrolyte imbalances, and seizures. Worse than ganciclovir!
Lamivudine (3TC)
What is its mechanism of action?
What are its indications?
What are its side effects?
Lamivudine (3TC)
It is a nucleoside analog that is phosphorylated to inhibit reverse transcriptase (an NRTI)
Approved for hepatitis B (which apparently has an RT domain) and HIV (good against AZT-resistant strains and vice versa–synergistic).
Well tolerated, with some N/V/D and rash.
