3. ANTIVIRAL AGENTS PART 1 & 2 (AI)

What is the main challenge in antiviral chemotherapy compared to antibacterial therapy?

Viruses use host cell machinery, limiting selective toxicity

What is the primary target of most antiviral drugs?

Viral enzymes such as DNA polymerase and reverse transcriptase

What is the mechanism of most anti-herpes drugs?

Inhibit viral DNA polymerase after activation by viral or host kinases

What type of drugs are most anti-herpes agents classified as?

Antimetabolites

What is the mechanism of action of acyclovir?

Guanosine analog that inhibits viral DNA polymerase and causes chain termination

What enzyme activates acyclovir?

Viral thymidine kinase

What is the active form of acyclovir?

Acyclovir triphosphate

What is the mechanism of resistance to acyclovir?

Mutation or absence of viral thymidine kinase

Which strains of HSV are resistant to acyclovir?

Thymidine kinase-deficient strains

Which drugs show cross-resistance with acyclovir?

Famciclovir, ganciclovir, valacyclovir

What is the primary route of elimination of acyclovir?

Renal excretion

What adjustment is required for acyclovir in renal impairment?

Dose reduction

What are common oral side effects of acyclovir?

GI distress and headache

What are major IV toxicities of acyclovir?

Neurotoxicity and nephrotoxicity

What is valacyclovir?

Prodrug of acyclovir with better oral bioavailability

What is penciclovir’s mechanism of action?

Inhibits viral DNA polymerase without causing chain termination

What is famciclovir?

Prodrug of penciclovir

What is the mechanism of docosanol?

Inhibits viral fusion with host cell membrane

What virus is letermovir most specific for?

Cytomegalovirus (CMV)

What is the mechanism of letermovir?

Inhibits viral terminase complex

What is ganciclovir classified as?

Guanine analog

What is the mechanism of ganciclovir?

Inhibits viral DNA polymerase and causes chain termination

What is a major toxicity of ganciclovir?

Bone marrow suppression

What conditions is ganciclovir used for?

CMV infections in immunocompromised patients

What is valganciclovir?

Oral prodrug of ganciclovir with better bioavailability

What is the mechanism of cidofovir?

Inhibits viral DNA polymerase after activation by host kinases

Does cidofovir require viral kinase activation?

No

What is the major toxicity of cidofovir?

Nephrotoxicity

What is brincidofovir?

Prodrug of cidofovir with less nephrotoxicity

What is the mechanism of foscarnet?

Direct inhibition of viral DNA polymerase without phosphorylation

Does foscarnet require activation?

No

What viruses are treated with foscarnet?

HSV, CMV, and HIV

When is foscarnet used in herpes infections?

In acyclovir-resistant cases

What is a major toxicity of foscarnet?

Nephrotoxicity

What electrolyte abnormality is associated with foscarnet?

Hypocalcemia

What CNS effects are associated with foscarnet?

Seizures and hallucinations

What is vidarabine?

Adenine analog antiviral used topically

Why is vidarabine rarely used systemically?

High toxicity

What are idoxuridine and trifluridine used for?

Topical treatment of herpes keratitis

What is fomivirsen?

Antisense oligonucleotide against CMV mRNA

How is fomivirsen administered?

Intravitreal injection

What is the main mechanism of NRTIs?

Inhibit reverse transcriptase and cause DNA chain termination

What activation is required for NRTIs?

Phosphorylation by host cell kinases

What causes resistance to NRTIs?

Mutations in viral reverse transcriptase gene

What is the major toxicity class-wide for NRTIs?

Lactic acidosis and hepatic steatosis

What is the primary toxicity of zidovudine?

Bone marrow suppression

What serious toxicity is associated with didanosine?

Pancreatitis

What is the dose-limiting toxicity of stavudine?

Peripheral neuropathy

What toxicity is associated with tenofovir?

Renal toxicity and Fanconi syndrome

What is the mechanism of action of NNRTIs?

Directly inhibit reverse transcriptase by binding to a non-active site

Do NNRTIs require phosphorylation for activation?

No

What is a key advantage of NNRTIs over NRTIs?

Do not require intracellular activation

What causes resistance to NNRTIs?

Mutation in reverse transcriptase enzyme

What is a common side effect of efavirenz?

CNS disturbances (vivid dreams, dizziness)

What serious reaction is associated with nevirapine?

Stevens-Johnson syndrome

What cardiac effect is associated with rilpivirine?

QT prolongation

What is the mechanism of protease inhibitors?

Inhibit HIV protease, preventing maturation of viral particles

What is the result of protease inhibition in HIV?

Production of immature, non-infectious virions

What enzyme do most protease inhibitors affect in the liver?

CYP3A4

What is the function of ritonavir in HAART?

Boosts levels of other protease inhibitors by inhibiting CYP3A4

What metabolic complication is associated with protease inhibitors?

Lipodystrophy

What glucose-related effect is seen with protease inhibitors?

Hyperglycemia

What lipid abnormality is associated with protease inhibitors?

Hyperlipidemia

What is a unique toxicity of indinavir?

Nephrolithiasis

What is a unique effect of atazanavir?

Hyperbilirubinemia

What is the mechanism of entry inhibitors?

Block HIV entry into host cells

What receptor is blocked by maraviroc?

CCR5 receptor

What is the mechanism of enfuvirtide?

Inhibits fusion of HIV with host cell membrane via gp41

What is the mechanism of ibalizumab?

Monoclonal antibody that binds CD4 receptor

What is the mechanism of integrase inhibitors?

Prevent integration of viral DNA into host genome

What is the mechanism of raltegravir?

Inhibits strand transfer during viral DNA integration

What is the mechanism of dolutegravir?

Inhibits HIV integrase enzyme

What is the purpose of HAART?

Combination therapy to suppress viral replication and prevent resistance

What is the standard composition of HAART?

Two NRTIs plus one NNRTI, protease inhibitor, or integrase inhibitor

What is the purpose of PrEP?

Prevent HIV infection before exposure

What drugs are used in PrEP?

Tenofovir and emtricitabine

What is the purpose of PEP?

Prevent HIV infection after exposure

What drugs are used in PEP?

Tenofovir, emtricitabine, and raltegravir

What is the mechanism of action of oseltamivir?

Inhibits neuraminidase enzyme

What is the effect of neuraminidase inhibition?

Prevents release of viral particles from infected cells

What is the route of administration of oseltamivir?

Oral

What is the route of administration of zanamivir?

Inhalation

What adverse effect is associated with zanamivir?

Bronchospasm

What is the route of administration of peramivir?

Intravenous

What is the mechanism of adamantanes?

Block M2 ion channel, preventing viral uncoating

Which viruses are affected by adamantanes?

Influenza A only

Why are adamantanes rarely used?

High resistance rates

What is the mechanism of baloxavir?

Inhibits viral cap-dependent endonuclease

What is the mechanism of interferon-alpha?

Enhances antiviral immune response and inhibits viral replication

What are common side effects of interferon-alpha?

Flu-like symptoms, depression, myelosuppression

What is a contraindication to interferon therapy?

Autoimmune disease

What is the mechanism of tenofovir in hepatitis B?

Inhibits viral DNA polymerase and reverse transcriptase

What is the mechanism of lamivudine?

Inhibits reverse transcriptase and DNA polymerase

What is the mechanism of entecavir?

Inhibits HBV DNA polymerase

What is the mechanism of adefovir?

Inhibits viral DNA polymerase causing chain termination

What is the mechanism of sofosbuvir?

Inhibits RNA-dependent RNA polymerase (NS5B)

What is the mechanism of dasabuvir?

Non-nucleoside inhibitor of NS5B polymerase

What is the mechanism of NS5A inhibitors?

Inhibit viral replication and assembly

What is the suffix of NS5A inhibitors?

-asvir

What is the mechanism of NS3/4A protease inhibitors in HCV?

Inhibit viral polyprotein processing