T21 - Viral drug

What is the fundamental pharmacological property of antiviral drugs regarding their action on latent viruses?

They are virustatic

What host factor remains essential for recovery from viral infections despite antiviral therapy?

Host immunity

Why do many antiviral drugs require intracellular modifications before they become active?

They are prodrugs requiring phosphorylation

Which type of viral genome does Hepatitis C possess?

RNA

Which type of viral genome does Hepatitis B possess?

DNA

Which type of viral genome do Influenza A and B possess?

RNA

Which type of viral genome does HIV possess?

RNA

Which type of viral genome does SARS-CoV-2 possess?

RNA

What step of the viral life cycle is blocked by maraviroc?

Viral attachment and entry

What step of the viral life cycle is blocked by enfuvirtide?

Viral attachment and entry

What step of the viral life cycle is blocked by amantadine?

Uncoating

What step of the viral life cycle is blocked by integrase inhibitors?

Integration into genome

What step of the viral life cycle is blocked by oseltamivir?

Viral release

What step of the viral life cycle is blocked by nirmatrelvir?

Protein processing

What step of the viral life cycle is blocked by baloxavir?

Nucleic acid synthesis

Which influenza types are susceptible to adamantanes?

Influenza A only

Which influenza types are susceptible to baloxavir?

Influenza A and B

Which influenza types are susceptible to oseltamivir?

Influenza A and B

What is the mechanism of action of amantadine?

M2 ion channel blocker

Why are adamantanes no longer recommended for influenza treatment?

Greater than 99% resistance

What is a major contraindication for the use of amantadine?

Pregnancy

What is the primary central nervous system adverse effect of amantadine?

Insomnia, dizziness, confusion, or seizures

What is the mechanism of action of oseltamivir?

Neuraminidase inhibitor

What is the administration route for oseltamivir?

Oral

What is the administration route for zanamivir?

Oral inhalation

What is the administration route for peramivir?

Intravenous

What is the most common adverse effect of oseltamivir?

Nausea and vomiting

What is a major contraindication for the use of zanamivir?

Asthma or COPD

Which neuraminidase inhibitor is preferred for pregnant or hospitalised patients?

Oseltamivir

What is the specific molecular target of baloxavir marboxil?

Cap-dependent endonuclease

Which viral kinase is responsible for the initial phosphorylation of acyclovir?

Herpes thymidine kinase

How does acyclovir achieve selective toxicity?

Monophosphate forms only in infected cells

What is the mechanism of action of acyclovir triphosphate?

Viral DNA polymerase inhibitor and chain terminator

What is the most common mechanism of HSV resistance to acyclovir?

Thymidine kinase deficiency or alteration

What is the pharmacokinetic advantage of valacyclovir over acyclovir?

Higher oral bioavailability

What is the primary indication for intravenous acyclovir?

HSV encephalitis or severe disseminated disease

What is the primary indication for oral acyclovir or valacyclovir?

Genital herpes, herpes zoster, and varicella

What is the primary renal adverse effect of intravenous acyclovir?

Crystal nephropathy

What neurotoxic adverse effects are associated with acyclovir in the setting of renal impairment?

Confusion, tremor, or seizures

Which viral kinase activates ganciclovir in CMV-infected cells?

CMV UL97 kinase

What is the mechanism of action of ganciclovir?

Viral DNA polymerase inhibitor

What is the oral prodrug formulation of ganciclovir?

Valganciclovir

What are the primary clinical indications for ganciclovir?

CMV retinitis, colitis, pneumonitis, and pre-emptive therapy in transplants

What is the primary dose-limiting adverse effect of ganciclovir?

Myelosuppression

Why is the co-administration of ganciclovir and zidovudine generally avoided?

Additive bone marrow toxicity

What is the most common mechanism of CMV resistance to ganciclovir?

UL97 kinase mutation

What is the mechanism of action of foscarnet?

Direct DNA polymerase inhibitor

Does foscarnet require activation by viral kinases?

No

What is the primary indication for foscarnet?

Acyclovir-resistant HSV or ganciclovir-resistant CMV

What is the major dose-limiting toxicity of foscarnet?

Nephrotoxicity and electrolyte imbalances

What is the mechanism of action of cidofovir?

DNA polymerase inhibitor

Does cidofovir require activation by viral kinases?

No

What medication must be co-administered with cidofovir to prevent nephrotoxicity?

Probenecid

What is the primary indication for letermovir?

CMV prophylaxis in transplant patients

What is the specific viral target of maribavir?

UL97 kinase

What is the therapeutic goal for chronic Hepatitis B infection?

Long-term viral suppression

What is the therapeutic goal for chronic Hepatitis C infection?

Cure (sustained virological response)

What viral target is inhibited by HCV drugs with the suffix "-previr"?

NS3/4A protease

What viral target is inhibited by HCV drugs with the suffix "-asvir"?

NS5A replication complex

What viral target is inhibited by HCV drugs with the suffix "-buvir"?

NS5B polymerase

What are the preferred first-line nucleos(t)ide analogues for chronic HBV?

Tenofovir and Entecavir

What is the mechanism of action of tenofovir against HBV?

Reverse transcriptase inhibitor

What is the major renal adverse effect associated with tenofovir disoproxil fumarate (TDF)?

Renal tubulopathy (Fanconi syndrome)

What is the pharmacokinetic advantage of tenofovir alafenamide (TAF) over TDF?

Less renal and bone toxicity

What is a significant risk of abruptly stopping nucleos(t)ide analogue therapy in HBV patients?

Severe hepatitis flare

What is the mechanism of action of ribavirin?

Inhibits IMPDH

What is the primary dose-dependent adverse effect of ribavirin?

Haemolytic anaemia

What is a major absolute contraindication for the use of ribavirin?

Pregnancy

What is the mechanism of action of pegylated interferon-alpha?

Binds IFNAR to activate JAK-STAT pathway

What are the prominent psychiatric adverse effects of interferon-alpha?

Depression and suicidality

What is a major absolute contraindication for interferon-alpha therapy in liver disease?

Decompensated cirrhosis

What are the two primary cellular co-receptors for HIV entry?

CCR5 and CXCR4

Which viral envelope glycoprotein mediates HIV attachment to CD4?

gp120

Which viral envelope glycoprotein mediates HIV fusion with the host cell membrane?

gp41

What is the mechanism of action of maraviroc?

CCR5 antagonist

What pre-treatment testing is mandatory before initiating maraviroc?

Tropism test

What is the mechanism of action of enfuvirtide?

Fusion inhibitor

What is the mechanism of action of fostemsavir?

gp120 attachment inhibitor

What is the mechanism of action of ibalizumab?

Monoclonal antibody against CD4

What is the mechanism of action of Nucleoside Reverse Transcriptase Inhibitors (NRTIs)?

Competitive inhibition and chain termination

Do NRTIs require intracellular activation?

Yes, they require three phosphorylations by host kinases

What mandatory screening test is required before prescribing abacavir?

HLA-B*5701 testing

What is the classic adverse effect of zidovudine (AZT)?

Macrocytic anaemia and myelosuppression

What is the mechanism of action of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)?

Allosteric inhibition

Do NNRTIs require intracellular activation?

No

What is the mechanism of action of Integrase Strand Transfer Inhibitors (INSTIs)?

Chelate Mg2+ in integrase active site

What suffix identifies integrase strand transfer inhibitors?

"-tegravir"

Which integrase inhibitor requires boosting with cobicistat?

Elvitegravir

What is the mechanism of action of HIV protease inhibitors?

Prevent cleavage of Gag/Gag-Pol polyproteins

What suffix identifies HIV protease inhibitors?

"-navir"

What is the primary pharmacological role of ritonavir or cobicistat in modern ART?

Pharmacokinetic boosters

What are the classic metabolic adverse effects of HIV protease inhibitors?

Dyslipidaemia, insulin resistance, and fat redistribution

Which HIV protease inhibitor classically causes unconjugated hyperbilirubinaemia?

Atazanavir

What severe adverse effect can occur if ergotamine is co-administered with boosted protease inhibitors?

Ergotism (severe ischaemia)

Why is fluticasone co-administration cautioned with boosted protease inhibitors?

Risk of iatrogenic Cushing syndrome

What is the WHO preferred first-line ART regimen for most cases?

Tenofovir + Lamivudine (or Emtricitabine) + Dolutegravir

What is the mechanism of action of nirmatrelvir?

3CL (main) protease inhibitor

What is the mechanism of action of remdesivir?

RNA-dependent RNA polymerase inhibitor

What is the mechanism of action of molnupiravir?

Lethal mutagenesis

What is a major contraindication for the use of molnupiravir?

Pregnancy or age under 18