Anti-Virals

Question 1

Acyclovir
Valacyclovir (prodrug)
Penciclovir
Famciclovir (prodrug)

Answer 1

-Mech: Activated by viral thymidine kinase (TK) to forms that inhibit viral DNA pol.
-Use: HSV-1, HSV-2, VZV
-Tox: Oral forms cause nausea, diarrhea, and headache
IV acyclovir may cause renal and CNS toxicity. Acyclovir = take it w/lots of water or you may get kidney stones.

Question 2

Ganciclovir
Valganciclovir
Cidofovir
Foscarnet

Answer 2

• Mech: Viral activation of ganciclovir to form inhibiting DNA polymerase; no viral bioactivation of cidofovir and foscarnet.
• Use: CMV in immunocompromised.
• Tox:
  1) Ganciclovir: Bone marrow suppression, hepatic and neurologic dysfunction
  2) Cidofovir and foscarnet: Nephrotoxicity
  3) Foscarnet: CNS effects and electrolyte imbalance. Do not take w/pentamidine.

Question 3

Interferon- α  (IFN- α )
Adefovir-dipivoxil
Entecavir
Lamivudine
Ribavirin

Answer 3

-Mech: Degrades viral RNA via activation of host cell RNAase (IFN- α ), inhibition of HBV polymerase, multiple antiviral actions (ribavirin).
-Use: Suppressive treatment of HBV (all drugs except
ribavirin) • treatment of HCV (ribavirin +/− IFN- α )
-Tox:
1)IFN- α : Alopecia, myalgia, depression, flu-like
syndrome
2)Adefovir: lactic acidosis, renal and hepatic toxicity
3)Ribavirin: Anemia, teratogen

Question 4

Amantadine
Rimantadine
Oseltamivir
Zanamivir

Answer 4

• Mech: Amantadine and rimantidine: block of M2 proton channels
• Mech: Oseletamivir and zanamivir inhibit neuraminidase
• Use: M2 blockers virtually obsolete • others prophylaxis vs most current flu strains and shorten symptoms.
• Tox:
  1) Oseltamivir: Gastrointestinal effects
  2) Zanamivir: Bronchospasm in asthmatics

Question 5

Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
Zalcitabine
Zidovudine

Answer 5

NRTIs
-Mech: Inhibit HIV reverse transcriptase after phosphorylation by cellular enzymes • cross-resistance
common, but incomplete.
-Use: anti-retroviral (HIV)
-PK: Duration of action usually longer than half-life • most undergo renal elimination especially, didanosine,
emtricitabine, lamivudine, stavudine, tenofovir, and
zidovudine
-Tox:
1) Zidovudine: Bone marrow suppression
2) Abacavir: Hypersensitivity
3) Didanosine: Pancreatitis
4) Stavudine, zalcitabine: Peripheral neuropathy

Question 6

Delavirdine
Efavirenz
Etravirine
Nevirapine

Answer 6

NNRTIs
-Mech: Inhibit HIV reverse transcriptase • no phosphorylation required • cross-resistance between
NNRTIs but not with NRTIs.
-Use:
-PK: All current NNRTIs are metabolized via CYP450
isozymes • etravirine may induce formation of CYP3A4, but inhibits other CYP450s. Inducers of CYP450 isozymes (eg, phenytoin, rifampin) and inhibitors (eg, azoles, PIs) alter NNRTI duration of action.
-Tox:
1)Delavirdine, nevirapine: Rash, increased liver enzymes
2)Efavirenz: Teratogenicity

Question 7

Atazanavir
Darunavir
Fosamprenavir
Indinavir
Nelfinavir
Ritonavir
Saquinavir
Tipranavir

Answer 7

Protease Inhibitors
-Mech: Inhibit viral protein processing • cross-resistance
between PIs common.
-Use: HIV
-PK: Elimination mainly via metabolism by CYP450
isozymes • they act as substrates and inhibitors of P450
Fosamprenavir is a prodrug forming amprenavir, a substrate and inducer of CYP450.
-Ritonavir c and other PIs can inhibit CYP450 metabolism of many drugs including antihistamines, antiarrhythmics,
HMG-CoA reductase inhibitors, oral contraceptives and
sedative-hypnotics. Drugs known to induce or inhibit CYP450 isoforms may alter the plasma levels of PIs
-Tox:
1) Atazanavir, fosamprenavir, lopinavir, nelfinavir,
saquinavir: GI distress and diarrhea
2) Atazanavir: Peripheral neuropathy
3) Amprenavir: Rash
4) Indinavir: Hyperbilirubinemia and nephrolithiasis

Question 8

Enfuvirtide

Maraviroc

Answer 8

Entry inhibitors
-Mech: Block fusion between viral and cellular membranes (enfuvirtide) • CCR5 receptor antagonist (maraviroc)
-Use: HIV
-PK: Extrahepatic hydrolysis of enfuvirtide (subcutaneous
injection) • P450 metabolism (maraviroc). Inducers and inhibitors of CYP450 alter elimination of maraviroc
• no effects on enfuvirtide