Pharm Test 4: Antivirals

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  1. Acyclovir is most effective for what virus?
    Less effective for?
    • Most effective= replicating HSV
    • Less effective= VZV, EBV
  2. Why is CMV resistant to Acyclovir?
    • It either
    • 1) Lacks a thymidine kinase gene OR
    • 2) Viral encoded thymidine kinase is unable to phosphorylated acyclovir
  3. Used in prophylaxis of recurrent genital herpes

    *Oral therapy is also effectie in treating primary genital HSV infxn
  4. 3 uses of Acyclovir (other than HSV prophylaxis)
    • Can be given IV to manage:
    • 1) Severe genital herpes
    • 2) Herpes Encephalitis
    • 3) VZV infxn in immune compromised and burn patients
  5. 3 Acyclovir Prodrugs
    • Valacyclovir
    • Penciclovir
    • Famciclovir
  6. Acyclovir molecules entering the cell are converted to acyclovir monophosphate by
    virus-induced thymidine kinase

    *host cell enzymes then add two more phosphates to form acyclovir triphosphate which is transported to the nucleus
  7. Inserts acyclovir monophosphate rather than 2'-deoxyguanosine monophosphate into the viral DNA
    Viral DNA Polymerase
  8. Adverse Effects of Acyclovir
    • Minor- nausea, diarrhea, headache
    • Major- Reversible renal toxicity, neurologic effects
  9. Acyclovir Resistance
    • Long term use of acyclovir can cause resistant types of HSV and VZV.
    • These types lack thymidine kinase or have an altered DNA Pol.
    • Mutants are sensitive to foscarnet
  10. Ganciclovir has 100x more activity than acyclovir against this virus
  11. Acyclovir treats
    Gancyclovir treats
    • A= HSV, VZV
    • G= HSV, CMV
  12. Adverse Effects of Ganciclovir
    • Myelosuppression
    • CNS and hepato- toxicity
  13. Ganciclovir myelosuppression can be additive when taking
    • Zidovudine
    • Azathiprine
    • Mycophenolate mofetil
  14. Amantadine and Remantadine prevent
    Uncoating of M2 viral protein
  15. Prevent uncoating of M2 viral protein in RNA viruses
    • Amantadine
    • Rimantadine
  16. Treats Influenza A
    Amantadine, Rimantidine
  17. Treats influenza A and B
    Oseltamivir (tamiflu)
  18. Adverse Effects of Amantadine and Rimantadine
    • More common w/ Amantadine
    • Marked behavioral changes, delirium, hallucinations (due to dopamine neurotransmission)
  19. Adverse effects of amantadine/rimantadine may increase w/
    concomitant antihistamines, anticholinergic agents, hydrochlorothiazide, and TMP/SMX
  20. Tx of Influenza A and B
    Oseltamivir, Zanamivir
  21. Oseltamivir/ Zanamivir MoA
    • Interfere w/ release of progeny influenza virus from host infected cells
    • Halt spread of infxn in the respiratory tract
  22. Neuraminidase Inhibitors (Analogs of sialic acid)
    Oseltamivir, Zanamivir
  23. Adverse Effects of Oseltamivir
    • Minor:  Nausea (resolves spontaneously)
    • Major:  Neuropsychiatric events (self-injury or delirium in adolescents or Japanese adults)
  24. Not recommended for pts. w/ underlying airway disease
  25. Oseltamivir resistance
    Associated w/ point mutations in viral HA/NA genes
  26. Goal of chronic HBV therapy?
    Goal of HCV infxn?
    • HBV- Sustain suppression of HBV replication
    • Slow progression of hepatic disease
    • Prevent complications
    • Reduce need for liver transplantation
    • HCV- Eradication
  27. Most powerful tx against HBV, HCV
  28. Major MoA of IFN-a
    Inhibition of translation

    • Activates methylase, thereby reducing mRNA cap mythylation
    • Activates 2'5' oligoadenylate synthetase -> inhibits mRNA splicing and inactives RNase I -> cleaves viral RNA
    • Activates protein kinase P1 -> blocks eIL-2afunction -> inhibits initiation of mRNA translation
    • Activates phosphodiesterase -> blocks tRNA function
  29. IFN-a Contraindications
    • Pts. w/:
    • Hepatic decompensation
    • Autoimmune disease
    • Hx of cardiac arrhythmia
  30. IFN-a: Potential drug-drug interactions
    • Theophylline
    • Methadone
    • Didanosone (Increases risk of hepatic failure)
    • Zidovudine (Exacerbates cytopenias)
  31. Used in combination with IFN-a to treat HBV, HCV
    • Lamviudine (HBV)
    • Ribavirin (HCV)
  32. Treats HCV
    IFN-a, Lamivudine
  33. Treats HCV
    IFN-a, Ribavirin
  34. Lamivudine inhibits
    • HBV- DNA Polymerase
    • HIV- Reverse Transcriptase
  35. Lamivudine use w/ co-infxn of HIV can increase risk of
  36. Adverse Effects of Ribavirin
    Dose-dependent hemolytic anemia
  37. Contraindications for Ribavirin use
    • Anemia
    • End-stage Renal Disease
    • Ischemic vascular disease
    • Pregnancy
  38. Binds CCR5 receptor and prevents gp120 from binding and entering cells
  39. Maraviroc binds
    host CCR5 receptors (prevents gp120 from binding)
  40. Adverse Effects/ Contraindications of Miraviroc
    AE= Myocardial ischemia and infarction

    • Contraindicated in pts. w/:
    • Increase cardiovascular risk
    • End-stage renal empairment who are taking concurrent CYP3A inhibitors or inducers
    • Preexisting hepatic impairment
    • Co-infxn w/ HBC or HCV
  41. Miraviroc resistance is mediated by
    Mutations in the V3 loop of gp120
  42. Associated w/ mutations in V3 loop of gp120
    Resistance to maraviroc
  43. MoA of Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (e.g. Zidovudine)
    Triphosphate competes w/ native nucleotides -> loss of 3' OH -> chain termination
  44. Found in CSF at levels of 60-65% that of serum
    Zidovudine (AZT)
  45. Adverse Effects of Zidovudine
    Myelosuppression (macrocytic anemia, neutropenia)
  46. Zidovudine: Drug-Drug Interactions
    • Ganciclovir, Ribavirin = Increased hematologic toxicity
    • Stavudine (in vitro antagonism)
  47. Zidovudine resistance
    • Involves at least 3 or more of the following mutations:
    • M41L
    • D67N
    • K7OR
    • T215F
    • K219Q Reverse Transcriptase
  48. NNRTIs
    Efavirenz, Delavirdine, Etravirine
  49. NNRTI MoA
    • Binds to a nonessential site distant from enzyme catalytic site
    • *Doesn't compete w/ nucleotide triphosphates
    • *Doesn't require phosphorylation to be active
  50. Adverse Reaction of Delavirdine
    • Skin rash, increased AST
    • *Avoid in pregnant
  51. Inhibits CYP3A4, 2C9
    Extensively metabolized by
    • CYP3A
    • CYP2D6
  52. A single dose prevents spread of HIV from mother to fetus
  53. Adverse Effects of Etravirin
    Skin rash, increased serum cholesterol/triglyceride/glucose
  54. Substrate and inducer of CYP3A4
    Inhibits CYP2C9
  55. Binds to HIV integrase, prevents DNA strand transfer
    Raltegravir (integrase inhibitor)
  56. Metabolized by glucuronidation (does not interact with CYP450 system)

    What drug interacts with this?  How do you combat it?

    Rifampin interacts with this because it is a strong inducer of UGT1A1.  Dose of raltegravir should be doubled.
  57. Integrase enzyme is essential for replication of
    HIV-1 and -2
  58. Adverse Effect of Raltegravir
    Increased serum creatine kinase
  59. Increased serum AST
    Increased serum cholesterol/ triglyceride/ glucose
    Increased serum creatine kinase
    • AST= Delavirdine
    • C/T/G= Etravirin
    • CK= Raltegravir
  60. Prevents post-translational cleavage of Gag-Pol polyprotein, thus prevents viral proteins from becoming functional
  61. Do NOT administer Indinavir with
  62. Contraindicated w/ Protease Inhibitors
    Ant-Eaters Are Big 'In Hairy Herbivore Nomnoms

    • A= Antiarrhythmics (Quinidine)
    • E= Ergot Derivatives (Ergotamine)
    • A= Antimycobacterial Drugs (Rifampin)
    • B= Benzodiazepines (Triazolam)
    • I= Inhaled Steroids (Fluticasone)
    • H= Herbal Supplements (St. John's Wort)
    • H= HMG CoA Reductase Inhibitors (Lovastatin, Simvastatin)
    • N= Narcotics (Fentanyl)
  63. Antiretroviral Agents for use in Pregnancy
    • NRTIs:  Lamivudine, Zidovudine
    • NNRTIs:  Nevirapine
    • PIs:  Lopinavir/Ritonavir
Card Set:
Pharm Test 4: Antivirals
2013-02-08 18:08:02
Pharm Test Antivirals

Pharm Test 4 Antivirals
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