5. Agents to treat Herpes simplex (HSV), varicella- zoster (VZV) virus, cytomegalovirus (CMV) and respiratory syncytial virus (RSV) infection. Anti-influenza agents Flashcards

1
Q

What is the MOA of Acyclovir?

A

Acyclovir is a guanosine analog converted to acyclo-GTP by viral thymidine kinase (only HSV and VZV) and cellular enzymes → viral DNA polymerase inhibition + chain termination is specific to infected cells, because 1st P-ation requires viral enzyme! only works on replicating viruses; dormant DRG viruses not affected.

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2
Q

List the CMV agents.

A
  1. Ganciclovir
  2. Cidofovir
  3. Foscarnet
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3
Q

List the RSV medication.

A
  1. Ribavirin
  2. Pavilizumab
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4
Q

List the influenza medications.

A
  1. Amantidine
  2. Rimantidine
  3. Zanamivir
  4. Oseltamivir
  5. Peramivir
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5
Q

List the HHV+VZV agents:

A
  1. Acyclovir
  2. Valacyclovir
  3. Famicyclovir
  4. Trifluridine
  5. Docosonal
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6
Q

What is Famciclovir?

A

Oral prodrug converted to penciclovir, same MOA as acyclovir same indications as acyclovir, some EBV activity.

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7
Q

What are the indications for Valacyclovir?

A
  1. Suppressive Tx - 1x/day orally
  2. Shingles - for VZV (better activity than acyclovir); best w/in 3 days of sx onset but unclear efficacy in postherpetic neuralgia
  3. Prophylaxis - same as acyclovir
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8
Q

What is Docosonal?

A

It is an alcohol derivative that inhibits membrane penetration, 10% cream for herpes labialis.

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9
Q

What are the indications for Trifluridine?

A
  1. It is an older, less selective drug.
  2. Topical/local use as eye drop or solution.
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10
Q

What is the MOA of Ganciclovir?

A

It is similar to acyclovir, but uses a phosphotransferase in CMV for initial P-ation step.

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11
Q

What are the indications for Cidofovir?

A

Cidofovir is a dCMP analog, so no initial viral P-ation required → good for resistant HSV/CMV.

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12
Q

What is the MOA of Foscarnet?

A

Foscarnet causes direct inhibition of viral DNA polymerase, as a PPi analog.

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13
Q

What is the MOA of Amantadine and Rimantadine?

A

Amantadine and Rimantadine are cyclic amines that target M2 membrane proteins inhibiting uncoating of influenza-A viral mRNA and preventing replication.

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14
Q

What is the MOA of Zanamivir, Oseltamivir and Peramivir?

A

They are all neuraminidase inhibitors that inhibit neuraminidase needed for viral replication and release.

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15
Q

What is Ribavirin?

A

Guanosine nucleoside analog used as a Hep C medication.

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16
Q

What is the MOA of Pavilizumab and its indications?

A

It is a human mAb against F-glycoprotein on RSV surface, that prevents infection in high risk children.

17
Q

What are the side effects of Acyclovir?

A
  1. Renal Impairment - interstitial nephritis and crystalluria via IV use (↓ with slow infusion + hydration)
  2. CNS effects - delirium, confusion, vertigo, hallucinations (esp. ↑ dose or IV) … similar effects in all these drugs
18
Q

What is the resistance mechanism behind Acyclovir?

A

Some HSV strains may not have the necessary thymidine kinase.

19
Q

What is the route of administration of Acyclovir?

A
  1. given as topical creams, orally or IV
  2. good CNS penetration
20
Q

What are the indications for Acyclovir?

A
  1. Orally 7-10 days for oral/genital HSV daily suppressive tx for recurrent cases IV for HSV encephalitis, neonatal HSV and any serious HSV / VZV cases.
  2. Prophylaxis - in pregnancy (at wk 36) or immunocompromised / transplant pts (also prevents reactivation)
21
Q

What are some kinetic parameters to keep in mind with Valacyclovir?

A
  1. Valacyclovir is an acyclovir pro-drug
  2. Dosed 1x/day and better oral bioavailability
22
Q

What are the side effects of Ganciclovir?

A
  1. Myelosuppression - dose-limiting; causes all the -penias; worse in combo with HIV drugs (AZT, etc.)
  2. mucositis
  3. fever
  4. rash
  5. crystalluria (hydrate!)
  6. teratogenic
  7. overdose can cause seizure
23
Q

What are the indications for Ganciclovir?

A
  1. CMV - main use, prophylaxis and tx for retinitis, pneumonia, esophagitis, colitis, combined with anti-CMV hyperimmune serum
  2. also active against HSV, VZV, EBV, CMV, HHV-6 and 8.
24
Q

What are the kinetic like for Ganciclovir?

A
  1. given IV only but valganciclovir form is oral
  2. good tissue/CNS penetration
  3. renal elimination
25
Q

What are the indications for Cidofovir?

A
  1. CMV retinitis - in AIDS patients
  2. Resistant HSV/VZV infections - strains without thymidine kinase also active against adeno-, polyoma-, pox- and papillomaviruses.
26
Q

What are the side effects of Cidofovir?

A
  1. Nephrotoxic - via tubular secretion of drug; co-admin of probenecid blocks tubular secretion and thus toxicity symptoms (proteinuria, azotemia + metabolic acidosis)
  2. may cause neutropenia
  3. teratogenic
27
Q

What is the mechanism behind Cidofovir resistance?

A

Viruses with mutated DNA polymerase

28
Q

What are the kinetics like for Cidofovir?

A
  1. Give by IV admin only
  2. poor CNS penetration (↓ CNS sfx)
  3. renal elimination
29
Q

What are the indications for Foscarnet?

A

Resistant HSV, VZV, CMV strains (Resistance mechanism is the same as cidofovir)

  1. good for HIV patients that can’t take ganciclovir due to marrow suppression.
30
Q

What are the indications for Amantadine + Rimantadine?

A
  1. Prophylaxis - in high risk groups
  2. Also work to prevent disease progression in existing infection - ↓ symptoms if taken in first 48 hrs.
31
Q

What are the indications for Zanamivir, Oseltamivir and Peramivir?

A

Both influenza A + B, but only within 72 hours of infection.

32
Q

What is the route of administration for Foscarnet?

A

given IV and penetrates CNS

33
Q

What are the side effects of foscarnet?

A
  1. Nephrotoxic - causes ATN; ↓ Ca/K/Mg plus pH imbalance
  2. Seizures - via electrolyte disturbances
  3. Interaction with pentamidine (for P. jirovecii) → serious hypocalcemia
34
Q

What are the side effects of Amantadine + Rimantidine?

A
  1. GI intolerance and CNS issues (nervousness + ↓ concentration)
  2. Use reduced dosages in pt > 65 and renal insufficiency
35
Q

What is the mechanism behind Amantidine and Rimantidine resistance?

A

Resistance by M2 mutation

36
Q

What are the side effects of Zanamivir, Oseltamivir and Peramivir?

A

They are generally well-tolerated.

37
Q

What is the route of administration for Oseltamivir and Zanamivir?

A
  1. Oseltamivir is an oral pro-drug
  2. Zanamivir is only given nasally are renally cleared