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

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
**What are the indications for Cidofovir?**
1. **CMV retinitis** - in AIDS patients 2. **Resistant HSV/VZV infections** - strains without thymidine kinase also **active against adeno-, polyoma-, pox- and papillomaviruses.**
26
**What are the side effects of Cidofovir?**
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
**What is the mechanism behind Cidofovir resistance?**
Viruses with mutated DNA polymerase
28
**What are the kinetics like for Cidofovir?**
1. Give by IV admin only 2. poor CNS penetration (↓ CNS sfx) 3. renal elimination
29
**What are the indications for Foscarnet?**
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
**What are the indications for Amantadine + Rimantadine?**
1. **Prophylaxis** - in high risk groups 2. Also work to **prevent disease progression in existing infection** - ↓ symptoms if taken in first 48 hrs.
31
**What are the indications for Zanamivir, Oseltamivir and Peramivir?**
Both **influenza A + B**, but **only within 72 hours of infection**.
32
**What is the route of administration for Foscarnet?**
given IV and penetrates CNS
33
**What are the side effects of foscarnet?**
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
**What are the side effects of Amantadine + Rimantidine?**
1. **GI intolerance** and **CNS issues** (nervousness + ↓ concentration) 2. Use reduced dosages in **pt \> 65** and **renal insufficiency**
35
**What is the mechanism behind Amantidine and Rimantidine resistance?**
Resistance by M2 mutation
36
**What are the side effects of Zanamivir, Oseltamivir and Peramivir?**
They are generally well-tolerated.
37
**What is the route of administration for Oseltamivir and Zanamivir?**
1. Oseltamivir is an **oral pro-drug** 2. Zanamivir is only given **nasally are renally cleared**

Pharmacology (Topic C) (20 decks)

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