Herpes Viral Infxns Treatment Flashcards
Agents used for herpes viral infections are…
acyclic guanosine analogs
Acyclic guanosine analogs are:
1) Acyclovir
2) Valacyclovir
3) Famciclovir
4) Penciclovir
Two drugs that treat herpes viral infections that are NOT acyclic guanosine analogs:
1) Trifluridine (Viroptic)
2) Docosanol (Abreva)
Herpeviridae causes a family of viruses such as:
1) HSV-I
2) HSV-II
3) VZV
4) EBV (Epstein Bar Virus)
5) CMV (cytomegalovirus)
Acyclovir is effective against:
1) HSV-I
2) HSV-II
3) VZV
Acyclovir has weaker activity against which viruses?
1) EBV
2) CMV
3) Human herpes virus 6
What is acyclovir’s MOA?
1) Viral thymidine kinase converts to monophosphate
2) Host enzyme phosphorylate monophosphate to di & triphosphate
3) Triphosphate is used during polymerization which causes chain termination
Acyclovir is only activated where?
Viral infected cells
Acyclovir acts as a what?
competitive inhibitor of viral DNA polymerase by forming an irreversible complex on DNA and causing chain termination due to lack of OH groups required for chain extension
The only antiherpes drug available for IV admin?
Acyclovir
In HSV-I and HSV-II acyclovir’s clinical use is used to what?
1) Shorten duration of symptoms
2) Decrease virus shedding
3) Shorten time of resolution of lesion by 5 days
In recurrent genital herpes, acyclovir shortens time course by:
1-2 days
Long term chronic therapy of acyclovir decreases what?
1) symptomatic reoccurrences
2) asymptomatic viral shedding (prevents viral shedding)
3) Reduces sexual transmission
If acyclovir for long term therapy of HSV is d/c’d, what will happen?
outbreaks will resume
For varicella zoster virus, if oral acyclovir is administered within 24 hours of rash, what will happen?
It will decrease total number of lesions AND duration
Acyclovir will decrease lesions and duration of cutaneous zoster (shingles) if administered within how many hours?
72 hours
Acyclovir will decrease lesions and duration of herpes zoster virus (chicken pox) if administered within how many hours?
24 hours
What prevents reactivation of HSV in TRANSPLANT patients on immunocompromised therapy?
Acyclovir
IV Acyclovir is the the treatment of choice for what SEVERE infections?
1) herpes simplex encephalitis
2) neonatoal HSV infection
3) serious HSV or VZV infection
Are high doses of Acyclovir required for treatment of HSV or VZV?
Higher doses are needed for VZV therapy
In immunocompromised patients, IV acyclovir reduces both…
cutaneous (skin) AND visceral (organ) dissemination (spread)
Topical acyclovir has what effect on reoccurence of herpes?
Less effective, no benefit
Resistance of Acyclovir occurs do to:
mutations in either the Viral Thymidine Kinase or Viral DNA Polymerase
Cross resistance of acyclovir occurs in what drugs?
1) Valacyclovir
2) Famciclovir
3) Ganciclovir
Cross resistance of acyclovir occurs b/c:
drugs require activation by viral TK
What drugs are used when there is resistance to acyclovir?
1) Foscarnet
2) Cidofavir
IV Infusion of Acyclovir may cause what adverse effects?
Reversible renal dysfunction due to crystalline nephropathy and neurotoxicity, but rare.
The L-valyl ester of acyclovir is?
Valacyclovir
Valyl derivation does what?
improves bioavailability (48%) and gets rapidly converted to acyclovir
Valacyclovir is indicated for what?
1) HSV-I
2) HSV-II
3) VZV
4) CYTOMEGALOVIRUS (NEW***)
Which is slightly more effective for treatment of HSV I, II, and VZV?
Valacyclovir
What is considered a high doses of Valacyclovir?
8g/ day
High doses of Valacyclovir causes what in AIDS patients?
1) GI Intolerance
2) thrombotic thrombocytopenia purpura (TTP) (can be fatal!)
3) Hemolytic-uremic syndrome
High doses of Valacyclovir can cause what in transplant patients?
Confusion and hallucinations
A diacetyl ester prodrug of 6-deoxypenciclovir is…?
Famciclovir (Famvir)
Famciclovir (Famvir) is what kind of ester?
a di-acetly ester prodrug of 6-deoxy-penciclovir
Famciclovir’s MOA?
1) activated by phosphorylation into monophosphate by VIRAL TK (same as Acyclovir)
2) inhibits Viral DNA polymerase
Famciclovir’s MOA is the same as Acyclovir’s except…
it does not cause chain termination
Famciclovir’s resistance is due to:
TK mutation
Famciclovir shows cross resistance to:
1) Acyclovir
2) Valacyclovir
What is the preferred treatment for Shingles (cutaneous zoster)?
Famciclovir
What drug has better oral bioavailability and is a pro-drug, so it is often prescribed?
Famciclovir
What is the oral bioavailability of Famciclovir?
70%
Famciclovir undergoes what elimination?
Renal
First line treatment for recurrent genital herpes (HSV-2)?
Famciclovir
First line treatment for acute herpes zoster (shingles)?
Famciclovir
Viral proliferation in what infection causes neuralgia?
Herpes zoster virus (shingles)
Famciclovir does not prevent what complication in shingles?
postherpatic neuralgia
Famciclovir is accompanied by what drugs to alleviate neuralgia in herpes zoster patients?
1) Gabapentin
2) carbamazepine
3) Pregablin (lyrica)
Famciclovir should be used cautiously in what patient population?
Elderly, due to neuralgia
Viral proliferation in the dorsal root ganglia can cause…
neuralgia
What is the active metabolite of Famciclovir?
Penciclovir (denavir)
What therapy is effective for reoccurrent herpes libialis (oral HSV-I) in immunocompromised adults?
Penciclovir 1% topical cream
Penciclovi 1% topical cream must be administered how to be effective?
1) Within an hour of eruption
2) Applied every 2 hours during waking hours for 4 days
Trifluridine (virpotic) is actually…
tri-fluro-thymidine
Trifuluridine MOA?
1) It is phosphorylated by CELLULAR TK
2) and becomes incorporated into BOTH viral and chromosomal DNA
3) This is why it cannot be used systemically!!**
4) So, it inhibits viral DNA synthesis
Trifluridine is an effective treatment for what?
1) viral keratoconjunctivitis (eye infxn)
2) recurrent epithelial keratitis due to HSV-1 and HSV-2
How should Trifluridine be used?
as a topical 1% solution
What can be used in conjunction with INF-a for acyclovir resistant HSV?
Trifluridine
Docosonal is a what?
saturated 22-carbon aliphatic alcohol
How is Docosonal available?
an OTC 10% cream for topical application
Docosonal MOA?
inhibits fusion b/w the plasma membrane and HSV envelope, preventing viral entry into the cells
You must use Docosonal when?
As soon as you have symptoms!
Docosonal (abreva) shortens duration of…
recurrent oro-labial herpes (oral herps, HSV-1)
