Pharmacology Exam 1

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Viruses consist of particles containing
- nucleic acid
- either RNA or DNA
- single or double stranded
Enveloped viruses
- herpes simplex
- varicella
- HIV
non-enveloped viruses

adenovirus
Envelope protein antibodies found in HIV patients

GP120
Latency stage

cannot be targeted by current therapeutics
Targets of antiviral therapy
- attachment
- entry
- uncoating
- puring and pyrimidine analogs
- reverse transcriptase inhibitors
- protease inhibitors
- viral release
Antiviral agents against herpes simplex & varicella zoster
- acyclovir
- valacyclovir
- famciclovir
Herpes simplex latency is controlled by

the immune system
Acyclovir is active against
- HSV-1, 2 (most effective)
- VZV
- CMV
- EBV
Acyclovir is a _____ analog

acyclic quanine nucleoside
Acyclovir has ____ oral bioavailability and a half life of ____.
- low
- 2-3 hr
Acyclovir works by
- preventing 5'=>3' synthesis
- results in chain termination
Mechanism of action for Acyclovir

phosphorylation of viral thymidine kinase blocks 5'-3' elongation
Side effects of acyclovir
- pain at injection site
- crystalline nephropathy
Valacyclovir
- prodrug converted to acyclovir
- increased stability & bioavailability (54%)
Famciclovir
- Prodrug converted to penciclovir
- guanosine analogue
Famciclovir is active against
- HSV 1&2
- VZV
- EBV
- HBV
Famciclovir is activated by

viral thymadine kinase
Mechanism of action for famciclovir
- inhibits DNA polymerase directly
- no effect on chain elongation/termination
Famciclovir compared to Acyclovir
- lower affinity for viral TK than acyclovir
- achieves higher intracelluar concentrations than acyclovir
Penciclovir use

available for topical application against herpes labialis
Cytomegalo virus
- Large DNA virus
- Herpes virus
- associated with salivary glands
- problem in immunocomprimised pt
Cytomegalovirus is considered to be

an AIDS defining infection
Antiviral agents used to compbat cytomegalovirus
- ganciclovir
- valganciclovir
- foscarnet
- cidofovir
Ganciclovir
- guanosine analog
- Prodrug
- short half life (2-4hrs)
Mechanism of action for ganciclovir

prevents chain elongation
Resistance to ganciclovir
- mutations in the drug target phosphotransferase
- cross resistance with strains resistant to acyclovir
Uses for ganciclovir

CMV retinitis
Side effects of ganciclovir
- bone marrow suppression
- lack of neutrophils (bad for HIV pt)
Valganciclovir
- ganciclovir prodrug
- same MoA and effects as ganciclovir
- activated by intestines and liver
Foscarnet

pyrophosphate analog
Foscarnet is active against
- HSV
- VZV
- CMV
- EBV
- HHV-6
- KSHV
- HIV-1
Foscarnet availability
- IV only due to poor absorption
- 30% deposit into bone making half life months
Foscarnet compared to ganciclovir for CMV

same efficacy
Foscarnet side effects
- nephrotoxicity
- hyperphosphatemia
- hypomagnesemia
- n/v
- CNS toxicity
Cidofovir mechanism of action

binds viral DNA polymerase blocking DNA synthesis
Cidofovir uses
- CMV retinitis
- acyclovir resistant herpes
- papilomavirus
- poxvirus
- adenovirus
- polumavirus
Cidofovir side effects
- nephrotoxicity
- uveitis
- ocular hypotony
- neutropenia
Ways to reduce nephrotoxicity of Cidofovir

administer probenecid 3h before, 2h and 8hr after
Hep A
- no long term liver damage
- low mortality
- developing countries
Hep B
- hepadenavirus
- DNA polymerase activity
- Reverse transcriptase activity
Hep C

single stranded RNA virus
Commonalities between Hep B, Hep C and HIV
- Reverse transcriptase activity (B)
- single stranded RNA virus (C)
Hepatitis compared to Herpes viruses

not genetically related
Drugs for Hep B
- Lamivudine
- Adefovir
- Entecavir
- Interferon alpha 2B
Lamivudine
- Hep B
- nucleoside analog (NRTI)
- once daily
Adefovir
- Hep B
- NRTI
- not for HIV
- nephrotoxic at high doses
Entevavir
- Guanosine nucleoside analog
- once daily
- Hep B
Interferon alpha 2B
- Hep B & C
- once daily or 3 times weekly injection
Drugs for Hep C
- Ribavirin
- Interferon alpha 2A and B
Ribavirin
- Hep C
- inhibits capping of viral mRNA
- teratogenic
Influenza A
- part of its life cycle in another host and can mutate differently than B
- more recombinant events with A
Influenza B

more genetic drift
Zanamivir
- prodrug activated by esterase in GI and liver
- inhibitor of influenza A & B neuraminidases
- low oral bioavailabilty
Zanamivir mechanism of action

prevents release of virus from infected cells
Osteltamivir
- prodrug activated by esterase in GI and liver
- inhibitor of neuraminidase
- prevents viral release
- high oral bioavailability
Amantadine & Rimantadine
- inhibit uncoating of viral RNA
- well absorbed
- Rimantidine 4-10x stronger than amantadine
- influenza A
- may be used with zanamivir and oseltamivir

Author

Rx2013

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Card Set

Pharmacology Exam 1

Description

Anti-Viral Agents

Updated

2011-01-22T18:03:20Z

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