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Antivirals
Lecture 13
22
Pharmacology
Professional
02/07/2013

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Cards

Term
What are features of viruses?
Definition
Nonliving! DNA or RNA genomes covered by a capsid. Capsid may or may not have an outer envelope of glycoproteins
Term
What is caused by Papillomavirus?
Definition
51 strains cause warts and cervical cancer
Term
What are caused by Picornaviruses?
Definition
Polio, Meningitis, Colds (Rhinovirus)
Term
What virus is an Orthomyxovirus?
Definition
Influenza
Term
What are the steps in DNA viral replication?
Definition
- Absorption into the cell membrane
- Capsid uncoats
- Genome replicates inside host cell. Viral proteins assembled
- Virions bud out, sometimes taking envelop with them
Term
What are the steps in RNA viral replication?
Definition
- RNA virus makes contact and is absorbed by receptors
- A low pH allows release from endosome
- RNA translated to DNA --> protein.
- Viruses bud to release
Term
What are the 2 major components of the Influenza virus?
Definition
- Hemagglutinin - recognizes cells containing sialic acid (in the lungs). Ligand for receptors
- Neuraminidase - Cleaves sialic acid so virus can bud off
**H1N1 = Hemagglutinin1 Neuraminidase1
Term
What are the 3 types of influenza virus?
Definition
- A - bird flu. Most virulent! Antigenic change in H and N
- B - No serotypes, less mutation
- C - humans and pigs only. Mild in children
Term
What is the difference between H1N1 and H5N1
Definition
- H1N1 - a human flu that spreads through contact. Uses 2-6 Sialic acids
- H5N1 - more severe bird flu, does not spread human-human. But it could with a 1 AA substitution!!
Term
What is the cytokine storm?
Definition
Caused by all flus, especially H5N1: A potentially fatal rxn by positive feedback of immune response and cytokines
Term
What is the seasonal flu?
Definition
Any flu not pandemic related. Vaccine consists of 3 strains each year they think will be most prevalent.
Term
What dopamine mimics are used to treat the flu?
Definition
- Amantadine/Symmetrel - only Type A, within 48 hours and for prophylaxis. Crosses BBB
- Rimantadine/Flumantadine - Type A only, less CNS side effects
**Block M1/M2 channels in the endosome to prevent the virus from uncoating, virus dies in lysosome. Quickly become resistant
Term
What neuraminidase inhibitors are used to treat the flu?
Definition
- Zanamivir/Relenza - type A/B. Good against resistance. Seeing mutations in H and N. Inhaled within 48 hours
- Oseltamivir/Tamiflu - active in GI and against H5NI in high doses. Sometimes given w/ probenecid. Resistant mutants exist
- Peramivir - unapproved, used for emergencies
**Virus cannot be released from host by competing w/ Sialic acid
Term
What strains of herpes virus (HHV) cause human infection?
Definition
- HHV 1 and 2 - oral and genital herpes. HHV1 can cause blindness. HHV 2 is the most common cause of viral meningitis
- HHV 3 - chicken pox and shingles
- HHV 4 - Epstein Barr virus = mono
- HHV5 - CMV = infectious retardation
- HHV6 and 7 - Roseola, baby measles
- HHV8 - Kaposi's sarcoma, oncogenic
Term
How does Varicella reinfect a host?
Definition
Once a host has been infected with HHV3/chickenpox, HHV3 can hide in the nerves and affect individual dermatomes
Term
What drug is the gold standard for herpes tx?
Definition
Acyclovir/Zovirax - a guanine analog. Acyclovir gets tri-phosphorylated and incorporated into DNA instead of guanine - obligate chain termination
**Requires thymidine kinase, a virus only enzyme. Mycophenolate potentiates effects even more.
**Resistance: mutation in thymidine kinase, altered specificity for guanine, affinity for viral DNA polymerase
Term
What is the spectrum for Acyclovir and Valacyclovir?
Definition
HSV 1 and 2, HHV 3 (shingles), EBV (Valtrex), CMV (Valtrex)
Term
What other therapies for DNA viruses are obligate chain terminators?
Definition
- Cidofovir/Vistide - used for acyclovir resistance, HPV, pox. Obligate chain terminator, replaces Cytosine. MANY side effects: give with probenecid to prevent nephrotoxicity. Mutagenic, teratogenic
Term
What other therapies for DNA viruses are DNA kinkers?
Definition
- Penciclovir/Denavir - Very long half life, only used topically. Kinks the DNA due to structure
- Famciclovir/Famvir - Prodrug of denavir that's orally available. HSV, HHV3, HBV
- Ganciclovir/Cytovene - All HHV, especially CMV. A kinker. Used for Ocular CMV, tx of cancer by giving HSV TK first
- Valganciclovir/Valcyte - prodrug of ganciclovir, can use orally
Term
What other therapies for DNA viruses interrupt hydrogen bonding?
Definition
Idoxuridine/Virudox
Trifluridine/Viroptic
**Thymine analogs, side chains affect hydrogen bonding, DNA falls apart. Polymerase has a high affinity for these drugs = only used topically
Term
How does Vidarabine/Vira-A or Ara-A work?
Definition
An adenosine analog that inhibits viral polymerase, inserted into growing chain.
Term
What anti-viral is available OTC?
Definition
Docosanol/Abreva - A saturated alcohol. Inhibits the fusion of HSV w/ host membrane - only approved for topical oral HSV
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