T2 - Micro - Virology - Pharm 1 - Antivirals

Front 1

what are the challenges with developing anti viral drugs?

Back 1

lack of specific viral targets

the fact that the busiest time of viral growth is usually asymptomatic.

intracellular replication.

immune surveillance escape due to antigenic shifting.

latent reservoirs

and drug resistance generation.

Front 2

what types of influenza viruses are there?

Back 2

A, B, and C.

type A is the bad one - epidemics/pandemics are the result of these. Severe illness.

B is not as bad, C is even better.

Note that H and N stand for hemaglutenin and neurominidase. These are antigens on the surface that can be typed.

Front 3

what drugs can you use to attack influenza? what is their general mechanism of action?

Back 3

Amantadine and Rimantadine are two antivirals that prevent UNCOATING of the virus. Note that they work only on type A influenza.

Zanamivir and Oseltamivir are Relenza and Tamiflu, respectively - these work on both influenza A and B, and inhibit Neuraminidase.

Front 4

talk in more detail about our capsid-uncoating-blockers

Back 4

Amantadine and Rimatadine work through similar mechanisms and are both only effective against influenza A. Both are not used in pregnant moms.

Note that Amantadine can be a CNS stimulant and is not recommended for people with seizure disorders (though it is used as a therapy for parkinson's).

note that both are really only effective when taken prophylacticly (if exposed).

and because it has lower CNS toxcities, Rimatadine is preferred in this role.

Also note, 100% of H1N1 viruses are resistant to both amantadine and rimantidine.

Front 5

so if you can't use amantadine and rimantadine, what else can you use and how does it work?

Back 5

relenza and tamiflu, which are Zanamavir and Oseltamivir. Both of these work on Influenza A and B. Both work by stopping the cleavage of Neraminidase which stops viral particle release from infected cells.

Note that Zanimivir is available in an inhaled form. Oseltamivir is oral. Both can be used for PEP and Tamiflu (oseltamivir) be taken within 2 days of symptom onset.

Front 6

what are our herpes viruses?

Back 6

those that are NEUROTROPIC:
HSV1 (cold sores, herpes, encephalitis).

HSV2 (genital herpes, neonatal herpes).

VZV (varicella and shingles)


LYMPHATROPIC

CMV
HHV6/7 = encephalitis
HHV8 = KS
EBV - mono, BL, NPC.

Front 7

give a few special things about herpes viruses:

Back 7

complex genomes, expressing intermeiate early, early, and late genes.

Also uses rolling circle replication to make new DNA.

Front 8

what drug categories are good for treating herpes infections?

Back 8

Thymidine analogs,

purine analogs, guanosine analogs, phosphate analogs, and riboside analogs.

Front 9

talk about thymidine analogs - details?

Back 9

end with "DINE". Idoxuridine and trifluidine.

note that nucleoside analogues have to be ACTIVATED IN SEVERAL STEPS by host enzymes (need phosphates added). In contrast to nucleotides, which require a single step.

in the end, they STOP DNA POLYMERASE ACTIVITY

Idoxuridine and trifluradine are both used for the HSV's and for keratitis in the eye.

note that underline for trifuradine is the fact that it's the drug of choice for keratitis (topical) and can be used for acyclovir resistant strains of HSV.

Front 10

talk about acyclovir - how does it work, what does it work against, etc...what does it not work against?

Back 10

Acyclovir is a guanasine analogue. it is ACTIVATED BY THE VIRAL TK (thymidnine kinase) - this makes the monophosphate. The host enzymes make the di and tri phosphate versions.

STOP VIRAL DNA POLYMERASE and leads to chain termination. Note that resistance can come from mutations to TK enzyme. Doesn't work against CMV B/C the TK enzyme is different.

For treating HSV2 and shingles (VZV). Also for herpes encephalitis.

NOT FOR TREATING CMV - it's got a different TK that won't work on acyclovir

Front 11

what's another drug drug closely related to acyclovir?

Back 11

valacyclovir - also called VALTREX - it's really just acyclovir, 'cept here it's a PRODRUG and the stomach acids comvert it to acyclovir. So, it also stops viral DNA polymerase and leads to chain termination.

Again, good for ZOSTER and GENITAL HERPES.

Front 12

what's gancyclovir?

Back 12

another guanosine analog.

looks a lot like acyclovir, but with another group - it's NOW EFFECTIVE AGAINST CMV infection. Same deal, get chain termination/DNA pol inhibition.

NOT administered orally - given IV.

SERIOUS BONE MARROW TOXICITY.

Front 13

what's closely related to gancyclovir?

Back 13

valgancyclovir - here, another prodrug that gets converted into the real thing (gancyclovir) by the stomach acids.

Again, good for CMV infections, especially retinitis.

Front 14

what's our pyrophosphate analog?

Back 14

foscarnet. It competes for the pyrophosphate binding site on DNA polymerase, preventing it from working.

Good for Acyclovir resistant strains HSV or VZV infections, thoguh it's got lots of ion gradient side effects.

Front 15

what's ribivirin?

Back 15

it's a riboside analogue. Good for RESPIRATORY SYNCITIAL VIRUS (rsv) and, with interferon alpha for Hep C virus.

Prevents viral RNA polymerase from making proteins.

side effects include flu like symptoms.

Front 16

what do we use interferon alpha for?

Back 16

we make our own - so it supports natural immunity, kinda.


it ups ribonuclease activity, cleaves singel stranded RNA's floating around, stops protein synthesis.

Choice drug for Hepatitis B and Hepatatis C infections.(given alongside ribivirin, a riboside analog).

causes flu-like symptoms (using our own cytokines for stuff is an easy way to do this).

Front 17

how can we make interferon alpha last longer/

Back 17

pegylate it - lasts loger, requires fewer doses and is mroe effective. Note that normally, interferon alpha is given only IM and subQ.