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23 Cards in this Set

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What are obligate intracellular pathogens? What does this mean re: drug tx?
viruses; drugs must penetrate into cells to be effective.
Put in the txments
Poxviruses, Herpesviruses, Adenoviruses, Hepadnaviruses, and Papillomaviruses are all what type of viruses?
DNA
Rubella virus, rhabdovirus, arenaviruses, arborviruses, orthomyxoviruses, and paramyxoviruses are all what types of viruses?
RNA
I'm giving the drug, give the stage of viral lifecycle it blocks:

Protease inhibitors
NRTIs, NNRTIs
Rimantadine
Acyclovir
Admantadine
Interferon-a
Enfuvirtide
Neuramidase inhibitors
Palivizumab
Acyclovir
Foscarnet
Docosanol
Entecavir
Viral attachment/entry:
- enfuvirtide, docosanol, palivizumab

Penetration:
- interferon-a

Uncoating:
- Admantadine, Rimantadine

Nucleic acid synth
- NRTIs, NNRTIs, Acyclovir, Foscarnet, Entecavir

Late protein synth/processing:
- Protease inhibitors

Packaging/assembly/release:
- neuramidase inhibitors
What agents are used to tx herpes simplex & varicella-zoster virus infections?
- what does it need for actv?
- What is the difference between the two agents?

What viral enzyme ensure selectivity?
Acyclovir and Valacyclovir
- phos'ed to triphosphate form
- Valc. is the prodrug form of Acyc. that is converted in intestine and liver.

viral TKase converts these to monophosphate derivative w/ 100x selectivity.
What are the three ways Acyclovir and Valacyclovir inhibit DNA synth?
Competition with dGTP for the viral DNA polymerase
Incorporation into and termination of the growing viral DNA chain
Inactivation of the viral DNA polymerase
What are the pharmacoKinetics of Acyclovir and Valacyclovir?

Toxicities?
Resistances?
Given topically, orally, or IV
Valacyclovir achieves 3-5x conc. when given orally

Virtually none at normal doses.

Alterations in either viral TKase or viral DNA polymerase.
CMV reactivations leading to:
CMV retinitis
Colitis
CNS dz
Esophagitis
Pneumonia

.... are common in what pt population?
AIDS pts.
How do we tx CMV?
- similarities to Acyclovir and Valacyclovir?
- Which of the two is preferred orally?
- Most common SE? Do we also see nausea, diarrhea, fever, rash, HA, etc?
- mech of resistance?
Ganciclovir and Valganciclovir
- basically the same but have an additional CH2OH group
- Valganciclovir; b/c of higher serum concentrations.
- myelosuppression; yes, we see these as well.

decrease in formation of the triphospate form
muts in DNA polymerase
What is Phosphonoformic acid?
- mech?
- does it require phos to be actv?
- uses?
- Toxic to kidneys? Liver? Effects on ions? HA, hallucinations and seizures?
- resistances

Can it still be used in ganciclovir resistant CMV?
Forcarnet
- inhibits DNApoly @ diff site than acyc or gancic.
- no, it doesn't.
- CMV retinitis w/ gancic; HSV&VZV that are acyclovir resistant.
- Nephrotoxicity, messes w/ calcium lvls (up or down), kypokalemia, hypomagnesemia
.... HA, hallucinations, and seizures --> yes.

point mutations in DNA polymerase.

Yes.
Amantadine and rimantadine effect which influenza strains?
H5N1; H1 & H3
How does amantadine work?
Uses?
SE?
Resistances?
blocks M2 proton channel; prevents virus from acidifying/uncoating it's RNA
- very effective prophylaxis, reduces duration of Sx
- GI distress, CNS effects
- point mut in M2 proton channel
What are Zanamivir (Relenza) and Oseltamivir (Tamiflu)? Work against influenza A or B?
When must they be given?
Administration?

Side effects (diff for each)?

Resistance?
sialic acid deriviatives that act as neuramidase inhibitors.
- Both.
- early on
- Zanamivir --> inhalation
- Oseltamivir --> orally

Coughing, bronchospasm (zanamivir)
CNS effects (oseltamivir)

Rarely observed worldwide.
What is HAART?

What are the four classes of antiretrovirals that are available for use?
Highly Active AntiRetroviral Therapy.

NRTIs
NNRTIs
Protease inhibitors
Fusion inhibitors
What are the three NRTIs I should know?
- mech?
- Side effects?
Abacavir, Lamivudine (3TC), and Zidovudine (AZT)
- compet. inhib of HIV rev. Transcriptase & cause chain termination when incorporated into viral DNA.
- mitochondral toxicity,
- increases risk of lactic acidosis with hepatic steatosis
- lipid metabolism disorders
NNRTIs (3)?
- mech?
- b/ site re: NRTIs?
- require phos?
- general SEs?
+ which two should be avoided in pregnancy?
- All three are substrates of what?
+ which is an inhib? inducer? mixed?
Delaviridine, Efavirenz, Nevirapine
- inhibit HIV rt.
- close but distinct
- no.
- skin rash, GI intolerance
- delaviridine and efavirenz
- CYP3A4
+ inhib: delaviridine; induc: nevirapine; mix: efavirenz
What are the two protease inhibitors I should know?
- mech?
- result?
- Which can cause increased spontaneous bleeding in pts with hemophilia A or B? How about a redistribution & accumulation of body fat?
- all PIs are substrates of what?
- How is this useful?
Atazanavir and Lopinavir/Ritonavir combo
- block cleavage of Gag-Pol polyprotein --> structural proteins can't be produced in mature viron core.
- immature, non-infectous particles.
- all three; Lopinavir/Ritonavir
- CYP3A4
- subtherapeutic doses of ritonavir inhib CYP3A4 --> \met of lopinavir --> ^blood lvls of lopinavir.
What is Enfuvirtide?
- mechanism?
- used when?
- SE?
- $?
Fusion inhibitor
- b/gp41 in viral particle membrane, prevents fusion with host membrane.
- in combo w/ other drugs
- local injection site rxns, eosinophilia
- very $$$
What is a new integrase inhibitor?
- mech?
- resistance?
- when used?
Raltegravir
- targets integrase that gets the viral DNA into the host genome
- mut of integrase
- only in combo w/ other drugs
What is CCR5? What is Maraviroc?

Did resistance occur anyway?

Uses?
- CCR5 is the coreceptor for HIV viral entry
- antagonist of CCR5
- yes, some viruses have mutated to use CXCR4 instead of CCR5 for a co-receptor

Only in combo w/ other drugs.
What is used to tx Hep B and C infections?
- mech?
- what 4 things happen as a result?
interferon-a
- increases synth of proteins that lead to host viral resistance.
- these proteins inhibit:
1) synth of mRNA
2) translation of viral proteins
3) protein processing
4) viral assembly and release
How is interferon-a administered? What does pegylation do?
- Therapeutic uses of interferon-a?
- SE?
+ contraindications?
subQ or intraM
- lengthens the time for elimination
- HBV, HCV, Papillomavirus infections
- Flu-like syndrome that resolves upon continued administration
- neurotoxicity
- abortifacient in primates
**PREGNANCY*** see above