Antiviral Drugs

Front 1

Acyclic drugs -- acyclovir-- MOA, use, and selectivity

Back 1

MOA: guanosine analog which inhibits DNA polymerase and acts as a terminator
Use: HSV, VZV
Selectivity: viral TK has much increased affinity to acyclovir then cellular kinase-- approx 300kX

Front 2

Acyclic drugs-acyclovir-- PK, toxicities, and drug resistance

Back 2

PK: need intracellular activation to triphosphates to work, and have higher affinity for viral enzymes than cellular counterpart. Have poor water solubility and poor oral bioavailability--due to short half life (b/c quickly degraded)
Toxicity: generally well tolerated b/c high selectivity but crystalluria if pt not well hydrated.

DR: gene mutn in TK or DNA pol

Front 3

Acyclovir-- cogeners

Back 3

- valcyclovir-- ester with improved oral bioavailability
- penciclovir-- higher intracell stability (longer half life)
- famciclovir - ester of penciclovir with improved oral bioavailability

Front 4

Vidarabine-- MOA, use, resistance

Back 4

MOA: adenosine analog which is activated by viral TK, inhibits viral DNA pol but is NOT chain terminator
Use: topical treatment of herpes keratititis (lim use b/c rapid metabolic inactivation and high genetic toxicity)
Resistance: due to freq mutn of viral DNA pol

Front 5

Ganciclovir-- MOA, USE, resistance

Back 5

MOA: derivative of acyclovir by one side chain, sim to acyclovir except activated by CMV encoded kinase (UL97)
USE: CMV
Resistance: mutn in UL97

Front 6

Ganciclovir-- PK and toxicity

Back 6

PK-- poor oral bio-availability (improved in valganciclovir), renal elimination
Toxicity-- myelosuppression leading to severe neutropenia when used with AZT

Front 7

CidoFOvir- MOA, use, resistance

Back 7

- MOA- is cytidine monophosphate analog-- virus indep drug activatn, DNA pol inhibitor and chain terminator
- use: HSV, VZV, when acyclovir resistance and CMV. Given as IV and must be prehydrated and also give probenecid (which uses the same transporters in the kidney) to reduce excretion and protect kidneys

Front 8

CidoFOvir-- toxicity, USE

Back 8

Tox- renal tox is rate limiting
Use: HSV (via TK), VZV (via TK), CMV (via UL97)

Front 9

FOscarnet- MOA, resistance, PK, tox, use

Back 9

MOA: analog of pyrophosphate which blocks pyrophosphate bindings site on viral DNA pol
Resistance: viral DNA pol mutn
PK: IV injection, renal elimination
Tox- renal impairment, pts need to be well hydrated
USE: HSV (via TK), VZV (via TK), CMV (via UL97)

Front 10

Lamivudine- MOA, PK, resistance, and use

Back 10

MOA-- cytidine analog which is RT inhibitor and chain terminator
PK- oral, renal elimination
Resistance -- rapid
Use: HBV and HIV (but at much higher dosage)

Front 11

Lamivudine alternative
Use

Back 11

AdeFOvir dipivoxil- diester of adefovir
Use: HBV

Front 12

Adefovir dipoxil-- MOA, resistance, PK, toxicity, Use

Back 12

MOA: AMP nucloetide analog (cidoFOvir is CMP analog for HSV), acts as NRTI
Resistance: no resistance for up to a yr, which is advantage over lamivudine
PK: oral and renally eliminated as adeforvir
Tox- dose limiting renal toxicity
Use: HBV

Front 13

Interpheron alpha- use and MOA

Back 13

Use: recomb protein used for HBV, prophylactically for HCV, and for treating chronic hep C
MOA: a cytokine which binds to cell memb receptors to cause gene expression, inhibits viral replication inside infected cells by interfering with viral rep cycle, and stims systemic immune responses by activating macrophages and NK

Front 14

Interpheron alpha- PK

Back 14

PK- subcut or IM injection, drug in serum is filtered and proteolytically degraded, pegylted form with polyethylene glycol has longer half life

Front 15

Interpheron alpha- Toxicity

Back 15

pyrogen, fever and flu like symptoms, injection site tissue damage, bone marrow suppression at high doses

Front 16

Interpheron alpha- contraindication, use

Back 16

hypersensitivity, autoimmune disease, hepatic decompensation (when liver cannot compensate for damage anymore)
use: HBV, HCV

Front 17

Ribavirin- Use, MOA, Contraindication

Back 17

- adjunctive HCV drug, monotherapy NOT effective, aden/guan analog (dual analog)
MOA- inhibits RNA replication by hypermutn-- NOT a chain terminator
Contraindication: pregnancy!

Front 18

Amantidine and Rimantidine- use, class, MOA, resistance

Back 18

Use: Influenza A
Class: M2 inhibitors--adamantane derivatives NOT nucleoside analogs
MOA: M2 blocker-- useful only for prophylaxis and early treatment of influenza A infec
Resistance--highly frequent and strain dependent

Front 19

FLU

Back 19

Orthomyxovirus: negative-stranded RNA virus
Influenzavirus A: infects humans and birds (avian flu)
• Viral RNA-dependent RNA transcriptase does not proof-read
• Virus codes for and uses
1) Hemagglutinin (binds to sialic acid) for entering cells
2) Neuraminidase (cuts sialic acid) for leaving infected cells
• Strain designation by H and N variants, e.g. H1N1 (the swine
flu!)
• Virus uncoating requires viral M2, an H+ channel

Front 20

Amantdaine and Rimantadine- PK and Tox

Back 20

PK- oral, renal elim (amant), liver metab and renal elim (Rim)
Tox- GI, CNS side effects, aman is more CNS tox than rimantidine, Aman overdose cause agitation, Hallucinations, cardiac arrythmia, and death

Front 21

Oseltamivir and Zanamivir--chem, MOA, PK

Back 21

Chem-- sialic acid analog
MOA: neuraminidase blocker, used prophylactically for influenza A and B
PK: oral (oseltamivir)and intranasal inhalant (zanamivir), renal elim

Front 22

Oseltamivir and Zanamivir- use, tox, resistance

Back 22

Use: influenza A and B
Tox- GI irritaiton for oseltamivir or bronchospasm for zanamivir
Resistance:98% for oseltamivir (tamiflu) and 1 resported case to Zanamivir