Antivirals

Herpesviruses
Drug

Mechanism

Resistance

Clincial

Acyckovir (guanosine analog)

Thymidine kinase P initially followed by intracellular

enzymes to ACV-TP.

Reduced or absent TK
Altered
viral DNA pol (less affinity ACV-TP) both w/
prolonged treatment in immunocomp pt

HSV-1>HSV-2>VZV
recurrent genital herpes; suppressive
therapy 80% reduction

Oral bioavailability 15-30% first

pass. IV more serious

Valacyclovir (guanosine analog)

ACV-TP compet inhib DNA Pol (chain terminator bc no 3

hydroxyl)
Cross resitance to ganciclovir NOT foscarnet

Toxic

Herpes encephalitis: prompt = better

outcome
Genital herpes, VZV bc more drug
required

Oral prodrug of ACV, 3-5x bioavailability

Genital herpes, VZV bc more drug

Famciclovir (guanosine analog)

~ACV (same clinical spectrum) prolonged intracellular

half-life compared ACV

Gancilovir ((guanosine analog)

intraocular implant (retinitis) or IV
Prodrug: valganciclovir, good oral

Intracellular P by UL97 (CMV encoded kinase) inhibits

viral DNA synth

Absence UL97, use foscarnet, cidofovir,

fomivirisen

Foscarnet (pyrophosphate analog) Inhib DNA pol of herpes virus, no metab req
by IV

CMV disease; AIDS pt, organ/BMT as

prophylaxis for donor+/recip-. CMV
pneumonitis

HSV, CMV, VZV when ACV or GCV

resistant

main problem: renal/electrolyte

abnormal

Clincial

Toxic

Influenzae
Drug

Mechanism

Amantidine and rimantidine

Inhibit viral M2 channel (ion), prevent lowering endosomal

pH required for hemaglutinin (HA) unfolding

Resistance

Mutation in HA, develops rapidly

Only effective vs Influenzae A, not B or

avian

Neurotoxicity (dizziness, ataxia) esp in

elderly w/ amantidine

Inhibit uncoating and entry of nucleocapsid

Prophylactic, tx w/ 36 hr of exposure

Neuroamidase inhibitrs, blocks release new virions

Influenzae A/B, effective vs strains

resistant to Aman and Rima

Shortage due to stockpiling

Clincial

Toxic

Zanamivir and Oseltamivir (sialic

acid analogs)
Z: inhaled powder O: good oral absorb

rare

Hepatitis C
Drug

Mechanism

Resistance

Aggravate autoimmune disorders

Interferon-a (cytokine) SC inject

Modulates immune response potently, PEG formulations

have longer half life

HCV in combination with ribavirin

Malaise, myalgia, fever, depression,
bone marrow suppression,
neuropsychiatric sx

Ribavirin (guanosine analog)

done by PO, IV, inhaled

Intracellular P by host cell decreases nucleotide pools and

inhibit viral mRNA

Active vs many RNA viruses

RSV in high risk infants/immuncomp
HCV in combo with IFN-a
Lassa virus in West Africa

Hemolytic anemia
Teratogenicity

Clincial

Toxic

Hepatitis B
Drug

Mechanism

Resistance

Chronic, active HBV

Lamuvidine nucleoside analog of
cytidine

Adefovir nucleotide analog of

adenosine monophosphate

Chain terminator of HBV RNA in RT of genome

Low threshold for development of resistance

Stoping lamividine may cause hepatitis

flare

HIV

Chain terminator of HBV DNA

High threshold for development of resistance

Mechanism

Resistance

Chronic HBV
Active vs WT and lamuvidine resitant

Others
Drug
Cidofovir monophosphate
nucleotide analog of dCTP
Admin by IV

Clincial

Toxic

CMV retinitis in AIDS pt.

Cellular P not by viral kinase will reduce DNA pol
function

Associated with mutations in DNAPol

Renal
Some activity vs smallpox

RSV prophylaxis in high risk infants

Palivizumab- injection

Monoclonal AB vs RSV

.
Vaccines
Live attenuated
Measles
Mumps
Rubella
Yellow fever
Oral polio (OPV)
Influenza (flumist)
Smallpox
Varicella

Inactivated

Hyperimmune globins (passive)

HAV
HBV
Polio (IPV)
Influenza
Rabies

HAV-IG
VZ-IG
HB-IG
R-IG
CMV-IG
RSV-IG