Class Mechanism of Action Clinical Use Toxicity/Resistan

Name
ce
Inhibitor of • Work on RNA Viruses • Must be used within 24-48 hrs • CNS- dizziness,
cell • Early Stages of Infection to be effective. ataxia, slurred
penetration • Prevents Uncoating or inhibit RNA • Active against Influenza A, speach
and transcription by targeting the M2 Matrix NOT B • Minor nervousness
uncoating • Light- headedness
protein • Used for prophylaxis and
(a man to DINE takes off his COAT) treatment of u=Influenza A
Amantadine, • Low doses may inhibit viral assembly Resistance:
• Taken orally
Rimantadine • May buffer pH of endosome Influenza A becomes
• Parkinson’s Disease
• Causes release of dopamine from intact “Amantadine blocks Influenza A resistant during
nerve terminals and rubellA and causes treatment-requires
problems with the cerebeallA” only a single amino
acid change in a
transmembrane M2
protein.
Inhibitor of • Selectively inhibit the Neuraminidase • Both influenza A and B
Neuraminida of influenza virus, decreasing the release • Taken Orally, inhaler
se of progeny virus. • Reduces influenza
Oseltamivir
(Neuraminidase is a spike on the virus that symptoms and shortens
Zanamivir
causes cleavage of sialic acid from illness
glycoprotiens on the host cell and destroys
the receptor for influenza )
Inhibitor of • Is a halogenated Pyrimidine that Herpetic Infections of the
Nucleic Acid incorporates into host DNA in place if Cornea
Synthesis Thymidine and blocks Nucleic acid
Idoxuridine synthesis.
( 5-iodo-2- • In systemic administration, thymidine
kinase phosphorolates (does first
deoxyuridine-
phosphorolation) the drug to form the active
IUdR) derivative that can be incorperated into host
DNA.
• Inhibits BOTH viral and cellular DNA
synthesis
Inhibitor of Pyrimidine analog Herpetic Corneal Infections
Trifluorothymid
Nucleic Acid including those resistant to
ine Synthesis IUdR
Adenine Inhibitor of • Purine • IV administration reduces Less toxic than IUdR
Arabinoside Nucleic Acid • Inhibits DNA polymerase mortality from Herpes and
(Vidarabine) Synthesis • It is phosphorolated to its active form encephalitis Trifluorothymidine
Intracellularly • Neonatal Herpes
• 15-30X’s more susceptible to Herpes DNA Simplex
Pol than Cellular DNA Pol • Herpes Zoster in IC pts.
 • Herpes of the eye
Inhibitor of • Guanosine Analog • Very active against Little toxicity
Nucleic Acid • Monophosphorolated by HSV/VZV replicating Herpes Simplex: Resistance:
Synthesis Thymidine Kinase genital and encephalitis • Emerges after long
• Herpes Virus has this enzyme • Herpes Simplex term
• CMV and human cells lack this, so prophylaxis in administration due
it NOT toxic to them. Immunocomprimised patients to development of
and for frequent reccurences mutations in
• Triphosphate formed by cellular kinase.
Acyclovir of genital herpes. Thymidine Kinase
• Inhibits viral DNA Polymerase by chain and alteration of
(Acycloguanisi termination 100X more than Cellular • Less effective for varicella
and EBV viral DNA
ne) DNA Polymerase. polymerse.
• Causes termination if herpes DNA • Does not work on CMV
• Resistant mutants
elongation. • Topical, Oral and IV
are sensitive to
preparations.
foscarnet and
vidarbine b/c they
do not require viral
thymidine kinase
for activation
Inhibitor of Gaunosine analog • Inhibits growth of ALL Toxicity for
Nucleic Acid • 5-monophosphate formed by a CMV Viral human herpes viruses, uninfected host cells
Synthesis Kinase or an HSV/VZV Thymidine Kinase. including CMV (esp rapidly
• Ul97 gene and Cellular Kinase converts to • CMV in AIDS patients dividing):
Ganciclovir Di and Tri-phosphate forms • CMV retinitis • Leucopenia
Acyclovir • It is not dependent on virus-specific • Relapses common when • Neutropenia
analog thymidine kinase for phosphorylation, so the drug is stopped. • Spermatogen
- use after get kills all Herpes Viruses including CMV and is esis
mutants to toxic to human cells. • Gut mucosa
Acyclovir • ( - ) Viral DNA Polymerase • Bone marrow
precursors
Resistance: Mutated
CMV DNA Polmerase
r lack of Viral Kinase
Foscarnet Inhibitor of • Trisodium Phosphonoformate, a • Highly effective against Nephrotoxicity
- use after get Nucleic Acid Pyrophosphate analog. active CMV and acyclovir
mutants to Synthesis FOScarnet=pyroFOSphate analong resistant herpes simplex Resistance:
Ganciclovir • Directly inhibits DNA polymerase of all • Must be given by Mutated DNA
Herpes viruses by binding to the continuous IV polymerase
pyrophosphate binding site on the
enzyme, inhibits RNA polymerase of all
influenza viruses, and inhibits reverse
transcriptase of retroviruses.
• Does not require activation by a viral
 kinase
Ribavirin Inhibitor of • Guanosine Analog • RSV, Influenza A/B- aerosol • Hemolytic
Nucleic Acid • (-) the synthesis of guanosine 5-phosphate • Chronic Hep C- when Anemia
Synthesis required for synthesis or viral nucleic acids combined with Interferon • Taratogen
by ( - ) IMP Dehydrogenase • Arenavirus- Lassa fever

( - ) Viral acts on poxvirus infection by ( - ) late viral Poxvirus

Methisazone Assemb protein synthesis
•Are host proteins that provide first line of •Proved beneficial in the •Some toxicity
defense against viral infections treatment of chronic hepatitis because of effect on
•Recombinant interferons are commonly used B and hepatitis C host cell protein
•Active against HIV in vitro and synthesis
• They are glycoproteins from human
synergistic with AZT • Neutropenia
leukocytes that block the various stages of
viral RNA and DNA synthesis.
• Induce ribonuclease that degrades viral • IFN alpha- Chronic
mRNA Hepatitis B and C,
Kaposi’s Sarcoma
•In the presence of interferon, the synthesis of • IFN beta- MS
two cellular enzymes is induced
•The first is protein kinase that • IFN gamma- NADPH,
phosphorylates and thereby inactivates one of Oxidase Deficiency
Interferons
the subunits of an initiation factor necessary
for protein synthesis
•The second is 2’, 5’ -oligo synthetase that
activates a constitutive ribonuclease that
degrades mRNA and the action of both
enzymes requires double stranded RNA
and prevents adverse effect on uninfected
cells
•Viral infection of a cell that has been
exposed to interferon results in general
inhibition of protein synthesis, leading to
cell death and no virus production
Gene Antisense synthetic oligonucleotide
Fomivirsen Therapy complement to CMV mRNA

HIV Therapy
Name Class Mechanism of Action Clinical Use Toxicity/Resistance
Maraviroc Entry and • Blocks the HIV co-receptor • Used as part of • Concern that it may
Fusion (chemokine receptor) CCR5 (mostly combination therapy push patient to HIV
Inhibitor macrophages). CCR5 is what binds to the • Lowers viral load in X4 that uses CXCR4
HIV envelope protein gp120, aids in entry patients with coreceptor
of virus predominantly HIV R5 predominantly on
Tcells and therefore
 induce AIDS faster
• Cough
• Fever
• Dizziness
• Headache
• Hypotension
• Nasea
• Bladder irritation
• Liver problems
• Cardiac events
• Elevated cholesterol
Entry and • Inhibits envelope protein gp41 from • In patients with persistant • Injection only, high
Fusion fusing to host plasma membrane by replication despite risk of infection at
Inhibitor binding to gp41 and inducing a antiretorviral therapy injection site
Enfuvirtide conformational change • High risk of bacterial
• So blocks entry and replication pneumonia

Nucleoside Inhibits HIV replication • Always use in • Bone marrow

Reverse • Phosphorolates to 5-triphsphate form by combination toxicity-severe
Transcriptas cellular enzymes in vivo. • Reduces anemia and
e Inhibitor • Inhibits reverse transcriptase by opportunistic neutropenia
Zidovudine/ terminating viral DNA elongation- gets infections in AIDS
AZT incorporated into the chain b/c looks like a patients Resistance: becomes
nucleotide. • Reduce vertical resistant over time due
transmission when to mutation in the
given in pregnancy reverse transcriptase.

Nucleoside •Inhibit HIV replication by blocking •Causes increased CD4+ peripheral

Reverse reverse transcription T lymphocyte count and neuropathy
Transcriptas •Phosphorylated to active triphosphate form decrease in HIV p24 pancreatitis
e Inhibitor like AZT by cellular enzymes antigen levels
Didanosine- •ddI is approved for
ddl advanced HIV infection after
Zalcitabine- AZT resistance
ddC •ddC is approved in
combination with AZT for
adults with advanced HIV
infection who show
deterioration
Stavudine- Nucleoside nucleoside analog that inhibits HIV replication HIV • headache
D4T Reverse •D4T is phosphorylated by cellular enzymes to • nausea and vomiting
Transcriptas active triphosphate • confusion
e Inhibitor •Terminates viral nucleic acid synthesis • elevated serum
 transaminase and
creatine kinase
• peripheral neuropathy
Name Class Mechanism of Action Clinical Use Toxicity/Resistance
Nucleoside Reverse transcriptase inhibitor •Used in combination with comparatively safe and
Reverse AZT or other inhibitors usually well-tolerated
Transcriptas •3TC and AZT have unique
e Inhibitor interactions; 3TC
suppresses the
Lamivudine-
development and
3TC persistence of AZT
resistance mutants
Hepatitis B when combined
with interferon alpha

Non- •Non-nucleoside analogs also inhibit HIV •Active against both AZT- •Less toxic because
Nevirapine, Nucleoside replication sensitive and AZT-resistant they do not inhibit host
delavirdine Reverse •These compounds do not require isolates DNA polymerase
and Transcriptas phosphorylation and bind to reverse •Useful when combined with •Drug resistance readily
eavirenz e Inhibitors transcriptase other antivirals emerges
• Bone marrow
“Never Ever suppression
• Peripheral
Deliver
neuropathy
nucleosides” • Rash
Integrase • Newest Agents. • Patients who have
Inhibitor • Prevent integration of HIV DNA into developed
host chromosomes. resistance to other
Raltegravir HAART drugs.
• Shows rapid decline in
viral load
• Use in Combo therapy
Protease •-Protease inhibitors inhibit the HIV •Used in combination with •May be hepatotoxic
Inhibitor protease that is required to process HIV other inhibitors because • GI Intolerance
Ritonavir, gag precursors to mature gag (capsid, monotherapy results in rapid • Hyperglycemia
Saquinavir, matrix and nucleocapsid) proteins and drug resistance • Dyslipdemia
Indinavir, thus inhibits viral assembly and release • Lipodystrophy
Nelfinavir • Thrombocytopeni
a -Indinavir

NRTI’s- all associated with:

• Peripheral Neuropathy- most common with “D” drugs
• Lactic Acidosis- most common with Didanosine and Stavudine
• Fat redistribution