Flashcards in antivirals Deck (28):
targets of antivirals
release of virus
GAMMA GLOBULIN (Gammagard S/D®
Prevention of attachment and penetration of viral particles into the host cell (first phase)
used parentally, not effective orally
Mean half-life is 2-3 weeks.
-When injected IM during early stages can partially alleviate progression of hepatitis, measles, rabies, polio, and other viral disorders.
preps: Immune globulin, VZIG, HepB-IG
SEs: rare, ha, myalgias, nausea, chills, systemic anaphylaxis
*Pavilizumab (SynagisR) is a ?? (KNOW)
monoclonal antibody to the F protein of *RSV* and is used in high risk infants by i.v. administration.
acts on the host cell to block viral *penetration and uncoating*, oral admin
-inhibits the release of infectious nucleic acid into the cell cytoplasm, by buffering the pH of endosomes
-blocks the M2 viral protein channel required for nucleocapsid release
*specific for *Influenza A virus* (KNOW)
*also used as an antiparkinsonian agent*, also for shingles and rubella
*SEs: CNS: hallucination, confusion, anxiety, irritability, N/V, vision changes, etc
influenza viruses can be classified into subtypes based on the antigenic characteristics of their surface antigens, ?? and ??
hemagglutinin (HA antigen) and neuraminidase (NA antigen)
-HA is responsible for the attachment of the virus to sugary “ hooks” on cells known as sialic acid residues and for penetration of the virus into the cell during the initial stages of infection)
NA cleaves linkages between sialic acid and HA from both itself and the infected cell surface.
NA good target for anti flu: why?
1) viral NA is very different to human NA;
2) the “business end” of the viral NA, the part of the enzyme that actually breaks the HA-sialic acid bond is chemically identical in all strains of influenza, and
3) NA is critical for influenza virus replication.
good for influenza A, B, and C
ZANAMIVIR (RelenzaR) MOA
inhibition of influenza virus neuraminidase (NA), effective against influenza A and B
rare SEs: malaise, fatigue, fever, etc.
same mechanism of can ZANAMIVIR (RelenzaR) but can be taken as a pill rather than inhaled, available systemically
SEs: N/V, ha
Purine nucleoside analog, needs to be phosphorylated; ribavirin-5'-triphosphate is the principle intracellular form
MOA: inhibits viral RNA polymerases and thus messenger RNA synthesis (greater affinity for viral inhibition)
-aerosol to infants and is absorbed systemically
RIBAVIRIN (VirazoleR) SEs
Infants: sudden deterioration of respiratory function
Adults: ribavirin is not indicated for use in adults.
HCW who are pregnant should
consider avoiding direct care of patients receiving aerosolized ribavirin. Observed effects: headache (51%), conjunctivitis (32%),
RIBAVIRIN (VirazoleR) uses
RSV infection (RNA virus)
Chronic hepatitis C virus infection (RNA virus): Ribavirin in combination with interferon alfa-2a: adults and children
needs to be phosphorylated by thymidine kinases
-incorporated into the growing DNA strand and causes chain termination, nhibits viral and cellular DNA polymerases
- inhibits viral DNA synthesis in mammalian cells. It is active in vitro against HSV1 and 2
TRIFLURIDINE (ViropticR) SEs
-Visual haze: Trifluridine sometimes causes burning or stinging and palpable edema.
-Teratogenic: Trifluridine is mutagenic in vitro; its oncogenic potential is currently being evaluated in rodents.
TRIFLURIDINE (ViropticR) uses
solution for topical treatment of keratoconjunctivitis (Ocular involvement usually first develops in young adults) and recurrent epithelial keratitis due to HSV.
phosphorylation reaction occurs much more rapidly (30-300 times faster) in herpes infected host cells than in non-infected human cells
-herpes virus - specific Thymidine Kinase is responsible for the rapid phosphorylation of Acyclovir in the infected cells.
(specificity, virtually non-toxic)
-Acyclovir triphosphate inhibits herpes viral DNA polymerase and thereby inhibits viral DNA synthesis and viral replication.
ACYCLOVIR (ZoviraxR) SEs
Non-toxic: serious adverse reactions with Acyclovir are virtually nil.
Emergence of Acyclovir-resistant herpes simplex after
intravenous treatment with this agent has been recently reported.
ACYCLOVIR (ZoviraxR) uses
IV: mucocutaneous herpes simplex in immuno-compromised patients and prophylaxis of herpes simplex, herpes zoster, herpes simplex encephalitis, and neonatal herpetic dissemination.
Topical: mucocutaneous herpes virus infections, genital herpes, herpes simplex keratitis.
Oral: mucocutaneous herpes infection immuno-compromised patients, varicella-zoster virus in the children, etc.
GANCICLOVIR SODIUM (CytoveneR)
Phosphorylated in cells infected with cytomegalovirus to a triphosphate, inhibits cytomegalovirus (CMV) DNA polymerase. (same MOA of acyclovir)
-When ganciclovir triposphate is incorporated into CMV DNA,
suppresses chain elongation and inhibits CMV replication.
GANCICLOVIR SODIUM (CytoveneR) SEs (KNOW)
Teratogenic and carcinogenic in animals.
-The most frequent dose-limiting toxicities are granulocytopenia
and thrombocytopenia, which are usually reversible after
-Severe myelosuppression .
GANCICLOVIR SODIUM uses
IV for CMV infections
FOSCARNET (FoscavirR) MOA and uses
Inhibits viral DNA polymerase
used for *CMV retinitis in patient with AIDS*, IV
FOSCARNET (FoscavirR) SEs
Main toxicity is renal
drugs for HepB (see antivirals 2)
Tenofovir (Viread®), Lamivudine (Epivir®) and Emtricitabine (Emtriva®)
glycoproteins; work as messengers ("alarm molecule") informs neighboring cells there is an infection-->the alerted cells inactivate the virus
-Once bound to the cell membrane, interferon α acts mainly as inhibitor of viral replication in cells, by inducing the host cell to produce enzymes that inhibit the translation of viral messenger RNA to viral proteins and thereby inhibit viral replication
interferons: 3 cellular enzymes that are synthesized which inhibit viral replication:
2'5' oligo adenylate synthetases (polymerase)
Chronic hepatitis B
*Chronic hepatitis C with ribavirin*
Interferon α may act as an anticancer agent against
AIDs-related Kaposi's sarcoma
Hairy cell leukemia