antivirals

Question 1

targets of antivirals

Answer 1

cell entry
uncoating
transcription/translation
release of virus

Question 2

GAMMA GLOBULIN (Gammagard S/D®

Answer 2

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

Question 3

*Pavilizumab (SynagisR) is a ?? (KNOW)

Answer 3

monoclonal antibody to the F protein of RSV and is used in high risk infants by i.v. administration.

Question 4

AMANTADINE (SymmetrelR)

Answer 4

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

Question 5

influenza viruses can be classified into subtypes based on the antigenic characteristics of their surface antigens, ?? and ??

Answer 5

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.

Question 6

NA good target for anti flu: why?

Answer 6

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

Question 7

ZANAMIVIR (RelenzaR) MOA

Answer 7

inhibition of influenza virus neuraminidase (NA), effective against influenza A and B
oral inhalation
rare SEs: malaise, fatigue, fever, etc.

Question 8

OSELTAMIVIR (TamifluR)

Answer 8

same mechanism of can ZANAMIVIR (RelenzaR) but can be taken as a pill rather than inhaled, available systemically
SEs: N/V, ha

Question 9

RIBAVIRIN (VirazoleR)

Answer 9

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

Question 10

RIBAVIRIN (VirazoleR) SEs

Answer 10

Infants: sudden deterioration of respiratory function
Adults: ribavirin is not indicated for use in adults.
teratogenic
HCW who are pregnant should
consider avoiding direct care of patients receiving aerosolized ribavirin. Observed effects: headache (51%), conjunctivitis (32%),

Question 11

RIBAVIRIN (VirazoleR) uses

Answer 11

RSV infection (RNA virus)
Chronic hepatitis C virus infection (RNA virus): Ribavirin in combination with interferon alfa-2a: adults and children

Question 12

TRIFLURIDINE (ViropticR)

Answer 12

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

Question 13

TRIFLURIDINE (ViropticR) SEs

Answer 13

• 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.

Question 14

TRIFLURIDINE (ViropticR) uses

Answer 14

solution for topical treatment of keratoconjunctivitis (Ocular involvement usually first develops in young adults) and recurrent epithelial keratitis due to HSV.

Question 15

ACYCLOVIR (ZoviraxR)

Answer 15

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.

Question 16

ACYCLOVIR (ZoviraxR) SEs

Answer 16

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.

Question 17

ACYCLOVIR (ZoviraxR) uses

Answer 17

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.

Question 18

GANCICLOVIR SODIUM (CytoveneR)

Answer 18

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.

Question 19

GANCICLOVIR SODIUM (CytoveneR) SEs (KNOW)

Answer 19

Teratogenic and carcinogenic in animals.
-The most frequent dose-limiting toxicities are granulocytopenia
and thrombocytopenia, which are usually reversible after
withdrawal.
-Severe myelosuppression .

Question 20

GANCICLOVIR SODIUM uses

Answer 20

CMV retinitis
IV for CMV infections
(resistance reported)

Question 21

FOSCARNET (FoscavirR) MOA and uses

Answer 21

Inhibits viral DNA polymerase

used for CMV retinitis in patient with AIDS, IV

Question 22

FOSCARNET (FoscavirR) SEs

Answer 22

Main toxicity is renal

Question 23

drugs for HepB (see antivirals 2)

Answer 23

Tenofovir (Viread®), Lamivudine (Epivir®) and Emtricitabine (Emtriva®)

Question 24

interferons

Answer 24

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

Question 25

interferons: 3 cellular enzymes that are synthesized which inhibit viral replication:

Answer 25

2’5’ oligo adenylate synthetases (polymerase)
protein kinase
phosphodiesterase

Question 26

INF-a

Answer 26

Cutaneous warts
herpes conjunctivitis
Chronic hepatitis B
Chronic hepatitis C with ribavirin

Question 27

Interferon α may act as an anticancer agent against

Answer 27

Bladder tumors
AIDs-related Kaposi’s sarcoma
Hairy cell leukemia

Question 28

Interferon SEs

Answer 28

flu-like: fever, fatigue, malaise, chills, ha
musculoskel: myalgia, arthralgia
GI: anorexia, N/V
CNS: mild mental disturbances, fatigue, ha
blood: neutropenia, amemia, thrombocytopenia
hepatic: inc. AST, ALT
CV: edema, hypotension