Antivirals

Question 1

Aciclover

Answer 1

Guanine nucleoside analog - DNA polymerase inhibitor

Prodrug (phosphorylated by viral thymidine kinase & further phosphorylated to triphosphate by cellular enzymes)

Notes - Used for HSV1&2 > V2V > CMV > EBV. Used topically prophylactically for non-life threatening HSV infections. SE - local irritation, funny taste. Used orally for genital herpes or HSV1 if frequent episodes recurrence >6/year but S.E of nausea, diarrhea, headache. Used IV for severe infection but S.E of rashes emesis, hypotension, nephrotoxicity @ high dose so patient should drink lots of water to flush kidneys.

Question 2

Valaciclovir

Answer 2

Guanine nucleoside analog - DNA polymerase inhibitor

Prodrug of aciclovir cleaved in GI tract. Longer duraction of action

Notes - better oral bioavailability but more expensive. Used for HSV1&2

Question 3

kids

Valganciclovir

Answer 3

Guanine nucleoside analog - DNA polymerase inhibitor

Prodrug of ganciclovir

Notes - used for CMV retinitis in immunocompromised patients. SE - hematological issues - neutropenia, thrombocytopenia, anemia & teratogenicity, nausea, vomiting

Question 4

Penciclovir

Answer 4

Guanine nucleoside analog - DNA polymerase inhibitor

Similar to aciclovir but active triphosphorylated form has longer half life (phosphorylated by viral thymidine kinase & further phosphorylated to triphosphate by cellular enzymes)

Use similar to aciclovir - topical Herpes

Question 5

adults

Famciclovir

Answer 5

Guanine nucleoside analog - DNA polymerase inhibitor

Prodrug of penciclovir

Notes - better bioavailability. Used for Herpes zoster - shingles but SE - stomach upset, headache, fever

Question 6

Cidofovir

Answer 6

DNA polymerase inhibitor - non-nucleoside analog

Notes - Prodrug, monophosphate nucleoside of cytosine. Made into into its active form by CELLULAR not viral thymidine kinase

Used for CMV retinitis if ganciclovir fails. Used IV & topical and always given with probenecid bc alone its extremely nephrotoxic (probenecid protects kidney by blocking tubular secretion)

Question 7

Foscarnet

Answer 7

DNA polymerase inhibitor

Inhibitor of all DNA polymerase & RT
Not prodrug- doesn’t need phosphorylation

Notes - inhibits pyrophosphate exchange from dNTP by binding DNA polymerase or RT during replication. Used for HSV, V2V, HIV, CMV only administered I.V. SE- nephrotoxicity, neurotoxicity, hypocalcemia, hypomagnesemia, anemia

Question 8

Zidovudine

Answer 8

NsRTI - requires triP

Notes - Prodrug, analog of thymidine. SE- anemia and other shared S.E of NsRTI - affect CNS (neurotoxicity, headache, insomnia, dizziness), lipodystrophy & ANEMIA

Question 9

Didanosine

Answer 9

NsRTI - requires triP

Notes - Prodrug, analog of deoxyadenosine. Shared S.E of NsRTI that affect CNS (neurotoxicity, headache, insomnia, dizziness), lipodystrophy

Question 10

Zalcitabine

Answer 10

NsRTI - requires triP

Notes- Prodrug, analog of cytosine. Shared S.E of NsRTI that affect CNS (neurotoxicity, headache, insomnia, dizziness), lipodystrophy

Question 11

Iamivudine

Answer 11

NsRTI - requires triP

Notes - Prodrug, analog of cytidine. Shared S.E of NsRTI that affect CNS (neurotoxicity, headache, insomnia, dizziness), lipodystrophy

Question 12

Tenofovir

Answer 12

NtRTI - requires diP

Question 13

& nevirapine

Efavirenz

Answer 13

NNRTI

Notes - not prodrug - does not require P, non competitive inhibitor of RT. SE neurocognitive impairment, teratogenicity, hepatotoxicity, + SE of NsRTIs

Question 14

Rotanavir

Answer 14

Protease inhibitor

Notes - prevent cleavage of large immature viral polyproteins which stops replication bc they are too large to package. Used to boost levels of other medications. One of the most potent CYP inhibitor. SE GI disturbance, CNS, atherosclerosis, blood disorders, hyperglycemia, dyslipidemia

Question 15

Enfurvitide

Answer 15

Fusion inhibitor

Notes - binds gp41 and prevents it binding to host cell aka. prevents infection, specifically adsorption of the viral replication cycle. SE- flu symptoms, CNS effects, GI disturbances, hypersensitivity reactions

Question 16

Maraviroc

Answer 16

Co-Receptor Inhibitor (CRI)

Notes - CCR5 antagonist (only works for this serotype of HIV). Blocks binding of gp120 to CCR5 and prevents membrane fusion - prevents infection! WARNING hepatotoxicity & some people can have allergic reactions.

Question 17

Raltegravir

Answer 17

Integrase inhibitor (INI)

Notes - prevent 3’ processing and strand transfer to nucleus. SE- nausea, hyperglycemia, Stevens Johnson syndrome (skin and mucosal membrane problems), hepatotoxicity

Question 18

Amentadine/Rimantadine

Answer 18

M2 inhibitors

Notes - inhibit viral uncoating by inhibiting M2 channels which prevents ion flux. Used for Influenza A only (benefit within 36-48h) and given orally. SE- GI toxicity & CNS toxicity in elderly. Should be cautious with elderly

Question 19

Oseltamivir

Answer 19

Neuraminidase inhibitor

Notes - prevent release of new virions by preventing neuraminidase from cleaving receptor that detaches virion form host so the virus can’t infect neighbouring cells. It is ORALLY administered and activated by liver enzymes to oseltamivir carboxylase. Used for Influenza A & B. Also used for H1N1.

Question 20

Zanamivir

Answer 20

Neuraminidase inhibitor

Notes - prevent release of new virions by preventing neuraminidase from cleaving receptor that detaches virion form host so the virus can’t infect neighbouring cells. It is INHALED. Used when resistance to oseltamivir. Used for Influenza A & B. Also used for H1N1.

Question 21

How to treat HIV

Answer 21

HART

2 nucleoside analogs + PI

2 nucleoside analogs + NNRTi

Question 22

Interferon alpha

Answer 22

leukocyte modulation

Used for treatment of chronic hep B & C, Hairy cell leukemia, Kaposi’s sarcoma

Parenteral administration

Question 23

Interferon beta

Answer 23

fibroblast modification

Used to treat MS

Question 24

Interferon gamma

Answer 24

T and NK modification

Used to treat chronic granulomatous disease & Hodgkins lymphoma

Question 25

Saquinavir

Answer 25

PI

Question 26

Indinavir

Answer 26

PI