Antivirals

Question 1

Prophylaxis against influenza A but not B; Blocks viral uncoating by interfering with influenza A M2 protein; SE: CNS effects

Answer 1

Amantadine

Question 2

Prodrug; competitive inhibitor of influenza neuraminidases; interferes with viral release and viral penetration; Used for the treatment of uncomplicated influenza A and B; Give within 48 hours of symptom onset; SE: nausea/vomiting/diarrhea, bronchitis,

Answer 2

Oseltamivir

Question 3

Inhibitor of nucleic acid synthesis; interferes with DNA synthesis; thymidine analog; Used opthalmic for Herpes simplex types 1 and 2

Answer 3

Trifluridine

Question 4

Inhibits herpes DNA polymerase 10-30x more than host cell DNA polymerase; acts as a competitive inhibitor of dGTP and as a DNA chain terminator; Used IV, Oral and topical; generally well-tolerated, SE: rash, itching, nausea, vomiting, headache, fatigue

Answer 4

Acyclovir

Question 5

Prodrug converted to penciclovir, then phosphorylated which is what inhibits viral DNA polymerase; Used for acute herpes zoster <3 days duration and for genital herpes

Answer 5

Famciclovir

Question 6

Used for recurrent herpes of the lips and face; topical administration

Answer 6

Penciclovir

Question 7

Monophosphorylation catalyzed by CMV protein kinase; Used for CMV retinitis in AIDS patients and for CMS prophylaxis for transplant patients; Toxicity: BM suppression, leukopenia, thrombocytopenia, anemia, may enhance bone marrow suppression when given with AZT

Answer 7

Ganciclovir

Question 8

Inhibits CMV DNA polymerase by binding to its pyrophosphate-binding site; does not require conversion to triphosphate form to be active; Used for CMV retinitis and acyclovir-resistant herpes simplex

Answer 8

Foscarnet

Question 9

Toxicity of Foscarnet

Answer 9

Renal damage, electrolyte imbalances, seizures

Question 10

Nucleoside analog inhibitor of the reverse transcriptase domain of the hepatitis B DNA polymerase; approved for Hep B; SE: nausea, diarrhea

Answer 10

Lamivudine

Question 11

Adenosine monophosphate analog, inhibits reverse transcriptase domain of the hepatitis B DNA polymerase; Approved for Hep B; SE: GI upset

Answer 11

Tenofovir

Question 12

Interferes with viral mRNA synthesis; inhibits inosine-5-P dehydrogenase and thus GTP synthesis; inhibits GTP-dependent capping of viral mRNA; Used aerosol in infants and young children with severe RSV, and for Hep C (oral) in combo with interferon-a

Answer 12

Ribavirin

Question 13

Toxicity of Ribavirin

Answer 13

Aerosol use: may precipitate in and clog respiratory equipment, pulmonary function deterioration, rash
IV or oral use: anemia, bm suppression

Question 14

Used for condyloma acuminata, Hep B and C, used in combo with ribavirin for Hep C; Toxicity: flu-like symptoms, Leukopenia, BM suppression, neurotoxicity, myalgia

Answer 14

Interferon

Question 15

Reversible inhibitor of Hep C NS3 protease, blocking formation of infectious virus particles; Used for Hep C genotype I in combo with PEG-interfereon + ribavirin; SE: anemia and neutropenia, contraindicated with drugs that are CYP3A substrates or inducers

Answer 15

Boceprevir

Question 16

Thymidine nucleoside analog; phosphorylated by cellular kinases; inhibits reverse transcriptase and is a DNA chain terminator; Used for treatment of HIV in adults and children

Answer 16

Zidovudine or AZT

Question 17

Toxicity of Zidovudine (AZT)

What types of drugs should be avoided if someone is on this drug?

Answer 17

Bone marrow suppression, neutropenia, anemia; drugs that inhibit glucuronyl transferase increase hematologic toxicity of AZT and should be avoided, myopathy

Question 18

Nucleoside analog inhibitor of RT, synergistic with AZT; SE: nausea, diarrhea

Answer 18

Lamivudine

Question 19

Nucleotide prodrug that is hydrolyzed to its active form, inhibits RT by competing with dATP for incorporation into DNA resulting in chain termination; used for combination therapy for HIV-infected patients

Answer 19

Tenofovir

Question 20

Fluorinated analog of 3TC inhibits RT by competing for dCTP incorporation into DNA, resulting in chain termination; used as combo therapy for HIV

Answer 20

Emtricitabine

Question 21

Nucleoside analog inhibitor of RT; used as combination therapy for HIV-infected patients; Toxicity: hypersensitivity reactions (assoc with HLA-B*5701 antigen)

Answer 21

Abacavir

Question 22

Two other side effects associated with NRTI’s as a group

Answer 22

lactic acidosis, hepatic steatosis

Question 23

non-nucleoside inhibitor of RT; does not require phosphorylation for activity; Used as part of multi-drug therapy for HIV; SE: rash, CNS/psychiatric symptoms, nightmares

Answer 23

Efavirenz

Question 24

Inhibitors of aspartic protease; used in combo with inhibitors of RT, significantly decrease viral blood load; Prevents viral protease from cleaving Gag-pol polypeptide into separate functional proteins

Answer 24

Lopinavir, Ritonavir

Question 25

Toxicities of protease inhibitors

Answer 25

Diabetes, alterations in lipid metabolism, fat redistribution, alters metabolism of many other drugs
Lopinavir – Diarrhea
Ritonavir – avoid drugs metabolized by CYP3A

Question 26

Effective against HIV-1 only, detectable viral replication despite ongoing therapy; inhibits fusion of viral (HIV-1) and cellular (CD4+) membranes, binds gp41 subunit of HIV glycoprotein, blocking membrane fusion; Toxicity: local injection site reactions, diarrhea, nausea, fatigue

Answer 26

Enfuvirtide

Question 27

Chemokine co-receptor (CCR5) antagonist, blocks entry of HIV into cells; SE: hepatotoxicity, cardiovascular events

Answer 27

Maraviroc

Question 28

Treatment of HIV-1, works on virus that is resistant to other drugs; inhibits HIV-1 integrate preventing integration of HIV-1 DNA into the genome

Answer 28

Raltegravir

Question 29

How are drugs prescribed for HIV in clinic?

Answer 29

Used 3 (or more) drugs per patient (2 or more drug classes) 
Keep replication at zero to prevent resistance