Antivirals

Question 1

Acyclovir/Valacyclovir

Answer 1

M: phosphorylated by viral thymidine kinase (required), then phosphorylated twice more by cellular kinases making ACV-TP (active drug), then it competitively inhibits viral DNA polymerase preventing DNA from being replicated (nucleoside analogue)

I: HSV and VZV (VZV requires higher doses than HSV)

SE: Generally well tolerated but can cause acute renal failure due to precipitation of drug in renal tubules; neurologic side effects

R: Reduced or absent thymidine kinase; decreased affinity of viral DNA polymerase for ACV-TP

Question 2

Penciclovir

Answer 2

M: Nucleoside analogue

I: Herpes labialis (topical)

Question 3

Famiciclovir

Answer 3

M: Nucleoside analogue - pro-drug of penciclovir

I: HSV and VZV

SE: Generally well tolerated, can cause headaches, dizziness, GI intolerance

Question 4

Ganciclovir/Valganciclovir

Answer 4

M: Nucleoside analogue; requires phosphorylation by viral UL97 (CMV encoded kinase), inhibits viral polymerase and DNA synthesis

I: CMV in immunocompromised patients, HSV

SE: Bone marrow suppression, headaches, fever, rash

R: Mutations in UL97 kinase; mutation in CMV viral polymerase is rare

Question 5

Cidofovir

Answer 5

M: monophosphate nucleotide analogue requiring further phosphorylation by cellular kinase only (no need for viral kinase); active form is diphosphate form

I: Ganciclovir resistant CMV infections in organ transplant patients; BK virus; may be active against smallpox

SE: Nephrotoxicity, GI intolerance, neutropenia

R: Mutation of the viral polymerase leading to decreased affinity for drug

Question 6

Foscarnet

Answer 6

M: Pyrophosphate analogue; inhibits DNA polymerase by reversibly blocking the pyrophosphate binding site (pyrophosphate is required cofactor for polymerase); not dependent on viral kinases

I: HSV, CMV, VZV; mainly used for HSV resistant to acyclovir and CMV resistant to ganciclovir

SE: Nephrotoxicity - directly toxic to renal tubules causing electrolyte abnormalities, penile ulcers

R: Mutation of viral polymerase

Question 7

Amantadine/ Rimantadine

Answer 7

M: Ion channel blocker - inhibits viral M2 ion channel, preventing unfolding of hemagglutinin and thus blocking the uncoating of the virus and entry into the cytoplasm

I: Influenza A, effective if given early in course or prophylaxis

SE: Reversible neurotoxicity (dizziness, ataxia), nausea, dry mouth

R: Mutations in hemagglutinin/M2 protein that prevents binding of the drug

Question 8

Oseltamivir

Zanamivir

Answer 8

M: Neuraminidase inhibitor (sialic acid analogue) - blocks the release of new virions by competitively inhibiting the viral neuraminidase

I: Influenza A and B treatment, prophylaxis, or preemptive therapy

SE:
O - N/V
Z - bronchospasm, cough, N/V (caution for pts with COPD/asthma)

R: Mutations in neuraminidase preventing binding of the drug

Question 9

INF-alpha

Answer 9

M: Cytokine promoting immune function in host cells - inhibition of virus replication, suppression of cell proliferation, enhances phagocytic activity; use pegylated form (PegIFN)

I: HCV (combined with ribavirin), HPV

SE: Flu like symptoms, depression, bone marrow suppression, rash, alopecia, retinopathy

Question 10

Ribvarin

Answer 10

M: Synthetic nucleoside analogue of guanine; requires intracellular phosphorylation by host enzymes; inhibits viral RNA

I: HCV (combined with IFN-a), RSV, Lassa virus

SE: Hemolytic anemia, headaches, rash, teratogenicity

Question 11

Bocepravir

Telaprevir

Answer 11

M: Protease inhibitor - prevents cleavage of the virally encoded polyprotein into smaller functional proteins; bind to active site of HCV NS3/4A protease to inhibit it

I: HCV (combined with ribavirin and IFN-a)

SE:
T - anemia, rash, puritis, nasuea, anorectal discomfort
B - anemia, dysgeusia

R: Low barrier for resistance so should be used in combination with PegIFN and ribavirin

Question 12

Lamivudine, 
Emtricitabine, 
Entecavir, 
Telbuvidine; 
Tenofovir, 
Adefovir

Answer 12

M: Nucleoside/nucleotide analogues that act as chain terminators of HBV RNA in reverse transcriptase of the genome, thus suppressing viral replication

I: HBV - only chronically active hepatitis

Lam, Ten, and Emt also used for HIV

SE: 
L - negligible
Em - nausea, headache
En - negligible
Tel - negligible 
Ten - nephrotoxicity
A - nephrotoxicity	

R: Mutation of viral polymerase;
YMDD mutation causes resistance to Lamivudine

Question 13

Zidovudine, Lamivudine,
Emtricitabine,
Tenofovir,
Abacavir

Answer 13

M: Nucleoside analog reverse transcriptase inhibitors (NRTI) - provides alternate substrate for reverse transcriptase, terminating the DNA chain

I: HIV

L, E, T for chronic HBV also

SE:
Z - Bone marrow suppression
T - renal insufficiency
A - hypersensitivity

Question 14

Efavirenz,

Nevirapine

Answer 14

M: Non-nucleoside reverse transcriptase inhibitors (NNRTI) - binds to reverse transcriptase at hydrophobic pocket, making it unable to function

I: HIV

SE:
E - Dizziness, vivid dreams, rash
N - hepatitis, rash

Question 15

Ritonavir,
Nelfinavir,
Lopinavir,
Atazanavir,
Darunavir

Answer 15

M: Protease inhibitors - compete with normal substrate for binding protease, thus blocking activity

I: HIV

SE:
N - diarrhea
A - hyperbilirubinemia

Question 16

Enfurvtide

Answer 16

M: Fusion inhibitor - blocks interaction required for fusion of virion with host membrane

I: HIV
Given subcutaneously (not ideal)	

SE: Subcutaneous nodules at site of injection

Question 17

Raltegravir

Answer 17

M: Integrase inhibitor - blocks viral DNA from being inserted into host genome

I: HIV

Question 18

Maraviroc

Answer 18

M: Entry inhibitor - occupies the CCR5 coreceptor and blocks virus entry, not active against strains that can utilize CXCR4

I: HIV

SE: Requires test to determine co-receptor usage of the patient’s virus

Question 19

Atripla

Answer 19

M: Combination ART - Efavirenz, Tenofovir, Emtricitabine in one

I: HIV