Antivirals

Question 1

What is the mechanism of action of the nucleoside reverse transcriptase inhibitors (NRTI’s)?

Answer 1

Viral DNA chain termination via inhibition of reverse transcriptase enzyme

Question 2

Name the NRTIs (Nucleoside reverse transcriptase inhibitors…

Answer 2

Zidovudine
Lamivudine
Emtrictabine
Tenofovir
Abacavir

Question 3

What are the side effects of tenofovir?

Answer 3

nephrotoxicity

Question 4

What are the side effects of abacavir?

Answer 4

HSR

Question 5

What are the side effects of Lamivudine/emtricitabine

Answer 5

HA
N/V
Rash
Neutropenia
Pancreatitis

Question 6

What are the side effects of zidovudine?

Answer 6

Anemia

Granulocytopenia

Question 7

What is the major side effect of all NRTIs?

Answer 7

Lactic acidosis

Question 8

Name the NNRTIs (Non-Nucleoside Reverse transcriptase inhibitors…

Answer 8

Efavirenz
Nevirapine
Rilpivirine
Etravirine

Question 9

What are the NRTIs used for?

Answer 9

HIV

HBV–Lamivudine/Emtricitabine/Tenofovir

Question 10

What is the mechanism of action of the NNRTIs (Non-Nucleoside Reverse transcriptase inhibitors?

Answer 10

Inhibit reverse transcriptase through direct enzyme inhibition

Question 11

What are the common side effects of Efavirenze (NNRTI)?

Answer 11

CNS symptoms
Vivid dreams
Drowsiness
Teratogenic

Question 12

What are the common side effects of Nevirapine (NNRTI)?

Answer 12

Rash

Hepatitis–including hepatic necrosis

Question 13

What are the common side effects of Etravirine (NNRTI)?

Answer 13

Rash

Increased LFTs

Question 14

What are the common side effects of Rilpivirine (NNRTI)?

Answer 14

Rash

QT prolongation

Question 15

What are the NNRTIs used for?

Answer 15

HIV

Question 16

Name the HIV protease inhibitors…

Answer 16

Ritonavir
Fosamprenavir
Atazanavir
Darunavir
Lopinavir

Question 17

What is the mechanism of action of the protease inhibitors?

Answer 17

Bind within active pocket of protease inhibiting binding of virus–without protease cleavage, virus cannot cause infection

Prevent cleavage of protein chain into functional subuntis

Question 18

What is the primary use of Ritonavir

Answer 18

At low doses enhances blood levels of other PI’s when given together

P4503A4 inhibition in the liver and gut

Reduces frequency of dosing
Improves adherence/reduce ADRs
Improves ability to suppress strains of resistant virus
Improve regimen efficacy

Question 19

What are the side effects of the protease inhibitors?

Answer 19

Metabolic toxicities

• Dyslipidemia
• Hyperglycemia
• Lipodystrophy

Question 20

What is the mechanism of action of enfuvirtide?

Answer 20

Peptide molecule that binds directly to the HR1 region of gp41–> Preventing viral cell entry

Question 21

What are the HIV viral entry inhibitors?

Answer 21

Enfuvitide and Maraviroc

Question 22

What are the side effects of Enfuvirtide?

Answer 22

Injection site reaction

Question 23

What is the mechanism of action of Maraviroc?

Answer 23

CCR5 Antagonist–HIV uses CCR5 as a co-receptor necessary to enter T-cells

Question 24

What are the side effects of Maraviroc?

Answer 24

Hepatotoxicity

Question 25

What is the mechanism of action of the integrase inhibitors?

Answer 25

Inhibit the viral enzyme integrase--which is necessary for insertion of viral DNA into human genomic DNA

Question 26

What are the 3 integrase inhibitors used to tx HIV?

Answer 26

Raltegravir Elvitegravir Dolutegravir

Question 27

What are the goals of HAART?

Answer 27

Suppression of viral load Restoration of immune function--increase CD4 count Improve quality of life Reduce HIV-related morbidity and mortality Minimize risk for antiretroviral resistance--Resistance only occurs during replication--so goal is to keep CD4 count up to prevent replication of virus

Question 28

What is the mechanism of action of Interferon?

Answer 28

Induce interferon-stimulating genes to establish antiviral state within cells Used for HCV--old

Question 29

What are the side effects of interferon?

Answer 29

Flu-like symptoms Cytopenias Depression Fatigue

Question 30

What is the mechanism of action of Ribavirin?

Answer 30

Nucleoside analog--competes with viral nucleotides and cause chain termination Used fro HCV--old

Question 31

What are the side effects of Ribavirin?

Answer 31

Hemolytic anemia--very high risk!! | Tetratogenic

Question 32

Name the NS5B polymerase inhibitors?

Answer 32

Sofosbuvir | Paritaprevir

Question 33

What is the mechanism of action of the NS5B inhibitors used for HCV?

Answer 33

Compete with viral nucleotide to cause viral chain termination of HCV RNA Inhibitor of HCV NS5B RNA-dependent RNA polymerase--once phosphorylated, competes with natural viral nucleotide (uridine) to cause chain termination of HCV RNA

Question 34

Name the HCV NS5A inhibitors...

Answer 34

Ledipasvir Daclatasvir Ombitasvir

Question 35

What is the mechanism of action of the HCV NS5A inhibitors?

Answer 35

Inhibit the viral phosphoprotein, NS5A, that is required for viral replication

Question 36

Name the NS3/4A protease inhibitors...

Answer 36

Simeprevir Bocepravir Telapravir

Question 37

What is the mechanism of action of the NS3/4A protease inhibitors?

Answer 37

Prevent viral maturation through the inhibition of protein synthesis

Question 38

Why are acyclovir and penciclovir only phosphorylated/active within infected cells?

Answer 38

Because phosphorylation requires viral thymidine kinase

Question 39

What antiviral is used for the treatment and prophylaxis of CMV infection?

Answer 39

Ganciclovir

Question 40

What is the mechanism of action of Ganciclovir?

Answer 40

After phosphorylation in infected cell--causes viral DNA chain termination

Question 41

What is the mechanism of action of acyclovir?

Answer 41

After phosphorylation by cellular enzymes--acyclovir triphosphate competes with DNA analogues to cause viral DNA chain termination

Question 42

What is acyclovir used for?

Answer 42

HSV and VZV

Question 43

What is a prodrug of acyclovir?

Answer 43

Valacyclovir--converted to acyclovir after oral administration

Question 44

Why is penciclovir given topically?

Answer 44

Very poor bioavailability MOA--similar to acyclovir

Question 45

What is a prodrug for penciclovir?

Answer 45

Famciclovir--administered orally

Question 46

What are the side effects of acyclovir and penciclovir?

Answer 46

CNS changes and renal dysfunction possible when used at higher doses

Question 47

What are the side effects of ganciclovir?

Answer 47

Neutropenia and thrombocytopenia

Question 48

What antiviral is a pyrophosphate congener and is broad spectrum--used for HSV/VZV/CMV and HIV?

Answer 48

Foscarnet--used when resistance occurs with others

Question 49

What is the mechanism of action of Foscarnet?

Answer 49

Directly inhibits herpesvirus DNA polymerase or HIV reverse transcriptase

Question 50

What are the side effects of Foscarnet?

Answer 50

Nephrotoxicity--1/3 of pts Electrolyte/metabolic abnormalities CNS side effects--tremor, irritability, seizures, hallucinosis Myelosuppression

Question 51

What is the mechanism of action of Oseltamivir, Zanamivir, and Peramivir?

Answer 51

Inhibit viral neuraminidase--an enzyme critical in penetration of respiratory tract mucus and in the release of virus from infected cells --prevent viral release from host cells Active against both influenza A and B

Question 52

What are the side effects seen with the neuraminidase inhibitors used to tx the flu--Oseltamivir, Zanamivir, and Peramivir?

Answer 52

Neuropsychiatric toxicity GI side effets Bronchospasm with zanamivir

Question 53

Which neuraminidase inhibitor should not be used if a pt has asthma?

Answer 53

Zanamivir--inhaled therapy and can cause bronchospasm

Question 54

Which neuraminidase inhibitor is reserved for therapy among critically ill pts?

Answer 54

Peramivir