Antivirals

Question 1

what are the five major classes of antiretroviral medications for HIV

Answer 1

1. nucleoside reverse transcriptase inhibitors (NRTI’s)
2. non-nucleoside reverse transcriptase inhibitors (NNRTI’s)
3. protease inhibitors (PI’s)
4. Entry inhibitors
5. Integrase inhibitors

Question 2

MOA for NRTI’s?

Answer 2

viral DNA chain termination via inhibition of reverse transcriptase enzyme

serve as analog “posers”

Question 3

Tenofovir

1. class?
2. specific side effects?

Answer 3

1. NRTI’s

2. nephrotoxicity

Question 4

Abacavir

1. class?
2. specific side effects?

Answer 4

1. NRTI’s

2. hypersensitivity rxns

Question 5

Lamivudine/emtricitabine

1. class?
2. specific side effects?

Answer 5

1. NRTI’s

2. few, generally well-tolerated

Question 6

Zidovudine

1. class?
2. specific side effects?
3. PEARLS?

Answer 6

1. NRTI’s
2. anemia
3. used in pregnant women

Question 7

NRTI class side effects?

Answer 7

lactic acidosis (much less with new agents)

GI side effects

Question 8

MOA for NNRTI’s?

Answer 8

bind directly to reverse transcriptase and inhibit its action

Question 9

Efavirenz

1. class?
2. specific side effects?

Answer 9

1. NNRTI’s
2. CNS symptoms; vivid dreams, drowsiness
   Teratogenic

Question 10

Etravirine

1. class?
2. specific side effects?

Answer 10

1. NNRTI’s

2. rash, increased LFTs

Question 11

Rilpivirine

1. class?
2. specific side effects?

Answer 11

1. NNRTI’s

2. rash, QT prolongation

Question 12

MOA of protease inhibitors (PIs)?

Answer 12

bind within active pocket of protease, inhibiting binding of virus

minimize cross-reaction between drugs in the same class

Question 13

Ritonavir Boosting

1. Ritonavir at ___ doses enhances blood levels of other PIs when given together
2. MOA?

Answer 13

1. low doses

2. P4503A4 inhibition in gut and liver, P-glycoprotein inhibition

Question 14

Cobiscistat

1. function?
2. PEARLS?

Answer 14

1. pharmacokinetic enhancer

2. similar to ritonavir but NO antiretroviral therapy

Question 15

PI class toxicities; what two main categories?

Answer 15

1. GI = N/V, diarrhea

2. Metabolic toxicities = dyslipidemia, hyperglycemia, lipodystrophy

Question 16

what are the 3 steps of HIV entry?

Answer 16

1. specific binding of HIV gp120 to CD4 molecule
2. Conformational change followed by co-receptor binding (CCR5 or CXCR4)
3. Exposure of gp41 that mediates fusion of viral and cell membranes

Question 17

Enfurvirtide

1. MOA?
2. PEARLS?
3. side effects?

Answer 17

1. blocks gp41
2. injectable, only oral form of HIV treatment
3. local injection sight reaction, increased rate of bacterial pneumonia, hypersensitivity

Question 18

Maraviroc

1. MOA?
2. side effects?
3. PEARLS?

Answer 18

1. CCR5 antagonist as HIV uses CCR5 as a co-receptor necessary to enter T-cells
2. hepatotoxicity, upper respiratory infections, rash, MSK symptoms
3. can test for co-receptor; CCR5 vs. CXCR4

Question 19

1. MOA of integrase inhibitors?

2. adverse reactions?

Answer 19

1. Inhibit enzyme which is necessary for viral insertion into human DNA genome
2. nausea, headache, diarrhea, pyrexia, myopathy and rhabdomyolysis

Question 20

Raltegravir, Elvitegravir, Dolutegravir

what class of drugs?

Answer 20

Integrase inhibitors

Question 21

antiretroviral therapy (ART) is recommended for ____ HIV-infected patients to ____ disease progression

Answer 21

1. all HIV-infected patients

2. reduce risk of disease progression

Question 22

2 basics of HAART?

Answer 22

1. Combination therapy - at least 3 active agents

2. Utilization of multiple classes

Question 23

why is Hepatitis C Virus the most genetically diverse virus?

Answer 23

Variability in RNA sequence

Question 24

what is the important predictor of poor IFN treatment in HCV?

Answer 24

genotype

Question 25

true or false? sustained virologic response is NOT equivalent to a cure?

Answer 25

FALSE, it is!

Question 26

Sofosbuvir, Paritaprevir 1. class? 2. MOA? 3. HCV genotypes active across? 4. toxicity concerns?

Answer 26

1. NS5B polymerase inhibitors 2. inhibitor of NS5B, RNA-dependent RNA polymerase and competes with natural viral nucleotide to cause chain termination 3. ALL! 4. relatively safe; fatigue, HA, GI, anemia possible

Question 27

Ledipasvir, Daclatasvir, Ombitasvir, Elbasvir, Velapatasvir 1. class? 2. MOA? 3. Toxicity concerns?

Answer 27

1. NS5A inhibitors (HCV) 2. inhibits HCV NS5A, viral phosphoprotein required for viral replication 3. relatively safe; fatigue, headache, GI side effects possible

Question 28

Grazoprevir, Simeprevir, Boceprevir, Telaprevir 1. class? 2. MOA? 3. toxicity concerns?

Answer 28

1. NS3/4A protease inhibitors 2. prevent viral maturation through inhibition of protein synthesis 3. slightly variable depending on the agent; possibly anemia, rash, itching, GI side effects, drug interactions

Question 29

Acyclovir 1. class? 2. MOA? 3. spectrum? 4. RoA? 5. toxicity?

Answer 29

1. guanosine nucleoside antivirals 2. competes with DNA analogous to cause viral chain termination 3. herpes simplex 1+2. varicella-zoster 4. IV, PO, topical 5. CNS (malaise, headache, confusion), N/V, diarrhea, renal dysfunction

Question 30

Ganciclovir 1. spectrum? 2. RoA? 3. toxicity?

Answer 30

1. HSV, VZV, and CMV 2. IV/PO but poor bioavailability with PO 3. myelosuppresion, CNS toxicity (headache, seizure, confusion), hepatotoxicity, GI intolerance

Question 31

Foscarnet 1. MOA? 2. PEARLS? 3. Adverse effects?

Answer 31

1. directly inhibits herpesvirus DNA polymerase or HIV reverse transcriptase 2. active against acyclovir and ganciclovir resistant viruses 3. dose-limiting nephrotoxicity, electrolyte/metabolic abnormalities, CNS side effects, myelosuppression

Question 32

Influenza 1. class/drug of choice? 2. names? 3. spectrum? 4. MOA? 5. side effects?

Answer 32

1. neuramindase inhibitors 2. Oseltamivir (Tamiflu), Zanamivir (Relenza), Peramivir (Rapivab) 3. influenza A and B 4. inhibits viral neuraminidase which is critical in penetration of respiratory tract mucus and in release of virus from infected cells 5. GI (N/V, diarrhea), neuropsychiatric (agitation, anxiety, altered mental status)