Antivirals and HIV Therapy

Question 1

Neuraminidase Inhibitors

1. Name 3 (and their brand names+Admin route)
2. MOA? Usually, neuraminidase does what?
3. When should you give these drugs?
4. Which virus has neuraminidase on surface and is target virus for these drugs?

Answer 1

1. Zanamivir (relenza, Inhalation), Oseltamivir (tamiflu, PO), Peramivir (Rapivab, PO)
2. Inhibits Viral neuraminidase which interferes with release of progeny influenza virus from infected cells .
   -usually neuraminidase mediates removal of sialic acid moieties and permits the release of progeny virus
3. Give these drugs as early as possible within 1-2 days from first sx’s
4. Influenza

Question 2

Zanamivir -> Ae’s ? (2) CI? (3)

Oseltamivir -> AE’s (2)

Peramivir –> AE? (1)

Answer 2

Cough and HA , CI in milk protein hypersensitivity, COPD, Asthma

HA and N/V

Diarrhea

Question 3

Amantadine MOA?
AE? (4)

Answer 3

Interferes with M2 protein on influenza A virus –> Inhibition of acid mediated dissociation of the ribo-nuclein-protein complex

-CNS (insomnia, nervousness, light headedness)
G-I Effects

Question 4

HIV Stands for?
What does it target?
Describe the RNA and the RNA enveloped

Answer 4

Human immunodeficiency virus
CD4 T cells
Positive RNA with ssRNA enveloped

Question 5

Name the 3 enzymes brought by the virus that allows viral replication (And the steps)

Answer 5

1. Reverse transcriptase . converts viral RNA to viral DNA
2. Integrase. convert viral DNA to integrated DNA –> mRNA to protein
3. Protease. allows for protein –> virus assembly

Question 6

NRTIs : Nucleoside Reverse Transcriptase Inhibitors

1. Name 6
2. MOA?
3. Class AE? (5) How?

Answer 6

1. Didanosine, zidovudine, lamivudine, abacavir, tenofovir, emtricitabine
2. Competitively inhibits nucleotide binding to reverse transcriptase to terminate DNA chain
3. mitochondrial toxicity -> inhibit RNA dependent DNA polymerase. high affinity for DNA polymerase gamma
   -Pancreatitis
   -Lactic Acidosis
   -Anemia
   -Neuropathy (peripheral)

Question 7

Which NRTIs are dosed once daily?
Which NRTIs have signif mitochondrial toxicity?
Which NRTIs have minimal mitochondrial toxicity?

How are their class interactions compared to other HIV Drug classes? Are there any CYP interactions?

Answer 7

Tenofovir and Emtricitabine

Starvudine, didanosine, zidovudine

Lamivudine, abacavir, tenofovir , emtricitabine

Fewer! NO

Question 8

State the following Special AE’s

1. Abacavir . BBW . Needs what?
2. Tenofovir? Needs what? State the diff between new and old formulation
3. Zidovudine?

Answer 8

1. Hypersensitivity rxns HLA-B5701
   causes rash 70%, fever and fatigue . NEEDS HLA B5701 testing before starting
2. Renal/bone toxicities
   needs dose adjust for renal dysfunction
   new : Tenof+Alefenamide (Decr renal and bone toxicities)
   Old : Tenof+ disoproxil fumarate
3. Lipoatrophy

Question 9

Other AE : Lamivudine, Tenofovir, Emtricitabine ? BBW for?

BBW for Didanosine?
BBW for zidovudine ?

Answer 9

1. Have activities against HepB -> hepatic flare with acute removal of agents in pt’s co-infected with HepB
   -HepB exacerbation (with removal of drug)
2. Pancreatitis and hepatotoxicty or lactic acidosis
3. Hepatotoxicty or lactic acidosis

Question 10

NNRTI’s : Non Nucleoside reverse transcriptase inhibitor

1. Name 4
2. MOA?
3. Class AE? (2)
4. Class Interactions?
5. Efavirenz needs to be given on ?
   -What does a high fat calorie diet do?
   -Etravirine and Rilpivirine need to be given with?
   -Nevirapine take w/o regards to ___

Answer 10

1. Efavirenz, nevirapine, etravirine , rilpivirine
2. Binds to RT, causes a conformational change and disrupts the catalytic center of the RT
3. rash –> SJS, hepatotoxic (incr in LFT)
4. Cyp interactions (inducers or inhibitors) . exception is rilpivirine
5. empty stomach.
   -increases absorption and incr AE’s
   -food, to incr absorption
   -meal

Question 11

Special AE for Efavirenz? (2)

Answer 11

CNS sx’s like vivid nightmares and is teratogenic

Question 12

INSTIs : Integrase Strand Transfer Inhib

1. Name 4
2. MOA?
3. Class AE?
4. Elvitegravir is metabolized via ? WHich is why it needs to be used with a ?

Answer 12

1. Raltegravir, Elvitegravir, Dolutegravir, Bictegravir
2. Interfere with integration of viral DNA into host DNA
3. Very well tolerated ; GI AE’s
4. cyp 3A4, booster such as cobicistat

Question 13

PI : Protease Inhibitor

1. Name 5 , state which one is only used as a booster
2. MOA?
3. Class AE? (4)
4. Class Interactions?
5. Special AE of Atazanavir ?
6. These drugs are generally _____ with ritonavir or cobicistat. Which one does not require boosting?

Answer 13

1. Atazanavir, Darunavir, Ritonavir (booster), Nelfinavir, Indinavir
2. Block proteolytic cleavage of protein precursors that r necessary for production of infectious particles
3. Metab abnorms like hyperlipidemia, hyperglycemia, fat re-distribution. Avoid in pt’s with H/O CAD or diabetes
   -hepatotoxicty (Incr LFT)
4. Cyp inhibitors
5. Hyperbilirubinemia (inhibits UDP glucuronyl transferase)
6. BOOSTED. Nelfinavir

Question 14

TX Regimens in HIV Therapy
1. What’s the rec therapy?
2. What are the two other options?

Answer 14

1. 2 NRTIs + 1 INSTI
   -Biktarvy = Bictegravir/TAF/Emtricibitabine
   -Triumeq = Dolutegravir/Abacavir/Lamivudine
2. 2NRTIs + 1 NNRTI
   and 2NRTIs + 1 PI

Question 15

In selected populations there are 2 drug regimens possible
-State what the drug is
-However, you cant use 2 drug regimen if ? (2)
- For follow up labs with pt’s on regimen what should you see?

Answer 15

Dolutegravir + Lamivudine

NOT IF HIV RNA >500K copies/mL or if they have HBV coinfection

CD4 T cell count should be up
HIV RNA (viral load) should decrease

Question 16

Entry Inhibitors : Maraviroc

1. Admin route?
2. MOA? Must do what test b4 therapy?
3. AE?
4. DDI?

Answer 16

1. PO
2. CCR5-R antag -> blocks fusion and viral entry into cell
   -Tropism Test
3. Incr risk of infections
4. 3A4 inhibitors/inducers (maraviroc is metab via 3A4)

Question 17

Entry Inhibitors : Enfuvirtide

1. Admin route?
2. MOA?
3. AE?

Entry Inhibitors : Ibalizumab

4. Admin route?
5. MOA?
6. USE?
7. AEs? (3)

Answer 17

1. SQ
2. Binds to GP 41 -> Blocks fusion and viral entry into the cell
3. Injection site reactions
4. IV
5. MAB against CD4 -> inhibits HIV from entering cells
6. HIV with multi drug resistance
7. Diarrhea, Dizziness , Immune reconstitution inflamm syndrome (IRIS) -> inflamm response to opportunistic infections (MAC, CMV, PCP,TB)

Question 18

Coronavirus

1. State the 3 virulence factors, what kind of RNA and what the receptor is
2. TX : What is supportive tx and antipyretic tx?
3. What’s an IV drug tx u can use?
4. State the MOA of this drug
5. Remdesivir : AE? (2)

Answer 18

1. S protein (Spike), E (envelope protein), M (membrane protein)
   - + RNA
   -ACE2 receptor
2. IV fluids, tylenol
3. Remdesivir
4. Prodrug that is monophosphate –> remdesivir-triphosphate
   -Adenosine analog that acts as an inhibitor of RNA dependent RNA polymerase
5. Incr liver enzymes and infusion related rxns

Question 19

Nirmatrelvir and Ritonavir (Paxlovid)

1. MOA of Nirmatrelvir?
2. MOA of Ritonavir?
3. Efficacy : DECR hospitalizations and death by ___ % when given within how many days of sx onset?
4. Indicated for?
5. AE? (2)

Answer 19

1. SarsCOV2 protease inhibitor , Decr viral replication
2. booster, CYP3A4 inhibitor -> supports longevity of nirmatrelvir
3. 89, 3
4. > 12 yo and high risk of developing a severe case of COVID19 (Cancer, diabetes, obesity or others ; or >65 yo)
5. Diarrhea and Dysgeusia (Task interference)

Question 20

If Paxlovid and Remdesivir not avail use :

Molnupiravir

1. Admin route?
2. MOA?
3. AE? (2)

Answer 20

1. PO
2. Prodrug, nucleoside analog , gets incorp into SARS COV2 RNA by viral polymerase —> accumulation of errors in viral genome and inhibition of viral replication
3. Dizziness and diarrhea