Antivirals/retrovirals

Question 1

Purine/pyrimidine Analog which is the

DOF IN: HSV ENCEPHALITIS

Answer 1

ACYCLOVIR

Question 2

Neuraminidase Inhibitors. Name them:

Answer 2

Oseltamivir, Zanamivir

Question 3

Synthetic Guanosine analogue that is:

• Active against broad spectrum of RNA & DNA viruses (eg, RSV, HCV, Lassa fever)
• Commonly used in combination with interferon for the treatment of HCV

name the Antiviral

Answer 3

Ribavirin

Purine/pyrimidine Analogs

Question 5

which drug is commonly used in combination with interferon for the treatment of HCV?

Answer 5

ribavirin

Question 6

if you attempt to treat HBV or HIV (hepatic infections) with Lamivudine but have no luck what is drug you can use that you can use? pick one.

Interferon

Ganciclovir

Ribavarin

Entecavir

Cidofovir

Answer 6

Entecavir

(must monitor after discontinuation in case of exacerbation of severe hepatitis

Question 7

whats the most common AE related to the Fusion inhibitor Enfuvirtide

Answer 7

Injection site-related rxs

Question 8

The herpes antiviral drug which does NOT require phosphorylation to be active is indicated in the treatment of… name 3 things

What is the drug?

Answer 8

CMV

CMV retinitis (in immunocompromised patients)

Acyclovir-resistant HSV & CMV retinitis

Ganciclovir-resistant CMV & VZV

The drug is Foscarnet

Question 9

list all the NRTI’s

ST. Z’ LEAD

Answer 9

Stavudine

Tenofovir

Zidovudine

Lamivudine

Emtricitabine

Abacavir

Didanosine

Question 10

Herpes Simplex Labialis (cold sores) is treated with this drug and the AE associated with it is Mild erythema.

Answer 10

Penciclovir

Question 11

which herpes antiviral DOES NOT require phosphylation to be active?

Answer 11

Foscarnet

Question 12

Are protease inhibitors metabolized by CYP3A4 and P glycoprotein?

Answer 12

yes, extensively.

Question 13

which antiviral….

prevents viral mRNA capping.

used to treat

• *1. RSV
  2. HCV**

3.LASSA FEVER

Answer 13

Ribavirin

Question 14

List the 5 Protease Inhibitors (PIs)

L’ D I N A

Answer 14

Lopinavir

Darunavir

Indinavir

Nelfinavir

Atazanavir

Question 15

which vacciens are CI in pts with a CD4+ count of < 200?

Answer 15

LIVE VACCINES!

• MMR
• Varicella and • Zoster

Other vaccines may be administered without regard to the patient’s CD4+

Question 16

which is the only ONCE daily PI’s

Answer 16

Atazanavir

Question 17

Blocks viral membrane protein, M2 (H+ ion channel)

• Channel is required for fusion of viral with cell membrane to endosome (requirement for viral uncoating)

which drug is this?

Answer 17

the -tadines!

Amantadine

Rimantadine

Question 18

name the antiviral with the following pattern of pharmodynamics & AE

• Oral, IV, & aerosolized
• Distribution significantly prolonged in RBC (16-40 days)

Adverse Effects

• Dose-dependent transient anemia (can bind to RBC)

Answer 18

Ribavirin

Question 19

• GI discomfort, nausea (alleviated when taken with food)
• airway irritation (avoid in severe asthma, COPD)

match the drug with the AE of the following Neuramidase inhibitors.

options are: Oseltamivir & Zanamivir

Answer 19

• GI discomfort, nausea (alleviated when taken with food)=Oseltamivir
• airway irritation (avoid in severe asthma, COPD)=Zanamivir (side note, the med is inhaled/intranasal and is NOT orally active)

Question 20

Upon exposure to HIV, healthcare personnel should immediately receive a postexposure prophylaxis regimen containing at least 3 antiretroviral drugs. what are the preffered 3 drugs in this regiment

Answer 20

Raltegravir (INSTI) + tenofovir (NRTI) + emtricitabine (NRTI)

Regimen is given for 28 days and can be stopped if source is shown to be HIV-negative.

Question 21

Do NNRTI’s have in vitro activity against HIV 2?

Answer 21

NO.

from SGD.

Question 22

the absorption of which protease inhibitor decreaes if take with a meal

Answer 22

INDINAVIR

main AE: hematuria, Rash, blurred vision, nephrolithiasis & hyperbilirubinemia

Question 23

which class of drugs is being described? • Currently most popular antiretroviral class due to good side-effect profile and favorable effects on lipid metabolism

Answer 23

INSTI’s (integrease inhibitors)

Question 24

Name that NNRTI

AE list: Rash, dizziness, headache, insomnia, difficulty concentrating, vivid dreams, nightmares, reductions in vitamin D levels, hyperlipidemia,

teratogenic (avoid in 1st trimester)

Substrate of CYP3A4

Inducer of CYP3A4 and 2B6

Answer 24

Efavirenz

Question 25

Transient eye irritation, light intolerance & **palpebral (eyelid) edema** are the main AE for which Anti Herpes anti-viral?

Answer 25

Trifluridine (its an opthalmic ointment) DOC for **HSV Keratoconjunctivitis**

Question 26

does Acyclovir or Valacyclovir (its prodrug) have greater ORAL bioavailbility?

Answer 26

**Val**acyclovir Val gives better ORAL.

Question 27

What is an important toxicity common to all approved **protease inhibitors?**

Answer 27

the potential for metabolic drug interactions. Most of these drugs inhibit **CYP3A4**

Question 28

* Effective against hepatitis B and HIV * **Triphosphate** form inhibits HBV and HIV reverse transcriptase * **Monophosphate** form is incorporated into DNA (by HBV polymerase) resulting in **chain termination** * Well tolerated (headache, dizziness, GI complaints)

Answer 28

**Lamivudine**

Question 29

all Herpes antivirals Require phosphorylation by viral kinases and work by Inhibiting DNA polymerase /DNA synthesis. which is the only one that is phosphorylated by **host cellular kinases only?**

Answer 29

**Cidofovir (does not require any viral enzymes)**

Question 30

Resistance to drug is acquired by Mutations in phosphotranferase (UL97), or viral DNA polymerase AND its the **DOC** for: **CMV retinitis** & **CMV prophylaxis in** **immunocompromised**

Answer 30

**Ganciclovir**

Question 31

which NNRTI is CI in the first trimester if pregnancy

Answer 31

Efavirenz

Question 32

The following class of antiretrovirals has the following AE: ## Footnote **hyperglycemia**, insulin resistance and **hyperlipidemia,** in addition to **altered body fat distribution.** **Buffalo hump, gynecomastia,** and truncal obesity may occur with facial and **peripheral lipodystrophy**. They are also associated with *parathesias, nausea, vomiting and diarrhea.*

Answer 32

Protease Inhibitors

Question 33

which Integrase inhibitor has the following drug interactions **Drug Interactions** • **Rifampin, tipranavir & efavirenz** may decrease its conc • **PPI’s** may increases it conc

Answer 33

raltegraivr side note. Can cause increases in creatine phosphokinases

Question 34

What do Efavirenz and Nevirapine share in common in relation to the CYP P 450 system

Answer 34

Inducer of **CYP3A4 and 2B6**

Question 35

Lets say an adult pt has Hep C, and you've tried interferon and ribavirin but no luck there. whats an alternative?

Answer 35

The -previrs! **Boceprevir, Telaprevir (Protease Inhibitors)**

Question 36

due to its poor intrinsic bioavailability, WHICH Protease inhibitor requires the avoidance of Enzyme inducers such as St. Johns worts andn Rifampin this is a PREFFERED PI by the way

Answer 36

**LOPINAVIR**

Question 37

which class of antiretrovirals is being being described are more susceptible to high-level drug resistance than other classes because **a single-amino acid change in the NNRTI-binding pocket renders the virus resistant to all available drugs in the class** and this is their major disadvantage.

Answer 37

The NNRTIs

Question 38

• ___________ form inhibits HBV and HIV reverse transcriptase • \_\_\_\_\_\_\_\_\_\_\_form is incorporated into DNA (by HBV polymerase) resulting in chain termination fill in the blank with with either "Monophosphate" or Triphosphate" in relation to which type of **Lamivudine** mechanism is being described.

Answer 38

• **Triphosphate** form inhibits HBV and HIV reverse transcriptase • **Monophosphate** form is incorporated into DNA (by HBV polymerase) resulting in chain termination

Question 39

Prevents viral mRNA capping inhibition of RNA polymerase Teratogenic (Cat X) can bind to RBC and therefore causes transient dose dependent anemia

Answer 39

Ribavirin (guanosine analogue)

Question 40

Do **Amantadine or Rimantadine** fit the following description? * \_\_\_\_\_\_\_\_is widely distributed & **crosses BBB** and is **not extensively metabolized** & excreted into urine where it may accumulate * ________ IS metabolized before elimination in urine

Answer 40

**Amantadine (first blank)** **Rimantadine (second blank)**

Question 41

• Major use is treatment of **CMV-induced retinitis in HIV/AIDS** * **NOT** phosphorylated by viral kinases * **Requires activation by *host cell kinases (no viral enzymes necessary!)***

Answer 41

**CIDOFOVIR**

Question 42

Name that NNRTI Rash, fever, nausea, headache, **severe hepatotoxicity, hepatic failure and death** **Inducer of CYP3A4 and 2B6**

Answer 42

**Nevirapine**

Question 43

The following MOA belongs to which class or ANTIRETROVIRALS competitively inhibit the action of the virus aspartyl protease. These drugs **prevent proteolytic cleavage of HIV gag and pol polyproteins** that include essential structural and enzymatic (reverse transcriptase, protease and integrase) components of the virus. This **prevents the metamorphosis of HIV particles into their *_mature_* infectious form.** OVERALL, THEY ***_PREVENT PROCESSING OF VIRAL PROTEINS_***, **RESULTING IN THE PRODUCTION OF IMMATURE NON INFECTIOUS VIRAL PARTICLES**

Answer 43

HIV **protease inhibitors** **Lopinavir** **Darunavir** **Indinavir** **Nelfinavir** **Atazanavir**

Question 44

Which purine/pyrimidine analogue (which is a Pyrophosphate analogue) **does NOOOOTTTTTTT** require phosphorylation?

Answer 44

**FOSCARNET**

Question 45

which PI **CANNOT** be boosted by Ritonavir bc its metabolized by several CYPS and it also has a ton of CI's and Generally well tolerated, diarrhea, nausea and **flatulence** are common

Answer 45

**Nelfinavir**

Question 46

* Effective against HSV & ganciclovir resistant HSV * Must be co-administered with ***_probenecid_*** (blocks renal tubular secretion) name that drug.

Answer 46

**CIDOFOVIR**

Question 47

which of the following are AE/CI are associated with **Ganciclovir** ## Footnote a. Myelosuppressionb. b. insomnia, dizziness, ataxia leading to hallucinations, seizures] c. Severe dose-dependent neutropenia d. Pregnancy (FDA Category C) e. Flu-like (fever, chills, myalgias & GI disturbances) f. Fatigue & mental depression

Answer 47

**a. Myelosuppression​** **c.** **Severe dose-dependent neutropenia** **d. Pregnancy (FDA Category C)**

Question 48

**Zidovudine (thymdidne analogue**) is an NRTI whose main AE is **Bone suppression** in pts with advnaced HIV diseae). When combined with\_\_\_\_\_\_\_ (antiviral), pt could get **Neutropenia**

Answer 48

**Ganciclovir**

Question 49

* Used in combination with most protease inhibitors **(not nelfinavir**) * **Never used alone** \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ * Used commonly in combination with the **INSTI elvitegravir** * Also found in combination with **darunavir and atazanavir** (which are both PI's)

Answer 49

1. RITONAVIR 2. COBICISTAT

Question 50

**Guanosine analogs.** **Monophosphorylated** by **HSV/VZV thymidine kinase** and **not** phosphorylated in **uninfected cells**

Answer 50

**ACYCLOVIR**

Question 51

the following MOA is associated with which antiviral drug? MOA * Use innate immune response. * **DO NOT** target viral gene products *directly* * Inhibit RNA & DNA synthesis by activating / inducing protein expression that inhibit virus infection eg, **PKR**

Answer 51

Interferon

Question 52

**a. Neuraminidase Inhibitors [for Influenza A & B]** **b. Inhibitors of Viral Uncoating [for Influenza A ONLY!!!]** **c. Synthetic Guanosine Analog (inhibits RNA dep-RNA pol)-****[for RSV, HCV, Lassa Fever]** * Amantadine, Rimantadine * Ribavirin * Oseltamivir, Zanamivir match the desciption with the name of the dru

Answer 52

**a. Neuraminidase Inhibitors [for Influenza A & B]** • Oseltamivir, Zanamivir **b. Inhibitors of Viral Uncoating [for Influenza A ONLY!!!]** • Amantadine, Rimantadine **c. Synthetic Guanosine Analog (inhibits RNA dep-RNA pol)-[for RSV, HCV, Lassa Fever]** • Ribavirin

Question 53

List the 3 Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Answer 53

Nevirapine Efavirenz Rilpivirine