Antiviral Drugs

Question 1

What are the 4 types of antivirals?

Answer 1

1. Nucleoside analogs (Nucs)
2. Non-nucleosides (Non-nucs)
3. Protease Inhibitors
4. Entry inhibitors

Question 2

What virus functions are targeted by antivirals?

Answer 2

1. Entry
2. Genome replication
3. Assembly
4. Release from cell

Question 3

What host cell defenses are targeted by antiviral therapies?

Answer 3

Intrinsic immunity via interferon pathway

Question 4

What is an issue of the specificity of antiviral drugs?

Answer 4

1. Most drugs only target one virus
2. Broad spectrum drugs are rare

Question 5

What type of cytotoxic effects result from antiviral use?

Answer 5

• “Off target” effects can harm cells
• “On target” drugs directed at viral enzymes can be defeated by resistance mutations

Question 6

What are some issues with duration of antiviral effects?

Answer 6

1. They are reversible competitive inhibitors
2. Virus replication can resume when drug is cleared
3. Tx may need to be lifelong

Question 7

Describe viral drug resistance

Answer 7

1. Resistance mutations often exist before Tx
2. Drugs select for resistant virus strains

Question 8

What characteristics favor emergence of resistant viral variants?

Answer 8

1. High rate of virus replication
2. High mutation rate (RNA >>> DNA)
3. High selective drug pressure (longterm/multiple Tx)
4. Immunosuppressed hosts that can’t clear virus-infected cells

Question 9

What are the strategies to limit drug resistant viral infections?

Answer 9

1. Alleviate immunosuppression in the patient (lower doses of anti-T cell drugs)
2. Combine drugs with different targets (lower probablility that multiple resistance mutations will be present
3. Target host fns (infected cells may have unique targetable profile)

Question 10

Who should be treated for HSV1, HSV2, VZV?

Answer 10

Neonates (HSV), Patients with frequent recurrence (1/2), Those w/ HSV complications (encephalitis, dissemination, eye infections), Those with zoster

Question 11

What is the leading drug for HSV infections? What type of drug is it? How effective is it against VZV?

Answer 11

Acyclovir; Guanosine nucleoside analog (NUC); Less effective than for HSV 1/2

Question 12

What is the mechanism of acyclovir action?

Answer 12

1. Viral (HSV) thymidine kinase takes up A and phosphorylates it
2. Host kinases (GMPK and NDPK) phosphorylate A
3. Viral DNA polymerase incorporates A into viral DNA halting synthesis

Question 13

What is Ganciclovir used for? What type of drug is it? What are complications of use? Who should be treated?

Answer 13

CMV; Guanosine nucleoside analog (NUC); similar to acyclovir; Highly toxic - BM suppresion, Mutagenic/teratogenic, severe SEs; Bone marrow and organ transplant patients, immunosuppressed people with active CMV, or those with CMV retinitis

Question 14

What type of drug is Foscarnet? What is its mechanism? What is it effective against? Route of administration?

Answer 14

Trisodium phosphonoformate Broad Spectrum antiviral; Inhibits viral DNA polymerase; All herpes viruses; IV only

Question 15

What type of drug is Cidofovir? What is it effective against? Route of administration?

Answer 15

Broad spectrum nucleoside analog of cytosine (NUC); DNA viruses: herepesvirus, adenovirus, papillomavirus, poxvirus; IV

Question 16

What is the major side-effect of broad spectrum antivirals?

Answer 16

renal toxicity

Question 17

What are the treatment options for HBV? Who should be treated?

Answer 17

PEG-IFN-ALPHA, Entecavir, Tenofovir disoproxil fumarate; People with chronic active HBV, those coinfected with HCV/HIV, and those progressing to cirrhosis, liver failure, or hepatocellular carcinoma

Question 18

What are the treatments for Influenza virus? Mechanism? Who should be treated?

Answer 18

Zanamivir, Oseltamivir; Both are sialic acid analogs that inhibit viral neuraminidase (sialidase) vausing virions to remain attached to the cell; Severely ill, children < 2 yo, Adults > 65 yo, Pregnant women, Immunosuppressed, ANYONE who has influenza

Question 19

What is a broad spectrum RNA antiviral? What type of drug is it? Route of administration? Approved uses?

Answer 19

Ribavirin; Nucleoside analog of guanosine (NUC); Oral, IV, Aerosol; HCV, RSV

Question 20

What is the general Tx for HCV? What are issues with Tx?

Answer 20

PEG-INF-ALPHA and ribavirin; Not all HCV genotypes respond, difficult Tx regimen complicated by bad sideffects

Question 21

What was the earliest Tx for HIV? What type of drug is it? Why is it no longer in use?

Answer 21

AZT; Nucleoside analog of thymidine (NUC)/Nucleoside Reverse Transcriptase Inhibitor)

Question 22

What are the 4 methods for HIV treatment?

Answer 22

1. Entry inhibition
2. Reverse transcriptase inhibitor
3. Integrase inhibitor
4. Protease inhibitor

Question 23

What is an example of an anti-HIV entry inhibitor?

Answer 23

Maraviroc

Question 24

What is an example of an anti-HIV Nucleoside/tide RT inhibitor?

Answer 24

Tenofovir

Question 25

What is an example of an anti-HIV Non-nucleoside RT inhibitor?

Answer 25

Efavirenz

Question 26

What is an example of an anti-HIV integrase inhibitor?

Answer 26

Raltegravir

Question 27

What is an eample of an anti-HIV protease inhibitor?

Answer 27

Darunavir

Question 28

What is Stribild used to treat? What four drugs make up Stribild and what are their functions?

Answer 28

HIV

1. Elvitegravir - integrase inhibitor
2. Cobicistat - inhibits CYP3A4 that breaks down drugs in liver
3. Emtricitabine - reverse transcriptase inhibitor
4. Tenofovir disoproxil fumarate - reverese transcriptase inhibitor