43 - Antiviral drugs, Part 1: Non-HIV Antiviral Drugs

Overview

1. How are viruses different from bacteria? (LP p437)

They lack cell and cell

2. Viruses are obligate parasites. (LP p437)

Respiratory Virus Infections

Oseltamivir
Zanamivir
Amantadine
Rimantadine
Ribavirin

3. Why is it so difficult to predict what influenza virus will cause problems in our population?
• Antigenic (Pandemic)
• Antigenic (Epidemic)

4. What is antigenic shift?

Two or more strains combine to form a new

5. What is antigenic drift?

Change in virus occurs from

6. What is the preferred method of dealing with influenza? (LP p437)

Preventing infection with a

Neuraminidase Inhibitors
7. What viral enzyme is a target for anti-influenza therapy? (LP p437)

8. What is the mechanism of action for neuraminidase inhibitors? (LP p437-438)

•
• Selectively inhibit neuraminidase and block the release of

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9. List some therapeutic uses for neuraminidase inhibitors. (LP p437)
• Influenza
• Prophylaxis

10. What are some adverse effects of neuraminidase inhibitors? (LP p438)
• Oseltamivir
- GI symptoms (avoided if taken with food)
• Zanamivir
- (caution with COPD and asthma patients)

Adamantanes
11. What is the mechanism of action for adamantanes? (LP p438)
• Blocks the viral membrane matrix
• Fusion of the membranes creates an acidic endosome required for
• A man to dine takes off his coat
• Interfere with the release of

12. What are some therapeutic uses for amantadine? (LP p438)
•
• Influenza A

13. What are some adverse effects of the adamantanes? (LP p439)
• GI symptoms
• CNS side effects
-
- Dizziness
-
• Fewer CNS side effects with rimantadine

Ribavirin
14. What are the therapeutic uses for ribavirin? (LP p439)
• (respiratory syncytial virus)
• Hepatitis C (with interferon alpha)
•

15. What is the mechanism of action for ribavirin? (LP p439)

• Prodrug converted into
• Inhibits guanosine-triphosphate formation
• Prevents viral
• Blocks RNA-dependent RNA polymerase

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16. What are the adverse effects of ribavirin? (LP p439)
• Transient dose-related
• Elevated bilirubinemia
• Aerosol administration associated with rapid deterioration in respiratory function
• and embryocidal (pregnancy category X)

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Quick Review 1

1. What is the difference between antigenic shift and antigenic drift?

• Antigenic shift is when two or more strains combine to form a
• Antigenic drift is when a change in virus occurs from

2. Neuraminidase inhibitors cover what type of influenza? (LP p436)

3. When should the neuraminidase inhibitors be started when a patient is diagnosed with influenza?

4. Why should zanamivir be used with caution in patients with COPD or asthma? (LP p438)

5. Amantadine stimulates dopamine release from nerve terminals and because of this it can be used in the
treatment of what disease? (LP p438)

6. Amantadine should be used cautiously in patients with a history of what medical problems? (LP p439)
• Patients with history of
• Patients with history of psychiatric disorders
• Patients with

7. Because ribavirin is teratogenic and embryocidal it is a pregnancy category X. How long must a patient wait to
become pregnant after stopping this medication?

8. Which type of influenza can amantadine potentially treat?

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Hepatic Viral Infections

Interferon
Lamivudine
Adefovir
Entecavir
Telbivudine

1. What types of hepatitis are the most common causes of chronic hepatitis, cirrhosis, and hepatocellular
carcinoma? (LP p440)

2. What is the treatment for hepatitis B? (LP p440)

3. What is the treatment for hepatitis C? (LP p440)

Pegylated interferon with

Interferon
4. What are the therapeutic uses for interferon ? (LP p440)
• Hepatitis
• Condyloma acuminata
• Hairy cell leukemia
•

5. Interferon  is used for what disease? (LP p440)

6. What is the mechanism of action for interferon? (LP p440)

• Incompletely understood
• May induce host cell enzymes that block of viral RNA
• Reduce viral and

7. What are the adverse effects of interferon? (LP p440-441)

• Flu-like symptoms
• (e.g., depression)
• Fatigue

8. What are the dose-limiting side effects of interferon? (LP p440-441)

• Bone marrow suppression
•
• Autoimmune disorders
• Cardiotoxicity
• Weight loss

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Lamivudine
9. What is the mechanism of action for lamivudine? (LP p441)
•
• Phosphorylated to the active triphosphate form
• Inhibits DNA polymerase and reverse transcriptase

10. List some therapeutic uses for lamivudine. (LP p441)

• (low-dose)
• HIV (high-dose)

11. What are the adverse effects of lamivudine? (LP p441)

• Headache
•
• Lactic acidosis
•

Adefovir
12. What is the mechanism of action for adefovir? (LP p441)
•
• Phosphorylated to adefovir diphosphate and incorporated into viral DNA
• Prevents

Entecavir
13. What is the mechanism of action for entecavir? (LP p441)
• Guanosine analog
• Phosphorylated to the triphosphate form
•

14. List some therapeutic uses for entecavir. (LP p441)

-resistant strains of HBV

15. When using entecavir, what other drugs should you avoid? (LP p441)
Avoid with drugs that have

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Telbivudine
16. What is the mechanism of action for telbivudine? (441-442)
•
• Phosphorylated intracellularly to the active triphosphate form
• Causes termination of

17. What viral disease is telbivudine not active against? (LP p441)

Tenofovir
18. What are the therapeutic uses for tenofovir?

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Quick Review 2

1. Hepatitis B and C are the most common types of hepatitis known for causing what hepatic diseases?
(LP p440)
• Chronic hepatitis
• Cirrhosis
•

2. Which interferon has been approved for the treatment of hepatitis B and C? (LP p440)

3. A patient is diagnosed with both HIV and hepatitis B. What dose of lamivudine should be used in this patient
and why?

4. What are the adverse effects of interferon? (LP p440-441)

•
• Psychiatric symptoms (e.g., depression)
• Fatigue
•
• Neurotoxicity
• Autoimmune disorders
•
• Weight loss

5. What is a potential consequence of abruptly stopping hepatitis B treatment?

6. Which antiviral can be used for hepatitis B that is resistant to lamivudine? (LP p441)

7. Match the mechanism of action with the drug. (LP p440-442)

Interferon Inhibits HBV DNA polymerase and HIV reverse transcriptase

Lamivudine May induce host cell enzymes that block translation of viral RNA

Telbivudine Thymidine analog; causes termination of the DNA chain

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Herpesvirus Infections

Acyclovir Penciclovir
Cidofovir Famciclovir
Fomivirsen Vidarabine
Foscarnet Trifluridine
Ganciclovir

1. Herpesvirus causes a broad spectrum of what diseases?

• Cold sores
•
•
• Genital infections

2. All herpesvirus drugs are purine or pyrimidine analogs except for what two drugs? (LP p442)

Acyclovir
3. List the therapeutic uses for acyclovir. (LP p442)
• HSV
• VZV (varicella zoster virus)
•
• Herpes encephalitis
• Genital herpes
• Prophylaxis

4. What is the mechanism of action of acyclovir? (LP p442)

• Guanosine analog
• Phosphorylated by the herpes
• Phosphorylated to its active triphosphate form
• Incorporated into viral DNA and the DNA chain

5. List the adverse effects of acyclovir when taken orally. (LP p442-443)
•
• Diarrhea
• Nausea
• Vomiting

6. List the adverse effects of acyclovir when given intravenously. (LP p442-443)
• Reversible
• Increase liver function tests (LFTs)

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7. List the adverse effects of acyclovir if given in high doses. (LP p442-443)
•
• GI symptoms

Cidofovir
8. List one therapeutic use for cidofovir. (LP p443)
in AIDS patients

9. What is the mechanism of action of cidofovir? (LP p443)

• Nucleotide analog of cytosine
• Inhibits viral synthesis

10. What are the adverse effects of cidofovir? (LP p443)

•
• Neutropenia
• Metabolic acidosis
•

Fomivirsen
11. What is the mechanism of action of fomivirsen? (LP p443)
Antisense oligonucleotide directed against

12. What is the clinical use of fomivirsen? (LP p443)

When patients who have failed other treatments for

13. What are some adverse effects of fomivirsen? (LP p443)

• Iritis
•
• Visual changes

Foscarnet
14. List some therapeutic uses for foscarnet. (LP p443)
•
• Herpes zoster
• CMV retinitis (immunocompromised)

15. What is the mechanism of action for foscarnet? (LP p443)

• Reversibly inhibits viral polymerases
• Interferes with viral DNA and RNA synthesis

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16. List the adverse effects for foscarnet. (LP p443)
• Nephrotoxicity
• Anemia
• Nausea
• Fever
• Hypomagnesemia
•
• Seizures
•

Ganciclovir
17. What are the therapeutic uses for ganciclovir? (LP p444)
• (immunocompromised)
• CMV prophylaxis (transplant patients)

18. What is the mechanism of action for ganciclovir? (LP p444)

• Competitively inhibits viral DNA polymerase
• Causes DNA

19. List the adverse effects of ganciclovir. (LP p444)

•
• Thrombocytopenia
•
• Carcinogenic
• Teratogenic and embryotoxic

Penciclovir and Famciclovir

20. What are the therapeutic uses for penciclovir? (LP p444)
•
• VZV (varicella zoster virus)

21. What is the mechanism of action for penciclovir and famciclovir? (LP p444)
• Phosphorylated by viral
• Penciclovir triphosphate inhibits viral DNA polymerase
• Famciclovir is the acyclic analog of 2’-deoxyguanosine, a prodrug of penciclovir

22. What are some therapeutic uses for famciclovir? (LP p444)
•
• Recurrent, labial, or genital herpes

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Vidarabine
23. What is the mechanism of action of vidarabine? (LP p444-445)
• Adenosine analog, converted to its 5’-triphosphate analog in the cell
•

24. What are some therapeutic uses for vidarabine? (LP p444-445)
•
• VZV
• Ophthalmic ointment only

Trifluridine
25. What is the mechanism of action of trifluridine? (LP p445-446)
• Pyrimidine nucleoside analog
• Leads to defective DNA synthesis
• Irreversible inhibitor of viral

26. What are the therapeutic uses for trifluridine? (LP p445-446)
• HSV 1 and 2
•
• HSV keratoconjunctivitis
• Recurrent epithelial

27. List some adverse effects for trifluridine. (LP p445-446)

• Transient
• Eyelid (palpebral) edema

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Quick Review 3

1. Herpes viral infections can only be treated when in what phase, active or inactive?

2. Why can’t acyclovir be used to treat CMV (cytomegalovirus)? (LP p443)

3. What is the benefit of valacyclovir over acyclovir?

4. What medication must be given with cidofovir to reduce the risk of nephrotoxicity? (LP p443)

5. What antiviral medications discussed can be used in the treatment of CMV? (LP p445)
• Cidofovir (only for virus-induced retinitis)
•
• Foscarnet

6. Ganciclovir can cause severe, dose-dependent neutropenia. What medications can result in an additive
neutropenia when combined with ganciclovir? (LP p444)
• Zidovudine (AZT)
•
• Mycophenolate mofetil

7. Which antiviral medications used for the treatment of herpes infections can be given topically? (LP p442-446)
• Acyclovir
•
• Trifluridine (as a solution in the eye)

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End of Session Quiz

1. Match the following diseases with the treatment. (LP p437-439)

Chronic hepatitis C Amantadine

Influenza A and B Ribavirin

Parkinson’s Oseltamavir

2. Match the following mechanisms of action with the associated therapeutic agent. (LP p437-455)

Inhibits viral uncoating Zanamivir

Viral entry inhibitor Enfuvirtide

Neuraminidase inhibitor Amantadine

3. Name the drugs most commonly used in viral hepatitis treatment. (LP p440-441)

4. Name the antiviral drug used in the following presentations. (LP p437-445)

Presentations Antiviral drug

Prophylaxis for influenza A

Inhibits CMV DNA polymerase

Used in treatment for chronic hepatitis C 

First-line for HSV or EBV

Blocks viral penetration and uncoating

Treats both influenza A and B

Second-line for CMV retinitis

Derivative of amantadine with fewer side effects

Inhibits viral DNA polymerase when phosphorylated by

viral thymidine kinase

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5. For which infections is interferon used? (LP p440)

6. What is the mechanism of action of acyclovir? For which viruses is it commonly used? (LP p442)

7. Which antiviral drug can be used for both H5N1 Avian Influenza and H1N1 “Swine Flu”? (LP p437-438)

8. What is the major method of protecting humans from the influenza virus? (LP p437)

9. A newborn has an MRI that shows temporal lobe encephalitis. What is the causative virus, how did the
newborn contract the disease, and what is the treatment?

10. A 10-year-old male patient with a history of asthma presents with influenza type A. His symptoms began less
than 24 hours ago. The patient’s parents ask if he can have the inhaled influenza medication because he is
already familiar with inhalers because of his asthma. What should you tell the parents?

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