Antivirals

Question 1

Oseltamavir: Mechanism of Action

Answer 1

Neuraminidase inhibitor

• inhibits the release of virus form infected cells
• reduces viral spread in respiratory tract

Question 2

Oseltamavir: Therapeutic Uses

Answer 2

• Treament and phrophylaxis of influenza A & B

- Can reduce the duration of infection if administered within 48 hr following the onset of clinical illess

Question 3

Acyclovir: Mechanism of Action

Answer 3

Blocks viral DNA synthesis

• Inhibits viral DNA polymerase
• Causes DNA chain termination when it becomes incorporated into viral DNA

Question 4

What type of drug is Acyclovir?

Answer 4

Prodrug; selectively phosphorylated by viral thymidine kinase

Question 5

Acyclovir: Therapeutic Uses

Answer 5

• Herpetic infections (Herpes simplex, Varicella zoster)

- Not very active against Cytomegalovirus

Question 6

Acyclovir: Adverse Effects

Answer 6

Renal toxicity when the solubility limits of drug are exceeded (drug precipitates)

Question 7

What is a nucleoside analogue that is more active against Cytomegalovirus?

Answer 7

Ganciclovir

Question 8

Ganciclovir: Adverse Effects

Answer 8

Bone marrow suppression (can interfere with our DNA polymerase)

Question 9

In which population would you see resistance to Acyclovir?

Answer 9

Immunosuppressed patients (loss of viral thymidine kinase)

Question 10

What are the 4 types of Anti HIV drugs?

Answer 10

(1) Reverse transcriptase inhibitors
- Nucleoside reverse-transcriptase inhibitors
(NRTI)
- Non-nucleoside reverse-transcriptase
inhibitors (NNRTI)
(2) Protease inhibitors
(3) Entry inhibitors
(4) Integrase inhibitors

Question 11

NRTI- AZT/Zidovudine: Mechanism of Action

Answer 11

Pyrimidine nucleoside analogue of thymidine

- Incorporation into viral nucleic acid causes chain termination

Question 12

What do NRTI’s require to inhibit viral reverse-transcriptase?

Answer 12

Activation to a tri-phosphate form

Question 13

AZT/Zidovudine: Adverse Effects

Answer 13

• Bone marrow suppression (myelosuppression)
• Mitochondrial syndrome (lactic acidosis)
  ~ Probably due to inhibition of
  mitochondrial DNA polymerase (gamma)
  leading to decreased expression of mtDNA
  encoded functions required for aerobic
  respiration

Question 14

AZT/Zidovudine: Therapeutic Uses

Answer 14

Anti-HIV drug

Question 15

NNRTI- Nevirapine: Mechanism of Action

Answer 15

Binds to a different site than NRTIs

Question 16

Nevirapine: Syngergy

Answer 16

Synergistic in combination with nucleoside HIV inhibitors (i.e. AZT)

Question 17

Nevirapine: Therapeutic Uses

Answer 17

Active against HIV-1 but NOT HIV-2 infections

Question 18

Nevirapine: Adverse Effects

Answer 18

• Hypersensitivity: SJS

- Liver toxicity

Question 19

Nevirapine: Drug Interactions

Answer 19

Can increase the hepatic metabolism of other drugs

Question 20

What are 2 HIV Protease Inhibitors?

Answer 20

Atazanavir, Ritonavir

Question 21

HIV Protease Inhibitors: Mechanism of Action

Answer 21

peptidomimetic drug that inhibits HIV-encoded aspartate protease

Question 22

HIV Protease Inhibitors: Therapeutic Uses

Answer 22

Atazanavir used in combination with low-dose ritonavir (ritonavir inhibits atazanavir metabolism)

Question 23

HIV Protease Inhibitors: Adverse Effects

Answer 23

• Lipodystrophy (loose fat tissue that goes somewhere else)

Question 24

HIV Protease Inhibitors: Drug Interaction

Answer 24

Inhibits metabolism of other drugs

Question 25

HAART therapy: Purpose

Answer 25

Primary purpose

 - Suppress viral replication
 - Minimize emergence of drug-resistant virus

Question 26

What is HAART therapy?

Answer 26

Highly-Active Anti-Retroviral Therapy
- Typically a minimum of 3 drugs representing several different classes of drugs (NRTI, NNRTI, PI, II, EI) VARIATIONS; always multi-drug thearpy; at least 2 mechanistic classes of drugs