Antiviral

Question 1

What are the steps to viral replication?

Answer 1

1. attachment/entry
2. uncoating
3. early protein synthesis
4. DNA/RNA replication
5. Late protein synthesis
6. Assembly/maturation
7. Release

• antiviral drugs will target these

Question 2

Oseltamivir

Answer 2

Use

• prevent/treat early influenza A & B
• H1N1 = subtype of influenza A

Mechanism

• neuraminidase inhibitor
• sialic acid analog
  
  • cleaves sialic acid of infected host cell -> release virus
• prodrug to be metabolized by liver and GI tract

Adverse Effects

• nausea, GI discomfort

Resistance

• mutation in neuraminidase, however if there is a mutation virus is usually less virulent

Question 3

Amantadine

Answer 3

Use:

• treat early influenza A
• NOT H1N1

Mechanism:

• inhibit proton ion channel M2 –> inhibit virus binding to endosome –> inhibits coating of virus.
• distributed thoughou body, CNS, UNCHANGED BY KIDNEY

Adverse Effects

• GI disturbances
• CNS disturbance
• renal damage w/ renal insufficiency

Resistance

• mutation to M2

Question 4

acyclovir

Answer 4

Use:

• herpes infection

Mechanism

• guanosine analogy –> activcated by thymidine kinase –> infected cells susceptible tri-phosphate acyclovir that compete w/ dGTP during DNA synthesis = DNA termination
• oral, IV or topical formulation distributed though body, CNS

Adverse Effects:

• nausea, vomitting, diarrhea, headache, renal damage

Resistance:

• altered or deficient thymidine kinase

Question 5

zidovudine (AZT)

Answer 5

Use:

• HIV

Mechanism

• nucleoside reverse transcriptase inhibitor
• thymidine analogue –> phosphorylated by mammalian kinase viral reverse transcriptase –> compete with dTTP during DNA synthesis –> DNA termination
• well distributed, CNS, metabolized in liver (glucoronidation)

Adverse Effects:

• Bone marrow
  
  • anemia, netropenia
• Heaptotoxicity
• drug interactions
  
  • drugs competing with glucoronidation (acetaminophen, beznodiaszepines)

Resistance

• reverse transcriptase mutation, inefficient kinase

Question 6

nevirapine

Answer 6

Use:

• treatment of HIV

Mechanism:

• Non-nucleoside reverse transcriptase inhibitor (NNRTIs)
• binds to non-catalytic site inhibiting reverse transcriptase
• well absored, CNS, fetus, tit milk, metabolized in liver –> glucoronidation

Adverse effects:

• rash, psychiatric effects
• heptatotoxicity
• inc CYP3A4 –> inc metabolism of other drugs ex itselff, AZOLES, protease inhibitors

Resistance:

• reverse transcriptase mutation

Question 7

ritonavir

Answer 7

Use

• treat HIV

Mechanism:

• Protease inhibitor
• inhibit HIV aspartyl protease
• inhibits CYP450, given as enhance of other PIs
• give with choco MILK! or nutritional suppplement cause unpalatable!
• metabolized by CYP3A4

Adverse effects:

• nausea, vomiting, diarrhea, numbness, elevated liver enzymes
• high bl glucose and lipid levels

Resistance

• mutation in protease

Question 8

maraviroc

Answer 8

use:

• treat HIV

Mechanism:

• viral entry inhibitor
• CCR5 reveptor antagonist blocks binding of viral gp120 to CCR5 –> prevent viral entry
• dec viral load in patients

Adverse Effects

• hepatotoxicity and cardriovascular

Question 9

raltegravir

Answer 9

Use:

• treat HIV

Mechanism

• Integrase inhibitor
• dec transfer of viral DNA into host genome

Question 10

HAART

Answer 10

what is it

• highly active antiretroviral therapy
• First line treatment = combo of 3 antiviral drugs

HAART = 2 NRTIs + NNRTI or PI