BIIC Pharmacology Lecture 4_Antimicrobials 2 - Antivirals

Question 1

What is the predominant MOA of antivirals?

Answer 1

They act by arresting viral replication and are there for more viral static than viracidal

Question 2

Why are viruses often difficult to treat?

Answer 2

Viruses are obligate intracellular parasites. Because they use host cell machinery, it is difficult to target them without harming the host cell. Successful antivirals manage to target something specific to the viral biochemistry.

Question 3

Why are nucleotide analouges effective in treating viruses?

Answer 3

Viral thymadine kinase has 200-300 times more affinity for the analoge than host thymadine kinase. This gives specificity to the drug (aka it harms the virus far more than it does the host) because the analog will accumulate significantly more in infected cells leading to cell death. Also, the analogs seem to inhibit viral DNA polymerase more than host.

Question 4

What are the 5 stages of the viral life cycle that can be targeted?

Answer 4

1. attachment and penetration of virus to host cell
2. uncoating of the viral genome within the host cell
3. synthesis of viral components within the host cell
4. assembly of viral particles
5. release of the virus to spread and invade other cells

Question 5

What kind of genome do herpes viruses have?

Answer 5

DNA

Question 6

What is the general MOA of herpes antiviral agents?

Answer 6

They are nucleocide analogs that inhibit DNA/RNA polymerase

Question 7

What are the typical mode of administration, MOA, Pharmacokenetics, ADR, DDIs, of acyclovir and valacylovir?

Answer 7

acyclovir: IV
valacylovir (prodrug): PO
MOA: guanosine analog, inhibits viral DNA polymerase and terminates synthesis
Pharmacokenetics: acyclovir 15-20% avalability PO, valcyclovir 54-70%
ADR: Acyclovir can cause nephrotocicity with IV administration. This can be mitigated with good hydration and slow administration rates. NVD reaction with PO administration.
DDIs: Diuretics increase risk of nephrotoxicity. Probenecid and cimetidine decrease clearance

NOTE: Acyclovir is the only anti HSV agent approved for IV administration in the US

Question 8

What are the

Administration
MOA:
Pharmco:
ADR:
DDI:

of Penciclovir and famciclovir (prodrug)?

Answer 8

Administration: Penciclover (topical) famciclovir (PO)
MOA: Similar to acyclovier but does not terminate DNA chain
Pharmco:
ADR: Typical
DDI:

Question 9

What are the

Administration
MOA:
Pharmco:
ADR:
DDI:

of Ganciclovir and valganciclovir (prodrug)?

Answer 9

Administration: Ganciclovir (IV), Valganciclovir (PO)
MOA: Same as acyclovir
Pharmco: Renally cleared
ADR: Myelosuppression (causes cytopenia), Neurotoxicity, carcinogenic and tertatogenic
DDI:

Question 10

What are the

Administration
MOA:
Pharmco:
ADR:
DDI:

Foscarnet?

Answer 10

Administration: IV
MOA: Direct inhibition of HSV DNA/RNA polymerase by binding to pyrophosphate binding site.. Foscarnet does not require activation by viral thymadine kinase.
Pharmco: Distributes through entire body including crossing BBB
ADR: Nephrotoxicity, electrolyte imbalance
DDI:

NOTE: often used to treat cytomegalovirus

Question 11

What are the

Administration
MOA:
Pharmco:
ADR:
DDI:

Cidofovir?

Answer 11

Administration: IV
MOA: cytosine nucleotide analog, does not need viral activation
Pharmco: Parent drug has shorter half life (2.6 h) than active metabolite (17-65 hours)
ADR: Nephrotoxicity
DDI:

Question 12

What are the

Administration:
MOA:
Pharmco:
ADR:
DDI:

Amantadine and rimantadine?

Answer 12

Administration: PO
MOA: Bind and block the M2 hydrogen ion channel. This prevents acidification in the virus capsule and thus prevents release of the genome into the cellular enviornment.
Pharmco: amantadine-renally cleared rimantadine-hepatically metabolised then renally cleared. Dose needs to be adjusted for patients with impared kidney function and in the elderly
ADR: typical
DDI: AMantidine causes neurotoxicity with antihistamines, psychotropic or anticholinergic drugs

NOTE: both drugs are only active against influenza A

Question 13

What does Neuraminidase do?

Answer 13

It helps release newly formed viruses into the extracelluar enviornment.

Question 14

What are the

Administration:
MOA:
Pharmco:
ADR:
DDI:

oseltamivir, zanamivir, peramivir?

Answer 14

Administration: oseltamivir (PO), zanamivir (inhalation), preamivir (IV)
MOA: Neuraminidase inhibitor (prevents viral release to the extracellular enviornment)
Pharmco: oseltamivir is a pro drug
ADR: Zanamivir can be dangerouse for use in people with COPD and asthma.
DDI:

NOTE: These can treat Influenza A and B

Question 15

How is ribavirin given, what is it used to treat and what is its ADRs?

Answer 15

Aerisol ribavirin treats RSV, PO is used as a combination therapy for Hep C. It can cause dose dependent hemolytic anemia (and thus elevate bilirubin). It is contraindicated in pregnancy

Question 16

What is palivizumab?

Answer 16

It is a monoclonal antibody that is given via IM injection to treat RSV. It is only used in high risk pediatric patients