Pharmacology Of Influenza and Anti-Viral (Fitz)

Question 1

This drug blocks viral M2 ion (H+) channel; prevents uncoating and used for influenza A only

Answer 1

Amantadine

Question 2

What is the anti viral spectrum of amantadine?

Answer 2

A

Question 3

What is the antiviral spectrum of Oseltamivir and Zanamavir?

Answer 3

A and B

Question 4

These drugs are neuraminidase inhibitors and target Influenza A and B

Answer 4

Oseltamivir and Zanamavir

Question 5

List the neuraminidase inhibitors:

Answer 5

Oseltamivir and Zanamavir

Question 6

This neuraminidase inhibitor is PO (suspension, capsule) and can cause nausea (20% incidence)

Answer 6

Oseltamivir

Question 7

This neuraminidase inhibitor is inhaled and can cause bronchospasm in asthmatics (rare)

Answer 7

Zanamavir

Question 8

Zanamivir is not recommended in these types of pts:

Answer 8

Asthma, COPD, resp disease

Question 9

What age groups is Oseltamivir approved for? What about zanamavir?

Answer 9

Oseltamivir-tx and prevention in 1 yr and older

Zanamivir-tx=7 yrs and up; prevention=5 yrs and up

Question 10

Which groups have the greatest burden of influenza?

Answer 10

Elderly

Persons with underlying medical conditions such as COPD, asthma, CHF, diabetes, pregnant women and young children

Question 11

What is the MOA of Amantadine?

Answer 11

M2 ion channel inhibitors –> No H+ enters capsid

Question 12

When is Amantadine not recommended?

Answer 12

Not recommended for antiviral tx or chemoprophylaxis of currently circulating Influenza A virus strains

Question 13

Name the Acyclic nucleosides that act selectively on virus infected cells:

Answer 13

Acyclovir
Valacyclovir
Gancyclovir
Valganciclovir

Question 14

Name the non-nucleoside anti-viral drugs:

Answer 14

Foscarnet

Question 15

These anti-vitals work for HSV and Herpes zoster:

Answer 15

Acyclovir and valacyclovir

Question 16

This drug works for acyclovir-resistant HSV and VSV

Answer 16

Foscarnet

Question 17

These drugs are used for CMV infx:

Answer 17

Ganciclovir: IV (nucleoside)

Valganciclovir: PO, high bioavailability (ester of nucleoside)

Foscarnet: IV, topical (pyrophosphate)

Question 18

What type of analogs are Acyclovir and Ganciclovir?

Answer 18

Purines

Question 19

HSV and VSV activation of acyclovir involves this kinase:

Answer 19

Thymidine kinase

Question 20

CMV activation of gangiclovir involves this kinase:

Answer 20

UL97 kinase

Question 21

How do HSV, HZV, and CMV viruses acquire drug resistance?

Answer 21

By neutralizing viral dependent drug activating processes –> Kinases/phosphotransferases

Neutralizing drug targets –> DNA polymerases

Question 22

These drug types are pro-drugs with High ORAL bioavailability

Answer 22

Nucleoside esters

Question 23

This pro-drug (PO) gets converted to the activated Acyclovir

Answer 23

Valacyclovir

Question 24

How is Acyclovir administered, where is it distributed, how is it eliminated

Answer 24

IV, PO (low bioavailability)

Distributed into CNS and systemic

Renal elimination

Question 25

At clinically achievable concentration, acyclovir is active against:

Answer 25

Best against: HSV-1, sort of against HSV-2

1/10 relative potency against VZV and EBV (NOT CMV)

Question 26

What are acyclovir toxicities?

Answer 26

• well tolerated by most pts-Pregnancy category B
• precipitation of acyclovir in renal tubules can lead to ACUTE RENAL FAILURE
• NEUROLOGIC TOXICITY-particularly in pts with renal failure

Question 27

What is the prodrug of Gancyclovir? How is it administered? How is distributed? Eliminated?

Answer 27

Valganciclovir

IV

Distributed into CNS and systemic

Renal elimination

Question 28

What is Ganciclovir most active against?

Answer 28

CMV

Tx and suppress CMV retinitis in immunocompromised pts and prevention of CMV disease in transplant pts

Question 29

What are toxicities/complications of Ganciclovir?

Answer 29

• associated with BM suppression (leukopenia)
• need to monitor for hematologic and renal toxicity, especially pts taking nephrotoxic, immunosuppressive drugs cyclosporine

Question 30

Does Foscarnet require activation? What is it used for clinically?

Answer 30

No activation required –> independent of viral or cell kinases

Used for :CMV retinitis, Acyclovir-resistant HSV and VZV

Question 31

How is Foscarnet administered? What is its toxicities? Where does it accumulate? What are consequence of it chelating Ca and Mg?

Answer 31

IV-low solubility and short t1/2 requires frequent injection

Nephrotoxic

Accumulates in bone matrix

Hypocalcemia and hypomagnesemia