Pharmacology Of Influenza and Anti-Viral (Fitz) Flashcards
This drug blocks viral M2 ion (H+) channel; prevents uncoating and used for influenza A only
Amantadine
What is the anti viral spectrum of amantadine?
A
What is the antiviral spectrum of Oseltamivir and Zanamavir?
A and B
These drugs are neuraminidase inhibitors and target Influenza A and B
Oseltamivir and Zanamavir
List the neuraminidase inhibitors:
Oseltamivir and Zanamavir
This neuraminidase inhibitor is PO (suspension, capsule) and can cause nausea (20% incidence)
Oseltamivir
This neuraminidase inhibitor is inhaled and can cause bronchospasm in asthmatics (rare)
Zanamavir
Zanamivir is not recommended in these types of pts:
Asthma, COPD, resp disease
What age groups is Oseltamivir approved for? What about zanamavir?
Oseltamivir-tx and prevention in 1 yr and older
Zanamivir-tx=7 yrs and up; prevention=5 yrs and up
Which groups have the greatest burden of influenza?
Elderly
Persons with underlying medical conditions such as COPD, asthma, CHF, diabetes, pregnant women and young children
What is the MOA of Amantadine?
M2 ion channel inhibitors –> No H+ enters capsid
When is Amantadine not recommended?
Not recommended for antiviral tx or chemoprophylaxis of currently circulating Influenza A virus strains
Name the Acyclic nucleosides that act selectively on virus infected cells:
Acyclovir
Valacyclovir
Gancyclovir
Valganciclovir
Name the non-nucleoside anti-viral drugs:
Foscarnet
These anti-vitals work for HSV and Herpes zoster:
Acyclovir and valacyclovir
This drug works for acyclovir-resistant HSV and VSV
Foscarnet
These drugs are used for CMV infx:
Ganciclovir: IV (nucleoside)
Valganciclovir: PO, high bioavailability (ester of nucleoside)
Foscarnet: IV, topical (pyrophosphate)
What type of analogs are Acyclovir and Ganciclovir?
Purines
HSV and VSV activation of acyclovir involves this kinase:
Thymidine kinase
CMV activation of gangiclovir involves this kinase:
UL97 kinase
How do HSV, HZV, and CMV viruses acquire drug resistance?
By neutralizing viral dependent drug activating processes –> Kinases/phosphotransferases
Neutralizing drug targets –> DNA polymerases
These drug types are pro-drugs with High ORAL bioavailability
Nucleoside esters
This pro-drug (PO) gets converted to the activated Acyclovir
Valacyclovir
How is Acyclovir administered, where is it distributed, how is it eliminated
IV, PO (low bioavailability)
Distributed into CNS and systemic
Renal elimination
At clinically achievable concentration, acyclovir is active against:
Best against: HSV-1, sort of against HSV-2
1/10 relative potency against VZV and EBV (NOT CMV)
What are acyclovir toxicities?
- 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
What is the prodrug of Gancyclovir? How is it administered? How is distributed? Eliminated?
Valganciclovir
IV
Distributed into CNS and systemic
Renal elimination
What is Ganciclovir most active against?
CMV
Tx and suppress CMV retinitis in immunocompromised pts and prevention of CMV disease in transplant pts
What are toxicities/complications of Ganciclovir?
- associated with BM suppression (leukopenia)
- need to monitor for hematologic and renal toxicity, especially pts taking nephrotoxic, immunosuppressive drugs cyclosporine
Does Foscarnet require activation? What is it used for clinically?
No activation required –> independent of viral or cell kinases
Used for :CMV retinitis, Acyclovir-resistant HSV and VZV
How is Foscarnet administered? What is its toxicities? Where does it accumulate? What are consequence of it chelating Ca and Mg?
IV-low solubility and short t1/2 requires frequent injection
Nephrotoxic
Accumulates in bone matrix
Hypocalcemia and hypomagnesemia
