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30 Cards in this Set

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What is hemagglutin?
- a glycoprotein on the surface involved in binding to the infected cells
Name some tricyclic amines, against influenza A?
- amantadine
- rimantadine
MOA of amantadine or rimantidine?
1. inhibit viral rep. at an early stage probably by uncoating.
2. Alt. in hemaglutinin processing.
3. Site Influenza A Virus M2 protein, an integral membrane protein that act as an ion channel.
Resistance of amantidine or rimantidine?
- Single nucleotide changes leading to a.a. sub. in the M2 Protein.
How is amantidine and rimantidine xcreted?
Amantidine: excreted unchanged in the urine.
Rimantidine: extensive metabolism then urinary excretion.
Adjust dose in renal and hepatic?
rimantadine

Amantidine (renal)
Adverse Effects of Amantadine and Rimantadine?
BOTH agents share cross-resistance and sensitivity.
- A.E.:
GI tolerance
CNS: (greater with amantadine: increased with antihistamines, antichol, CNS stimulants)
Drug - Drug Concentration:
Amantidine + quinidine = REDUCED amantidine clearance.

Cimetidine, ASA, APAP = REDUCED rimantadine level.
Neuroaminidases inhibitor: (potent selective inhibitor of influenza A and B virus neuraminidase)
Oseltamavir
Zanamivir.

MOA: neuroaminidase is a viral enzyme and cleaves terminal sialic acid residues.
Resistance to neuramindase inhibitors:
mutations in neuraminidase.
Oseltamivir Phosphate (must be cleaved by hepatic esterases to active carboxylate)
- (80%)
- Food does not decrease bioavailability.
- Excreted by the kidney.
Adverse Effect of Oseltamivir:
Nausea, Abdominal discomfort, emesis

- Self Injury and delirium
Zanamivir (oral inhalation)
- 17% absorbed, less protein binding, poor oral biavaliability.

- Excreted by the kidney
- 90% found in urine
Resistance to Zanamivir
- viral hemmagglutinin and/or neuramindase
Adverse Effects of Zanamivir
- Wheezing, Bronchospasm
- Acute deteriorationin patients with asthma or COPD (NOT RECOMMENDED)
What is Famciclovir?
Competitive inhibitor of DNA polymerase.
Resistance to famciclovir?

ORAL BIO. increased with famiciclovir (70%)
- TK Deficient.
- cross resistance to acyclovir
Adverse Effects of FAMICICLOVIR?
- ORAL product:
- headache, diarrhea, and nausea
Foscarnet:
Trisodium Phosphonofomate

MOA: binds directly to herpes virus DNA polyerase (no phosphorylation)
Resistance to foscarnet:
- point mutations in the viral DNA polymerase.
Foscarnet is sequestred:
- in bone and gradual release (10-20%)
- plasma cl is decreased prop. w/ CrCl.
- excreted unchanged in the urine.
- I.V. Formulation.
Adverse Effect of foscarnet?
NEPHROTOXICITY.
ELECTROLYTE DISTURBANCES:
(hypocalcemia, hypomag, hypokal, hypo(er)phoshatemia
CNS (HA, tremor, irritabiliity, seizurs, hall.)
Drug Drug interactions of foscarnet:
Avoid aminoglycosides and amphotericin B
Ganciclovir and Valganciclovir:
- inhibits viral DNA synthesis
- mono-phosphorylated by virus.
MOA of ganciclovir and valganciclovir?
- incorporation into VIRAL DNA causes cessation of chain elongation.
Valganciclovir:
reduced intracellular ganciclovir phosphorylation due to mutations in the viral phosphotransferase
- mutations in viral DNA POLYMERASE.
Adverse Effect of Valganciclovir?
- Myeosuppression: neutropenia an thrombocytopenia.
- CMV.
Cidofovir:
cytidine nucleotide analog.

phosphorlated by CELLULAR KINASE not virus kinase.
Cidofovir excreted:
90% excreted unchanged in the urine

cleared by glomerular filtration and tubular secretion.
Adverse effect of cidofovir:
Dose limiting --> nephrotoxicity with I.V. route.
Concomitant use of PROBENECID and hydration lowers the risk of nephrotoxic.