Term
| what are the Hep B nucleoSide drugs? |
|
Definition
Lamivudine
ENtecavir
TELbivudine
nucleoSide
-think LENTELS, s for nucleoSide |
|
|
Term
| what are the Hep B nucleoTide drugs? |
|
Definition
Adefovir
TeNofovir
nucleoTide drugs
-think ATnT (AT&T) |
|
|
Term
| what makes nucleoside/tide drugs selective? |
|
Definition
| -are selective for the Hep B reverse transcriptase |
|
|
Term
| what non-nucleoside/tide drug is also used against Hep B? |
|
Definition
|
|
Term
| what is the abbreviation for lamivudine? which enantiomer is more active as an antiviral? |
|
Definition
3TC (ThioCytidine)
-3TC is more active |
|
|
Term
what features makes lamivudine (3TC) a good drug to use clinically?
-what are its clinical uses? |
|
Definition
-good bioavailability (~85%)
-once phosphorylated, has long half life (>10hrs)
-low toxicity to normal tissues (think sweet as a LAMb): headache, arthralgias, myalgias
-used for HBV, HIV |
|
|
Term
| what is one big difference in pharmacokinetics between nucleotide and nucleoside analog drugs, specifically between Lamivudine and Tenofovir? what accounts for this difference? |
|
Definition
-bioavailability: tenofovir has much lower bioavailability (25-50%) vs. lamivudine (>85%)
-due to polarity of phosphate group |
|
|
Term
| against which nucleotide/side analog drug do viruses acquire resistance most quickly? most slowly? |
|
Definition
-fastest dev. resistance against lamivudine
-slowest dev. resistance against TENofovir, ENTecavir (think of a TENENT who's late on rent, you slowly try to evict them) |
|
|
Term
| what are the two forms in which ribavirin can have an antiviral effect? what are its mechanisms of action? |
|
Definition
-monophosphate: inhibits purine biosynth
-the triphosphate form targets RNA synth, not DNA synth |
|
|
Term
describe ribavirin's:
-absorption
-distribution
-metabolism
-excretion |
|
Definition
-absorption: good oral bioavail ~45%; can be given as aerosol
-distribution: to most body tissues
-metabolism: prolonged terminal elim; hepatic metabolism
-excretion: renal |
|
|
Term
| what accounts for ribavirin's toxicity? |
|
Definition
| -neither its activation (phosphorylation) nor integration into RNA (polymerase-binding) is specific to viral enzymes; affects host processes |
|
|
Term
what is a major C/I for ribavirin? why?
-what other drugs have we learned about that are C/I for this same population? |
|
Definition
-pregnancy
-is teratogenic, mutagenic, embryotoxic
-also C/I in pregnant women: tetracyclines, fluoroquinolones |
|
|
Term
| what are the ribavirin's adverse effects? |
|
Definition
-hemolytic anemia (due to long half life in RBCs; promotes lysis)
-bone marrow toxicity
-increases serum bilirubin, uric acid |
|
|
Term
| how is ribavirin used clinically? |
|
Definition
-used against Hep C
-given with INTERFERON ALPHA
think "sea ribbon" (hep C RIBavirin + INterferon) = C RIBIN |
|
|
Term
| what class of drugs other than nucleotide/side analogs are used in hepatitis therapy? |
|
Definition
|
|
Term
| T/F: interferon a and B are produced by many cell types |
|
Definition
|
|
Term
| T/F: interferon B has greater than 24 species |
|
Definition
| F: interferon ALPHA has 24+ species |
|
|
Term
| how do interferons gain entry into cells? |
|
Definition
|
|
Term
what are the effects of interferons?
what is thought to be the major way interferons produce antiviral effects? |
|
Definition
-effects: inhibit virus penetration or uncoating, synthesis of mRNA, translation of viral proteins, and/or viral assembly or release
*inhibition of protein synth thought to be major mechanism of antiviral action |
|
|
Term
| to what kind of patients would you NOT prescribe ribavirin? |
|
Definition
-patients w/ leukemia (due to potential bone marrow toxicity)
-depressed pts (depression, suicidal ideation is an adverse effect)
-pts on other drugs metabolized by P450 (decreases metabolism via P450) |
|
|
Term
| what are the adverse effects of interferons? |
|
Definition
-Acute viral like syndrome
-Bone marrow toxicity
-CNS effects: depression, suicidal ideation
-Decreases P450 metabolism
(think ABCD) |
|
|
Term
| how are interferons used clinically (i.e. in which diseases and how is it administered)? |
|
Definition
-Hep B, Hep C (usu. in combo with other drugs)
-genital warts (papillomavirus)
-usually administered as PEG (polyethylene glycol)interferon to extend half life to 1-2 days |
|
|
Term
determine if each drug below is a nucleoside/nucleotide, what disease it is used to treat, and info about resistance:
cidofovir
entecavir
lamivudine
tenofovir |
|
Definition
-cidofovir - nucleoside; CMV, or 2nd line tx for HSV
-entecavir - nucleoside; HBV; viruses dev resistant to this very slowly
-lamivudine - nucleoside; HBV; resistance against it dev quickly
-tenofovir - nucleotide; HBV; resistance dev slowly |
|
|
Term
| What is the relationship between penciclovir and famciclovir? How is each administered? |
|
Definition
famciclovir is the prodrug form of penciclovir
-famciclovir - ORAL
-penciclovir - TOPICAL |
|
|
Term
| which nucleoside analogs used in tx of herpesviruses are least toxic? why? |
|
Definition
| acyclovir, penciclovir - are selective for viral enzyme at both activation and DNA synthesis phase |
|
|
Term
| how are acyclovir and ganciclovir able to withstand degradation in the stomach? |
|
Definition
| -are administered as valine esters (valacyclovir, valganciclovir) |
|
|
Term
| which drugs are useful against CMV? what else are these drugs used for? |
|
Definition
cidofovir
foscarnet
ganciclovir
*all these drugs can be used as 2nd line tx in resistant organisms |
|
|
Term
which drug has the following toxicities:
-bone marrow toxicity (neutropenia, thrombocytopenia)
-CNS effects: dizziness, confusion, headache
- |
|
Definition
|
|
Term
| if foscarnet and ganciclovir were given together, would they be in competition for the viral polymerase? |
|
Definition
| NO, foscarnet works at a different phosphate binding site than that used by the nucleoside analog drugs |
|
|
Term
which drug causes:
-nephrotoxicity
-granulocytopenia |
|
Definition
|
|
Term
| to which of the drugs used to treat CMV are organisms LEAST resistant? |
|
Definition
|
|
Term
| how often do you need to dose cidofovir? |
|
Definition
| -less than once a week or less frequently; very LONG half life |
|
|
Term
| which of the herpesvirus drugs have nephrotoxicity? |
|
Definition
-acyclovir
-cidofovir (administer with probenecid to reduce drug in renal tubules)
-foscarnet |
|
|
Term
| T/F: Acyclovir is not usually used in VZV |
|
Definition
| T: has minimal effect; reduces length of illness by ~1 day so usually don't treat. Acyclovir is used for HSV (encephalitis, genital and mucocutaneous herpes) |
|
|
