Dr. Timmins Flashcards
Fuzeon
- Long peptide
- Blocks entry into CD4+ cell
- Works on HIV 1 only
- Not orally active
Why is Fuzeon not used?
- Poor compliance
- Expensive
Maravioc (Selzentry)
- Has oral bioavailability
- Binds to host CCR5 coreceptor
- Works on some strains of HIV 1
- Need to test for virus tropism
- Dose dependent on other CYP3A drugs
Maraviroc (Selzentry) Dosing for CYP3A inhibitors
-150mg BID
Maraviroc (Selzentry) Dosing for CYP3A inducers
-600mg BID
Maraviroc (Selzentry) Dosing for a patient with no other CYP3A drugs
-300mg BID
Purpose of Maraviroc (Selzentry) two ends (Med chem)
-Used for oxidation
What is the middle section of the Maraviroc (Selzentry) center of molecule used for?
- N dealkylation
- This is major site of metabolism
Should you use Rifampin with Maraviroc (Selzentry)
- Consider using rifabutin instead
- If you use Rifampin then you need to change the dose to 600mg BID
Which HIV drugs inhibit Reverse Transcriptase?
1) Nucleoside reverse transcriptase inhibitors
- modified at deoxyglucose function
- NOO 3’ hydroxyl group
2) Non-nucleoside reverse transcription inhibitors
- Uses a different mechanism of action
Viral Protease Inhibitors
- Viral proteins are made as one long string
- Needs to be cleaved by protease
- If not cleaved the protein will not fold correctly
Protease Inhibitors medchem
- All contain an amide or amide like group
- Are all big molecules
NRTIs and NNRTIs medchem
- Lack 3’ OH
- Modified sugar
HIV integrase inhibitors MoA
-Integrase inhibitors prevent viral genome insertion into human CD4 cell genomes
HIV integrase inhibitor medchem
-Binds to viral integrase and inhibits its activity
How to remember NRTI and NNRTI drug names
- Look like thymidINE so most end in “ine”
- Except for Abaracadabara, and abacavir (magically a NRTI)
- Ten middle fingers for TENofovir (awkward NRTI)
- Efavirenz (NNRTI)
How to remember Protease inhibitor drug names
- ProteAse has an Amide or Amide like group
- So the end in “Avir”
How to remember Integrase drug names
- IntegRAse
- So they all end in “Ravir”
Hep C treatment with old drugs
- Major side effects
- New treatments = much less severe side effects
NS5A medchem
- Used to treat HepC
- Dimeric protein
- 2 zinc binding portions
- Leading to symmetrical/near symmetrical drugs
NS5B MoA
- Used to treat HepC
- RNA dependent RNA polymerase
- Essential for viral replication
- Can be non nucleoside or nucleoside
What makes Sofosbuvir (Sovaldi) so special?
- Pro drug of DFMU monophosphate
- Cover up 2 negative charges
- Then it gets 2 more phosphates in cell
- Double prodrug
- Orally absorbed
- Gets into hepatocyte
Why do we not just give DFMU triphosphate?
-Its log P is even worse than DFMU monophosphate
How to remember HepC drugs
- NS3/4A = previr
- NS5A = asvir
- NS5B = buvir
What does NS3/4A target?
- previr
- Targets a pair of proteases
What does NS5A target?
- asvir
- A pair of Zinc Ions
What does NS5B target
- buvir
- inhibits the build of new RNA genomes
Are HIV/ Hep C drugs monotherapy or combination therapy
- Combo therapy duhhh
- Monotherapy leads to an increased risk of resistance in HIV infections
Why is resistance so much more likely to occur in viral infections over bacterial infections?
1) Time = you treat viral infections for much longer than bacterial
- Leading to an increased risk of mutation
2) Viral loads are many times higher than bacterial loads
3) Viral genome replication is more prone to error than bacterial replications
- Increased errors = increased mutations
