pharm 3B: virals Flashcards
brefily explain the DNA replication process**reread notes
- virion’s nuclear mateiral is surrounded by capsid. it has glycoproteion on the capsid which is needed to fuse w the host cell
- fuses w the host cell, uncoating process beging where the genetic viral material is released into the cytosol/nucleus of host cell
- viral DNA uses this to make mRNA throuhg translation+transcription
- cycle repeast
what type is papillomavirus, poxviruses, picornaviruses, falvivirus, orthomyxovirus, paramyxovirus?
papillomavirus - dna
poxviruses - dna
picornaviruse - rna, polio
falvivirus - rna, west nile, yellow fever zika
orthomyxovirus - flu
paramyxovirus - meseals + mumps
what connects to the 1 2 3 4 5’ of the pentose sugar?
1’ - connects pentose sugar to base via glycosidic bond
2’ has OH/H depending on dna/rna
3’ OH group to attach to phosphate of next NS
4’ dont matter
5’ has phosphoric acid for binding
whcih direction do you add NT to ?
add NT to the 3’ group
how does DNA polymerase work?
- DNA POLYMERASE can only work if the NT is a triphosphate
- we have a base, it needs to be converted to monotriphosphate VIA THYMIDINE KINASE
- now we have a monophosphate which need to be converted to triphosphate VIA **NUCLEOSIDE MONOPHISPHATE KINASE **
- now we have a triphosphate that DNA polymerase can work with
- DNA polymerase will add the deoxy triphosphate to the growing chain fo the DNA molecuel and a PYROPHOSPHATE IS RELEASED
- the releeasing of pyrophispahte is NEEDED for growing chain to continue
whats the diff between acylovir and valacyclovir?
aclyclovir - without cyclic structure
valacyclovir - sterofide PRO DRUG of acyclovir
what is the MOA for acyclovir?
- the cell infected takes up the aylcovir rx
- acyclovir is turned into monophosphate to get activated VIA VIRAL THYMIDINE KINASE
- acylcovir monophosphate gets turned into acylcovir triphosphate via **HOST NUCLEOSDIE MONOPHOSPHATE KINASE **
- DNA polymerase adds this to the growing chaine –> casues termination –> the new molecular has NO 3’ postion (since theres no cyclic structure) so ELONGATION STOPS
how deos ganciclovir work?
- its difference than acylcivor and works best with CMV
1. it does get phospholated via viral thyimidien kinsase but it doesnt get changed into triphosphate via (ns monophopshate kinease) but instead HAS ITS OWN ** VIRAL TRANSFERSE** that converts it
what are the indication/pharmacokineitcs/S/E of acyclvoir meds?
indication: HSV1 HSV2, CMV (ganciclovir)
pharmacokinetics: PO, parental formation for serious infx (such as mengintitis w HSV1
S/E: GI, HA, renal dz –> MEDICATION is excreted in kidney unmetbaolized so it can crystialize and cause crystialluria or azotemia
how does acyclovir become resisitant and how does HSV reoccur?
HSV travels up the sesnroy nerve and lies dormant in the ganglion until it comes out during stress, trauma, etc
Resistant happens when theres a mutation on the viral thymidine kinase (thats how acylcovir becomes activated)
what drugs do you use if you are resisitant to acylcovir or ganciclovir?
CTF
cidoflovir
trifluridine
foscarnet
what is the MOA/indication for cidofovir and trifluriidne?
CIDOFOVIR
- MOA: it gets activated by the HOST CELL (not the viral tymidine kinase) goes into the DNA cell and STOPS elongation
- indications: warts so papillomatosis, mossuslcom, aclyvoir/ganciclvoir resisitant
TRIFLURIDINE
- MOA: it gets activated to triphosphate trifluridine, goes into host cell and STOPS DNA elongation
what type of drug is foscarnet and its MOA and indication?
- foscarnet is a pyrophosphate analog
- MOA: it prevents the DNA polymerase from cleaving and releasing pyrophosphate which inhibits the growing chain
- THIS IS THE ONLY DRUG THAT DOES NOT NEED TO BE ACTIVATED, IT CAN GET TO WORK RIGHT AWAY
-indications: CMV - BEST TO USE with ganiciclovir + foscarnet
and acylcvior resisitnat HSV
what is the best combo tx for CMV?
ganciclovir and foscarnet = GOOD
which viral drug crystalizes in the kidney and can casue crystaluria or azotemia?
acylcovir since its unmetabolized in the kidney
which drug binds to JAK-STAT receptor to intiaite an immune resposne agaisnt virus?
INFERRON-A
what is the MOA + indication + pharmokinetics for interferon-a?
MOA - it binds to JAK-STAT receptor to bring in lymphocytes, NKC, macrophages to intiate an immune repsosne agaisnt virus
indication:
- warts condolyma
- hep B hep C
- kaposi sarcoma :(
pharmacokinets:
- given IM, subQ once weekly
which viral drug works best for kaposi sarcoma?
interferon - a
what are the s/e to interfeorn-a?
- flu like SX
- depression :( AMS changes
- myelosuppresion - more of an issue w those w aids
- neurotoxciity - seizures
- HYPOthyroidsim
- alopecia - hair loss :(
what is the MOA for HIV? expalin the MANY steps girl
- HIV envelope has three proteins: gp41 which helps it to fuse with the host cell, gp120 which binds to the CD4 receptors, and CCR5 which binds to chemokine 5 receptros to use as coreceptor to enter the host cell
- now the HIV is inside the host cell, it undergoes reverse transcriptase to turn RNA –> DNA
- DNA is not that good so theres alot of mutation so its good to gain retsisitant to drugs
- new viral DNA enters the nucleus with VIRAL INTERGRASE which helps it to integrate into the host cell genome
- now we have viral DNA in the host cell genome and it will make immature proteins called POL-GAG
- viral DNA will bud off and proteases will cleave the immature POL-GAG protein into mature proteins –> CAN INFECT OTHER CELLS
what are the three ways to prevent HIV form infecting other cells? think about the process
- you can inhibit the reverse transcriptase
- you can inhibit the integrade enzyme
- you can inhibit the protease enzyme
which is the first FDA approve drug for RTI?
lamivudine
what are the two types of RTI ?
nucleoside RTI and non nucleoside RTI
what are the nucleoside RTI drugs and their importnace?
- zidovudine - thymidine analog lacking OH 3’ group
- lamivudine - 1st FDA approved, high rate of resistance after 2-3 years, used to tx HEP B
- emtricitabine
- abacavir
- tenofovir
- stavudine
