HIV Flashcards
What are the antiviral therapies used to treat HIV?
1) reverse transcriptase inhibitors:
- nucleoside RTI: zidovudine(AZT) and Lamivudine
-non-nucleoside RTI:
Efravirenz
2) protease inhibitors: lopinavir and ritonavir
3) other mechanisms: Raltegravir and Enfuvirtide
What is zidovudine (Azidothymodine) AZT?
Protype-Nucleoside (thymidine analog) prodrug
Drug used to treat HIV and hepatitis B virus ?
Lamivudine
Drug used to prevent the transmission of HIV from infected mom to her baby (50%)?
Lamivudine
What we should do to make the treatment of HIV more effective?
Use a combination of NRTIs with protease inhibitors to achieve highly active anti-retroviral therapy (HAART)
Initiate treatment consist of three drugs; 2 RTI & PI
Indications of zidovudine or azidothymodine (AZT):
- in combination with other antivirals for HIV infection.
- used as mono therapy to prevent transmission of HIV from infected mom to her baby by >20%
- used to prevent post-exposure prophylaxis in healthcare workers.
M.O.A of zidovudine:
- It’s phosphorylated to the active triphosphate by host cell kinase:
1) insertion of activated ZTP into viral DNA by RT causes chain termination.
2) It also inhibits RT activity by competing with endogenous nucleoside.
AEs of zidovudine:
Myelosuppression (severe and dose-limiting)
Peripheral neuropathy
When resistance to zidovudine occur?
When it’s used as sole agent, resistance results from multiple mutations in the gene that codes for RT.
Indications for Efavirenz -N-NRTIs:
Used in combination with other antivirals to treat HIV-1 not HIV-2
M.O.A of Efavirenz NNRTIs?
- Efavirenz does not require phospharization.
- is not incorporated into DNA strand.
- It act allosterically and inhibits HIV-1 RT
AEs of Efavirenz?
- vivid dreams
- myelosuppression (less common compared to zidovudine)
Indications of Lopinavir (protease inhibitor):
Used in combination with other antivirals to treat HIV-1 infection.
M.OA of Lopinavir (protease inhibitor):
Competitive inhibitor of virus-soecific protease (aspartame protease) that cleave precursor polyproteins into vinous structural and functional proteins.
Inhibition of this enzyme will prevent the HIV maturation and remains non-infective.
AEs of Lopinavir (important)
- Anemia.
- Hyperglycemia
- Lipodystrophy خلل في توزيع الدهون syndrome that associated with increased risk of MI.
Indications of Ritonavir (protease inhibitor):
Used as booster of other protease inhibitors (lopinazvir) and not for its antiviral action,
M.O.A of ritonavir (protease inhibitor):
Inhibit host enzyme that metabolizes other PIs leading to:
- increased plasma concert. Of these latter inhibitors.
- Reduce dose.
- Decrease AEs
AEs of Ritonavir:
Same as lopinavir:
o Anemia and hyperglycemia
o Lipodystrophy syndrome that associated with increased risk of MI
Clinical indications of Raltegravir (integrate inhibitor):
- used orallin combination with other antiviral agents for the treatment of HIV-1 infection.
- It’s generally reversal for antiretroviral drug resistance.
It’s reversal for antiretroviral drug resistance:
Raltegravir (integrate inhibitor)
M.O.A of Raltegravir ?
-inhibit HIV integrate > prevent insertion of viral DNA into human chromosome.
AEs of Raltegravir:
Dizziness
Alteration in mood
Clinical indications of ENfuvirtide:
- SC in combination with other antiviral agents for the treatment of HIV-1 infection.
M.O.A of Enfuvirtide:
Bind to HIV gp41 protein and inhibit the fusion of HIV with the host cell membrane.
AEs of Enfuvirtide:
Flu-like symptoms
