Anti-Viral Drugs Flashcards
List the 4 key Anti-HIV drugs (in our syllabus)
- NRTI: nucleoside reverse transcriptase inhibitors
- Integrase inhibitor
- Protease inhibitors
- NNRTI: non-nucleoside reverse transcriptase inhibitors
What is the standard treatment for HIV pxs.
- 2 NRTIs in combination with
-
1 other active ARV drug
- integrase inhibitor (INSTI)
- protease inhibitor w PK enhancer
- non-nucleoside reverse transcriptase inhibitor (NNRTI)
What is the most favoured HIV regiment
2NRTIs + INSTI regimen
- INSTI: integrase strand transfer inhibitor
List the common causes of treatment failure in HIV pxs.
- Poor adherence
- Drug resistance
- Poor absorption of medication
- Inadequate dosing
- Drug-drug interactions
What are some long-term toxicities HIV pxs face from antiretroviral therapy?
- Metabolic syndrome
- HIV lipodystrophy syndrome (unwanted redistribution of fat)
List the 5 NRTIs
- Emtricitabine
- Tenofovir
- Lamivudine
- Abacavir
- Zidovudine
What are the 2 NRTIs that are cytosine analogues?
- Emtricitabine
- Lamivudine
thus, they should not be administered tgt as they will be competing w each other -> ineffective
Name the 3 NRTIs that have anti-viral activity against Hep B too.
- Emtricitabine
- Lamivudine
- Tenofovir
- hep B/HIV coinfection pxs on these drugs cannot just discontinue the drug as it well cause severe acute exacerbation of hepatitis should they discontinue
Which NRTI requires pxs to be genotyped for suitability before prescription?
Abacavir
- only pxs w the negative allele can take the drug (HLA-B*5701-negative individuals)
- will otherwise lead to fatal hypersensitivity syndrome
Which NRTIs can be taken during pregnancy?
- Emtricitabine
- Tenofovir
- these 2 are Cat B
- rest of NRTI drugs are Cat C
MOA of NRTIs?
- NRTIs are analogs of native ribosides, but lack a 3’-OH group => leads to chain termination
- as 3’,5’- phosphodiester bond between incoming nucleoside triphosphate & growing DNA chain cannot be formed
MOA of integrase inhibitors
- prevents integration of viral DNA into host genome
- by binding to the catalytic site of the HIV integrase enzyme
[T/F] Integrase inhibitor is active against both HIV-1 & HIV-2
True
Administration of integrase inhibitors (INSTI)?
Oral, tablets
Administration of NRTIs?
Oral
Which is the preferred INSTI for pregnant ppl?
Dolutegravir
(as of 2023)
What is Ritonavir?
Pharmacokinetic(PK) booster
- not to be mistaken as a protease inhibitor
- inhibitory effect on CYP450 enzymes => extends shelf life of protease inhibitors cuz all PIs are substrates for CYP450
MOA of Protease inhibitors
- inhibits proteases that cleave the long polypeptides into smaller fragments => prevents new viral particles from maturing & becoming infectious
Most of the HIV population is of which variant?
95% is due to HIV-1
What are some issues with the usage of Proteins Inhibitors (PIs)?
- DDIs
- Lots of adverse effects
- Easy development of drug resistance when used ALONE
- Poor patient compliance cuz high no. of capsules req
Why do PIs have lots of DDIs?
- not only substrates for CYP450 but potent inhibitors of CYP450 isoenzymes
- hepatic metabolism is extensive
List out the drugs (ABs, antifungals and antivirals) that interfere w CYP450.
- Macrolides
- Azoles
- Protease Inhibitors
What is Cobicistat?
PK enhancer of PIs
- inhibits CYP450 3A
- used PIs (Elvitegravir, Atanavir)
What are NNRTIs useful against?
(non-nucleoside reverse transcriptase inhibitor)
Only effective against HIV-1
-highly selective, non-competitive inhibitor of HIV-1
(binds to other site that is not the active site)
