Anti HIV Drugs Flashcards
list important proteins involved in HIV-host cell interaction
a trimer of gp120-gp41
CD4
CCR5
describe the origin of HIV
originated from simian immunodeficiency virus (SIV)
- primates to humans via preparation and consumption of bushmeat?
structure of HIV
The HIV-1 genome is ~ 9 kb
Important genes:
pol –> pol polyprotein –> protease, reverse transcriptase, integrase
env–> env polyprotein –> gp120, gp41
life cycle of HIV
10 step process
Important steps for drug action
1. binding - entry inhibitors
2. fusion - fusion inhibitors
4. reverse transcriptase - NRTIs, NNRTIs
5. integration - Integrase inhibitors
10. maturation - protease inhibitors
pharmacokinetics - HIV reverse transcriptase inhibitors
Nucleoside reverse transcriptase inhibitors (NRTIs)
- Administered a pro drugs- TDF and TAF
produces tenofovir which is hydrophilic
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- distinct binding site – a hydrophobic pocket in the p66 subunit
mechanism of action - HIV reverse transcriptase inhibitors
nucleoside reverse transcriptase inhibitors (NRTIs)
- phosphorylated to form a triphosphate - incorporated
into ssDNA to terminate elongation
Non-nucleoside reverse transcriptase inhibitors
- conformational change → inhibit enzyme activity
adverse effects - HIV reverse transcriptase inhibitors
nucleoside reverse transcriptase inhibitors (NRTIs) + (NNRTIs)
* GI disturbance, e.g., nausea, vomiting
* CNS effects, e.g., dizziness
mechanism of action - HIV protease inhibtors
Blocks protein binding inhibiton
adverse effects - HIV protease inhibitors
- insulin resistance
- hyperlipidemia
- cardiovascular disease
pharmacokinetics - HIV integrase inhibitors
mechanism of action - HIV integrase inhibitors
- a 288-amino acid protein - integrate the proviral DNA into the host cell genome
HIV inhibitors - bind to integrase and prevent DNA strand transfer
adverse effects - HIV integrase inhibitors
- GI disturbance, e.g., nausea, vomiting
- CNS effects, e.g., dizziness
explain the use of pharmacokinetic enhancer in anti-HIV treatment
the use of pharmacokinetic enhancers like Cobisistat prevent the early metabolism of target drugs allowing them to have a prolonged therapeutic window
explain the difference in toxicity between tenofovir alafenamide and tenofovir disoproxil in the context of pharmacokinetics
TAD - Metabolises once it reaches the lymphocytes limiting systematic exposure and related toxicities, meaning a lower concentrated dose is required to produce the same effect
TDF - metabolises when it reaches the blood plasma into tenofovir (hydrophilic) and causes systematic exposure leading to adverse effects
describe anti-HIV drug development
Pre -1987 could only treat HIV related opportunistic infections
single drug - NRTI –> dual drugs - NRTIs –> triple drugs - NRTIs + PI –> NRTIs + (NNRTI or boosted PI) –> NRTIs + INSTI (single dose)
