L3.1 Drugs to treat HIV Flashcards
1
Q
Viral structures
A
- All viruses exists as a nucleocapsid (Genome + protein coat)
- Nucleocapsid + Host derived lipid envelop = virion
2
Q
Viral replication mechanism
A
- Virus may be adsorbed to host cell
- Binds to SURFACE RECEPTORS
- Virus enter cells → uncoated → protein TRANSPLANTED & CLEAVED
- Virus, genomes REPLICATED → genome may be INTEGRATED into host
- New virus particles assembled & released
3
Q
Viral outcomes
A
- Spread to adjacent cells
- Death & lysis of host cells
- Persistent infection
- Some replication, virus not killed - Hep B, C
- Latent infection
- Genome integration, no replication until reactivation - herpes, Hep B, HIV
- Hard to eradicate, no replication = no target
- Genome integration, no replication until reactivation - herpes, Hep B, HIV
- Transformation into turmour cells
- Hep B
4
Q
Selective toxicity of anti-virals
A
- Target viruses without harming host
- Contrasts to antibiotic (wide range of treatment), antiviral has a narrow spectrum
- Antivirals are virustatic (Slow infection) but not virucidal (kills)
5
Q
Hep B
A
- ≥15% develop liver cirrhosis & cancer if left untreated
- 2nd most common carcinogen (after cigarettes)
- Treatment achieve viral clearance in ≤20% of patients
- But have safe & effective vaccines
6
Q
Hep C
A
- Cause of 25% Australian liver transplants
- Highly variable genome → hard to design drug & vaccines
- 15-40% infections spontaneously resolved
7
Q
HIV/AIDs
A
- Vertical transmission (from mother to child) common w/o treatment
- Infects CD4+ cells (t-cells, monocytes, dendritic cells)
- Initial immune response limits infection → but inevitable damage prevents viral clearnace
- ∴impaired immune responses → causes opportunistic infections & cancer
- Gp120 binds to CD4+ → functional changes, loss in CD4+ cells → depressed immune response → failure to eliminate infection → virus persists → immune defect ↑ (CD4+ count ↓) → AIDs
8
Q
Opportunistic infections
A
- Infections that occur more often as a result of weakened immune system
- Effects of anti-microbial
- Limited selective toxicity & has adverse interaction with anti-HIV drugs
- Anti-HIV then becomes more of an issue than infection
9
Q
HIV replication cycle
A
- Gp120 binds CD4+ & CCR5
- Fuse virus & cell mem through gp41
- Release cell contents (reverse transcriptase)
- Integration & replication
- Transcribed → translate → cleaved → new virus
10
Q
Challenges to making HIV drug
A
- High variation of virus → creates resistant mutants
- Hard to target latent virus (not replicating)
- No good animal model to test (limited cell culture & primate models)
- Choice of endpoints for long-term diseases (CD4+ count as markers)
11
Q
HIV treatments 1) Entry inhibitors
A
- Targets viral gp41 & CCR5
- Pfizer & T20
12
Q
HIV treatments 2) Nucleotide/Nucleoside Reverse Transcriptase inhibitors (nRTIs)
A
- Chain termination of nucleotide/side
- But most are not selective
- AZT
13
Q
HIV treatment 3) non-nucleotide RTIs (nnRTIs)
A
- Binds close to catalytic site
- Nevirapine
14
Q
HIV treatment 4) Protease inhibitors
A
- Blocks cleave of structural protein → defective viral proteins
- Limited selective toxicity
- Nelfinavir
15
Q
HIV treatment 5) Integrated inhibitors
A
- Integrate important viral enzymes
- Useful for patients with resistance to some drugs
- Used in combination therapy
- Raltegravir
