Drug Synergy Flashcards
How can using multiple drugs minimise drug toxicity?
Lower doses of individual agents can be used
Drugs may have different targets, limiting unwanted effects
How does HIV bind to and fuse with the host cell membrane?
Binds to CD4 and chemokine co-receptor (including CCR5 AND CXCR4) via gp120
Fuses with membrane via gp41
What is maraviroc? What is it used for clinically?
An allosteric modulator of CCR5, used to prevent HIV binding and entering host cells
What is enfuvirtide? What is it used for clinically?
A peptide that binds to gp41 to prevent HIV fusion with the host cell membrane in the treatment of HIV
What are the 2 classes of reverse transcriptase inhibitors used to treat HIV? What is the difference in their modes of action?
Nucleoside/nucleotide RT inhibitors (NRTIs): competes with viral RNA genome for binding to RT
Non-nucleoside RT inhibitors (NNRTIs): allosteric modulator of RT, inhibits its action
What is zidovudine (AZT)?
NRTI
What is nevirapine?
NNRTI
What is raltegravir? What is it used for clinically?
Inhibitor of the HIV integrase enzyme, which is responsible for integrating proviral DNA into the host genome
What is saquinavir? What is it used for clinically?
An inhibitor of the HIV protease enzyme, which is responsible for cleavage of polypeptide into mature viral enzymes and proteins
What is the limitation of drug monotherapy in the treatment of HIV?
Drug resistance develops (only of transient benefit)
What is HAART?
Highly Active Anti-Retroviral Therapy; “triple therapy” used to treat HIV
Give 3 examples of drug combinations used in HAART
2 x NRTIs + NNRTI
2 x NRTIs + PI
NRTI + NNRTI + PI
What is the benefit of using a combination of RTIs when treating HIV?
Each individual drug may be less than maximally active
If resistance emerges to 1, this does not mean resistance emerges to all
What is in the combined pill (polytherapy) used to treat HIV? What is the benefit of the combined pill?
Combined pill: tenofovir (NRTI), emtricitabine (NRTI), efavirenz (NNRTI)
May increase patient compliance
What is a bifunctional drug? What is the proposed benefit?
1 compound with 2 activities (e.g. NRTI linked to an NNRTI)
May produce synergistic activity (still experimental)
What is the benefit of using ritonavir with a PI?
Ritonavir is a PI which also (even at low doses) is a potent inhibitor of CYP3A4, which metabolises other PIs
This means that the administration of ritonavir with another PI will enhance efficacy, improve dosing regimen and reduce resistance when compared to the use of a single PI alone