Antivirals Flashcards
Significance of HIV high rate of mutation of HIV per replicaition cycle
- Great potential for genotypic variation
2. Need for multi-drug treatment regimens (at least 3)
Selection criteria: which drug should you avoid if pt has
- Allergy hx
- Pregnant
- Kidney disease
- Allergy hx
- abacavir - Pregnant
- efavirenz - Kidney disease
- tenofovir
Initiation of therapy:
Backbone
Base
Backbone
2 NRTIs:
Tenofovir - Emtricitabine
or 1 NRTI and 1 Integrase Inhibitors
Base: 1. Integrase inhibitor or 2. Boosted PI combo or 3. NNRTI or 4. CCR5 antagonist
NRTIs MOA
prevents genome replication and establishment of provirus
Which are the only NRTIs that are eliminated via hepatic glucuronidation
Abacavir and Zidovudine
*rest are renal excretion
Side effects of NRTIs
- myopathy
- neuropathy
- Bone marrow suppression
- Lactic acidosis
- Pancreatitic / hepatic steatosis
- Renal impairment (with tenofovir)
Which of the antivirals do not require activation by intracellular kinases, NNRTIs or NRTIs?
NNRTIs
- prevent genome replication - establishment of provirus
SIde effect of efavirenz
Severe CNS effects
Rash
HA
cant [ ]
*only retroviral agent in preg category D
Nevirapine side effect
serious cutaneous rxns
Etravirine side effect
Rash (less than nevirapine, but still bad stuff)
Adverse drug rxns of PIs
- GI distress
- Hyperglycemia
- Hyperlipidemia
- INcreased risk of CAD
Integrase strand transfer inhibitors (INSTIs)
- IIs
- Dolutegravir
- Raltegravir
- Elvitegravir
Goal of antiretroviral therapy is to suppress HIV viral load to how many copies?
Less than 50
When is resistance testing recommended?
When pt is first seen, regardless of when therapy is first started
Drug combo for prevention of perinatal HIV transmission
PI: Ritonavir-Lopinavir (rLPV) \+ NRTI: Zidovudine (ZDV) \+ NRTI: Lamivudine (3TC)
Once NRTIs are incorporated into viral DNA, how do these antiretrovirala block further replication?
They terminate strand elongation due to their lack of 3’OH groups
How is tenofovir different from the other NRTIs?
Tenofovir is a nucleoTide
and does not need to be phosphorylated to become activated (into their triphosphorylated fully active forms) like the other NRTIs
*NNRTIs do not require phosphorylation
Unlike NRTIs that bind to the active site of HIV reverse transcriptase, where do NNRTIs bind?
a non catalytic hydrophobic pocket in the p66 subunit of HIV rev. transcriptase –>
induce conformational change
(noncompetitively inhibit HIV rev trans.)
does developing resistance to the older NNRTIs mean that you developed resistance to all NNRTIs?
What about resistance to one PI?
yes
(except the newest one, etravirine)
No to PI, resistance is only specific for that PI
pts with drug resistance to both PIs and NNRTIs can use which drug?
the newest NNRTI, etravirine
Preg D category,
Rash
CNS effects
Hepatotoxicity
Efavirenz
NNRTI
How do protease inhibitors work?
prevent maturation of new virus by inhibiting HIV-1 protease (aspartyl protease)
(cant cleave HIV mRNA into fxnal parts)
