Antiretrovirals Flashcards
What are Nucleoside/Nucleotide Reverse Transcriptase Inhibitors NRTIs
Analogues of nucleotides/nucleosides that inhibit Reverse transcriptase Enzymes
Name the NRTIs
Abacavir: ABC
Emtricitabine: FTC
Lamivudine: 3TC
Tenofovir: TDF
Zidovudine: AZT,ZDV
MOA of NRTIs
compete with original host nucleotides binding on active site of reverse transcriptase
–>serve as false substrate–> viral DNA chain elongation and viral replication stops
*require activation
Activation of NRTIs
Nucleotide analogue: Diphosphorylation
Nucleoside analogue Triphosphorylation
AEs of Nucleotide analogues
TDF: nephrotoxicty
Fanconi’s syndrome
Bone mineralisation disorder
AEs of Nucleoside analogues
AZT: anemia
ABC: rash
Peripheral neuropathy
Lactic acidosis
Pancreatitis
Lipdystrophy
NH
Imp. AE of ABC in people wirh HLA-B*5701 gene
fatal hypersensitivity rxns
Name the Non-Nucleoside Reverse Transcriptase Inhibitors NNRTIs
Efavirenz: EFV
Nevirapine: NVP
Etravirine: ETR
Rilpivirine: RPV
MOA of NNRTIs
inhibit HIV Reverse Transcriptase by binding to allosteric site of enzyme
Diff. between NNRTIs and NRTIs
NNRTIs bind at different site than NRTIs
NNRTIs do not compete with nucleoside triphosphates
NNRTIs do not require intracellular activation
AEs of EFV
Psychosis
abnormal dreams
Gynecomastia
Maculopapular rash
AEs of NVP
rash: sever or life threatening- SJS
Heaptitis
AEs of ETR
rash: severe or life threatening-SJS
Triglyceridaemia
Which are the Integrase Inhibitors IIs
Dolutegravir: DTG
Raltegravir: RAL
Cabotegravir: CAB
MOA of IIs
inhibit viral integrase enzyme
–> prevent transfer of viral DNA strand into host-cell genome
AEs of DTG
Teratogenic: not used in 1st trimester
Insomnia
weight gain
diarrhea
CNS effects
DIs of DTG
Antacids and Fe supplements: decr DTG [plasma]
Anticonvulsants: decr DTG [plasma]
Metformin: incr Metformin conc.
DIs of RAL
Rifampicin: decr. RAL plasma levels
AES of RAL
generally well tolerated
Headaches
nausea
fatigue
myopathy
rhabdomyolysis
Name the Protease Inhibitors PIs
Atazanvir: ATV
Lopinavir: LPV
Ritonavir: RTV
Darunavir: DRV
Saquinavir: SQV
MOA of PIs
inhibit HIV protease
–> prevent cleavage of viral precursor proteins
–> results in immature and non0infectious virions
General DIs of PIs
drugs metabolised by CYP3A4: ketoconazole, Carbamazepine, diazepam, midazolam, sildenafil= incr. plasma conc.
AEs of Lopinavir/ritonavir LPV/r
Dyslipidemia
Hyperglycaemia
diarrhea
Atherosclerosis
When is Atazanavir/ritonavir ATV/r used
if LPV/r is not well tolerated
DIs of ATV/r
warfarin–> decr. INR–> potential anticoagulant effect
AEs of ATV/r
jaundice
abdominal pain
DIs of Darunavir/ritonavir DRV/r
warfarin–> decr. INR
AEs of DRV/r
abdominal pain
fatigue
headache
AEs of Saquinavir/ritonavir SQV/r
Prolonged QT and PR intervals
1st line Regimen of ARV
2NRTIs + NNRTI or IIs
TLD= tenofavir+ Lamivudine/Emtricibine + Dolutegravir
*TLD: fixed once dail dose
*patients >_30 kg and >_10yrs
Alternative 1st line Regimen in TB patients and in Pregnant women
Rifampicin decr DTG in TB and its Teratogenic
*Tenofovir+ L/E+ EFV(TEE)
What to replace EFV is TB patients 1st line regimen
TDF+ L/E+ LPV/r
Alternative 1st line if EFV is CIed
T+ L/E + DTG
Alternative 1st line if EFV AND DTG are CIed
T+ L/E + LPV/R
Alternative 1st line if TDF is CIed
ABC + L
OR
AZT+ L
Alternative 1st line if TDF & ABC are CIed
AZT+ L+ DTG/EFV
When are 2nd line Regimens used
if patient is failing on 1st regimne
2nd line regimen if patient failed on NNRTIs
AZT + L + DTG
*if HBsAg (HBV) +ive: T+L+DTG
*stopping TDF in chroni HBV patient leads to fatal hepatitis flare
2nd line regimen if DTG is CIed
AZT + L + LPV/R
*HBsAg +ive: TDF + L + LPV/R
2nd line regimen if TDF & AZT is CIed
ABC + L + LPV/R
2nd line regimen if patients is failing IIs 1st line regimen
AZT + L + LPV/R
*HBsAg +ive: TDF+ L/E + LPV/R
What to do in 2nd line regimens if Dyslipidemia/diarrhea associated with LPV/r occures
Replace with ATV/r
Which drugs are available for 3rd line regimens
PI: DRV
IIs: RAL
NNRTIs: ETR, RPV, MVC
CCR5 blocker: Maraviroc MVC
Pre-exposure Prophylaxis
PrEP: TDF/ L OT TDF/E
*continued risk of aquiring HIV
Post-exposure Prophylaxis
PEP: TDF+ L+ DTG
*if DTG is CIed: T+L/E+ ATV/r OR LPV/r
*if TDF CIed or failing: replace with AZT
** HIV -ive people 72 hrs after substantial exposure
Combinations to avoid
Didanosine+stavudine
Zidovudine+stavudine
L+E
Didanosine+TDF
