Flashcards in Anti-virals Deck (33)
What does a HIV antiretroviral regimen generally comprise of?
2 nucleoside reverse transcriptase inhibitors and either a(n)
integrase strand transfer inhibitor OR
protease inhibitor OR
non-nucleoside reverse transcriptase inhibitor.
Name 2 examples of long-term toxicities associated with HIV antiretroviral treatment
1. metabolic syndrome
2. lipodystrophy syndrome
Name the nucleoside reverse transcriptase inhibitors (NRTIs) and state which riboside’s analogue they each are
1. Abacavir - guanosine
2. Emtricitabine - cytosine
3. Tenofovir - adenosine
4. Lamivudine - cytosine
5. Zidovudine - thymidine
What is the mechanism of action of nucleoside reverse transcriptase inhibitors?
NRTIs are analogs of native ribosides.
Upon cell entry, they are phosphorylated to the corresponding triphosphate analog, which is preferentially incorporated into the viral DNA by reverse transcriptases. Because the 3′-OH group is not present, a 3′,5′-phosphodiester bond between an incoming nucleoside triphosphate and the growing DNA chain cannot be formed, and DNA chain elongation is terminated.
Which 2 NRTIs should not be co-administered?
Emtricitabine and lamivudine as they are both cytosine analogues
Which NRTIs can also be used in the management of Hepatitis B?
(An ART regimen for patients with both HIV and HBV should include (TAF or TDF) plus (3TC or FTC))
Name 2 advantages of tenofovir alafenamide over tenofovir disproxil fumarate?
Tenofovir alafenamide has more favorable effects on renal and bone markers
Which NRTI can only be used in HLA-B*5701–negative individuals?
A test that detects the presence of HLA-B*5701. HLA-B*5701 is a genetic variation that is linked to hypersensitivity to the antiretroviral (ARV) drug abacavir. A person who tests positive for HLA-B*5701 should not use abacavir or any other abacavir-containing medicine.
What is the mechanism of action of integrase inhibitors?
The inhibitor binds and inhibits the catalytic site of the HIV integrase, which terminates integration of HIV DNA into the host genome.
Name 3 examples of integrase inhibitors
What is the mechanism of action of protease inhibitors?
Protease inhibitors bind to the site where protein cutting occurs, and prevent the viral enzyme protease from releasing the individual core proteins.
Name 2 examples of protease inhibitors
Name at least 3 adverse effects associated with protease inhibitors
1. GI disturbances: Nausea, vomiting, and diarrhea.
4. Hepatic injury
What is the mechanism of action via which the pharmacokinetic enhancer such as ritonavir works?
Low doses of ritonavir used have no significant anti-protease activity, but sufficient CYP450- inhibitory activity that interferes with the metabolism of protease inhibitors.
Drug-drug interactions is a common problem associated with which class of HIV anti-viral drugs?
(Drug interactions are a common problem for all protease inhibitors as they are not only substrates but also potent inhibitors of CYP450 isoenzymes.)
What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors (NNRTI)?
NNRTIs bind HIV reverse transcriptase at an allosteric hydrophobic site to induce a conformational change resulting in enzyme inhibition.
How does the entry inhibitor enfurvitide work?
Enfuvirtide is a polypeptide that binds to HIV fusion protein gp41, preventing the conformational change, and interfering with HIV-1 entry by inhibiting the fusion of viral and cellular membranes.
How is enfurvitide administered?
What is the mechanism of action of maraviroc?
Maraviroc blocks the binding of the HIV outer envelope protein gp120 to the CCR5 chemokine receptor
How may HIV acquire resistance to maraviroc?
They may preferentially express CXCR4 co-receptor, which would then limit the ability of maraviroc to block HIV entry.
Who is pre-exposure prophylaxis used for?
It is useful when people are at a high risk of getting infected with HIV. (e.g. sex workers)
Name an anti-viral combination that is used as PrEP.
Tenofovir disoproxil fumarate and emtricitabine (Truvada®)
How long after the last possible exposure to HIV should an individual taking PrEP continue the medication before he/she stops?
He/she should continue for at least 4 weeks after the last significant exposure.
Name 2 examples of NNRTIs
How soon after an exposure to HIV should an individual initiate Post-Exposure Prophylaxis?
He should initiate PEP within the first 72 hours.
Is PEP and PrEP treatment regimen the same?
No. PEP treatment is similar to the treatment used for an established HIV infection. It will use the recommended 3 anti retrovirals regimen.
How long must an individual take PEP following an exposure?
Name a drug that is used in the management of conditions related to Herpes simplex virus type 1 and 2 and varicella-zoster virus such as cold sores, oral and genital herpes, and chicken pox.
(More effective against HSV than VZV)
Can acyclovir and ganciclovir be used at full dose in patients with renal impairment?
No. Caution is advised as the drug is cleared by glomerular and tubular filtration. Hence it can accumulate in patients with renal dysfunction. Dose adjustment will be required.