Pharmacology CornerAntiretrovirals | Pharmacology Corner

Animation: NRTIs mechanism of action

Flavio Guzmán, MD — Sun, 13 Dec 2009 16:23:56 +0000

NRTIs mechanism

Nucleoside analog reverse transcriptase inhibitors (NRTIs) are nucleoside analogues that act as competitive inhibitors of HIV-1 reverse transcriptase. As shown in the animation, these drugs compete with nucleoside triphosphates for access to reverse transcriptase.

All NRTIs lack a 3-hydroxyl group; thus, their incorporation into a growing DNA chain results in its termination. They require intracytoplasmic activation via phosphorylation by cellular enzymes to the triphosphate form. Most have activity against HIV-2 as well as HIV-1.

NRTIs mechanism of action

List of NRTIs

Zidovudine or azidothymidine (AZT) (also called ZDV): first approved drug in its class.
Didanosine (ddI): second FDA-approved drug for the treatment of HIV infection.
Tenofovir (TDF): first nucleotide analog. It has significant drug interactions.
Lamivudine (3TC): also used in the treatment of HBV infection.
Emtricitabine (FTC): acts as an inhibitor of HBV and HIV transcriptase.
Abacavir (ABC): a guanosine analog.

Animations depicting mechanisms of other antiretrovirals

References

Katzung, B. “Basic & Clinical Pharmacology”, 11th Edition. Mc Graw Hill Medical: 2009

Etravirine (Intelence) for HIV infection: not recommended by the Scottish Medicines Consortium

Flavio Guzmán, MD — Tue, 24 Feb 2009 20:38:44 +0000

This is an excerpt from the Scottish Medicines Consortium (SMC) advice on etravirine (Intelence).

ADVICE: following a full submission
etravirine (Intelence), in combination with a boosted protease inhibitor and other antiretroviral medicinal products, is not recommended for use within NHS Scotland for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients.
In HIV-1 infected adults with resistance to currently available non-nucleoside reverse transcriptase inhibitors (NNRTIs) and at least three primary protease inhibitor (PI) mutations who were receiving an optimized background regimen that included boosted darunavir, nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and optional enfuvirtide, etravirine produced significant improvements in virological, immunological and clinical outcomes when compared with placebo.
The manufacturer’s justification of the treatment’s cost in relation to its health benefits was not sufficient to gain acceptance by SMC.
The license holder has indicated their intention to resubmit.

Antiretrovirals drugs: video review for nurses (NCLEX)

Flavio Guzmán, MD — Mon, 02 Feb 2009 22:48:00 +0000

This video review covers the medications used for the treatment of HIV infection. The target audience of the review is nursing students and nurses, it covers mainly adverse effects of the different drug classes.