Non-Nucleoside Reverse Transcriptase

Inhibitors
Nevirapine, Delavirdine, Efavirenz,
and Etravirine
Mechanism of action
These drugs are direct noncompetitive inhibitors of HIV-1
reverse transcriptase. Non-nucleoside reverse transcriptase
inhibitors block RNA-dependent and DNA-dependent polymerase
activities by inducing a conformational change that
disrupts the enzymes catalytic site. Unlike the nucleoside
reverse transcriptase inhibitors, these drugs do not require intracellular
phosphorylation for their actions. These drugs potentiate
the actions of other antiretroviral drugs.
Clinical use
Non-nucleoside reverse transcriptase inhibitors are used in
combination with other antiretroviral agents to treat HIV
infections.
Pharmacokinetics
These drugs are metabolized by the P450 enzymes and are
susceptible to numerous drug interactions by drugs that
induce or inhibit the hepatic P450 microsomal enzymes.
Adverse effects
This drug class has been associated with potentially fatal
hepatotoxicity, although etravirine appears to be the safest
in this regard. Efavirenz has been associated with adverse psychiatric
effects. Severe, life-threatening skin rashes, including
Stevens-Johnson syndrome and toxic epidermal necrosis, may
also occur.