REVERSE TRANSCRIPTASE INHIBITORS

A. NUCLEOSIDE DERIVATIVE

DRUG MECHANISM OF ACTION THERAPEUTIC USES   OTHER INFORMATION      
Zidovudine (AZT, Retrovir) Inhibitis reverse transcriptase by incorporating into DNA and terminating chain elongation HIV   Major DDI with Methotrexate. Do not use with Stavudine (Antagonizes kinase activity)      
Didanosine (ddI, Videx) Same as Zidovudine, except there is no buildup of monophosphate metabolite HIV-1, HIV-2, AZT-resistant HIV   ddI inhibits mitochondrial DNA and causes myopathies (muscle weakness, cramping, peripheral neuropathies, and pancreatitis). Can combine with AZT since no additive side effects and you get additional therapeutic effects. DO NOT GIVE WITH ZALCITABINE (Will give additive toxic effects)      
Zalcitabine (ddC, Hivid) Same as Zidovudine     Least potent and least used in this class due to rapid resistance      
Stavudine (d4T, Zerit) Same as Zidovudine     Equal to potency as AZT and same SE's as ddI. Short t1/2      
Lamivudine (3TC, Epivir) Same as Zidovudine, except highly resistant to ENDONUCLEASE cleavage of incorporated Lamivudine-DNA All HIV types, Hepatitis B   Least toxic overall. Good activity against Hepatitis B. Single dose formation (150mg BID) gives better compliance. Also available as a combination with AZT (Combivir). Toxicity like AZT but less frequent and less severe.      
Abacavir Same as AZT HIV-1, HIV-2          

 

B. NUCLEOTIDE DERIVATIVES

DRUG MECHANISM OF ACTION THERAPEUTIC USES   OTHER INFORMATION      
Adefovir (Preveon) Inhibits Reverse Transcriptase HIV, HSV, HHV-G, CMV, HBV   First nucleotide reverse transcriptase inhibitor. 50% of patients get Proximal Tubular Dysfunction. Not FDA approved.      

 

B. NON-NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (nnRTI's)

DRUG MECHANISM OF ACTION THERAPEUTIC USES   OTHER INFORMATION      
Nivirapine (Viramune) Binds to reverse transcriptase, but on a site away from nucleotide binding site. Causes allosteric inhibition of the enyzme. Syndergistic in combination with nucleotide and nucleoside reverse transcriptase inhibitors HIV   Used in combination with Nucleoside analogs for HIV. Inhibits reverse transcriptase without muscarinic or benzodiazepine activity. Low toxicity for uninfected cells. An ENZYME INDUCER. Taken BID. Can cause severe Stevens-Johnson syndrome.      
Delavirdine (Rescriptor) Same as Nivirapine HIV   Taken TID. An ENZYME INDUCER. Rash is least severe of these drugs.      
Efavirenz (Sustiva) Same as Nivirapine HIV   Once a day dosing. ENZYME INDUCER (CYP3A4). DO NOT USE WITH SAQUINAVIR. If using with Indinavir, must increase the dose of Indinavir