Antiretroviral Drugs- (NRTI's) Flashcards
Current anti-retroviral drugs for treatment of HIV are:
1) nucleoside reverse transcriptase inhibitors (NRTIs)
2) Nucleotide inhibitors
3) non-nucleoside reverse transcriptase inhibitors (NNRTIs)
4) Protease inhibitors
5) Fusion inhibitors
7) Integrase inhibitors
Why should monotherapy of anti-retrovirals by avoided?
Increased risk of resistance
What is HAART?
Combination therapy (Highly active anti-retroviral therapy)
What must be monitored in HAART?
viral load and CD4 cell count in case of development of resistance
In HIV diagnosis, you should look for what?
Abs against virus, not virus species
What are Nuclease Transcriptase Inhibitors (NRTI)?
Nucleoside analogs that inhibit viral reverse trancriptase (RT) and also cause chain termination during viral DNA synthesis.
NRTI’s MOA?
Require intra-cytoplasmic activation by phosphorylation by cellular enzymes including TK to the triphosphates
Name the 6Nuclease Transcriptase Inhibitors (NRTI):
1) Zidovudine
2) Didanosine
3) Lamuvudine (SULFUR RING, HEP B ALSO)
4) Zalcitabine
5) Stavudine
6) Abacavir
Zidovudine is a…
deoxythymidine analog that contains an azido group on the 3’ carbon of the dideoxyribose pentose sugar
Ziduvudine bioavailability?
Good oral bio, tissue dist and cns distribution (60-65% in cerebrospinal fluid compared to plasma) (35% plasma protein bound)
ZIduvudine undergoes what kindof elimination?
hepatic glucuroniation and renal elimination (glom filtration and tubular secretion)
Ziduvudine has increased toxicity due to?
Renal and hepatic insufficiency
What drug reduces the rate of clinical disease progression and prolongs survival in HIV infected patients?
Ziduvudine (AZT)
What drug reduces viral transmission of HIV to the fetus in pregnant women and what dosage forms?
1) Oral AZT during pregnancy
2) IV during labor
3) syrup to the new born
Ziduvudine resistance may be due to?
mutations in the pol gene, withdrawal of AZT may permit reversion to susceptible wild type strain
Adverse effects of Ziduvudine:
myelosuppression- causing anemia, neutropenia, GI intolerance, headache, and insomnia, but may resolve.
AZT co-admin with other myelosuppressive drugs may cause what?
increased hematoxicity
What other myelosuppresive therapies when co-admin’d with AZT may cause hematoxicity?
1) Ganciclovir
2) Ribavirin
3) other cytotoxic agents
Didanosine is what analog?
a deoxyadenosine analog
How should didanosine be taken and why?
It should be taken on an empty stomach bc it is unstable at a low pH
Resistance to didanosine is due to?
RT mutation at 74 and may confer cross resistance to abacavir, lamivudine, and zalcitabine.
Adverse effects of didanosine?
1) Dose dependent pancreatitis
Didanosine is contraindicated in?
cases of alcoholism and hypertriglyceridemia due to the AE pancreatitis
Patients on high dose therapy of didanosine may require what monitoring?
periodic retinal examination
Didanosine may reduce GI absorbtion of what drugs and why?
FQ’s and tetracyclines due to CHELATION so must be admin’d 2 hours apart
How does ganciclovir affect didanosine and vice versa?
Increases AUC
What drug causes decreased serum of didanosine?
Methadone
Lamvudine is a what analog?
deoxy-cytosine analong
Why is Lamivudine best used in combo therapy?
bc M184V mutation causes high levels of resistance to 3TC, and reduced susceptibility to abacavir, didanosine, and zalcitabine
Lamivudine is synergistic with what drugs?
1) Zidovudine
2) Stavudine
What is combivir?
Lamvudine + Zidovudine
Trizivir
Avacavir + Lamvudine + Zidovudine
Why is combivir beneficial?
Bc the m184V mutation that increases resistance to lamvudine also increases susceptibility to zidovudine
Lamivudine is also effective against what?
HBV (Hep B)
What increases AUC of lamivudine?
Bactrim
Emtricitabine is what analog?
a flourinated analog of lamivudine
Emtricitabine has cross resistance with what drug?
lamivudine
Zalcitabine is what analog
cytosine
Zalcitabine absorbtion is decreased by?
food and antacids, >80% oral bioavailability
Adverse effects of Zalcitabine?
Pancreatitis
Dose dependent neuropathy
Oral or esophageal ulceration
Zalcitabine is CI’d with what drugs?
Neuropathy inducing drugs
1) stavudine
2) didanosine
3) isoniazid
What decreases renal clearance of Zalcitabine?
ampho B
foscarnet
aminoglycosides
What increases plasma drug concentrations of Zalcitabine?
Probenecid and cimetidine
Stavudine is what analog?
thymidine analog
Stavudine oral bioavail?
86%
Stavudine potential adverse effects?
Dose related peripheral sensory neuropathy
pancreatitis
arthralgias
elevation of serum aminotransferase
Zidovudine reduces the phosphorylation of what drug? *
Stavudine, so not used together
Abacavir is what analog?
guanosine analog
Abacavir undergoes what metabolism and by what enzymes?
hepatic- alcohol dehydrogenase and glucuronosyl-transferase and renal elimn.
What effect will alcohol have on abacavir?
it will decrease metabolism of abacavir- so increase levels in serum
Adverse reactions of Abacavir?
hypersensitivity rxns (could be fatal) -rash, n/v/d, fatigue, ha
