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NUCLEOSIDE REVERSE

TRANSCRIPTASE INHIBITORS
(NRTIs)
NUR FADZLINA ZABRI
082013100006
SERIAL NO.4

INTRODUCTION
This drug blocks the HIV replication
and the infection of the cells
No action on treating the already
infected cells

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS


(NRTIs)

Zidovudine (Azidothymidine, AZT)


Didanosine
Stavudine
Lamivudine
Abacavir
Zalcitabine
Lamivudine
Emtricitabine
Tenofovir

Mechanism of action
Drugs are converted to active
triphosphate forms by cellular
kinases
Competitively inhibit HIV reverse
transcriptase
They get incorporated with growing
viral DNA
Hence, termination of chain
elongation of proviral

General therapeutic uses


Used in combination with other drug
Highly Active Anti
Retroviral Therapy (HAART)

NRTIs

Protease Inhibitors

2 NRTIs + 1 NNRTI
2 NRTIs + 1 Protease Inhibitor
2 NRTIs + 1 Protease Inhibitor +
Ritonavir
Preferred drug regimens are ;
Zidovudine + Lamivudine + Efavirenz
Zidovudine + Lamivudine +
Lopinavir/Ritonavir

General toxicity
NRTIs inhibit cellular as well
mitochondrial DNA polymerase
Cell mediated immunity starts
declining, drug toxicity is more
May cause fatal lactic acidosis ,
severe hepatomegaly and hepatic
steatosis

Zidovudine
A thymidine analogue
First retroviral drug approved for
treatment of HIV
The prototype drug of NRTIs
Secreted in milk

Orally effective
Absorbed from GI tract
Metabolized in liver by glucoronide conjugation
Excreted in urine

Uses
Treatment of HIV-1, HIV-2, HTLV-1, HTLV-2
For post-exposure prophylaxis
To prevent vertical transmission to HIV

Adverse effects
Bone marrow depression
Anemia
Neutropenia
Initial stage : nausea, vomiting,
headache,
insomnia
Long-term therapy: hepatotoxicity,
myopathy with fatigue, lactic acidosis

Drug interaction
1. Zidovudine + Paracetamol

Both are metabolized by glucoronide


conjugation
Paracetamol competes for the
conjugation
Rise in plasma concentration of
zidovudine and its toxicity

2. Zidovudine + Azoles
Azole antifungal agents are
hepatic microsomal enzyme
inhibitor
Inhibit the metabolism of
zidovudine
Rise in plasma concentration of
zidovudine and its toxicity
3. Zidovudine + Stavudine
Both should not be combine
together

Stavudine
Thymidine nucleoside analogue
Use along with other multidrug
therapy
Increase in CD4+ cells in patients
who do not respond to zidovudine
Adverse effect :
Peripheral neuropathy, pancreatitis, joint
pain

Lamivudine
A cytosine nucleoside analogue
Active against HIV-1, HIV-2, hepatitis-B virus
Uses : Post exposure prophylaxis
Treating patients with Hepatitis B
infection
A part of multidrug regimen
Adverse effect : nausea, headache, fatigue,
increase risk of pancreatitis,

Abacavir
Guanosine nucleoside analogue
Commonly use as combination with
zidovudine + lamivudine
Uses : HIV-1 infection therapy in adult
Post exposure prophylaxis
Adverse effect : Generalized
hypersensitivity

Didanosine
Adenosine nucleoside analogue
Part of multidrug regimen
Uses : HIV-1 , HIV-2, HTLV-1
Post exposure HIV prophylaxis
Adverse effect : peripheral neuropathy,
pancreatitis, optical neuritis

Emtricitabine
Cytosine nucleoside analogue
Usual combination with protease
inhibitor/NNRTI
Best tolerated, least toxic
Adverse effect : hyperpimentation of
skin, hepatotoxicity and pancreatitis

Tenofovir

A nucleotide analogue of adenosine


Undergoes intracellular phosphorylation
Inhibits reverse transcriptase
Termination of chain elongation of HIV DNA
Cautiously used in patients with renal
disease

Uses : treatment of AIDS


(combination with other antiretroviral agents )

REFERENCES
Principle of Pharmacology 2nd Edition
by HL Sharma and KK Sharma