Wednesday, February 14, 2018

Didanosine-antiviral(anti retrovirus) drug and its pharmacology

DIDANOSINE-
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains.
Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite

Pharmacology:
Indication -For use, in combination with other antiretroviral agents, in the treatment of HIV-1 infection in adults.

Pharmacodynamics-Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Didanosine differs from other nucleoside analogues, as it does not have any of the regular bases, instead it has hypoxanthine attached to the sugar ring. Didanosine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. Didanosine is effective against HIV, and usually used in combination with other antiviral therapy. Switching from long term AZT treatment to didanosine has been shown to be beneficial.  Didanosine has weak acid stability and therefore, it is often combined with an antacid.
Absorption-Rapidly absorbed (bioavailability 30-40%) with peak plasma concentrations appearing within 0.5 and 1.5 hrs.

Protein binding-Low (<5%)

Route of elimination-Based on data from in vitro and animal studies, it is presumed that the metabolism of didanosine in man occurs by the same pathways responsible for the elimination of endogenous purines. Purines are eliminated by the kidneys.

Half life- 30 minutes in plasma and more than 12 hours in intracellular environment.

Drug Drug interactions:
Atazanavir+Didanosine= The serum concentration of Atazanavir can be decreased when it is combined with Didanosine.
Ciprofloxacin+didnosine=The serum concentration of Didanosine can be decreased when it is combined with Ciprofloxacin.
Darunavir+Didanosine= The serum concentration of Didanosine can be decreased when it is combined with Darunavir.
Ethanol+Didnosine= The risk or severity of adverse effects can be increased when Ethanol is combined with Didanosine.
Febuxostat+Didnosine= The serum concentration of Didanosine can be increased when it is combined with Febuxostat.
       
 Food Interactions
 > Avoid alcohol.
 >Take on empty stomach: 1 hour before or 2 hours after meals.

Therapeutic Uses:
>Didanosine is used to treat HIV, which causes the acquired immunodeficiency syndrome (AIDS).

Side effects:
>Difficulty with sleeping
>irritability
>restlessness
> heartburn
> indigestion
>lack or loss of strength
>passing gas
>redistribution or accumulation of body fat

REFERENCE:-Tripathi K D"Essential of medical pharmacology",7th edition ,page no.798,807,814

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