Dihydroartemisinin-antimalarial drugs and its pharmacology.

DESCRIPTION:

Dihydroartemisinin (also known as dihydroqinghaosu, artenimol or DHA) is a drug used to treat malaria. Dihydroartemisinin is the active metabolite of all artemisinin compounds (artemisinin, artesunate, artemether, etc.) and is also available as a drug in itself. It is a semi-synthetic derivative of artemisinin and is widely used as an intermediate in the preparation of other artemisinin-derived antimalarial drugs. It is sold commercially in combination with piperaquine and has been shown to be equivalent to artemether/lumefantrine.

MECHANISM OF ACTION :

The proposed mechanism of action of artemisinin involves cleavage of endoperoxide bridges by iron, producing free radicals (hypervalent iron-oxo species, epoxides, aldehydes, and dicarbonyl compounds) which damage biological macromolecules causing oxidative stress in the cells of the parasite. Malaria is caused by apicomplexans, primarily Plasmodium falciparum, which largely reside in red blood cells and itself contains iron-rich heme-groups (in the form of hemozoin). In 2015 artemisinin was shown to bind to a large number targets suggesting that it acts in a promiscuous manner.Recent mechanism research discovered that artemisinin targets a broad spectrum of proteins in human cancer cell proteome through heme-activated radical alkylation.

DOSING   :

Dihydroartemisinin is available as a fixed drug combination with piperaquine (each tablet contains 40 mg of dihydroartemisinin and 320 mg of piperaquine).

The adult dose is 1.6/12.8 mg/kg per dose (rounded up or down to the nearest half tablet) given at 0 h, 8 h, 24 h, and 48 h. Alternatively, the same total dose may be given once daily for three day.          

THERAPEUTIC USES  :

Uncomplicated falciparum  malaria

Severe and complicated falciparum malaria

ADVERSE  EFFECT :

Nausea

Vomiting

Abdominal pain

Itching

Headache

Dizziness

Bleeding

Dark urine

Q-T  Prolongation

DRUG DRUG INTERACTION :

Dihydro Artimisinin + Astemizole   = cause Q-T Prolongation 

Dihydro Artimisinin + tricyclic antidepressant  =  Increase the risk of cardiac conduction defects

Dihydro Artimisinin +  phenothiazines  =   Increase the risk of cardiac conduction defects

REFERENCE:-Tripathi K D"Essential of medical pharmacology",7th edition ,page no. 829,830.