Artemisinin and its derivatives in malaria treatment

Gaurav Chhabra
M. Pharm(Pharmacology)
ARTEMISNIN AND THEIR DERIVATIVES IN
MALARIA TREATMENT
iamgauravchhabra@gmail.com

CONTENTS
 INTRODUCTION
 EPIDEMIOLOGY OF MALARIA
 THE MALARIA PARASITE
Life cycle of P. falciparum
 CHEMOTHERAPY OF MALARIA
Drug resistance in P. falciparum malaria
 ARTEMISININ AND ITS DERIVATIVES
The plant Artemisia annua
Chemical structure and metabolism
Antimalarial activity
Mechanism of action
Pharmacokinetics
 FAMOUS MARKETED FORMULATIONS OF ARTEMISNIN AND COMBINATION
THERAPY
 RESULT
 CONCLUSION
 SPECIAL POINT
 REFERENCESiamgauravchhabra@gmail.com

INTRODUCTION
Epidemiology Of Malaria:-
Malaria is a public health problem in more than 90
countries.
Almost one half of the world’s population lives under the
constant threat of malaria.
Global burden of malaria can be described as: 2.7 million
deaths, 300-500 million cases, and 44 million disability
adjusted life years.
About 80-90% of all malaria deaths occur in Africa south of
Sahara, and the great majority of them are children under five.
Malaria kills one child every 30 seconds

Malaria Infection:-
Malaria is an intermittent and remittent fever caused by a protozoan parasite.
The human malaria is caused by four different parasite species, belonging to the genus Plasmodium. These
are: P. vivax, P. falciparum, P. malariae, and P. ovale.
Plasmodium falciparum is by far the most prevalent species and causes most problems a result of its
virulence and drug resistance.
It has a rapid rate of asexual reproduction in the host and an ability to sequester in small blood vessels,
with high risk for development of cerebral malaria

Life Cycle Of Malaria Parasite:-
• The parasite requires two hosts, a female Anopheles mosquito and a human. The malaria life cycle
begins when an infected female mosquito bites her prey (Figure).
• The mosquito injects sporozoite-containing saliva into the capillaries
of the skin. Sporozoite enters the liver cell and multiplies to form
about 30,000 merozoites. After about five days the merozoites are
released into the blood stream.
• Merozoites enter red blood cells and develop through the so-called
ring, trophozoite, and schizont stages.
• The erythrocyte provides the parasite with a safe haven from the
host’s immune system.
• Parasite growth is supported by the ingestion of host haemoglobin.
(Fig.- Life Cycle Of Malaria Parasite)iamgauravchhabra@gmail.com

• During a 48 hour cycle the merozoites burst from the mature schizonts,
releasing cell debris, which causes a febrile episode in the host.
• Within minutes, merozoites invade new red blood cells and the cycle
continues.
• After several cycles, some of the intraerythrocytic parasites develop into
sexual stage gametocytes.
• The gametes are ingested when a mosquito bites an infected individual. They
mate in the gut of the insect and they pass through the gut wall, where they
develop into oocysts that release sporozoites that migrate to the salivary
glands to be passed on to another individual.
Life Cycle Of Malaria Parasite(Cont.):-
(Fig.- Life Cycle Of Malaria Parasite)

Conventional Malaria Chemotherapy :-
1. 4-Amino Quinolones- Chloroquine
2. 8-Amno Quinolones- Primaquine
3. Quinolone Methanol- Mefloquine
4. Cinchona Alkaloids- Quinine
5. Biguanides- Proguanil
6. Diaminopyrimidines- Pyrimethamine
7. Sulphonamides- Sulfadoxime
8. Tetracyclines- Doxycyclines
9. Naphthoquinone- Atovaquinone.

Mechanism Of Action Of Conventional Antimalarials:-
Fig-Mechanism of action of conventional antimalarial drugs
(Art-Artimisnin CHQ-Chloroquine Sul-Sulfonamides ATO-Atovaquine
Pyr-Pyrimethamine)
• But the main of problems in these conventional
therapies are that the malaria parasite mainly
P.falsiparum may develop the resistivity against these
drugs and cause failure of treatment.
• Therefore to reduce this resistivity the perfect
combinations of these agents are used.
• Sometimes this combination is not effective in
P.falsiparum parasite infection and parasite develops
the resistivity against the combinations so now a new
agents such as Artemisnin and their derivatives are
given along with this combination therapy because the
parasite can not develop the resistivity against this
combination.

ARTEMISININ AND ITS DERIVATIVES:-
Obtain from leaves and flowering tops the Chinese medical plant qinghao (Artemisia annua L.)
By the end of the 1970s, several clinical studies conducted in China found qinghaosu to be an exceptional antimalarial
agent with negligible toxicity and high efficacy against human malaria parasites, including those resistant to
conventional malaria treatment
Derivatives of Artemisnin :-
1 Artemether
2.Arteether
3.Artesunte
4.Artenimol
5.Dihydroartemisnin(DHQ)

Molecular Structures Of Artemisinin And Its derivatives :-
Fig- Molecular Structures Of Artemisinin And Its derivatives Fig.- Interconversion Between Artemisinin Derivatives

Mechanism Of Action Of Artemisinin:-
Step1- Formation Of Free Radicals:- Step2- Action Of Free Radicales On Parasite

Excretion- Renal
Distribiution- 80-85% Protein bounded form(albumine)
Metabolism- Liver, Cytochrome P-450 enzyme 2B6 with some possible contribution of CYP3A4 and CYP2A6
Human Pharmacokinetics of Artemisnin:-
Absorption- Good Oral bioavailablity
Absorption lag-time of 0.5-2 hours with peak plasma concentrations at 1-3 hours after oral intake
Half-life - 1-3 hours
have been suggested to metabolise the compound.

Enzymes involve in the metabolism of Artemisnin and their derivatives-

FAMOUS MARKETED FORMULATIONS OFARTEMISNIN AND COMBINATION THERAPY :-

RESULT:-
Artemisnin and their derivatives are effective against multidrug resistant malaria parasites.
CONCLUSION:-
Combination therapy is an effective approach for the treatment of Plasmodium falciparum caused malaria infection.
There is no multi drug resistance has seen in malaria parasite against this therapy.
SPECIAL POINT:-
The Nobel Prize in Physiology or Medicine 2015 was awarded with one half jointly to William C. Campbell and
Satoshi Ōmura “for their discoveries concerning a novel therapy against infections caused by roundworm parasites”
and the other half to Youyou Tu “for her discoveries concerning a novel therapy against Malaria”

REFERENCES
1. Laderman, C. 1975. Malaria and progress: Some historical and ecological considerations, Page no.587-94.
2. Foley, M., and L. Tilley. 1998. Quinoline antimalarials: Mechanisms of action and resistance and prospects for new
agents, Page no.55-87.
3. Krishna, S., and N. J. White. 1996. Pharmacokinetics of quinine, chloroquine and amodiaquine. Page no.263-99.
4. Barnes, K. I., and N. J. White. 2005. Population biology and antimalarial resistance: The transmission of antimalarial
drug resistance in Plasmodium falciparum. Page no.230-40.
5. Foote, S. J., and A. F. Cowman. 1994. The mode of action and the mechanism of resistance to antimalarial drugs,
Page no.157-71.
6. The World Health Report 1997, Conquering suffering, enriching humanity. World Health Forum, Page no.248-60
7. Balint, G. A. 2001. Artemisinin and its derivatives: an important new class of antimalarial agents, Page no.261-5.
8. Brossi, A., B. Venugopalan, L. Dominguez Gerpe, H. J. Yeh, J. L. Flippen- Anderson, P. Buchs, X. D. Luo, W.
Milhous, and W. Peters. 1988. Arteether, a new antimalarial drug: synthesis and antimalarial properties, Page no.645-
50.
9. www.nobelprize.org/the-nobel-prize-in-physiology-or-medicine-2015.iamgauravchhabra@gmail.com

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