A.C.

T’s, NEW TREND IN

MALARIA TREATMENT
TO MR RAJU SHARMA FROM
ANEEK GUPTA

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P R E S E N T E D B Y A N E E K G U P TA
 MALARIA
• Parasitic infection
• Transmitted to humans by the bite of a
mosquito
• Develops and multiplies inside the
mosquito
• Serious morbidity and, if untreated,
high levels of mortality.
TO MR RAJU SHARMA FROM 2
ANEEK GUPTA
 Antimalarial drugs can be
classified in many ways
• Biological activity
- tissue schizontocide
- blood schizontocide
- gametocytocidal
• Their use
- prophylaxis
- acute treatment
- standby
• Chemical structure
TO MR RAJU SHARMA FROM 3
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 TO MR RAJU SHARMA FROM ANEEK GUPTA

CHLOROQUINE
Uses Features Disadvantages
Prophylaxis, acute Fast-acting blood schizonticide Drug resistance very
use and standby effective against sensitive common.
treatment. strains of all four forms of
Plasmodium. Some No radical cure of vivax or
Used to treat gametocidal activity. ovale malaria.
susecptible forms
of all types of Use in pregnancy. Retinopathy after long term
malaria use, vomiting,
Oral and i.v. treatment. neuropsychiatric disorders
(rare).
Inexpensive and widely
available. Overdosage very dangerous.
Unpleasant taste

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 QUININE
Uses Features Disadvantages
Treatment of Fast-acting blood Long treatment course
chloroquine- schizonticide. Effective
resistant against gametocytes of P. Poorly tolerated, especially
Falciparum vivax and P. malariae. given i.v.
malaria.
Resistance may not be a Tinnitus, potentially fatal
problem. hypoglycaemia, G.G. effects,
cardiovascular side effects
Oral, i.v. or i.m. (QT prolongation).
Hypersensitivity to quinine.
Use with caution in
pregnancy and in neonates. Extremely unpleasant taste

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TO MR RAJU SHARMA FROM ANEEK GUPTA
 AMODIAQUINE
Uses Features Disadvantages
Used to treat Blood schizonticide. May Resistance.
susceptible be effective against some
forms of all chloroquine resistant Risk of
types of malaria. Falciparum malaria. agranulocytosis,
especially when
Gametocytocidal activity administered with
against P. vivax and P. proguanil, hepatic
malariae. failure.

TO MR RAJU SHARMA FROM 6

ANEEK GUPTA
 TO MR RAJU SHARMA FROM ANEEK GUPTA

Sulphadoxine/pyrimethamine
Uses Features Disadvantages
Treatment of P. Folate synthesis Resistance in some
falciparum inhibitor. regions.
infection.
Blood schizonticidal Contraindicated in
activity. pregnancy and
neonates.
Single dose treatment.
Severe, potentially
Widely available. fatal skin reactions
(Stevens-Johnson
syndrome).

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 HALOFANTRINE
Uses Features Disadvantages
Acute therapy Blood Cardiac toxicity.
schizonticide.
ECG test
Short treatment mandatory before
course (3 doses, 24 treatment.
hours)
Unpredictable
Bioavailability.

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TO MR RAJU SHARMA FROM ANEEK GUPTA
 TO MR RAJU SHARMA FROM ANEEK GUPTA

Artemesinin, artemether and

other derivatives
Uses Features Disadvantages
Treatment of acute Rapidly acting blood Need for a minimum of
attacks. schizonticide. 5-day treatment.

Gametocidal activity. High doses lead to

Effective against sensitive and psychotic disturbances.
multi-drug resistant
P. falciparum, and P.vivax.

Well tolerated.

Rapid fever clearance

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ARTEMISIN, ARTESUNATE &
OTHER DERIVATES
Continuous research on these groups since
1998 show:
• Rapid onset of Action (within 2 hours of
dosing)
• Short duration of action
• High level of recrudescence inversely
proportional with duration of treatment.
TO MR RAJU SHARMA FROM 10
ANEEK GUPTA
 ARTEMISININ, ARTESUNATE
& OTHER DERIVATIVES
• Artemisinin derivatives cause a
rapid reduction in parasitism and
fever, however artemisinin
monotherapy for less than 7 days
commonly result in unacceptably
high rates.
(Barradell L. B et al. Artesunate: A review of its pharmacology and therapentic
effficacy in the treatment of malaria. Drugs 1995 Oct. 5 (4) 714-741).
TO MR RAJU SHARMA FROM 11
ANEEK GUPTA
 RECRUDESCENCE
Recrudescence results from the persistence of
The original erythrocytic phase in the blood
(usually within 28 days.

Whereas reinfection is a new infection of a

Patient who has previously been infected.

TO MR RAJU SHARMA FROM 12

ANEEK GUPTA
 ARTEMISIN, ARTESUNATE
& OTHER DERIVATES
• In a large number of dose-ranging studies. It
appears that for artesunate to have an
schizonticidal effect clinically, total doses of at
least 1mg/kg over 3 days were required.

• However other reports indicated that even with

doses over 5 days, the recrudesence rates were
unacceptably high
(Loareesuwan Set at Acta trop 1997 Sept. 30 (3) 197 – 205 (Monotherapy with Soduim artesunate for
uncomplicated falciparim malaria 1 Thailand a compassion of 5 to 7 study)

TO MR RAJU SHARMA FROM 13

ANEEK GUPTA
ARTEMISININ, ARTESUNATE
& OTHER DERIVATES
• Recrudescence rate was 49.4% in a
28 day follow up 89 patients given
a total dose of 240mg over 3 days.
It was reduced to 6.7% when a
total dose of 480mg was given
over 7 days.
(Report of W. H. O Scientific group (Practical chemo therapy of malaria Geneva
1990).

TO MR RAJU SHARMA FROM 14

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 THE NEED FOR NEW
ANTIMALARIAL DRUGS
• Drug resistance has increased rapidly.
• Drugs have been used until resistance
renders them ineffective.
• Sub-effective dosing is common in
developing countries.
• Incomplete therapy of existing drugs
and long treatment times.
• New and effective antimalarial drugs
are being developed. TO MR RAJU SHARMA FROM
ANEEK GUPTA
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 ARTEMISININ, ARTESUNATE
& OTHER DERIVATIVES
• The artemisin based combination
therapies (A.C.T) are the most
exciting prospect in new malaria
treatments. They kill malaria
parasites very fast, allowing the
patient to recover rapidly, and with
very few side effects.
TO MR RAJU SHARMA FROM 16
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 Key Attributes of Coartem
• Totally new combination of
artemether and lumefantrine
• Fastest-acting therapy
• Short treatment time
• Has gametocidal activity
• Provides excellent tolerability
• No reported resistance
TO MR RAJU SHARMA FROM 18
ANEEK GUPTA
 BENFLUMETOL
(LUMEFANTRINE)
• Synthesized by Academy of military
Science in Beijing in 1970.

• If conforms structurally, physico

chemically and in mode of action to
aryl amino alcohol gruoup of anti
malaria’s including quinine,TO MR RAJU SHARMA FROM

mefloquine and halofantrine. ANEEK GUPTA

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 BENFLUMETOL
(LUMEFANTRAINE)
• Peak plasma concentrations
were reached in 8 hours.

• Elimination is slow and the

biological half life exceeded 78
hours.
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 SIDE EFFECT PROFILE
• No potentially adverse side effects, mostly
mild G. I disturbances and headaches
mostly associated with malaria.

• No cardio toxicity effects.

• Benflumetol is not mutagenic, Teratogenic

or photo toxic and did not affect
reproduction in rats.
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