Page 94 - 80 guidelines for the treatment of malaria_opt

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Guidelines for the treatment of malaria – 2 edition

in approximately 1 in 10 000 travellers receiving mefloquine prophylaxis, 1 in 1000
patients treated in Asia, 1 in 200 patients treated in Africa, and 1 in 20 patients following
severe malaria (24–27). Other side effects reported rarely include skin rashes, pruritus
and urticaria, hair loss, muscle weakness, liver function disturbances and very rarely
thrombocytopenia and leukopenia. Cardiovascular effects have included postural
hypotension, bradycardia and, rarely, hypertension, tachycardia or palpitations and minor
changes in the electrocardiogram. Fatalities have not been reported following overdosage,
although cardiac, hepatic and neurological symptoms may be seen. Mefloquine should not
be given with halofantrine because it exacerbates QT prolongation. There is no evidence
of an adverse interaction with quinine (28).

Drug interactions
There is a possible increase in the risk of arrhythmias if mefloquine is given together with
CI N CI N
beta blockers, calcium channel blockers, amiodarone, pimozide, digoxin or antidepressants;
there is also a possible increase in the risk of convulsions with chloroquine and quinine. H N N
N
N
Mefloquine concentrations are increased when given with ampicillin, tetracycline and 2 CH 3
O
O
HN CH 3 metoclopramide. Caution should be observed with alcohol. S CH 3 N
HN
N CH 3 N O
H
O NH 2
OH CH 3 H N CH 3 CI
2
N CH 3 a3.6 artemisinin and its derivatives
H 3 C A3.6.1 Artemisinin
Molecular weight: 282.3
F
H 3 C
H 3 C Artemisinin, also known as qinghaosu, is a sesquiterpene H 3 C
F F
F lactone extracted from the leaves of Artemisia annua (sweet
F
N O wormwood). It has been used in China for the treatment O
O
O C O C O C
F O of fever for over a thousand years. It is a potent and O
O
ÿ O CH 3 rapidly acting blood schizontoci CH 3 O O CH 3
Ode and is active against all
H
H
H H H Plasmodium species. It has an unusually broad activity HO H H
H 3 C
O
HO O against asexual parasites, killing all stages from young rings O
H H H
HN CH 3 to schizonts. In P. falciparum malaria, artemisinin also kills O CH 3
CH 3
the gametocytes – including the stage 4 gametocytes, which
are otherwise sensitive only to primaquine. Artemisinin
and its derivatives inhibit an essential calcium adenosine
H 3 C H 3 C CI
triphosphatase, PfATPase 6 (29).
Artemisinin has now largely given way to the more potent dihydroartemisinin and its CH 3
O
C
O
O O C derivatives, artemether, artemotil and artesunate. The three latter derivatives are converted HN NH 2
O O
CH 3misinin. These drugs should be given as combination therapy
CH 3 back in vivo to dihydroarte CI CI N
O O
Hhem fr
H H to protect t Hom resistance.
H 3 C H 3 C
HO 80 H 3 C O O
H H
CH 3 CH 3 H 3 C N
OH
CI CI
H H H
N N N CH 3 CI O
H NH NH CH 3
H N S NH 2
2
NH NH CH 3
CI H H H O
O N N N CH 3
H
OH
O

H 2 C H H 3 C CH 3 OH CI
HO CH 3 H N OH O O O CH 3 O CH 3
OH OH N
NH N
N 2 H H
H 3 C O
HO H NH 2 CH 3
OH H HO S
OH H H
O OH O OH O O
H 3 C H 3 C OH N HO OH
H 3 C CH 3
N