Page 104 - 80 guidelines for the treatment of malaria_opt

CI
2
CH 3
HN
CH 3
2
F
H 3 C
F
F
F
N N F H 3 C N CH 3 CI HN N O OH N CH 3 CH 3 H N H 3 C O S O O N H N O N CH 3 O CH 3 H N N N NH 2 H 3 C O CI
O C O C O C
F O O O
ÿ O CH 3 O CH 3 O O CH 3
H H H H H H H
nd
Guidelines for the treatment of malaria – 2 edition H 3 C HO
HO O O O
H H H
HN CH 3 CH 3 O CH 3
to cycloguanil via CYP2C19 is reduced in pregnancy and women taking the oral
contraceptive pill (59,60,61).
H 3 C H 3 C CI
Toxicity
CH 3
O
O
Apart from mild gastric intolerance, diarrhoea and occasional aphthous ulceration HN NH 2
O
C
O
C
O
O
and hair loss there are few adverse effects associated with usual doses of proguanil CI CI N
CH 3
CH 3
O
O
hydrochloride. Haematological changes (megaloblastic anaemia and pancytopenia)
H
H
H
H
have been reported in patients with severe renal impairment. Overdosage may produce H 3 C H 3 C O
O
HO
H 3 C
epigastric discomfort, vomiting and haematuria. Proguanil should be used cautiously
H
H
CH 3
CH 3
in patients with renal impairment and the dose reduced according to the degree of H 3 C N OH
impairment.
Drug interactions
CI
Interactions may occur with concomitant administration of warfarin. Absorption of CI
H
H
H
N
proguanil is reduced with concomitant administration of magnesium trisilicate. CH 3 CI NH NH O
N
N
H
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
a3.11 Quinine
O
Molecular weight: 324.4
Quinine is an alkaloid derived from the bark of
H 2 C H H 3 C OH CI
the Cinchona tree. Four antimalarial alkaloids OH O O O CH 3 O
CH 3
N
HO
H
CH 3
can be derived from the bark: quinine (the main OH N CH 3
OH
alkaloid), quinidine, cinchonine and cinchonidine. NH N
N 2 H 3 C H H
NH
HO H Quinine is the L-stereoisomer of quinidine. O CH 3
2
Quinine acts principally on the mature trophozoite OH H HO S
OH
O stage of parasite development and does not prevent H H
OH
O
O
O
OH
H 3 C H 3 C OH HO
sequestration or further development of circulating N OH
ring stages of P. falciparum.
N H 3 C CH 3
Quinine acts principally on the mature trophozoite stage of parasite development and
does not prevent sequestration or further development of circulating ring stages of
P. falciparum. Like other structurally similar antimalarials, quinine also kills the sexual
stages of P. vivax, P. malariae and P. ovale, but not mature gametocytes of P. falciparum.
It does not kill the pre-erythrocytic stages of malaria parasites. The mechanisms of its
antimalarial actions are thought to involve inhibition of parasite haem detoxification in
the food vacuole, but are not well understood.
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