Page 101 - 80 guidelines for the treatment of malaria_opt

N
N
CI
CI
2
CH 3
HN
HN
CH 3
CH 3
2
N
CH 3
H 3 C
F
H 3 C
F
F
F
F
N
O O C OH N CH 3 CH 3 H N H 3 C O S O O N H C N O N O CH 3 H N N N NH 2 H 3 C O O CI C
O
F O O O
ÿ O CH 3 O CH 3 O O CH 3
H H H H 3 C H H HO H H ANNEX 3. Pharmacology of antimalarial medicines
HO O O O
H H H
HN CH 3 CH 3 O CH 3
a3.8 primaquine
Molecular weight: 259.4
H 3 C H 3 C CI
Primaquine is an 8-aminoquinoline and is
CH 3
O O NH effective against intrahepatic forms of all types of
O C O C 2
O O HN malaria parasite. It is used to provide radical cure
CH 3 CH 3 CI CI N
O O of P. vivax and P. ovale malaria, in combination
H H H H with a blood schizontocide for the erythrocytic
H 3 C H 3 C
HO H 3 C O O parasites. Primaquine is also gametocytocidal
H H A3
CH 3 CH 3 H 3 C N against P. falciparum and has significant blood
OH
stages activity against P. vivax (and some against
asexual stages of P. falciparum). The mechanism
of action is unknown.
Formulations
CI CI • Tablets containing 5.0 mg, 7.5 mg or 15.0 mg of primaquine base as diphosphate.
H H H
N N N CH 3 CI O
H NH NH CH 3 Pharmacokinetics
H N S NH 2
2
NH NH CH 3
O
CI H H H CH 3 Primaquine is readily absorbed from the gastrointestinal tract. Peak plasma concentrations
O N N N
occur around 1–2 h after administration and then decline, with a reported elimination
H
half-life of 3–6 h (51). Primaquine is widely distributed into body tissues. It is rapidly
metabolized in the liver. The major metabolite is carboxyprimaquine, which may
OH
accumulate in the plasma with repeated administration.
O
Toxicity
The most important adverse effects are haemolytic anaemia in patients with G6PD
deficiency, other defects of the erythrocytic pentose phosphate pathway of glucose
H 2 C H H 3 C CH 3 OH metabolism, or some other types of haemoglobinopathy (52). In patients with the African
CI
HO CH 3 H N OH O O O CH 3 O CH 3
N
OH OH variant of G6PD deficiency, the standard course of primaquine generally produces a
N
NH benign self-limiting anaemia. In the Mediterranean and Asian variants, haemolysis may be
N 2 H H
H 3 C much more severe. Therapeutic doses may also cause abdominal pain if administered on
O
CH 3
HO H NH 2 an empty stomach. Larger doses can cause nausea and vomiting. Methaemoglobinaemia
OH H HO S
OH H H may occur. Other uncommon effects include mild anaemia and leukocytosis.
O OH O OH O O
H 3 C H 3 C OH N Overdosage may result in leukopenia, agranulocytosis, gastrointestinal symptoms,
HO
OH
H 3 C CH 3
N haemolytic anaemia and methaemoglobinaemia with cyanosis.
Drug interactions
Drugs liable to increase the risk of haemolysis or bone marrow suppression should be
avoided.
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