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Pyrimethamine and sulphadoxine are very useful adjuncts in the
treatment of uncomplicated, chloroquine resistant, P. falciparum malaria.
Anti malarial activity: Pyrimethamine inhibits
the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines
and pyrimidines, which are so essential for DNA synthesis and cell multiplication. This
leads to failure of nuclear division at the time of schizont formation in erythrocytes and
liver.
Sulfadoxine inhibits the utilisation of
para-aminobenzoic acid in the synthesis of dihydropteroic acid. The combination of
pyrimethamine and sulfa thus offers two step synergistic blockade of plasmodial division.
Absorption, fate and excretion:
Pyrimethamine is slowly but completely absorbed after oral administration and is
eliminated slowly with a plasma half-life of about 80-95 hours. Suppressive drug levels
may be found in the plasma for up to 2 weeks. The drug is excreted in breast milk.
Sulfonamides are rapidly absorbed from
the gut and are bound to plasma proteins. They are metabolised in the liver and are
excreted in the urine. They pass through the placenta freely. Sulfadoxine is a long acting
sulfonamide with a half-life of 7-9 days.
Toxicity and contraindications:
Pyrimethamine can cause occasional skin rashes and depression of hematopoiesis. Excessive
doses can produce megaloblastic anemia.
Sulfonamides can cause numerous adverse
effects. Agranulocytosis; aplastic anemia; hypersensitivity reactions like rashes, fixed
drug eruptions, erythema multiforme of the Steven Johnson type, exfoliative dermatitis,
serum sickness; liver dysfunction; anorexia, vomiting and acute hemolytic anemia can also
occur. The drug is contraindicated in patients with known hypersensitivity to sulfa,
infants below 2 months of age, patients with advanced renal disease and first and last
trimesters of pregnancy.
Availability: Pyrimethamine and
sulphadoxine combined tablets are available, containing 25 mg of pyrimethamine and 500 mg
of sulphadoxine in each tablet.
Dose of Pyrimethamine/sulfadoxine:
| Age
in years |
0-1 |
1-5 |
5-9 |
9-14 |
>14 |
| Dose
of 25+500 mg tablet |
1/4 |
1/2 |
1 |
2 |
3 |
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