Beruflich Dokumente
Kultur Dokumente
Department of Pharmacology
LEARNING OBJECTIVES
Explain
MALARIA
Malaria is caused by protozoan parasites of the genus Plasmodium, of which 4 species infect man:
The parasites are transmitted by female mosquitoes of the genus Anopheles while taking a blood meal.
QUININE
Cinchona (Jesuits bark) first brought to Spain in 1639 Quinine, the main alkaloid in the bark of the Cinchona tree was isolated in 1820 Quinidine is also present, but is not used because of its actions on the heart Active against erythrocytic stages of the parasites Its mode of action is not clearly defined but may involve:
Synthetic Antimalaria
One of the first synthetic antimalarials was PAMAQUINE developed during World War (WW)-1 Pamaquine was active against avian malaria (the model) but not P. falciparum (the major human form) In addition, it was toxic in humans. However, it was found effective against the vivax relapses.
Synthetic Antimalaria
Primaquine
Active against liver stages of P. vivax Mechanism of action may involve oxidative stress in the parasite Effective against other stages of the life cycle, but it is too toxic Causes haemolysis and methaemoglobinamia
CHLOROQUINE
Synthesized during WW-II Based on the quinine structure Accumulates in the food vacuole of the parasite Interferes with haem digestion Effective against blood stages Relatively safe Resistance is a problem
Amodiaquine
Developed at the same time as chloroquine Effective against blood stages, even in some chloroquineresistant strains of P. falciparum Has an unacceptable risk of toxicity towards granulocytes and the liver
Mefloquine
Recommended for most risk areas. Minor side effects (nausea, dizziness, difficulty sleeping) do not last long and do not require stopping the drug. Not recommended for use if:
a known allergy to mefloquine a history of epilepsy, severe psychiatric disorders or cardiac conduction abnormalities.
Pyronaridine
Pyronaridine: potential replacement for chloroquine Too expensive Requires new routes for synthesis
Proguanil
It is a prodrug that requires metabolic activation to cycloguanil Effective against erythrocytic and liver stages of P. falciparum Inhibits dihydrofolate reductase and hence DNA synthesis Used as a prophylactic, but is too slow for a cure
Sulphonamides/Sulphone
Sulphones (e.g. Dapsone) and Sulphonamides (e.g. Sulphadoxine) inhibit dihydropteroate synthase
They act too slowly on their own, but act synergistically with proguanil and pyrimethamine because they act at different parts of the same pathway
Artemisinin Derivatives
Artemisinin derivatives are:
Highly effective Rapid have limited toxicity
However, inappropriate use may lead to the development of resistance and untoward toxicity.
Consider to life-cycle of parasites (Plasmodium) To have selective toxicity between host and parasite Good sensitivity in the various stages
Quinine
Generic quinine ethyl carbonate tablet 100 mg Chloroquine phosphate tablet 250 mg Sulfadoxin 500 mg-pyrimethamine 25 mg
Chloroquine
Sulphonamides/Sulphone
Prevention
1-2 tab ante noctum once/week (as long as out break situation)
3 x 1-2 tab daily 1-2 weeks
Therapy
Adult
Prevention
2 tab/week Semi imun (in endemic area) 2 tab /1-2 weeks Semi imun : single dosage 4 tab Non imun : 4 tab2 tab (after 6-8 hours) 2 tab daily for 2 days
Therapy
Child
Prevention
Therapy
Drug example
Adult
Semi imun (in endemic area) 2-3 tab /4 weeks NON Imun 2 tab /2 weeks
single dosage 2-3 tab
Therapy
Child
Prevention
Semi imune 9-14 th (2 tab), 4-8 th (1 tab), <4 th (1/2 tab) Non Imune 9-14 th (1 tab), 4-8 th (1 tab), <4 th (1/2 tab) 1-2 DAYS before until 4 week after exposure
Therapy
Drug example
See USalam