McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 2  Antiprotozoal agents

Cycle in mosquito

Growth of oocysts

Ruptured oocyst with sporozoites

Ookinete (penetrating midgut wall)

Sporontocidal drugs (Active against the parasites developing

in the mosquito) Pyrimethamine, primaquine

Sporozoites

Zygote

Infected salivary gland

Fertilisation

Gametes

Infected anopheles injecting sporozoites into man

Anopheles taking infected blood from man

No effective drug known

Mature gametocytes

Causal prophylactic drugs (Primary tissue schizont in liver cell) Pyrimethamine, primaquine

Gametocytocidal drug (Active against the gametocytes of all malaria parasites) Primaquine Gametocyte-sterilising drugs Pyrimethamine

RBC

Antirelapse drugs (Second tissue schizont in liver cell) Primaquine

Immature gametocytes

Early tropozoite

Ruptured RBC releasing merozoites

Schizontocidal drugs (Active against the erythocytic phase) Potent action: chloroquine, mefloquine Limited action: pyrimethamine, hydroxychloroquine

Mature schizont

FIGURE 12.1  Sites of action of antimalarials and other antiprotozoals. Antimalarials block protein synthesis and cause cell death. Other antiprotozoals block DNA synthesis, prevent cell reproduction and lead to cell death. RBC, red blood cell.

Cycle in humans

disease. In addition, the protozoa that cause malaria have developed strains resistant to the usual antimalarial drugs. This combination of factors has led to a world- wide public health challenge. Life cycle of plasmodium The parasites that cause human malaria spend part of their life in the Anopheles mosquito and part in the human host (see Figure 12.1). When a mosquito bites a human who is infected with malaria, it sucks blood infested with gametocytes, which are male and female forms of the Plasmodium . These gametocytes mate in the stomach of the mosquito and produce a zygote that goes through several phases before forming sporozoites (spore animals) that make their way to the mosquito’s salivary glands. The next person who is bitten by that mosquito is injected with thousands of sporozoites. These organisms travel through the bloodstream, where they quickly become lodged in the human liver and other tissues, and invade the cells.

Inside human cells, the organisms undergo asexual cell division and reproduction. Over the next 7 to 10 days, these primary tissue organisms called schizonts grow and multiply within their invaded cells, using the cell for needed nutrients (as trophozoites ). Merozoites are then formed from the primary schizonts and burst from invaded cells when they rupture because of over- expansion. These merozoites enter the circulation and invade red blood cells. Here they continue to divide until the blood cells also burst, sending more mero- zoites into the circulation to invade yet more red blood cells. Eventually, there are a large number of merozoites in the body, as well as many ruptured and invaded red blood cells. At this point, the acute malarial attack occurs. The rupture of the red blood cells causes chills and fever related to the pyrogenic effects of the protozoa and the toxic effects of the red blood cell components on the system. This cycle of chills and fever usually occurs about every 72 hours.