McKenna's Pharmacology for Nursing, 2e

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P A R T 2  Chemotherapeutic agents

Cilia with microtubules

Golgi apparatus

Peroxisomes

Cell membrane

Lysosomes

Nucleus: Nuclear membrane Nuclear pore Nucleolus Antimalarials

Centrioles

Microtubules

Other antiprotozoals

Polyribosomes

Antimalarials

Mitochondria

Smooth endoplasmic reticulum

Rough endoplasmic reticulum

Antimalarials

FIGURE 12.2  Types of antimalarial drugs in relation to the stages in the life cycle of Plasmodium .

With P. vivax and P. malariae malaria, this cycle may continue for a long period. Many of the tissue schizonts lay dormant until they eventually find their way to the liver, where they multiply and then invade more red blood cells, again causing the acute cycle. This cycle of emerging from dormancy to cause a resurgence of the acute cycle may occur for years in an untreated individual. With P. falciparum malaria, there are no extra­ hepatic sites for the schizonts. If the person survives an acute attack, no prolonged periods of relapse occur. The first attack of this type of malaria can destroy so many red blood cells that the person’s capillaries become clogged and the circulation to vital organs is interrupted, leading to death. ANTIMALARIALS Antimalarial drugs (see Table 12.1) are usually given in combination form to attack the Plasmodium at various stages of its life cycle. Using this approach, it is possible to prevent the acute malarial reaction in individuals who have been infected by the parasite. These drugs can be schizonticidal (acting against the red-blood-cell phase of the life cycle), gametocytocidal (acting against the

gametocytes), sporontocidal (acting against the parasites that are developing in the mosquito) or work against tissue schizonts as prophylactic or antirelapse agents. Quinine ( Quinate, Quinbisul ) was the first drug found to be effective in the treatment of malaria. Antimalar- ials used today include doxycycline ( Doryx , Frakas ), hydroxychloroquine ( Plaquenil ), mefloquine ( Lariam ) and primaquine ( Primacin ). Fixed dose combination drugs for malaria prevention and treatment are dis- cussed in Box 12.2. Therapeutic actions and indications Chloroquine has previously been the mainstay of anti- malarial therapy. However, due to resistance to this drug, it is no longer readily accessible in Australia, and is only available through the Special Access Scheme. This drug enters human red blood cells and changes the metabolic pathways necessary for the reproduction of the Plasmodium (see Figure 12.2). In addition, this agent is directly toxic to parasites that absorb it; it is acidic and it decreases the ability of the parasite to syn- thesise DNA, leading to a blockage of reproduction. Because many strains of the parasite are develop- ing resistance to chloroquine, the Centre for Disease Control and Prevention often recommends the use of certain antibiotics as part of combination therapy for