166
P A R T 2
Chemotherapeutic agents
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
Rough
endoplasmic
reticulum
Smooth
endoplasmic reticulum
Polyribosomes
Golgi
apparatus
Cilia with
microtubules
Peroxisomes
Lysosomes
Nucleus:
Nuclear
membrane
Nuclear pore
Nucleolus
Cell membrane
Microtubules
Mitochondria
Centrioles
Antimalarials
Antimalarials
Antimalarials
Other antiprotozoals
FIGURE 12.2
Types of antimalarial drugs in relation
to the stages in the life cycle of
Plasmodium
.
