trans

PRINCIPLES OF ANTIPARASITIC CHEMOTHERAPY 437
TABLE 17.2
Ideal properties of anti-parasitic drugs
Selectively active against a defined parasite target(s)
and not against related molecules in the host
Free of undesirable side-effects and interactions
with other drugs
Stable under a broad range of environmental
conditions
Easy to synthesize and inexpensive
Favorable pharmacodynamics
Effective in one or few doses
related molecules in the host; (b) free of undesirable
side effects and interactions with other
drugs; (c) stable under a broad range of environmental
conditions; (d) easy to synthesize and
inexpensive; and (e) characterized by favorable
pharmacodynamics.
While many anti-parasitic drugs have been
identified through mass screening programs,
a number were developed through a rational
approach. The recent advances in the molecular
and cell biology of parasites discussed earlier
in this book offer great hope for the future. It is
reasonable to predict that these, coupled with
advances in medicinal chemistry such as catalytic
asymmetric synthesis and microarray
screening technologies, will result in dramatic
improvements in anti-parasitic chemotherapy
in the decades to come.
PRINCIPLES OF
ANTI-PARASITIC
CHEMOTHERAPY
Given the biological diversity of parasites, it
is not surprising that a broad armamentarium
of drugs has arisen to treat them. When discussing
chemotherapy, it is helpful to group
parasites with similar sensitivities. The taxonomic
classification is a useful starting point,
with further subdivisions based on genetic
differences and/or common adaptations to
survival in humans.
Protozoa are single-celled organisms that
multiple by simple binary division. Many have
complex life cycles with sexual and asexual
stages. Arthropod vectors transmit some, while
others survive in the environment as cysts and
reach their host through contaminated food or
water. Theoretically, infection with one protozoan
can result in overwhelming infection, and
as a corollary, eradication of all protozoa by the
combined effects of drugs and the immune system
may be necessary for cure.
As noted in Chapter 7, protozoa can be
divided into the Apicomplexa, which include
Plasmodium spp., Babesia spp. and Toxoplasma
gondii; protozoa that reside under anaerobic
conditions in the lumen of the intestinal tract or
vagina, such as Entamoeba histolytica, Giardia
lamblia and Trichomonas vaginalis; and those
that live in the bloodstream or body tissues
under aerobic conditions, such as Leishmania
spp., Trypanosoma cruzi, Trypanosoma brucei
rhodesiense and Trypanosoma brucei gambiense.
With a few exceptions, eosinophilia is not
a characteristic of protozoal diseases.
In contrast to the protozoa, helminths, or
worms, are highly complex, multicellular
organisms with discrete organ systems. Many
have complex life cycles. Although a few
helminths such as Strongyloides stercoralis,
Hymenolepis nana and Capillaria philippinensis
are capable of autoinfection, most require
development outside their mammalian host
either in the environment or in an invertebrate
vector before they become infective.
Adult helminths have finite life spans. The
clinical severity of the infection is usually related
to worm burden. Reduction of the parasite load
is often sufficient to ameliorate the manifestations
of disease. It is not necessary to eradicate
all helminths in an individual patient, but with
fewer parasites, there is decreased likelihood of
MEDICAL APPLICATIONS