Upload Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз: Предмет: Файл:
12.08 Mб

294 Antiparasitic Drugs


The causative agents of malaria are plasmodia, unicellular organisms (Order Hemosporidia, Class Protozoa). The infective form, the sporozoite, is inoculated into skin capillaries when infected female Anopheles mosquitoes (A) suck blood from humans. The sporozoites invade liver parenchymal cells, where they develop into primary tissue schizonts. These give rise to numerous merozoites that enter the blood. The preerythrocytic stage is asymptomatic. In blood, the parasite enters erythrocytes (erythrocytic stage), where it again multiplies by schizogony, resulting in the formation of more merozoites. Rupture of the infected erythrocytes releases the merozoites and pyrogens. A fever attack ensues and more erythrocytes are infected. The generation period for the next crop of merozoites determines the interval between fever attacks. With Plasmodium vivax and P. ovale, there can be a parallel multiplication in the liver (paraerythrocytic stage). Moreover, some sporozoites may become dormant in the liver as “hypnozoites” before entering schizogony.

Different antimalarials selectively kill the parasite’s different developmental forms. The mechanism of action is known for some agents: Chloroquine and quinine accumulate within the acidic vacuoles of blood schizonts and inhibit polymerization of heme released from digested hemoglobin, free heme being toxic for the schizonts. Pyrimethamine in-

hibits protozoal



(p.274), as does



via its active metabolite cycloguanil. The sulfonamide sulfadoxine inhibits synthesis of dihydrofolic acid (p.274). Dihydrofolate reductase is also blocked by cycloguanil, the active form of proguanil. Atoquavone suppresses synthesis of pyrimidine bases, probably by interfering with mitochondrial electron transport. Artemesinin derivatives (artemether, artesunate) originate from the East Asian plant Qinghaosu (Artemisia sp.) Its antischizontal effect appears to involve a re-

action between heme iron and the epoxide group of these compounds.

Antimalarial drug choice takes tolerability and plasmodial resistance into account.

Tolerability. The oldest antimalarial, quinine, has the smallest therapeutic margin. All newer agents are rather well tolerated.

Plasmodium falciparum, responsibleforthe most dangerous form of malaria, is particularly prone to develop drug resistance. The prevalence of resistant strains rises with increasingfrequencyofdruguse.Resistancehas been reported for chloroquine and also the combination pyrimethamine/sulfadoxine.

Drug choice for antimalarial chemoprophylaxis. In areas with a risk of malaria, continuous intake of antimalarials affords the best protection against the disease, though not against infection. Primaquine would be effective against primary tissue schizonts of all plasmodial species; however, it is not used for long-term prophylaxis because of unsatisfactory tolerability and the risk of plasmodial resistance. Instead, prophylactic regimens employ agents against blood schizonts. Depending on the presence of resistant strains, use can be made of chloroquine, and/or proguanil, mefloquine, the tetracycline doxycycline, as well as the combination of atoquavone and proguanil.

These drugs do not prevent the (symp- tom-free) hepatic infection but only the dis- ease-causing infection of erythrocytes (“suppression therapy”). On a person’s return from an endemic malaria region, a two-week course of primaquine is adequate for eradication of the late hepatic stages (P. vivax and

P. ovale).

Protection from mosquito bites (with nets, skin-covering clothes, etc.) is a very important prophylactic measure.

Therapy. Antimalarial therapy employs the same agents, in addition to the combinations of artemether plus lumefantrine or pyrimethamine plus sulfadoxine.

Luellmann, Color Atlas of Pharmacology © 2005 Thieme

All rights reserved. Usage subject to terms and conditions of license.





A. Malaria: stages of the plasmodial life cycle in the human: therapeutic options













Primary tissue schizont







Preerythrocytic 1-4 weeks

P. falciparum























P. vivax





P. ovale




































































2 days :




Tertian malaria





P. vivax, P. ovale





3 days:





Quartan malaria




P. malariae









No fever










Pernicious malaria:




P. falciparum



not P. falciparum























Luellmann, Color Atlas of Pharmacology © 2005 Thieme

All rights reserved. Usage subject to terms and conditions of license.

296 Antiparasitic Drugs

extrapyramidal motor disturbances, Parkin-


Other Tropical Diseases

son-like signs, coma, and death. Therapy:




In addition to malaria, other tropical diseases

Long-term suramine i.v. or pentamidine(less


and their treatment will be considered for






the following reasons. (1) Owing to the tre-

highly toxic), when the CNS is involved.


mendous growth in global travel, inhabitants

T. cruzi is confined to Central and South


of temperate climatic zones have become

America and transmitted by blood-sucking


exposed to the hazard of infection with trop-

reduviid bugs. These parasites preferentially


ical disease pathogens. (2) The spread of

infiltrate the cardiac musculature, where


some tropical diseases is of unimaginable

they cause damage to muscle fibers and the


dimensions, with humans victims number-

specialized conducting tissue. Death results


ing in the millions. The pharmacotherapeutic

from cardiac failure. Therapy: unsatisfactory.



possibilitiesknown to date will be presented.














Amebiasis. The causative agent, Entamoeba

p.292). The causative organisms are trema-


histolytica, lives and multiplies in the colon

todes with a complex life cycle that need


(symptom: diarrhea), its cyst form residing

(aquatic) snails as intermediate hosts. Free-


also in the liver among other sites. In tropical

swimming larval cercariae penetrate the in-


regions, up to half the population can be

tact skin of humans. The adult worms (Schis-


infested, transmission occurring by the fe-

tosoma mansoni, D) livein thevenousvascu-


cal–oral route. The most effective treatment

lature. Occurrence: tropical countries rich in


against both intestinal infestation and sys-

aquatic habitats. About 200 million humans


temic disease is administration of metroni-

are af icted. Therapy: praziquantel, 10–


dazole. If monotherapy fails, combination

40 mg/kg,singledose,ishighlyeffectivewith


therapy with chloroquine, emetine or tetra-

minimal adverse effects. Substancesreleased


cyclines may be indicated.

from decaying worms may cause problems.


Leishmaniasis. The causative agents are flag-

Filariasis. In its microform, Wuchereria ban-


ellated protozoa that are transmitted by

crofti istransmittedbymosquitoes;theadult


sand flies to humans. The parasites are taken

parasites live in the lymph system and cause


up into phagocytes, where they remain in

inflammations and blockage of lymph drain-


phagolysosomes and multiply until the cell

age leading to elephantiasis in extreme cases


dies and the parasites can infect new cells.

(B). Therapy: diethylcarbamazepine for sev-


Symptoms: A visceral form, known as kala-

eral weeks; adverse reactions are chiefly due


azar, and cutaneous or mucocutaneous

to products from disintegrating worms.


forms exist (A). An estimated 12 million hu-








mans are affected. Therapy is dif cult; pen-

Onchocerciasis (“River Blindness”). The


tavalent antimonial compounds, such as sti-

causative organism is Onchocerca volvulus,


bogluconate, must be given for extended

a filaria transmitted by black flies (genus


periods. Adverse effects are pronounced.

Simulium). The adult parasites (several cen-



timeters long) form tangles and proliferating


Trypanosomiasis. The pathogens, Trypano-

nodules (onchocercomas) in the skin and


soma brucei (sleeping sickness) and T. cruzi

have a particular propensity for invading


(Chagas disease), are flagellated protozoa. T.

the eyeball, resulting in blindness. About 20


brucei (C) is transmitted by the tsetse fly,

million people inhabiting banks of fast-flow-


distributed in West and East Africa. An initial

ing rivers are af

icted with river blindness.


stage (swelling of lymph nodes, malaise,



(0.15 mg/kg,



hepatosplenomegaly, among others) is fol-

dose); adverse reactions are in part caused


lowedLuellmann,by invasionColor ofAtlastheofCNSPharmacologywith lethargy,© 2005by disintegratingThieme





All rights reserved. Usage subject to terms and conditions of license.









Other Tropical Diseases






A. Cutaneous leishmaniasis




B. Elephantiasis








Causative agent: Leishmania major



Causative agent: Wuchereria bancrofti








































C. Trypanosoma brucei




D. Schistosoma mansoni



Causative agent of sleeping sickness



Causative agent of bilharziasis








Luellmann, Color Atlas of Pharmacology © 2005 Thieme

All rights reserved. Usage subject to terms and conditions of license.

Тут вы можете оставить комментарий к выбранному абзацу или сообщить об ошибке.

Оставленные комментарии видны всем.

Соседние файлы в предмете [НЕСОРТИРОВАННОЕ]