Kwame Nkrumah University of
Science & Technology, Kumasi, Ghana
Drugs Acting Against
Parasitic Diseases
Pharm 451
J. Oppong–Kyekyeku (PhD)
Associate Professor
Department of Pharmaceutical Chemistry
Faculty of Pharmacy and Pharmaceutical Sciences
jamakegh@yahoo.com/jokyekyeku.pharm@knust.edu.gh
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2. Amoebicides & Anthelmintics
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Introduction
• Amoebiasis is a protozoal infection of the intestine (Intestinal
amoebiasis) and sometimes the liver (Hepatic amoebiasis) caused
by Entamoeba histolytica, a single-celled parasite
• The parasite exists in two forms during the cycle;
ü The active parasite (trophozoite)
ü Dormant parasite (cyst)
ü The trophozoites cause diarrhoea and are expelled from the body as a result
ü The cysts are hardy and may spread from person to person
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Chemotherapy
Nitroimidazoles
• They are the drugs of choice for both intestinal and systemic
amoebiasis
• They are also useful in trichomoniasis and schistosomiasis
• They are used in the treatment of giardiasis, cutaneous
leishmaniasis, acute ulcerative gingivitis and Trichomonas
vaginalis
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Chemotherapy
• Their 5-nitro group is essential for activity
• They include the nitroimidazoles and nitrothiazoles
• Examples include Metronidazole (flagyl), Tinidazole (fasigyn),
Ornidazole (tiberal), Secnidazole (flagentyl), Nimorazole,
Niridazole (ambilhar)
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Nitroimidazoles
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Mechanism of Action
• Antibacterial; antiprotozoal – Microbicidal, active against most obligate
anaerobic bacteria and protozoa
• Mechanism is mediated through oxidative reactive species
• Reduced metronidazole (2-hydroxy metabolite) which is cytotoxic but shortlived, interacts with DNA to cause a loss of helical structure, strand breakage
and resultant inhibition of nucleic acid synthesis and cell death
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Mechanism of Action
• They are generally excreted unchanged and as the 5-nitro
containing metabolites
• Metronidazole should not be taken with alcohol
• Tinidazole is similar to metronidazole but has a longer duration
of action
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Diloxanide furoate
• Diloxanide Furoate is 4-(N-methyl-2,2dichloroacetamido)phenyl-2-furoate
• It is the drug of choice for asymptomatic
patients with E. histolytica cysts in the
faeces
• Metronidazole and tinidazole are relatively
ineffective
• Hydrolysis of the ester is essential for
activity
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Anthelmintics
• Drugs with property of ridding the body of parasitic worms and act by
either destroying the helminths or by expelling them from the infested
patient
• These worms are generally divided into;
a) Nemathelminthes - Ascaris lumbricoides-roundworms, Ancyclostoma duodenalehookworms, Strongyloides stercolaris-whipworms, Enterobius vermicularis-thread or
pinworm
b) Platyhelminthes - Flatworms; mostly segmented eg the tapeworm, cestodes, taenia
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Sources of Infestations
Contact with;
• Infected animals
•
Ground contaminated by human or animal excrement
•
Water infested with cercariae
•
Ingestion of infested meat
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Treatment
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The selection of drug is very important with attendant side effects
Stool examination is important for identification of the worm
Nature of helminth
Lifecycle of parasite
Reservoir
Site of infection
Intermediate animal host
Definite human host
Hygiene is the most important key
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Chemotherapy
Classes of anthelmintics
• Chlorinated Hydrocarbons eg tetrachloroethylene
• Phenol and derivatives eg Niclosamide
• Piperazine and derivatives eg Diethylcarbamazine
• Heterocyclic compounds eg Mebendazole, thiabendazole
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Piperazine Derivatives
•
Piperazine is indicated for treating threadworms and roundworms
•
It is presented as the hydrate or citrate salt
•
It blocks the response of ascaris muscle to acetylcholine, causing flaccid paralysis of the
worm
•
Diethylcarbamazine (DEC), a piperazine derivative, is mostly for filariasis, ascaris and
river blindness
Piperazine citrate
Diethylcarbamazine
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Mebendazole
• Methyl (5-benzoyl-1H-benzimidazol-2-yl)carbamate is a broad-spectrum
anthelmintic effective against a variety of nematode infestations including
whipworm, pinworm, roundworm, and hookworm
• Mebendazole irreversibly blocks glucose uptake in susceptible helminths
thereby depleting glycogen stored in the parasite
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Albendazole
• Methyl [5-(propylsulfanyl)-1H-benzimidazol-2yl]carbamate is a broad-spectrum anthelmintic
• It is effective as a single-dose treatment for
ascariasis
• Undergoes rapid and extensive first-pass
metabolism to the sulfoxide, which is the active
form in plasma
• The elimination half-life of the sulfoxide ranges
from 10 to 15 hours
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Thiabendazole
• 2-(4-Thiazolyl)-1H-benzimidazole occurs as a white
crystalline substance that is only slightly soluble in water
but is soluble in strong mineral acids
• Inhibits the helminth-specific enzyme fumarate reductase
• Broad-spectrum anthelmintic activity; for treating
enterobiasis, threadworm, ascariasis, hookworm and
whipworm infection
• In addition to its use in human medicine, thiabendazole is
widely used in veterinary practice to control intestinal
helminths in livestock
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Niclosamide
• 5-Chloro-N-(2-chloro-4-nitrophenyl)-2hydroxybenzamide
• Potent taeniacide-causes phosphorylation in the
mitochondria, mostly interfering with vital life
processes
• The head of the taenia is left in the lumen of the
intestines and therefore saline purgative is given after
1-2 hours of niclosamide ingestion
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Pyrantel
• Drug of choice against infestations with
ascaris and enterobius
• Inhibits worm’s acetylcholinesterase
causing spastic paralysis in susceptible
helminths
• Should not be used together with
piperazine
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