Anthelmintics
ANTHELMINTICS
Anthelmintics are drugs used to treat parasitic infections due to worms.
Anthelmintics are drugs that either kill (vermicide) or expel (vermifuge) infesting
helminths
Worms that are pathogenic to human beings, namely, metazoa are conventionally
classified into round worms (nematodes) and two types of flatworms, that is, flukes
(trematodes) and tapeworms (cestodes).
Anthelmintics act locally either to expel the worms from the gastrointestinal tract or
systemically to eradicate the species and the developing forms of helmintics that
invade the organs and tissues
Drugs Classification
I. Benzimidazoles
These are effective against GI nematodes. These are highly effective against ascaris,
enterobius, trichuris, and hookworm infections as single or mixed infections.
Drugs: Mebendazole*, Albendazole, Thiabendazole, Flubendazole, Cyclobendazole,
Oxibendazole
II. Quinolines and isoquinolines: Oxamniquine, Praziquantal
III. Piperazine derivatives: Piperazine citrate, Diethyl carbmazine
IV. Vinyl pyrimidines: Pyrantel pamoate, Oxantel
V. Amides: Niclosamide
VI. Natural products: Ivermectins
VII. Organo phosphorus: Metrifonate
VIII. Imidazothiazoles: Levamisole
IX. Nitro derivatives: Niridazole
Source: KD Tripathi, Medical Pharmacology
MEDICINAL CHEMISTRY AND PHARMACOLOGY OF
ANTHELMINTICS
I. Benzimidazoles
MOA: Inhibit the cell division
These drugs act by blocking the glucose transportation in the parasites and lead to the depletion
of glycogen storage of the intracellular microtubules in the cells of the worms, thereby arresting
cell division in the metaphase. The major site of action is microtubular protein β tubilin of the
parasite. These drugs are bound with β tubilin and inhibit the polymerization.
A) Mebendazole
Synthesis
Pharmacology
It is benzimidazole derivative introduced in 1972.
The immobilizing and lethal action of mebendazole is slow and takes 2–3 days.
The site of action of mebendazole appears to be the microtubular protein ‘β-tubulin’
of theparasite as discussed above
Uses:
100 mg twice a day for 3 days: Roundworm, Hookworm, Whipworm
100 mg single dose, repeated after 2-3 week: Pin worm (Enterobius)
200 mg BD for 4 days: Trichinosis.
200–400 mg BD or TDS for 3–4 weeks: Hydatid disease.
B) Albendazole
It has broad-spectrum activity and excellent tolerability of its predecessor (mebendazole),and
has the advantage of single dose administration in many infestations.
One dose treatment has produced cure rates in ascariasis, hookworm (both species) and
enterobiasis which are comparable to 3 day treatment with mebendazole.
Three-day treatment has been found necessary for tapeworms including H. nana.
It is used in various infective diseases like Ascaris, hookworm, Enterobius and Trichuris,
Trichinosis, Neurocysticercosis, Hydatid disease, Filariasis.
C) Thiabendazole
This congener of thiabendazole became very popular because it retained the broad- spectrum
anthelmintic activity but not the toxicity of its predecessor.
It was the first benzimidazole polyanthelmintic introduced in 1961, which covered
practically all species of nematodes infesting the g.i.t.—roundworm, hookworm, pin
worm, Trichuris, Strongyloides and Trichinella spiralis.
It also inhibits development of the eggs of worms and kills larvae.
Thiabendazole affords symptomatic relief in cutaneous larva migrans and skeletal muscle
symptoms produced by migration of Trichinella spiralis larvae to muscles, because it has
anti-inflammatory action as well.
Symptomatic relief also occurs in guinea worm disease.
II. Piperazine derivatives
D) Diethylcarbamazine citrate*
Synthesis:
MOA: It involve in the sensitization the microfilariae to phagocytosis. It also involve in
inflammatory pathway by interfering with the COX pathways.
Uses:
it is the drug of choice for treating filariasis infections (Wuchereria bancrofti, Brugia
malayi, and B. timori). In adequate dosage, it clears the blood rapidly of the
microfilariae and appears to be curative. Antihistamines or corticosteroids may be
needed to control the allergic reaction caused by the disintegration of microfi lariae.
Also used in loiasis due to Loa loa (but it may cause encephalopathy)
III. Amides
E) Niclosamide
MOA: Niclosamide is also a potent mollusicide, which is effective against Biomphaloria
glabrata, the principle action of the drug may be to inhibit anaerobic phosphorylation of
adenosine diphosphate (ADP) by the mitochondria of the parasite, an energy producing
process.
Uses: It is mainly used in tapeworm infection.
IV. Vinyl pyrimidines
F) Oxamniquine
MOA: Inhibits the nucleic acid synthesis of the metabolism resulting in contraction and
paralysis of the worm and death.
Uses: It is used in treatment of schistosomiasis caused by Schistosima mansoni
G) Praziquantal
MOA: it causes rapid Ca2+ influx inside the schistosome resulting sever spasm and paralysis
of the worm muscle and death.
Uses: Used in variety of parasite worm infections like schistosomiasis, clonorchiasis,
opisthorchiasis, tapeworm infection, hydatid disease and other fluke infection.
V. Natural
H) Ivermectin
MOA: Avermectins specifically open the chloride channels in the invertebrate system distinct
from the GABA-gated and glutamate-gated chloride channels.
Uses:
The drug avermectin is now effectively being used to treat and control onchocera
volvulus, the filarial infection responsible for liver blindness.
Also used in head lice, scabies, river blindness (ochorcerciasis), and lymphatic
filariasis.
