Anthelmintic drugs

1. Anthelmintic Drugs
Dr. S. Parasuraman
Faculty of Pharmacy,
AIMST University,
Malaysia.

2. Anthelmintic Drugs
• Infections with helminths, or parasitic worms, affect more than two billion
people worldwide.
• Anthelmintics are drugs that either kill (vermicide) or expel (vermifuge)
infesting helminths. Helminthiasis is prevalent globally (1/3rd of world's
population harbours them).
• Helminthiasis is more common in developing countries with poorer
personal and environmental hygiene.
• In the human body, g.i.t. is the abode of many helminths, but some also
live in tissues, or their larvae migrate into tissues.
• They harm the host by depriving him of food, causing blood loss, injury
to organs, intestinal or lymphatic obstruction and by secreting toxins.
• Helminthiasis is rarely fatal, but is a major cause of ill health.

3. Geographic distribution of intestinal helminths

4. Geographic distribution of coinfection with
helminths
Source: World map showing the geographic distribution of coinfection with helminths together with
tuberculosis, malaria and/or HIV infection of adults. (Nature Immunology 2013;14:1118–26)

5. Effect of helminth-induced immunity on
infections with microbial pathogens
TTisisssuuee d daammaaggee
Induce the release of
cytokine alarmins (IL-
33, IL-25 and TSLP)
Induce the release of
cytokine alarmins (IL-
33, IL-25 and TSLP)
Promote the production of
cytokines, eosinophils and
basophils
Promote the production of
cytokines, eosinophils and
basophils
Excretory secretory molecules produced and
worms can shut down DC synthesis of
proinflammatory cytokines and promote DC
production of the immunoregulatory
molecules
Excretory secretory molecules produced and
worms can shut down DC synthesis of
proinflammatory cytokines and promote DC
production of the immunoregulatory
molecules
Bone marrow
precursors
Bone marrow
precursors
CD4+ cells
Increased Treg Cells, TH2 effector cells,
regulatory TH1 cells. Decreased TH1 and TH17
effector cells.
Source: World map showing the geographic distribution of coinfection with helminths together with
tuberculosis, malaria and/or HIV infection of adults. (Nature Immunology 2013;14:1118–26)

6. Relative incidence of helminth infections
worldwide.
Reference: Goodman & Gilman's The Pharmacologic Basis of Therapeutics - 11th Ed. (2006)

7. Tissue helminths

8. Soil Transmitted Helminth Infections
The major STH infections, which include ascariasis,
trichuriasis, and hookworm infection, are among the
most prevalent infections in developing countries.
Because STH worm burdens are higher in school-aged
children than in any other single group.

9. Anthelmintic Drugs
• Classification of anthelmintics based on chemical
structure
– Piperazines: Diethylcarbamazine citrate (DEC), Piperazine
citrate.
– Benzimidazoles: Albendazole, Mebendazole,
Thiabendazole.
– Heterocyclics: Oxamniquine, Praziquantel.
– Natural products: Ivermectin, Avermectin.
– Vinyl pyrimidines: Pyrantel, Oxantel.
– Amide: Niclosamide.
– Nitro derivative: Niridazole.
– Imidazo thiazole: Levamisole.

10. Anthelmintic Drugs
Worm Drug of Choice Alternative Drugs
Roundworms: Ascaris lumbricoides Mebendazole, Albendazole, Pyrantel. Piperazine, Levamisole,
Ivermectin.
Hookworm: Ancylostoma duodenale Pyrantel, Mebendazole, Albendazole. Levamisole.
Hookworm: Necator americanus Mebendazole, Albendazole. Pyrantel.
Pinworm: Enterobius vermicularis Pyrantel, Mebendazole, Albendazole. Piperazine
Threadworm: Strongyloides stercoralis Ivermectin Albendazole
Whipworm: Trichuris trichiura Mebendazole Albendazole
Whipworm: Trichinella spiralis Albendazole Mebendazole
Filaria
Wuchereria bancrofti,
Diethyl carbamazine, Ivermectin Albendazole
Brugia malayi
Guinea worm
Dracunculus medinensis
Metronidazole Mebendazole
Tapeworms
Taenia saginala
Taenia solium
Hymenolepis nana
Neurocy sticercosis
Praziquantel, Niclosamide
Praziquantel
Praziquantel
Albendazole
Albendazole
Niclosamide, Albendazole
Niclosamide, Nitazoxanide
Praziquantel
Hydatid Disease
Echinococcus granulosus
E. multilocularis
Albendazole
Albendazole
Mebendazole

11. Mebendazole
• Mebendazole is a synthetic benzimidazole that has a
wide spectrum of anthelmintic activity and a low
incidence of adverse effects.
• It is a drug of choice in the treatment of infections by
whipworm eggs, pinworm, hookworms, and roundworm.
• Mechanism of action:
– Mebendazole probably acts by inhibiting microtubule
synthesis. Its bind with parasite ‘β-tubulin’ and inhibit its
polymerization. In addition mebendazole probably blocks
glucose uptake in parasite and depletes its glycogen stores.
– Efficacy of the drug varies with gastrointestinal transit time,
with intensity of infection, and perhaps with the strain of
parasite.

12. Mebendazole
• Pharmacokinetics:
– Absorption of mebendazole from intestines is minimal.
– Less than 10% of orally administered mebendazole is absorbed.
The absorbed drug is protein-bound (> 90%), rapidly converted
to inactive metabolites (primarily during its first pass in the
liver), and has a half-life of 2-6 hours.
– 75 – 90% of oral dose passed in the faeces.
• Dose:
– 100 mg chewable tablet.
– 100 mg/5ml suspension.
– 100 mg tablet.
– Mebendazole is one of the preferred drugs for treatment of
multiple infestations and is more effective than albendazole in
trichuriasis.

13. Mebendazole
• Adverse effects:
– Well tolerated even by patient in poor health.
– Mild nausea, vomiting, diarrhea, and
abdominal pain have been reported
infrequently. Rare side effects, usually with
high-dose therapy, are hypersensitivity
reactions (rash, urticaria), agranulocytosis,
alopecia, and elevation of liver enzymes.
– Mebendazole is teratogenic in animals and
therefore contraindicated in pregnancy.
– It should be used with caution in children
younger than 2 years of age because of limited
experience and rare reports of convulsions in
this age group.

14. Albendazole
• Albendazole, a broad-spectrum oral anthelmintic agent.
• It is the drug of choice for treatment of hydatid disease and
cysticercosis. It is also used in the treatment of pinworm and
hookworm, round worm, whip worm, and thread worm
infections.
• One dose treatment is effective against round worm, pin
worm and hook worm infections which are comparable to 3
days treatment with mebendazole. Three days treatment is
necessary for tapeworms including H. nana. It has weak
microfilaricidal action.
• MOA is similar to mebendazole.

15. Albendazole
• Clinical Uses:
– Albendazole is administered on an empty stomach when used against
intraluminal parasites but with a fatty meal when used against tissue
parasites.
– Ascariasis, trichuriasis, hookworm and pinworm infections: 400 mg oral/
adult and children older than 2 years of age (repeated for2-3 days for
heavy ascaris infections and in 2 weeks for pinworm infection).
– Hydatid disease: Adjunct to surgical removal or aspiration of cysts. 400
mg twice daily with meals for one month or longer. Daily therapy for up
to 6 months has been well tolerated.
– Neurocysticercosis: Corticosteroids are given with the anthelmintic drug
to decrease inflammation caused by dying organisms. Albendazole is
given in a dosage of 400 mg twice a day for up to 21 day.
– Other infections: Treatment of cutaneous larva migrans (400 mg daily for
3 days); visceral larva migrans (400 mg twice daily for 5 days);
microporidial infection (400 mg twice for 2 weeks or longer);
gnathostomiasis (400 mg twice daily for 3 weeks).

16. Albendazole
• Pharmacokinetics:
– Albendazole is erratically absorbed after oral administration, but
absorption is enhanced by a high-fat meal.
– Its metabolized in liver and primarily excreted in urine.
– t½ = approx. 8.5 hours.
• Side effects:
– When used for 1-3 days, albendazole is nearly free of significant adverse
effects.
– Mild and transient epigastric distress, diarrhea, headache, nausea,
dizziness, lassitude, and insomnia can occur.
– In long-term use for hydatid disease, albendazole is well tolerated, but it
can cause abdominal distress, headaches, fever, fatigue, alopecia,
increases in liver enzymes, and pancytopenia.
– It has exhibited embryotoxicity in animals, use in pregnant women is
contraindicated. It should be given with caution to patients with hepatic
or renal disease.

17. Thiabendazole
• Thiabendazole effective against threadworm,
cutaneous larva migrans, and early stage of trichinosis.
• PK: insoluble in water but readily available for oral
absorption. It is hydroxylated in the liver and excreted
in urine.
• MOA: Same as mebendazole. Thiabendazole has
antiinflammatory, analgesic and antipyretic actions.
These may contribute to its effect in cutaneous larva
migrans and other inflammatory conditions produced
by larvae or worms in tissues.
• ADR: Nausea, vomiting, loss of appetite, headache,
giddiness are most common

18. Pyrantel pamoate
• Pyrantel pamoate, along with mebendazole is effective in the
treatment of infections caused by roundworms, pinworms
and hookworms.
• Pyrantel causes activation of nicotinic cholinergic receptors in
the worms resulting in persistent depolarization, slowly
developing contracture and spastic paralysis.
• Its poorly absorbed orally and exerts its effects in the
intestinal tract.
• Adverse effects : Adverse effects are mild and include nausea,
vomiting, and diarrhea.

19. Piperazine
• Piperazine causes hyperpolarization of Ascaris
muscle by GABA agonist action (opening of chloride
channels  relaxation and decresses responsiveness
to contractile action of Ach).
• Orally active and partly metabolized in liver and
excreted in urine.
• ADR: Its safe and well tolerated. Dizziness and
excitement occur at high doses. Toxic dose produce
convulsion and death, due to respiratory failure.
• Contraindicated in renal insufficiency and epileptics),
but safe in pregnant.

20. Diethyl carbamazine citrate (DEC)
• DEC developed in 1948, and its is the first drug for
filariasis.
• DEC absorbed after oral ingestion, well distributed,
metabolized in liver and excreted in urine. Excretion
is faster in acidic urine. Plasma t½ is around 4-12
hours.

21. Diethyl carbamazine citrate (DEC)
• Diethylcarbamazine has a highly selective effect on
microfilariae (Mf) at a dose of 2 mg/kg TDS. The
most important action of DEC appears to be
alteration of Mf membranes so that they are readily
phagocytosed by tissue fixed monocytes, but not by
circulating phagocytes.
• Use: Used for the treatment of filariasis, tropical
eosinophilia, Loa loa and O. vovulus infections.
• ADR: ADR is common but not serious. Nausea, loss of
appetite, headache, general weakness and dizziness.

22. Ivermectin
• Is the drug of choice for the treatment of onchocerciasis (river
blindness) caused by Onchocerca volvulus and for cutaneous
larva migrans and strongyloidiasis.
• Ivermectin targets the parasite’s glutamate-gated chloride
channel receptors. Chloride influx is enhanced, and
hyperpolarization occurs, resulting in paralysis of the worm.
• The drug is given orally. It does not cross the blood-brain
barrier and has no pharmacologic effects in the CNS.
However, it is contraindicated in patients with meningitis,
because their blood-brain barrier is more permeable, making
CNS effects possible.
• Dose: 10-15 mg oral dose with 400 mg of albendazole. Given
annually for 5-6 years for filariasis.

23. Niclosamide
• MOA: Inhibiting oxidative phosphorylation in
mitochondria and interfering with anaerobic
generation of ATP by the tapeworm.
• ADR: Niclosamide is safe during pregnancy and in
patients with poor health. It is well tolerated; minor
abdominal symptoms are produced occasionally.

24. Drug for fascioliasis
• Bithionol:
– Used for the treatment of fascioliasis and cerebral
paragonimiasis.
– Bithionol is also an alternative drug in the treatment of
pulmonary paragonimiasis.
– Dose: 30-50 mg/kg
– ADR: Mild and transient. Bithionol should be used with
caution in children younger than 8 years.

25. Thank you

26. Echinococcus multilocularis
Hydatid disease
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27. Anthelmintic Drugs
Roundworms
Hookworm
Pinworm
Threadworm
Whipworm

28. Anthelmintic Drugs
Filaria
Wuchereria bancrofti,
Brugia malayi
Guinea worm
Dracunculus medinensis
Tapeworms

30. Neurocysticercosis
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