Basics on Antihelmitics

1. Anti Helminthic Drugs
Binaya Subedi
BDS 4th batch
Chitwan Medical college

2. Introduction
• Helminthes; means worms
• Helminthiasis is prevalent globally; 1/3rd of world
population harbor them.
• But, more common in developing countries with
poorer personal and environmental hygiene.
• They are commonly transmitted through feco-oral
route thus GIT becomes the common site of
lodgment.

3. Symptoms
Clinical symptoms arise mainly due to the toxins production .
• Acute or chronic blood loss leading to anemia.
• Dysentery, Diarrhoea
• Abdominal pain
• Subcutaneous nodules
• Allergic Reactions, Urticaria
• Injury to the visceral organs
• Intestinal or lymphatic obstruction
• Conjunctivitis, Retinitis, Blindness
• Hepatosplenomegaly

4. Classification of Helminthes
Class Example
Tapeworms (cestodes) Taenia solium, Taenia saginata,
Hymenolepis nana, Echinoccocus
granulosus
Flukes (Trematodes) Schistosoma , Fasciola hepatica
Roundworms (Nematodes) Ascaris, Onchocerca, Trichuris, Neactor
americanus, Anchylostoma duodenale

5. Pharmacological targets
• Helminths depend on host glucose for their basic metabolism.
So, glucose uptake can be blocked. Eg: Benzoimidazoles,
Levamisole
• They have moderately developed muscular system which can
be stimulated or inhibited to produce tonic or flaccid paralysis
through different receptors mediated mechanisms. Eg:
Piperazine, pyrantel pamoate, Levamisole
• They produce energy by anerobic pathway as well as from
oxidative phosphorylation. Eg: Niclosamide
• Cell membrane acts as barrier between internal and external
environment which can be perforated, surface adhesion
molecules can be altered. Eg: DEC, Praziquantel

6. Anti Helmintics Drugs
Classification
A. Benzimidazoles: albendazole, mebendazole, thaibendazole
B. Pryantel pamoate
C. Diethyl carbamazine: DEC
D. Ivermectin
E. Levamisole
F. Salicylanilides :Niclosamide
G. Praziquantel

7. Choice of Drugs for Helminths

8. Mebendazole
• Benzimidazole; congener of thiabendazole
• Became popular because of it retained board spectrum
antihelmintic activity but not the toxicity of it’s
predecessors.
• 100% cure rate/ reduction in egg count in roundworm,
hook worm, Enteroius, Trichuris infestations but much
less active on Strongyloides.
• Upto 75% cure reported in tapeworms. H. nana is
relatively insensitive.
• Action of mebendazole is rather slow, takes 2-3 days to
develop. Poor intestinal absorption (10-15%).

9. Contd..
Mechanism of action:
• It binds to ß-tubulin of susceptible worms with high affinity and
inhibits its polymerization
• It acts probably by blocking glucose uptake by parasites and
depletion of its glycogen stores. Microtubules in the worms are
gradually lost.
ADRS:
Well tolerated even by the pts. with poor health.
• Diarrhea, nausea and abdominal pain
• Expulsion of Ascaris from mouth and nose has occurred.
(Starvation)
• Allergic reactions, loss of hairs, and granulocytopenia at high dose.

10. C/I:
Pregnancy. (being based on animal data).
Uses:
T/t of multiple infestations (Roundworm, hookworm,
whipworm, Enterobius, Trichinella Spiralis, Hydatid disease)
Trichuriasis (effective than albendazole)
Mass treatment but need of large dose is a drawback.

11. Albendazole
• Congener of mebendazole with retained board spectrum anti
helmintic activity and well tolerability.
Adv:
• Single dose is enough in many cases. Eg: Ascariasis,
Hookworm and Enterobiasis . (3 day treatment with
mebendazole)
• Superior to Mebendazole in Strongyloidosis, Hookworm,
Hydatid disease.
But, inferior in Trichuriasis.
MOA:
Similar to that of Mebendazole.

12. ADRS:
• GI side effects (abdominal pain, diarrhea, bowel upset, n/v
• Dizziness in few cases
• headache, fever, alopecia, jundice, neutropenia in prolonged
use
Note: It should be given in empty stomach for intestinal worms but
for cysticercosis , hydatid disease and cutaneous larva margins it
should be given with fatty meal.
Uses:
• Ascaris, Hook worm, Enterobius, Trichuris infestations.
(400mg, 200 mg)
• Tapeworm and strongyloidosis
•Neurocysticercosis (400 mg BD for 8-15 days)
•Cutaneous Larva margins
•Hydatid disease
•Filariasis

13. Thiabendazole
• First benzimidazole introduced, polyantihelmintic, practically
covers all species of nematodes. Also inhibits development of
egg and kills the worm.
MOA:
• as same of mebendazole
• Also exerts antipyretic, analgesic and anti-inflammatory
effect. Contributes in cutaneous larva margin and larva or
worm induced inflammation.
ADRS:
• N/V, loss of apatite, headache are common.
• Impaired alertness, interferes with normal activities
• Itching, abdominal pain, diarrhea

14. Uses: practically against all nematodes infesting the GIT
But, because of frequent side effects and poor patient
acceptability it isn’t used regularly these days.
It is used only when other better tolerated drugs are in
effective.

15. Pyrantel pamoate
• High and comparable efficacy to that of mebendazole against
Ascaris, hookworm, Enterobius.
• But less active against Strongyloids and inactive against
Trichuris
MOA:
• It causes activation of nAch receptors in worms resulting in
persistent depolarization thus spastic paralysis . But, have very
low affinity to human nAch receptors.
ADRS:
• Almost free of side effects. Occasional GI symptoms,
headache, dizziness has been reported.
Safe during pregnancy.

16. Uses:
• For Ascaris, Ancyclostoma, and Enterobius; single dose
recommended
• For Nector and Strongyloides ; 3 day course
Note: Piperazine though used for same purpose antagonize the
action of pyrantel pamoate.

17. Piperazine
• Highly active drug against Ascaris and Enterobius with 90-100% cure
rates. But, second choice of drugs these days.
MOA:
• Causes hyperpolarization by GABA agonistic action opening Cl-
channels resulting in relaxation, decreased responsiveness of worm
muscles to Ach flaccid paralysis
Don’t effect NM transmission in man.
ADRS:
Safe and well tolerated.
• N/V, abdominal discomfort, urticaria
• Dizziness and excitement at high doses.
• Toxic dose produces convulsions and death d/t respiratory failure.

18. C/I: in Renal failure and in epilepticus.
But safe during pregnancy.
Uses:
• Ascaris and Enterobius infestations
•Intestinal obstruction d/t Ascaris
• In pregnancy when other anti-helmintics are
contraindicated.

19. Levamisole, Tetramisole
• Tetramisole (D) and levamisole (L) are optical isomers.
Levamisole is more active and more preferred.
• They are active against large number of nematodes but their
use is restricted to only ascariasis and ancyclostomiasis
because of poor action against other worms.
MOA:
• They stimulate ganglia in worms and cause tonic paralysis 
explusion of live worms.
• May also interfere with carbohydrate metabolism (inh.
Fumarate reductase)
ADRS:
Nausea, abdominal pain, fatigue, drowsiness or insomnia is low.

20. Uses:
•Ascariasis
• Second line in A. duodenale infestations
It was used:
•as DMARDS ??
• as adjuvents in malignancies
• aphthotus ulcers
• Recurrent herpes
But recurrent use produces reactions , not used now as
immunomodulators.

21. Diethy Carbamazine Citrate (DCE)
• First drug for filariasis
• Highly selective effects on microfilariae (mf)
MOA:
• Alters the mf membrane so that they are readily phagocytosed by
tissue fixed monocytes but not by circulating monocytes.
• Muscular activity of MF is also affected causing hyperpolarization
d/t piperazine moiety.
ADRS:
• Not serious. Nausea, loss of appetite, headache, weakness and
dizziness are usual.
• Rash, pruritus, lymphadenopathy, hypotension may occur d/t mass
mf destruction.
(If it occurs DEC is temporarily withheld and antihistamine and/or
corticosteroids are given)

22. Uses:
• Filariasis: produces rapid symptomatic relief, mf
disappears form the blood and pts. Becomes noninfective
to mosquito in 7 days.
• Tropical eosinophilia
• Loa Loa and O. volvulus infections

23. Ivermectin
• Extremely potent semisynthetic derivative of antinematodal
principle obtained from Streptomyces avermitilis
MOA:
• It acts through special type of glutamate gated Cl- channel found
only in invertebrates.
• Potentiates GABAergic transmission in the worms.
The ultimate effect is tonic paralysis in worms.
(Has low affinity for mammalian GABA receptors)
ADRS:
• Mild side effects; Nausea, abdominal pain, constipation, pruritus,
lethargy and transient ECG changes
• More important are d/t degradation products of MF as in DCE.

24. USES:
• DOC for single dose T/t for onchocerciasis and strongyloidosis
• Comparable to DCE for bancroftian and brugian filaria
• Highly effective in cutaneous larva migrans and ascaris
A single 10-15 mg oral dose of ivermectin with 400 mg
albendazole given annually for 5-6 years has been used for
filariasis.

25. Niclosamide
• Highly effective against cestodes infecting man
MOA:
• It acts by inhibiting oxidative phosphorylation in mitochondria and
interfering with anerobic generation of ATP in tapeworm.
• Injured by niclosamide, they are digested in intestine but the
degradation products are more hazardous. Why??
ADRs:
Tastless and nonirritant, minimal absorption from GIT so minimal
systemic toxicity
• Minor GI symptoms are produced. Malaise, pruritus, light
headacheness
It is safe during pregnancy.

26. Praziquantel
• Novel antihelmintic, board range of activity against trematodes
(Schistosomes), cestodes but not nematodes.
MOA:
Rapidly taken by the susceptible worms and causes leakage of
intracellular calcium  contracture and paralysis Loss of
intestinal mucosal gripexpelled.
ADRS:
• Bitter taste, nausea, abdominal pain
• Headache, dizziness and sedation.
Uses:
• Tapeworm infestations
• Neurocysticercosis
• Schistosomes
• DOC for all flukes except liver fluke.

27. Any questions?
References:
1. Essentials of Medical Pharmacology, K.D Tripathi
2. Deo’s Basics of clinical Pharmacology, Dr. Satish Deo
3. Journel on Pharmacological Targets on Helminths, Dr.
Arnold Grew
4. https://en.wikipedia.org/wiki/Helminths
5. https://web.opendrive.com/api/v1/download/file.js
on/72032104_QPWwd_e5e1?inline=1
6. http://ebooks.cambridge.org/chapter.jsf?bid=CBO97
80511546440&cid=CBO9780511546440A030

28. Thank You!!