Introduction Classification of Helminthiasis Classification of Anthelmintics Drugs Mebendazole Albendazole Pyrentel pamoate Peperazine Levamisole Praziquantel Niclosamide Ivermectin Diethylcarbamazine Helminthiasis, also known as worm infection, is any macroparasitic disease of humans and other animals in which a part of the body is infected with parasitic worms, known as helminths. There are numerous species of these parasites, which are broadly classified into tapeworms, flukes, and roundworms. The helminths worms are macroscopic, multicellular organisms having their own digestive, excretory, reproductive and nervous system. The helminths could be nemathelminths (round bodied worms) or platyhelminths (flat bodied worms). Nematodes (round worms) are long, round bodied segmented worms that are tapered at both ends . In festation occurs if the embryonated eggs or tissues of infested host contain larva of the nematode.

1. Presented By:
Dinesh M Gangoda
Roll no: MPL04
Mpharm (Sem-II)
Guided By:
Dr. Poonam D. Sachdeva
Professor
M. Pharm, Ph. D
Department of Pharmacology
Subject: Advance Pharmacology- II
A.R College of Pharmacy and G. H Patel Institute of Pharmacy,
Vallabh Vidyanagar – 388120
Seminar on-
‘‘DRUGS USED IN HELMINTHIASIS”
1

2. • Introduction
• Classification of Helminthiasis
• Classification of Anthelmintics Drugs
• Mebendazole
• Albendazole
• Pyrentel pamoate
• Peperazine
• Levamisole
• Praziquantel
• Niclosamide
• Ivermectin
• Diethylcarbamazine
• References
Contents

3. • Helminthiasis, also known as worm infection, is any macroparasitic disease
of humans and other animals in which a part of the body is infected with
parasitic worms, known as helminths. There are numerous species of these
parasites, which are broadly classified into tapeworms, flukes, and
roundworms.
• The helminths worms are macroscopic, multicellular organisms having their
own digestive, excretory, reproductive and nervous system. The helminths
could be nemathelminths (round bodied worms) or platyhelminths (flat
bodied worms).[1]
Introduction
3

4. is personal and environmental hygiene. Goodman
• Helminthiasis is prevalent globally
(1/3rd of world's population them),
but is more common in developing
countries with poorer personal and
environmental hygiene.[4]
Relative incidence of helminth infections world wide
Figure: Relative incidence of infections world wide[4]4

5. Helminths
Platyhelminths
flatworms
Cestodes
tape worms
Trematodes
flukes
Nematodes
round worms
Mature in
humans
Fail to
mature in
humans
Classification of Helminthiasis[1]
5

6. NEMATODES (ROUND WORMS)
• Nematodes (round worms) are long, round
bodied segmented worms that are tapered at both
ends . In festation occurs if the embryonated
eggs or tissues of infested host contain larva of
the nematode.
• Most of the nematodes round worms, hook
worms, whip worms, pin worms and thread
worms. These are found primarily in intestine
where they attach to the mucosa and feed on host
blood and tissues fluid.[1]
Figure: Nematodes (round worms)
6

7. Characteristic and therapy for commonly encountered nematode
infections[3]
7

8. TREMATODES (FLUKES)
• Trematodes flukes are hermaphroditic, nonsegmented flattened
helminths. The larvae are acquired either through ingestion of
food as vegetable or fish or through skin penetration.
• After ingestion, those trematodes which mature in the
intestinal tract are called intestinal flukes; some may migrate
through the abdominal cavity to the lungs. Intestinal flukes
cause diarrhoea, abdominal pain and anorexia. Liver flukes
produce bile duct obstruction, jaundice, liver enlargement and
diarrhoea. Chronic infestation may cause cirrhosis of liver.
Figure: Trematodes (flukes)
8

9. Characteristic and therapy for commonly encountered Trematodes
infections
9

10. CESTODES (TAPE WORMS)
Cestodes (tape worms)
• Cestodes (tape worms) are ribbon-shaped
parasitic worms of the genus Taenia. These
are mainly intestinal parasites, though a few
invade other tissues in the larval stage.
Figure: Cestodes (tape worms)
10

11. Characteristic and therapy for commonly encountered Castetode
infections[3]
11

12. • Anthelmintics are drugs that either kill vermicide or expel vermifuge
infesting helminths.[2]
Classification of Anthelmintics Drugs[2]
12

13. Table: Choice of drugs for Helminthiasis[2]
13

14. • It is a Benzimidazole introduced in 1972.
• Mebendazole is a prototype Benzimidazole having 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.[2]
Mebendazole
14

15. 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.
15

16. 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 faces.
16

17. ADVERSE EFFECTS
 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.
17

18. CONTRAINDICATIONS
• 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.
18

19. • 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. It has weak microfilaricidal action.
Albendazole
19

20. PHARMACOKINETICS
• Albendazole is 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.
20

21. MECHANISM OF ACTION
• Albendazole causes degenerative alterations in
the intestinal cells of the worm by binding to
the colchicine-sensitive site of β-tubulin, thus
inhibiting its polymerization or assembly
into microtubules (it binds much better to the
β-tubulin of parasites than that of mammals).
21

22. • Albendazole leads to impaired uptake of glucose by the larval and adult
stages of the susceptible parasites, and depletes their glycogen stores.
• Albendazole also prevents the formation of spindle fibers needed for cell
division, which in turn blocks egg production and development; existing
eggs are prevented from hatching. Cell motility, maintenance of cell
shape, and intracellular transport are also disrupted.
• At higher concentrations, it disrupts the helminths' metabolic pathways
by inhibiting metabolic enzymes such as malate
dehydrogenase and fumarate reductase, with inhibition of the latter
leading to less energy produced by the Krebs cycle. Due to diminished
ATP production, the parasite is immobilized and eventually dies.
CONT….
22

23. 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 for 2-3 days for
heavy ascaris infections and in 2 weeks for pinworm infection).
23

24. CONT…
• 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 migraine (400 mg daily for
3 days); visceral larva migraine (400 mg twice daily for 5 days);
microporeida infection (400 mg twice for 2 weeks or longer);
gnathostomiasis (400 mg twice daily for 3 weeks).
24

25. ,
Adverse effects:
• Mild and transient epigastric distress,
• Diarrhea,
• Headache, nausea, dizziness, 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.
Contraindications:
• 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.
25

26. • Pyrantel pamoate, along with
Mebendazole is effective in the
treatment of infections caused
by roundworms, pinworms and
hookworms.
Pyrantel pamoate
26

27. MECHANISM OF ACTION
• Worms are then expelled. An anticholinesterase action has also been
demonstrated. Because Piperazine causes hyperpolarization and flaccid
paralysis, it antagonizes the action of Pyrantel.
• Pyrantel causes activation of nicotinic cholinergic receptors in the worms
resulting in persistent depolarization, slowly developing contracture and
spastic paralysis.
• Cholinergic receptors in mammalian skeletal muscle have very low affinity
for Pyrantel.
27

28. Pharmacokinetics:
• Its poorly absorbed orally
• Only 10-15% of an oral dose of Pyrantel pamoate is absorbed: and exerts
its effects in the intestinal tract.
• This is partly metabolized and excreted in urine.
Clinical Uses:
• Use and administration For Ascaris, Ancylostoma and Enterobius: a single
dose of 10 mg/kg is recommended.
• A 3 day course for Necator and for Strongyloides has been suggested.
• No fasting, purging or other preparation of the patient is needed.
28

29. Adverse effects:
• Pyrantel pamoate has no major adverse effects. Yet, headache, dizziness
and drowsiness may occur.
Contraindications
• Its safety in pregnant women but in children below 2 years has not been
established
29

30. Piperazine
Mechanism of Action
• Piperazine acts as a γ-aminobutyric acid (GABA) agonist, Piperazine
binds directly and selectively to muscle membrane GABA receptors
causing chloride channel opening, causing hyperpolarization of nerve
endings, resulting in flaccid paralysis of the worm. While the worm is
paralyzed, it is dislodged from the intestinal lumen and expelled live from
the body by normal intestinal peristalsis.
• Piperazine causes hyperpolarization of Ascaris muscle by GABA agonist
action (opening of chloride channels relaxation and decreases
responsiveness to contractile action of Ach).
30

31. Pharmacokinetics
• Orally active and partly metabolized in liver and excreted in urine.
Clinical Uses
• Piperazine, nowadays, is an alternative drug for the treatment of ascariasis
and pin worm( Enterobius vermicularis) infestation. It is not used for other
helminth infestations.
31

32. Adverse effects:
• Nausea, vomiting, abdominal pain and headache.
• Dizziness and excitement occur at high doses.
• Toxic dose produce convulsion and death, due to respiratory failure.
Contraindications
• Liver disease,
• Impaired renal function and epilepsy, but safe in Pregnancy period.
32

33. • DEC developed in 1948, and its is the first drug for filariasis.
Mechanism of action
• Proposed mechanisms of action include platelet-mediated triggering of the
release of excretory antigen from microfilariae, with killing involving free
radicals, drug-induced alteration of prostaglandin metabolism in microfilariae
and/or in host endothelial cells, leading to immobilization of microfilariae on
endothelial surfaces and adherence and killing by host platelets and
granulocytes and inhibition of microtubule polymerization.
Diethyl carbamazine citrate (DEC)
33

34. Pharmacokinetics
• Diethylcarbamazine is well absorbed oral administration with peak plasma
concentrations reached within 1-2 hours.
• The elimination half life ranges from 10-12 hours. If the urine is alkalinized,
renal excretion of unchanged drug is prevented and the half life of the drug
increases.
34

35. Clinical Uses:
• Used for the treatment of filariasis, tropical eosinophilia,
• Filariasis- DEC 2mg/kg TDS is the first line drug as used.
• Tropical pulmonary eosinophilia- DEC (2-4 mg/kg TDS) for 2-3 weeks
produce dramatic improvement in the sign and symptoms of eosinophilic
lung or tropical eosinophilia.
35

36. CONT….
• Loa and loa and O. volvulus infections can also be treated with DEC, but
the risk of life-threatening reaction to dying Microfilarial is high. DEC is
better avoided initially, or a small (25-50 mg) test dose as given first which
is unlikely to produce severe reaction. Ivermectin does not produce such
severe reactions and is preferred for initial treatment, but is less effective
against adult worms than DEC.
36

37. Adverse drug reaction:
• ADR is common but not serious.
• Nausea,
• loss of appetite,
• headache,
• general weakness and dizziness.
37

38. • Ivermectin is a semisynthetic macrocyclic
lactone and is a mixture of Ivermectin Bla
and Blb, which are derived from
Streptomyces avermitilis.
Ivermectin
38

39. Pharmacokinetics
• It is absorbed from GIT following oral administration.
• It is 93% plasma protein bound and has a plasma half life of 12 hrs.
• It is excreted mainly in the feces. The drug has a wide distribution in the
body.
Mechanism of Action
• Ivermectin targets the parasite’s glutamate-gated chloride channel receptors.
Chloride influx is enhanced, and hyperpolarization occurs, resulting in
paralysis of the worm.
39

40. CLINICAL USES
• Ivermectin has a wide spectrum of activity as it is active not only against
filarial nematodes but against other nematodes and some parasites also.
• It is the drug of choice in onchocerciasis as it reduces the microfilarial
load without the toxicity seen with Diethylcarbamazine.
• A single dose of 150 mg/kg orally, for patients over 5 yrs of age, is given
every 6 months on empty stomach for treatment of onchocerciasis.
• Ivermectin is very useful in treating disseminated Strongyloidiasis (200
µg/kg orally daily on two consecutive days).
40

41. CONT….
• There are some reports of ivermectin being effective in the treatment of
cutaneous larva migrans. A single oral dose of ivermectin (200 µg/kg)
was found to be effective in curing scabies but not preferred as cure rate
is slow (4 weeks).
• Ivermectin (200 µg/kg single oral dose) is also effective in the treatment
of pediculosis (lice infestation).
41

42. Adverse Effects
• These include fever, pruritus, arthralgia, postural hypotension, tachycardia,
oedema, lymphadenopathy, sore throat, cough and headache.
Contraindications
• Ivermectin should not be used in pregnancy and should be avoided in
children below 5 yrs of age.
42

43. • Niclosamide is a chlorinated salicylamide,
and is used for the treatment of most
cestodes (tape worm) infection. It is not
absorbed from the GIT; hence high
concentrations can be achieved in the
lumen.
Niclosamide
43

44. Mechanism of Action
• Inhibiting oxidative phosphorylation in mitochondria and interfering with
anaerobic generation of ATP by the tapeworm. Injured by niclosamide, the
tapeworms are partly digested in the intestine.
44

45. CLINICAL USES
• Niclosamide is a highly effective drug against Cestodes infesting man-
Taenia saginata, T. solium, Diphyllobothrium latum and Hymenolepis
nana, as well as pin worm (Enterobius), but is infrequently used now due
to availability of Praziquantel.
• The recommended adult dose of should Niclosamide is 2 g OD orally in
the morning on an empty having stomach. The tablet is to be chewed
thoroughly, and then swallowed with water. Niclosamide is not effective
avoid against cysticercosis and hydatid disease.
45

46. Adverse effects
• Niclosamide is tasteless and nonirritating,
• Malaise, pruritus and light headedness are rare.
• Niclosamide is safe during pregnancy and in poor health patients.
46

47. Mechanism of Action
• The drug's mode of action is not exactly known at present, but experimental
evidence indicates Praziquantel increases the permeability of the membranes
of schistosome cells towards calcium ions.
• The drug thereby induces contraction of the parasites' muscle, resulting in
paralysis in the contracted state.
• The dying parasites are dislodged from their site of action in the host
organism and may enter systemic circulation or may be destroyed by host
immune reaction (phagocytosis).
Praziquantel
47

48. Pharmacokinetics
• Praziquantel is rapidly absorbed from intestines; absorption is enhanced if it
is ingested with food.
• High first pass metabolism in liver limits its systemic bioavailability
Phenytoin, carbamazepine and dexamethasone induce Praziquantel
metabolism and further decrease it’s bioavailability. Patients of
neurocysticercosis are mostly receiving these drugs which may contribute to
therapeutic failure of Praziquantel.
• It crosses blood brain barrier and attains therapeutic concentrations in the
brain and CSF.
• The plasma half life is short 1.5 hrs. Metabolite are expected chiefly in urine.
48

49. CLINICAL USES:
• Other Flukes- Praziquantel is the drug of choice for all Schistosome and Flukes infestations except
Fasciola hepatica. The Flukes respond to 75mg/kg single treatment in must cases and on two occasions
in the remaining.
• Neurocysticercosis- Praziquantel was first drug found to be effective
in neurocysticercosis: 50mg/kg daily in 3 divided doses for 15- 30
days kills the larvae lodged in brain and tissues.
• Tapeworm: Praziquantel administered as a single dose has achieved
90- 100% cure rate in a all human tapeworms. This level of efficacy is
similar to or better than that of Niclosamide, particularly in case of H.
Nana.
49

50. CONT…
• Schistosomes- All 3 species can be treated with 40-75mg/kg given once
or in instalments over one day.
• Other Flukes- Praziquantel is the drug of choice for all Schistosome and
Flukes infestations except Fasciola hepatica. The Flukes respond to
75mg/kg single treatment in must cases and on two occasions in the
remaining.
50

51. Adverse effects
• Praziquantel has exhibited no systemic toxicity. It uses bitter can produce
nausea and abdominal pain Other side effects are headache, dizziness and
malaise.
• When used for Schistosomes and visceral flukes, symptoms like itching,
urticaria, rashes, fever and body ache occur as a reaction to the destroyed
parasites.
• No interaction with food, alcohol or tobacco has been noted.
•
51

52. • Tetramisole was developed in the late 1960s.
• It is racemic; it’s levo isomer (Levamisole) was found to be more active and
preferable.
• Both are active against may nematodes, but use is restricted to ascariasis and
ancylostomiasis as a second line drug.
Levamisole, Tetramisole
52

53. Mechanism of Action
• They stimulate ganglia in worms and cause tonic paralysis – expulsion of
live worms. May also interfere with carbohydrate metabolism (inhibitions
of fumarate reductase).
Pharmacokinetics
• It is rapidly absorbed from the GIT, and is extensively metabolised in the
liver.
• Plasma half life is 3-4 hrs. About 80% of the drug, as metabolites, is
excreted in urine.
53

54. Clinical Uses
• Ascariasis, Ancylostomiasis and Mixed ascariasis-hook worm infections.
• Levamisole primarily used for the treatment of round worm and hook
worm infections. Roundworms are parasites that live in your
intestine cause ascariasis (an infection of the small intestine caused
by Ascaris lumbricoides, which is a species of roundworm) and it also cause
infection in the lungs.
54

55. Adverse effects
• Nausea
• Abdominal pain
• Fatigue
• Drowsiness or insomnia is low.
55

56. REFERENCES
1. HL Sharma., and KK Sharma. A principle of pharmacology 5th edition;
Paras medical publisher, Hyderabad 2007, pp- 820-830.
2. KD Tripathi., Essential medical Pharmacology 8th edition Jaypee Brothers
medical publishers, New Delhi 2019, pp; 906- 914.
3. Michelle A. Clark., Richard Finkel., Jose A. Rey., and Karen Whalen, A
book of Lippincott’s Illustrated Reviews Pharmacology, 5th edition South
Asian wolters kluwer New Delhi, pp; 455- 460.
4. Laurence L. Brunton., John S. Lazo and Keith L. Parker, Goodman &
Gilman’s pharmacological basis of Therapeutics. 11th edition MC Graw-
Hill Medical publishing New Delhi, 668- 672. 56

57. 57