Good

1. By- Saud Aslam Ansari
M. Pharm (Pharmacology)
SPER, Jamia Hamdard
Anthelmintic

2. Presentation Outline:-
1) Introduction
2) Anthelmintics
3) Types of worms
4) GLOBAL SCENERIO
5) INDIAN SCENERIO
6) Classification of Drugs
7) Drug of Choice
8) References
2

3. Introduction
• Helminthiasis also known as worm infection is any macro
parasitic 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.
• They often live in the gastrointestinal tract of their hosts but
they may also burrow into other organs where they induce
physiological damage.
• Helminthiasis is prevalent globally about 1/3rd of world’s
population harbours them but is more common in developing
countries with poorer personal and environmental hygiene.
3

4. Anthelmintics
• Anthelmintics are drugs that either kill (vermicide) or expel
(vermifuge) infesting helminths.
• The choice of drug for each worm infestation is based not only
on efficacy but also on lack of side effects/toxicity ease of
administration (preferably single dose) and low cost.
• Development of resistance has not been a problem in the
clinical use of anthelmintics.
4

5. Pathogenesis
• Intestinal worms cause a variety of pathologic changes in the
mucosa, some reflecting physical and chemical damage to the
tissues, others resulting from immunopathologic responses.
Hookworms (Ancylostoma and Necator) actively suck blood
from mucosal capillaries.
• The anticoagulants secreted by the worms cause the wounds to
bleed for prolonged periods, resulting in considerable blood
loss. Heavy infections in malnourished hosts are associated
with anemia and protein loss.
• Diversion of host nutrients by competition from worms is
probably unimportant, but interference with normal digestion
and absorption may well aggravate undernutrition.
5

6. Cont.
• The tapeworm Diphyllobothrium latum can cause vitamin B12
deficiency through direct absorption of this factor.
• Many helminths undertake extensive migrations through body
tissues, which both damage tissues directly and initiate
hypersensitivity reactions. The skin, lungs, liver, and intestines
are the organs most affected.
• Feeding by worms upon host tissues is an important cause of
pathology, particularly when it induces hyperplastic and
metaplastic changes in epithelia.
For example, liver fluke infections lead to hyperplasia of the bile
duct epithelium.
6

7. Types of worms
Nemathelminthes (Roundworms)
• The migration of the larval forms and eggs transmission
through skin contact in moist soil and in tropical areas causes
migraine ,eosinophilia and pulmonary related problems.
• The common infections occurring with intestinal worms
include Ascaris lumbricoides, Trichuris trichiura, Necator
americanus and Ancylostoma duodenal with the household
aggregation of infection.
• The eggs are deposited on perianal area that is due to self
infection.
• These infections also occur due to the contaminated surfaces
like carpets, curtains etc.
7

8. Cont.
Trematoda (Flukes)
• Flukes are the parasitic trematodes of Schistosoma species
which are transmitted through direct contact with fresh water.
• They penetrate into the intact human skin and enter the
capillaries and then migrate to the central and portal system
where they mature.
• Acute schistosomiasis also known as Katayama fever, which is
a form of visceral larval migraines.
• The adult male and female pairs ultimately migrate to the
superior mesenteric veins and ureteric vesicles.
• The eggs are then shed in the faeces and urine.
8

9. Cont.
Cestoda (Tapeworms)
• Humans are the intermediate host for the Taenia solium with
the development of the tissue cysts.
• After the ingestion of the uncooked beef (T. saginata} or pork
it develops the cysts and it causes the mild abdominal
symptoms.
• The infestations of the central nervous systems caused due to
the pork tapeworm or flukes are known as neurocysticercosis
which is treated through albendazole and praziquantel.
9

10. GLOBAL SCENERIO:
• An estimated 120 million people in tropical and sub tropical
areas of the world are infected with lympathic filariasis of
these, 25 million men have genital disease (most commonly
hydrocoele) and almost 15 million; mostly women, have
lymphoedema or elephantiasis of the leg.
• A recent study suggests that during the past 13 years
>96.71million cases were prevented or cured with
MDA(Methylenedioxyamphetamine) treatment, yet, as many
as36 million cases of hydrocoele and lymphoedema remain.
• One of the leading causes of global disability LF(Lympathic
Filariasis) accounts for 2.8 million DALYs(Disability Adjacent
Life Year)
10

11. INDIAN SCENERIO
• A district-level endemicity map created in India in the year2000, shows that
of the 289 districts as many as 257 were found to be endemic.
• About 553 million people are exposed to risk of infection and of them
about 146 million live in urban and the remaining in rural areas.
• About 31 millions are estimated to be carriers and over 23million suffer
from filarial disease menifestations in India.
• B. Malayi is prevalent in the states of Kerela, Tamil Nadu, Andhra Pradesh,
Madhya pradesh, Orissa, Assam, West Bengal.
• Bihar has highest endemicity (over17%) followed by kerela (15.7%) and
UttarPradesh(14.6%).
• Andhra Pradesh and Tamil Nadu Has About 10%endemicity.
• Goa showed the lowest endemicity(>1%), followed by
Lakshwadeep(1.8%), Madhya Pradesh(above 3%)and Assam (5%).
11

12. TAPEWORM
INFECTION(CESTODIASIS):
GLOBAL SCENERIO:
• Greatest infection is found in the temperate zones including
several parts of Eurasia Australia, some parts of America and
Northeast Africa.
• Worldwide distribution of the zoonotic strains of Echinococcus
granulosus and geographical endemicity.
INDIAN SCENERIO:
• The disease is endemic in India.
• High prevalence is reported from Kashmir, Andhra Pradesh,
Tamil Nadu and Central India.
12

13. Classification of Drugs
13

14. 1. Mebendazole
• It is a benzimidazole introduced in 1972.
• This congener of thiabendazole became very popular because
it retained the broad-spectrum anthelmintic activity but not the
toxicity of its predecessor.
• It has produced nearly 100% cure rate/reduction in egg count
in roundworm, hook worm (both species).
• The immobilizing and lethal action of Mebendazole on worms
is rather slow takes 2-3 days to develop.
14

15. Mechanism of action-
• The site of action of Mebendazole is
the microtubular protein ‘B-tubulin’
of the parasite.
• It binds to B-tubulin of susceptible
worms with high affinity and
inhibits its polymerization.
• Intracellular microtubules in the
cells of the worm are gradually lost
• In addition, it probably blocks
glucose uptake in the parasite and
depletes its glycogen stores.
15

16. Cont.
Pharmacokinetics-
• Absorption of Mebendazole from intestines is minimal 75-
90% of an oral dose is passed in the faeces.
• The fraction absorbed is excreted mainly as inactive
metabolites in urine/faeces.
Adverse effects-
• Diarrhoea, nausea & abdominal pain have attend edits use in
heavy infestation.
• Allergic reactions, loss of hair & granulocytopenia have been
reported with high doses.
16

17. 2. Albendazole
• It is a subsequently introduced congener of Mebendazole.
• Retains the broad-spectrum activity and excellent tolerability
of its predecessor, and has the advantage of single dose
administration in many infestations.
• One dose treatment has produced cure rates in ascariasis,
hookworm (both species) & enterobiasis which are
comparable to 3 day treatment with Mebendazole.
MOA-
• The mechanism of action of Albendazole is similar to that of
Mebendazole.
17

18. Cont.
Pharmacokinetics-
• Absorption of Albendazole after oral administration is
significant, but inconsistent.
• It is enhanced when the drug is taken with fatty meal.
• The fraction absorbed is converted by first pass metabolism to
its sulfoxide metabolite which has potent anthelmintic action.
• Albendazole sulfoxide is widely distributed in the body, enters
brain and is excreted in urine & exert anthelmintic activity in
tissues as well.
Adverse effects-
• Gastrointestinal side effects, dizziness.
• Prolonged use has caused headache, fever, alopecia, jaundice. 18

19. 3. Thiabendazole
• It was the first benzimidazole poly antihelmintic introduced in
1961, which covered practically all species of nematodes
infesting the g.i.t— roundworm, hookworm, pin worm.
MOA-
• It also inhibits development of the eggs of worms & kills
larvae.
Pharmacokinetics-
• Since thiabendazole is well absorbed from g.i.t systemic
adverse effects are common.
• Adverse effects-
• nausea, vomiting, abdominal pain, diarrhoea, giddiness,
impairment of alertness, itching, etc. 19

20. 4. Pyrantel Pamoate
• It was introduced in 1969 for pin worm infestation in children
use soon extended to roundworm and hookworm as well.
• Efficacy against Ascaris, Enterobius and Ancylostoma is high
and comparable to that of mebendazole.
MOA-
• Pyrantel causes activation of nicotinic cholinergic receptors in
the worms resulting in persistent depolarization slowly
developing contracture and spastic paralysis.
• Worms are then expelled.
Pharmacokinetics-
• Only 10-15% of an oral dose of Pyrantel Pamoate is absorbed
this is partly metabolized and excreted in urine. 20

21. 5. Piperazine
• Introduced in 1950, it is a highly active drug against Ascaris
and Enterobius achieves 90-100% cure rates.
• However, because of the availability at more convenient and
better tolerated Albendazole/mebendazole it is now considered
a second choice drug.
Mechanism of action-
• Piperazine causes hyperpolarization of Ascaris muscle by a
GABA agonistic action.
• Opening of Cl channels causes relaxation and depresses
responsiveness to contractile action of ACh.
• Flaccid paralysis occurs and worms are expelled alive.
21

22. Cont.
Pharmacokinetics-
• A considerable fraction of the oral dose of Piperazine is
absorbed.
• It is partly metabolized in liver and excreted in urine.
Adverse Effect-
• Piperazine is safe, but nausea, vomiting, abdominal discomfort
and urticaria may be felt.
• Dizziness and excitement occur at high doses toxic doses
produce convulsions death is due to respiratory failure.
22

23. 6. Diethyl Carbamazine Citrate
• Developed in 1948, it is the first drug for filariasis caused by
the nematodes Wuchereria bancrofti (90% cases) &
Brugiamalayi.
MOA-
• Diethylcarbamazine is microfilaricidal.
• It has a highly selective effect on microfilariae (Mf).
• A dose of 2 mg/kg TDS clears Mf of W. bancrofti and B.
malayi from peripheral blood in 7 days.
• The most important action of DEC appears to be alteration of
organelle membranes of the Mf promoting cell death.
23

24. Cont.
Pharmacokinetics-
• DEC is absorbed after oral ingestion distributed all over the
body metabolized in liver and excreted in urine.
• Excretion is faster in acidic urine.
• Plasma t'z of usual clinical doses is 4—12 hours depending on
urinary pH.
Adverse Effects-
• Side effects are common but generally not serious.
• Nausea, loss of appetite, headache, weakness & dizziness are
the usual complaints
24

25. 7. Ivermectin
• It is an extremely potent semisynthetic derivative of the
antinematodal principle obtained from Streptomyces
avermitilis.
• It is the drug of choice in onchocerciasis and strongyloidiasis.
• It is effective against microfilaria of W.bacrofti and B.malayi.
25

26. MECHANISM OF ACTION
Ivermectin
Activates glutamate-gated chloride channels increase Gaba
(gama-aminobutyric acid) transmission in worms
Hyperpolarisation and paralysis of worms
Deaths/phagocytises of worms
26

27. Cont.
Pharmacokinetics
• It is given orally rapidly absorbed widely distributed to various
tissues metabolized in the liver and excreted mainly in faeces
Side effects
• Itching, skin rashes, oedema, headache, fever, muscle and joint
pain.
Clinical uses
• Onchoerciasis -Treatment is with a single oral dose of
ivermectin,150 mg/kg, with water on an empty stomach.
• Strongyloidiasis - Two daily of 200 mg/kg.
27

28. 8. Niclosamide
• Niclosamide is a highly effective drug against cestodes
infesting man—Taenia saginata, T. solium, Diphyllobothrium
latum andHymenolepis nana, as well as pin worm.
Mechanism of action
• Niclosamide act by inhibiting oxidative phosphorylation in
mitochondria and interfering with anaerobic generation of ATP
by the tapeworm.
28

29. Cont.
Adverse effects
• Niclosamide is tasteless and non irritating.
• It is minimally absorbed from g.i.t.—no systemic toxicity
occurs.
• It is well tolerated minor abdominal symptoms are produced
occasionally.
• Malaise (discomfort,illness), pruritus (severe itching of skin)
and light headedness are rare.
• Niclosamide is safe during pregnancy and in patients with
poor health
29

30. It is effective in the treatment of trematodes and cestodes but not for
Nematodes.
Mechanism of action
Praziquante
Influx of calcium ion into the tegument
Increased muscular contraction and spastic paralysis
At higher concentration
Damage tegument
Death of the parasite
9. Praziquantel
30

31. Cont.
Pharmacokinetics-
• It is readily absorbed after oral administration undergoes
extensive first-pass metabolism in liver, highly bound to
plasma protein, crosses the BBB and excreted mainly in urine.
Adverse effects-
• Dizziness, nausea, vomiting, abdominal discomfort,headache,
drowsiness, skin rashes, itching, muscle and joint pain.
31

32. Drug of Choice

33. worm First choice of drugs Alternative drugs
ROUND WORM
(NEMATODES)
Ascaris lumbricoides
MEBENDAZOLE,
ALBENDAZOLE,
PYRANTEL
PIPERAZINE,
LEVANISOLE,
IVERMECTIN
HOOK WORM
Accylostoma duodnale
Necator americanus
Pyrantel, Mebendazole
Albendazole,
Mebendazole, Albendazole
Levamisole
Pyrantel
PIN WORM
Enterobius
vermicularis
Pyrantel,
Albendazole,
Mebendazole
piperazine
Thread worm
Strongyloides stercoralis
Ivermectin Albendazole
Whip worm
Trichuris trichura
Trichinella spiralis
Albendazole,
Mebendazole
Albendazole,
Mebendazole
33

34. Guineaworm
Dracunculas medinesis Metronidazole Mebendazole
Tapeworm
(cestodes)
Taenia saginata
Taenia solium
Hymenolepis nana
Neurocysticercosis
Praziquantel
Praziquantel
Praziquantel
Albendazole
Niclosamide
Niclosamide
Niclosamide
Praziquental
Hydatid disease
Echinococcus granulosus
E.multilocularis
Albendazole
Albendazole
Mebendazole
Cont.
34

35. References
• Goodman and Gilman's The Pharmacological Basis of Therapeutics, by
Bjorn Knollmann (Author), Laurence Brunton (Author) ,14th Edition,
Section VII: Chemotherapy of Infectious Diseases, Chapter 68:
Chemotherapy of Helminth Infections.
• Essentials of Medical Pharmacology by K. D. Tripath, Edition-Eighth,
Publisher- Jaypee Brothers Medical Publishers.
• Rang & Dale's Pharmacology, 9th Edition, Authors: James M. Ritter, Rod J.
Flower, Graeme Henderson, Yoon Kong Loke, David MacEwan,
Humphrey Rang.
• https://www.ncbi.nlm.nih.gov/books/NBK8191/#:~:text=Pathogenesis%3A
%20direct%20damage%20caused%20by,suck%20blood%20from%20muc
osal%20capillaries.
35

36. Thank You