Drugs for helminthiasis.

1. DRUGS FOR HELMINTHIASIS
Presented by:- Lingaraj .V. Anawal
M Pharm
Department of Pharmacology
H.S.K College of Pharmacy. B.G.K
1

2. Anthelmintic are drugs used in the
treatment of Infection with helminths in the intestinal tract
or tissues of the body.
Anthelmintics that kill worms are called
vermicides and those that help to expel the worms are
called vermifuges.
2Goodman & Gilman’s. The Pharmacological Basis of Therapeutics. 12th edition.

3. ANTIHELMINTHS DRUGS
Roundworms Whipworm Tape worms Hydatid
disease Trichinella spiralis Praziquantel Albendazole
Hookworm Albendzole Niclosamide Mebendazole
Pinworm Mebendazole Albendazole
Mebendazole
Albendazole
Pyrantel pamoate
levamisole
Piperazine
Filariasis Threadworm
Diethylcarbamazine citrate Ivermectin
Ivermectin Albendazole
Albendazole
3
Essentials of Medical Pharmacology. K.D. Tripathi 8th edition.

4. WORM FIRST CHOICE DRUGS ALTERVATIVE 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(oxyuris)
Vermicularis
Pyrantel,
Mebendazole,
Albendazole
Piperazine
THREAD WORM
Strongyloides stercoralis
Ivermectin Albendazole
WHIP WORM
Trichuris trichura
Trichinella spiralis
Albendazole
Mebendazole
Albendazole
Mebendazole
FILARIA
Wuchereria bancrofti,
Brugia malayi
Diethyl carbamazine
Ivermectin
Albendazole
4
Essentials of Medical Pharmacology. K.D. Tripathi 8th edition.

5. WORM FIRST CHOICE DRUGS ALTERVATIVE DRUGS
GUINEAWORM
Dracunculus medinesis Metrondizole Mebendazole
TAPEWORMS
(Cestodes)
Taenia saginata
Taenia solium
Hymenolepis nana
Neurocysticercosis
Praziquantel
Praziquantel
Praziquantel
Albendazole
Niclosamide
Niclosamide
Niclosamide
Praziquantel
HYDATID DISEASE
Echinococcus granulosus
E. Multilocularis
Albendazole
Albendazole
Mebendazole
5Essentials of Medical Pharmacology. K.D. Tripathi 8th edition.

6. Mebendazole (Mebendazole is a Benzimidazole compound)
It is a Benzimidazole introduced in 1972. This congener of thiabendazole became
very popular because it retained the broad-spectrum anthelmintic activity.
Pharmacokinetics
 Mebendazole is administered orally.
 poorly absorbed from the GI tract.
 highly bound to plasma proteins and.
 metabolized in liver.
 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
Mebendazole is well tolerated even by patients in poor health and rarely causes
GIT side effects anorexia, nausea, vomiting, diarrhea, and abdominal Pain
But occasionally it may cause skin rashes, itching, drug fever, etc.
Dose:- 100mg chewable tablet, 100mg/5ml suspension, 100mg tablet.
6

7. Albendazole (Albendazole is a Benzimidazole compound)
It is benzimidazole and has broad spectrum of anthelmintic activity.
Pharmacokinetics
Absorption of albendazole after oral administration is significant, but inconsistent.
It is enhanced when the drug is taken with fatty meal (this may help in treating
neurocysticercosis and hydatid disease).
Side effects
Albendazole is well tolerated; only gastrointestinal side effects have been
noted. Few patients have felt dizziness.
Prolonged use, as in hydatid or in cysticercosis, has caused headache, fever,
alopecia(loss of hair), jaundice and neutropenia, nausea, vomiting,
epigastric, distress.
Dose and administration
 Single oral dose of 400mg for adults and childrens >2 years of age,
 200mg of single dose for children between 1 -2 yrs of age. No fasting or purging
required.
Uses
Trichinosis, Neurocysticercosis, Cutaneous larva migrans, Hydatid disease, Filariasis. 7

8. Albendazole
Ascariasis, Trichuriasis, and Hookworm and Pinworm Infections
For adults and children older than 2 years of age with ascariasis and
hookworm infections, the treatment is a single dose of 400 mg orally
(repeated for 2–3 days for heavy ascaris infections and in 2 weeks
for pinworm infections)
Hydatid Disease Dosing is 400 mg twice daily with meals for 1 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 organism. Albendazole
is given in a dosage of 400 mg twice a day for up to 21 day.
Other Infections Albendazole is the drug of choice in the treatment of
Cutaneous larva migrans (400 mg daily for 3 days),
Visceral larva migrans (400 mg twice daily for 5 days),
Intestinal capillariasis (400 mg daily for 10 days),
Microsporidial infections (400 mg twice daily for 2 weeks or longer),
Gnathostomiasis (400 mg twice daily for 3 weeks).
It also has activity against trichinosis (400 mg twice daily for 1–2 weeks) &
Clonorchiasis (400 mg twice daily for 1 week).
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9. Thiabendazole (Thiabendazole is a Benzimidazole compound)
A Benzimidazole, thiabendazole has broad spectrum of anthelmintic activity and
effective against most of the nematodes.
Thiabendazole is an alternative to ivermectin or albendazole for the treatment of
strongyloidiasis and cutaneous larva migrans.
Although it is a chelating agent that forms stable complexes with a number of
metals, including iron, it does not bind calcium.
The drug is almost completely metabolized in the liver to the 5-hydroxy form; 90% is
excreted in the urine in 48 hours, largely as the glucuronide or sulfonate conjugate.
Clinical Uses
The standard dosage, 25 mg/kg twice daily, should be given after meals.
Tablets should be chewed. For strongyloides infection, treatment is for 2 days.
Cure rates are reportedly 93%.
A course can be repeated in 1 week if indicated. In patients with hyperinfection
syndrome, the standard dose is continued twice daily for 5–7 days. For cutaneous
larva migrans, thiabendazole cream can be applied topically, or the oral drug can be
given for 2 days (although albendazole is less toxic and therefore preferred).
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10. Adverse effects:-
dizziness, anorexia, nausea, and vomiting, epigastric pain, abdominal
cramps, diarrhea, headache, drowsiness, and neuropsychiatric
symptoms.
Irreversible liver failure and fatal Stevens-Johnson syndrome have
been reported.
Experience with thiabendazole is limited in children weighing less
than 15kg. The drug should not be used in pregnancy or in the
presence of hepatic or renal disease.
MOA is similarly to Mebendazole and
Albendazole. rarely used because of
it is toxicity.
10

11. MOA of Benzimidazole (Mebendazole, Albendazole, Thiabendazole)
11

12. Pyrantel Pamoate
Pyrantel pamoate first was introduced into veterinary practice as a
broad-spectrum anthelmintic directed against pinworm, roundworm,
and hookworm infections.
Its effectiveness and lack of toxicity led to its trial against related
intestinal helminths in humans.
Pharmacokinetics
Pyrantel pamote is given orally but absorbed poorly(10-15%), about
80-90% of oral dose is excreted in faeces.
Side effects
Occasional G.I symptoms, headache and dizziness. It is tasteless,
Nonirritant, abnormal migration of worms is not provoked, nausea,
diarrhea, skin rashes, fever. 12

13. MOA Pyrantel pamoate inhibits cholinesterases in worms
stimulates nicotinic Ach concentration
receptors in the worm
persistent depolarisation(Na+, K+ )
spastic paralysis
worms are expelled(vermifuge)
Use and administration
Single dose of 10/11 mg/kg to maximum of 1g is recommended.
NOTE:- Pyrantel pamoate has not been studied in pregnanat women.
Thus its use in pregnant patients and children <2 years of age is not
recommanded. 13

14. Pyrantel pamoate
By stimulating the release of acetylcholine, inhibiting cholinesterase,
and stimulating ganglionic neurons, pyrantel acts as a depolarizing
neuromuscular blocking agent in helminthes.
These actions cause extensive depolarization of the helminth muscle
membrane, producing tension of the helminth's muscles, which
causes paralysis and release of their hold to the intestinal wall.
This action is unlike piperazine, which is a hyperpolarizing
neuromuscular blocking agent that relaxes helminth muscles, causing
a subsequent detachment from the intestinal wall. Expulsion of the
parasites from the GI tract occurs by normal peristalsis.
Precautions
When given parenterally to experiment animals, pyrantel can
produce complete neuromuscular blockade; only very large oral
doses produces toxic effects. 14

15. Diethylcarbamazine citrate (DEC)
Developed in 1948, it is the first drug for filariasis caused by
the nematodes Wuchereria bancroft (90% cases) and Brugia malayi.
Diethylcarbamazine is most effective drug in the treatment of
filariasis and tropical eosinophilia.
DEC is available as citrate salt.
It acts mainly on microfilaria but the adult worms are killed slowly
only on long-term treatment.
DEC damages the microfilaria membrane structure so that they are
destroyed by host defences.
The MOA of DEC against susceptible filarial species is not well
understood but the drug appears to exert a direct effect on
W. bancrofti microfilariae by causing organelle damage and apoptosis.
The MOA of filaricidal action of DEC against adult worms is unknown.
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16. Pharmacokinetics
 Well absorbed from GI tract,
 Widely distributed in body metabolized in liver and excreted
in urine.
Side effects
 Drug induced effects- Vomiting, headache, and dizziness
 Parasite induced reaction- Due to release of protein from dying
parasites.
 Diethylcarbamazine(DEC)- Produce a severe reaction,
characterized by severe itching, fever, skin rashes, nausea,
vomiting, headache, joint pain, lymphadenitis,
keratisis(inflammation of cornea).
Uses
Filariasis, Tropical pulmonary eosinophilia. 16

17. Clinical uses
Wuchereria bancrofti, Brugia malayi, Brugia timori, and Loa loa
These infections are treated for 2 or (for L loa) 3 weeks, with initial
low doses to reduce the incidence of allergic reactions to dying
microfilariae. This regimen is 50 mg (1 mg/kg in children) on day 1,
three 50 mg doses on day 2, three 100 mg doses (2 mg/kg in
children) on day 3, and then 2 mg/kg three times daily to complete
the 2–3 week course. Diethylcarbamazine may also be used for
chemoprophylaxis (300 mg weekly or 300 mg on 3 successive days
each month for loiasis; 50 mg monthly for bancroftian and Malayan
filariasis)
Other uses
Diethylcarbamazine is given orally at a dosage of 2mg/kg 3 times a
daily for 7 days.
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18. 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.
MOA
Ivermectin
Activates glutamate-gated chloride channels
Increases GABA(-aminobutyric acid) transmission in worms
Hyperpolarisation and paralysis of worms
Death/phagocytises of worms
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19. MOA OF IVERMECTIN
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20. Pharmacokinetics
It is given orally rapidly absorbed widely distributed to various tissues
metabolized in the liver and excreted mainly in faeces
Uses
Onchocerciasis/river blindness(caused by bites of infected simulius blackflies)
Kills microfilaria but has little effective in stronglyoidiasis, ascarais,
and cutaneous larva migrans. Treatment of scabies and pediculosis.
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.
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21. Niclosamide
Niclosamide is a highly effective drug against cestodes infesting man—
Taenia saginata, T. solium, Diphyllobothrium latum and
Hymenolepis nana, as well as pin worm.
The drug MOA appears to act by inhibiting oxidative phosphorylation
in mitochondria and interfering with anaerobic generation of ATP by
the tapeworm.
Adverse effects
Niclosamide is tasteless and nonirritating.
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
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22. Mitochondria
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MOA OF NICLOSAMIDE
Clinical Uses
The adult dose of Niclosamide is 2g once, given in the morning on an
empty stomach. The tablets must be chewed thoroughly and then
swallowed with water.

23. Praziquantel
It is effective in the treatment of trematodes and cestodes but
not for Nematodes.
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.
AD effects- Dizziness, nausea, vomiting, abdominal discomfort,
headache, drowsiness, skin rashes, itching, muscle and joint pain.
Uses
Schistosomiasis
Tapeworm infection
Neurocysticercosis.
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24. Clinical Uses
Praziquantel tablets are taken with liquid after a meal they should be
swallowed without chewing because their bitter taste can induce vomiting.
Schistosomiasis
Praziquantel is the drug of choice for all forms of schistosomiasis.
The dosage is 20 mg/kg per dose for two or three doses at intervals of
4–6 hours. High cure rates (75–95%) are achieved when patients are
evaluated at 3–6 months; there is marked reduction in egg counts in
those not cured.
Clonorchiasis, Opisthorchiasis, and Paragonimiasis
Standard dosing is 25 mg/kg three times daily for 2 days for each of these
fluke infections.
Taeniasis and Diphyllobothriasis
A single dose of praziquantel, 5–10 mg/kg, results in nearly 100% cure rates
for T saginata , T solium , and D latum infections. Because praziquantel
does not kill eggs.
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25. Neurocysticercosis
The praziquantel dosage is 100mg/kg/d in three divided doses for
1 day, then 50mg/kg/d to complete a 2 to 4 week course.
Hymenolepis nana
Praziquantel is the drug of choice for H nana infections and the
first drug to be highly effective.
A single dose of 25 mg/kg is taken initially and repeated in 1 week.
Other Parasites
Limited trials at a dosage of 25 mg/kg three times daily for 1–2 days
indicate effectiveness of praziquantel against fasciolopsiasis,
metagonimiasis, and other forms of heterophyiasis.
Praziquantel was not effective for fascioliasis, however, even at
dosages as high as 25 mg/kg three times daily for 3–7 days.
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26. Praziquantel
It is effective in the treatment of trematodes and cestodes but not for
Nematodes.
The mode of action is not exactly known at present, but experimental evidence
shows following mechanism.
MOA
Praziquantel
influx of ca2+ into the tegument
increased muscular contraction and spastic paralysis
At higher concentration
damage tegument
death of the parasite
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27. MOA OF PRAZIQUANTEL
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28. Metroimdazole:-
Metronidazole is an antibiotic that is used to treat a wide variety of
infections.
It works by stopping the growth of certain bacteria and parasites.
This antibiotic treats only certain bacterial and parasitic infections.
It will not work for viral infections (such as common cold, flu).
Metronidazole is of the nitroimidazole class.
Side effects:-Nausea, a metallic taste, loss of appetite, and
headaches. Occasionally seizures or allergies to the medication may
occur.
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29. METROIMIDAZOLE
Metronidazole diffuses into the organism, inhibits protein synthesis
by interacting with DNA and causing a loss of helical DNA structure
and strand breakage. Therefore, it causes cell death in susceptible
organisms.
It inhibits nucleic acid synthesis by disrupting the DNA of microbial
cells.
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30. PIPERAZINE
Piperazine can be used to treat infections with the common
roundworm (Ascaris lumbricoides) and the threadworm (Enterobius
vermicularis).
Piperazine is given orally and some, But not all is absorbed.
It is partly metabolised, and the remainder is eliminated, unchanged,
via the kidney.
The drug has little pharmacological action in the host. When used to
treat roundworm, piperazine is effective in a single dose.
For thread worm, a longer course (7 days) at lower dosage is
necessary.
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31. Side effects:- gastrointestinal disturbances, and bronchospasm occur
occasionally, and some patients experience dizziness.
The drug should not be given to pregnant patients or to those with
compromised renal or hepatic function.
MOA
It reversibly inhibits neuromuscular transmission in the worm,
probably by acting like GABA, the inhibitory neurotransmitter, or
GABA-gated chloride channels in nematode muscle.
The paralysed worms are expelled alive by normal intestinal
peristaltic movements.
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32. Reference:-
 Essential medical pharamcology 8th edition by KD Tripathi page no
906-914.
 Basic & Clinical Pharmacology 12th edition by Bertram G.
Katzung,Susan B. Masters, Anthony J. Trevor. Chapter 53 clinical
pharmacology of the antihelminthic drugs Philip J. Rosenthal MD
page no;937-947.
 Goodman & Gilman’s The pharmacological basis of therapeutics
page no;1443-1451.
 Modern pharmacology with clinical application 5th edition by
Charles R. Craig & Robert E. Stitzel page no;621.
 Rang and Dale’s Pharmacology 6th edition pageno;712-717.
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33. THANK U
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