Antihelmintics

Drugs used in the treatment of Helminthiasis

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 INTRODUCTION
Anthelmintic Drugs
• Infeksi cacing, atau cacing parasit, mempengaruhi lebih dari dua miliar orang di
seluruh dunia.
• Anthelmintik adalah obat yang dapat membunuh (vermicide) atau mengusir
(vermifuge) cacing yang menginfeksi. Helminthiasis lazim ditemukan secara global
(1/3 dari populasi dunia pernah mengalami).
• Helminthiasis lebih sering terjadi di negara berkembang dengan kebersihan pribadi
dan lingkungan yang buruk.
• Di dalam tubuh manusia, saluran pencernaan adalah tempat tinggal banyak cacing,
tetapi beberapa juga hidup di jaringan, atau larva mereka bermigrasi ke jaringan.
• Mereka membahayakan manusia dengan menghilangkan makanannya, menyebabkan
kehilangan darah, cedera pada organ, obstruksi usus atau limfatik serta dapat juga
mengeluarkan racun.
• Helminthiasis jarang berakibat fatal, tetapi merupakan penyebab utama masalah
kesehatan.
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 EPIDEMIOLOGY

Soil-transmitted helminth infections are widely distributed in tropical and subtropical areas and, since they are linked to a lack of sanitation, occur wherever
there is poverty. Latest estimates indicate that more than 880 million children are in need of treatment for these parasites.

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 HELMINTH

Cacing
- Cacing adalah organisme makroskopik, multisel, memiliki sistem
pencernaan, ekskresi, reproduksi, dan sarafnya sendiri.

Helminthiasis
- Penyakit di mana bagian tubuh terinfeksi satu atau lebih cacing parasit
usus seperti cacing gelang atau cacing pita
- Cacing biasanya menyerang usus tetapi kadang-kadang mereka dapat
menyerang organ lain.

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TYPES

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TYPES

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THERAPY

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 GENERAL MOA

Mechanism of action
Based on mechanism of action in parasites
a. Drugs affecting energy production i. Inhibitors of fumarate reductase
and glucose uptake, binding of tubulin in mitochondria. ii. Inhibitors of
(mitochdrial) phosphorylation iii. Inhibitors of glycolysis
b. Drugs causing paralysis i. Cholinergic agents ii. GABA agonists iii.
Muscle hyperpolarizer iv. Acetyl cholinesterase inhibitors v.
Acetylcholine mimic

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CLASSIFICATION

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 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.

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Cytoskeleton of helminths include
microfilaments, microtubules and beta
tubules. The formation of microtubules is
dependent on polymerisation of beta
tubulins. Albendazole, Mebendazole binds
to the beta tubulins and prevent their
assembly I.e., polymerisation resulting in
breakdown of cytoplasmic microtubules.
Albendazole

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 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.

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 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.

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 Albendazole

• Albendazole, a broad-spectrum oral anthelmintic of Benzimidazoles group

• 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.

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 Albendazole
• Clinical Uses:
– Against intestinal nematodes and cestodes as well as against liver flukes (Trematodes).
–Albendazole is administered on an empty stomach when used against intraluminal parasites
but with a fatty meal when used against tissue parasites.
– DOC for Ascariasis, trichuriasis, hookworm and pinworm infections: 4 0 0 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).
–Hydatid disease: Adjunct to surgical removal or aspiration of cysts. 4 0 0 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 4 0 0 mg twice a
day for up to 21 days.
–Albendazole + DEC or Ivermectin is a synergistic combination for treating or controlling
lymphatic filariasis.
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 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.
Adverse effects: (>3mon)
– 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.
–Use in pregnant women is contraindicated. It should be given with caution to patients with
hepatic or renal disease.

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 Ivermectin

• It is a semi synthetic macrolytic lactone and is a mixture of avermectin B1a and

B1b are obtained from “streptomycin avermitilis”.
M echanism of action:
• Ivermectin targets the parasite’s and activates nematode specific glutamate-
gated chloride channel receptors. Chloride influx is enhanced, and
hyperpolarization occurs, resulting in paralysis and expulsion of the Paralysed
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.

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 Ivermectin
Pharmacokinetics:
• Absorbed from GIT, Wide distribution in the body and excreted in the faeces.
• Dose: 10-15 mg oral dose with 4 0 0 mg of albendazole. Given annually for 5-6
years for filariasis.

Clinical Uses:
• Is the drug of choice for the treatment of onchocerciasis (river blindness) 6 mon,
age >5y, 150mg/kg oral dose with 4 0 0 mg of albendazole, Given annually for 5-6
years for filariasis. strongyloids, Scabies 200mg/kg 2 days.

Adverse effects: Fever, Pruritis, hypertension, tachycardia.

 Ivermectin

Ivermectin for COVID-19 (Corona virus) Treatment: Mechanism of action/ Ivermectin mechanism in
corona virus treatment
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 Praziquantel

It is synthetic isoquinoline and pyrazine derivative.

M echanism of action:
It causes influx in calcium from endogenous stores of the cestodes resulting
in intense contraction and expulsions of the worms from the GIT.
The influx of calcium causes damage to the tegument (in case of flukes)
causing vacolations which expose the antigens which are later destroyed
through phagocytosis.
 Praziquantel

Pharmacokinetics: Readily absorbed orally significant first Pass metabolism in

the liver.
Clinical Uses: DOC for Schistosomiasis (20mg/kg orally BD), In treatment of
tapeworm infestations (10mg/kg orally), in neurocysticercosis.
Adverse effects:
(CNS) Headache, dizziness and drowsiness, (GIT) Nausea, Vomiting & abdominal
pain (dermatological) Pruritis, urticaria, skin rashes with eosinophilia.
 (DEC)
Diethyl carbamazine citrate (DEC)
• DEC developed in 1948, and its is the first drug for filariasis.
• It is a synthetic piperazine derivative.

M echanism of action:
(i) it alters the microfilarial membrane surface characteristics so that they are
subsequently phagocytosed by tissue fixed monocytes.
(ii) It also hyper polarises the worms musculature so that these are expelled.
(iii)It also blocks the production of prostaglandins, resulting in capillary
vasoconstriction and impairment of the passage of microfilariae.

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 (DEC)

Pharmacokinetics:
• 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.
• Dose adjustments are needed in renal impairment.
Clinical Use: Doc for the treatment of Lymphatic filariasis,, Chemoprophylaxis
of loiasis (Loa loa) and filariasis, common regimen 2mg/kg TDS 2-3 weeks,
tropical eosinophilia 2mg/kg TDS 7days.
ADR: ADR is common but not serious. Nausea, vomiting, loss of appetite,
headache, general weakness and dizziness.

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 Piperazine

Piperazine
• Piperazine causes hyperpolarization of Ascaris muscle by GABA agonist action
(opening of chloride channels [1) 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.

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 Pyrantel .p

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.

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 Thiab..zole

• 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

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Obat Hebal

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 REFERENCES

•Pharmacology for medical graduates Third edition by Tara V Shanbhag.

•Goodman & Gilman’s The Pharmacological Basis of THERAPEUTICS
•Essentials of Medical Pharmacology [7th Edition] by KD Tripathi
•Rang and Dale 8th Edition By H.P.Rang, J.M. Ritter

T h a n k You
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