Anthelmintics - drdhriti

Anthelmintics
Dr. D. K. Brahma
Department of Pharmacology
NEIGRIHMS, Shillong

Introduction
• Anti – against and helminths – worms
• May be
 Vermicide – Drugs that kill worms
 Vermifuge – expel infesting helminths
 Peristaltic movement of Intestine
 Cathartic and purgative action

 Ideal anthelmintics:
 Orally effective
 Effective in single dose
 Inexpensive
 Wide safety of margin with highest toxicity to worms, but lesser toxic to the
host

Common Helminths
• Roundworm: Ascaris lumbricoides
• Hookworm: Ancylostoma duodenale and Necater
americanus
• Threadworm: Enterobius vermicularis and
Strongyloides stercoralis
• Whipworm: Trichuris trichiuria and Trichinella spiralis
• Filaria: W. Bancrofti, Brugia malayi
• Tapeworms: T. saginata, T. solium, H. nana
• Hydatid disease: E granulosus and E multilocuralis
• Guniea worm: Dracunculus medinensis

Available Drugs
1) Mebendazole
2) Albendazole
3) Pyrantel pamoate
4) Piperazine
5) Levamisole and tetramisole
6) Diethyl carbamazine citrate (DEC)
7) Ivermectin
8) Niclosamide
9) Praziquantel

Mebendazole
• Synthetic benzimidazole derivative
• Action:
o 100% cure rate for round worm, hook worm, enterobius (less for
Strongyloides) and trichuris (not for tissue Trichinella spiralis)
o 75% effective for tape worms but not for H. nana
o Hadatid cyst: prolonged treatment
o Hatching of nematode eggs and larva inhibited and Ascaris eggs are
killed

• MOA:
o Slow in action, takes 2-3 days to develop
o Blocks glucose uptake in the parasite and depletion of glycogen store
o Site of action: microtubular protein “ß-tubulin” – inhibits polymerization
o Intracellular mictotubules are grdually lost

Mebendazole – contd.
• Pharmacokinetics: Minimal absorption, 75-90% is passed
unabsorbed in the faeces. Excreted mainly in urine as
inactive metabolite

• Adverse effects:
o No adverse effects with short term therapy, mild GIT disturbanes-
nausea, diarrhoea and abdominal pain
o Allergic reactions, granulocytopenia, loss of hair and elevation of liver enzymes
o Enzyme inducers and inhibitors
o Pregnancy - ????

• Uses: Available as 100 mg chewable tablet and
100mg/ml suspension
o Common indications: 100 mg twice daily for 3 days
o Enterobius 100 mg single dose + repeat after 2-3 weeks
o Trichinella spiralis – 200 mg twice daily for 4 days Albendazole
o Hydatid cyst: 200-400 mg twice daily for 3-4 weeks
preferred

Albendazole
• Congener of Mebendazole
• Action: comparable efficacy with mebendazole for
round worm, hook worm and enterobius
o Less effective against trichuris
o But, more effective against strongyloides
o Trichinella effectiveness is almost same
o More effective in tape worm (including H. nana) and hydatid larvae and ova
of ascaris and hook worm
o Weak microfilarial action and cutaneous larva migrans
• Pharmacokinetics: Moderate and inconsistent oral
absorption
o Fatty meals enhance absorption
o Fraction absorbed is converted to “sulfoxide” metabolite – active
o Its active and penetrates brain with t1/2 of 8-9 Hrs – BASIS of TISSUE
Anthelmintic action
o For intesinal worm given in empty stomach and for tissue action – with fatty
meals

Albendazole – contd.
• Uses and dosage: Available as 400 mg tablet and
200 mg/5ml susp.
o Normal dosing: Single dose of 400 mg (200 mg below 2 years)
o Tape worm: 400 mg for 3 days
o Cutaneous larva migrans: treatment of choice - 400 mg for 3 days
o Neurocysticercosis: treatment of choice – 400 mg twice daily for 1-2
weeks
o Hydatid disease: 400 mg BD for 4 weeks, repeat after 2 weeks upto 3
courses. Treatment of choice before and after urgery
o Filariasis: with DEC or Ivermectin – in lymphatic filariasis
o Used in mass programmes – yearly dose for microfilaraemia transmission
o Contraindicated in pregnancy

Pyrantel pamoate
• Originally for thread worm but extended to hook worm
and round worms
• Less active against necater, strongyoides and trichuris
• MOA:
o Activation of nicotininic cholinergic receptors
o Persistent depolarization leding to contracture and spastic paralysis – expelling
of worms
o Piperazine causes flaccid paralysis – antagonizing action
• Pharmacokinetics: Only 10-15% is absorbed
• ADRs: free from ADRs – mild GIT symptoms, tasteless, non-
irritant and abnormal migration to tissues is not provoked
o Safety in pregnancy and children below 2 years not established
• Dose and Uses: 250 mg tabs and 50 mg/ml susp.
o Used in Ascaris, entarobius and ancylostoma – single dose
o 3 days course for necater and strongyloides

Piperazine
• Highly active drug against Ascaris and Enterobius – but
2nd choice drug
• Less/not active against hook worms
• MOA:
o Hyperpolarization of Ascaris muscles GABA agonistic action of Cl- channel
opening
o Decreased responsiveness to ACh contractile response – flaccid paralysis
o Recover – purgation required
o Does not excite Ascaris for abnormal migration
• ADRs: usually well tolerated - nausea, vomiting
o Dizziness and convulsion in high doses
o Contraindicated in renal insufficiency and epileptics
• Uses: Round worm infestation – 4 gm. once a day for 2
days
o Safe in pregnants
o Used in Intestinal obstruction

Levamisole and
Tetramisole
• Effective against any nematodes, but restricted to
Ascriasis and ancylostomiasis
• MOA: 2 mechanisms
o Tonic paralysis of worms and expulsion of live worms - by stimulating
ganglia of worms
o Inhibition of fumerate reductase enzyme: carbohydrate metabolism
interfered

• Dose: 50/100/150 mg single dose
o Ascariasis and A. duodenale
o Immunomodulator
o Safe and well tolerated – mass treatment of round worms

Diethyl carbamazine
citrate (DEC)
• Drug of choice for the treatment of filariasis, loiasis and
tropical eosinophillia
• Pharmacokinetics:
o It is synthetic piprazine derivative
o Rapidly absorbed from gut
o It has a half life of 2-3 hours which increases in alkaline urine to 10 hours
o It is excreted in urine unchanged
o Dosage is reduced in urinary alkalosis and renal impairment
• MOA: 2 mechanisms
o Alteration of Mf membrane – to be readily phagocytosed by tissue monocytes
o Since piperazine derivative – hyperpolarization and muscular weakness
• Uses: 50 mg, 100 mg tabs and susp available
o Filariasis: 2 mg/kg tds X 7 days – improved
• Intermittent microfilaria is problem (100 mg/kg for 3 weeks) – more than 1 course
of therapy in a gap of 3-4 weeks
• Elephantiasis not affected
o Tropical eosinophilia (2-4 mg/kg tds for 2-3 weeks)
• ADRs: Nausea, vomiting, loss of appetite etc.
o Febrile condition – rash, pruritus, enlargement of lymph nodes – withdraw the drug
and start antihistamines and corticosteroids
o Can be minimized by starting low dose

Ivermectin
• Obtained from Streptomyces avermitilis
• Action:
o Drug of choice for Onchocercosis volvulus and Strongyloides and equal to DEC in Filaria
o Also efective against cutaneous larva migrans and ascariasis – also scabies and head lice

• MOA:
o Acts via special type of glutamate gated Cl- channel found only in invertebrates
o Such channels are absent in man, flukes and tape worms – not effective
o Potentiation of GABA activity – paralysis of muscles of worms
• Pharmacokinetics: absorbed well orally, widely distributed but not
in CNS, long half-life – 48 to 60 Hrs

• Uses: 3/6 mg tablets
o Filaria: single dose 0.2 mg per kg with 400 mg Albendazole annually for 5-6 years
o Strongyloides: 0.2 mg/kg single dose
o Replaced DEC in O. volvulous by WHO

• ADRs: Pruritus, giddiness, nausea, abdominal pain and sudden
ECG changes

Niclosamide
• Against tape worms – saginata, solium, latum and
nana
• MOA: Inhibition of oxidative phosphorylation in
mitochondria and interference of anaerobic
generation of ATP
o Injured worms are digested or expelled (purgation)
o But, problem with T. solium – dangerous visceral cysticercosis

• Regimen: available as 0.5 gm tabs.
1. 2 gm stat – repeat after 1 Hr and saline purgation
2. 2 gm daily for 5 days in H. nana infestation

• ADRs: well tolerated, no systemic toxicity and can
be given in pregnancy

Praziquantel
• Novel anthelmintic with wide range of action
• Action: Mainly on Schisosomiasis and other
Trematodes, cestodes but not nematodes
• MOA:
o Rapidly taken up by worms
o Leakage of intracellular Ca++ causing paralysis
o Worms lose grip on intestinal wall including tissues and veins
o Acts against all stages of worms including larvae
o Other MOA – vacuolization of membrane and release of contents of tap
worms
• Pharmacokinetics: Rapidly absorbed and enhanced by
food
o High first pass metabolism
o Crosses BBB and attains therapeutic conc. In CSF
o Phenytoin, carbamazepine and steroids induce metabolism – failure of therapy

Praziquantel – contd.
• ADRs: Bitter in taste, produce nausea and vomiting
and abdominal pain
o Headache, dizziness and sedation
o Urticaria, rash, fever etc- destroyred flukes

• Uses: available as 500 mg/600 mg tabs
o First line of drug in all tape worms except Neurocysticercosis (10-25 mg/kg
per day single dose)
o Neurocysticercosis (50-100mg/kg/day for 2 weeks)
o First line of drug in all schistosome infestations and flikes except Fasciola
hepatica (50-75 mg/kg/day)

NLEM (INDIA) – 2011
• Deleted from 2003: Pyrantel
pamoate, Niclosamide, Mebendazole

• Present 2011: Albendazole, Piperazine and
Praziquintel

Important to learn
• Albendazole
• Piperazine
• DEC in Filariasis
• Ivermectin
• Praziquantel

THANK
YOU
- for the Hygienic
atmosphere

Anthelmintics - drdhriti

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