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Antihelminthics
Dr. Kaushik Mukhopadhyay
Dept. of PharmacologyESI PGIMSR & ESIC Medical College, Joka
Relative
incidence
of helminth
infections
worldwide
Helminths are macroscopic, multiceullar organism
having their own digestive system, excretory,
reproductive and nervous systems.
Helminths
NEMATHELMINTHS PLATYHELMINTHS
TREMATODES CESTODES
Nematodes
Long, round bodies, unsegmented worms, tapered at both
ends.
Most found primarily in intestine.
Attached to the mucosa and feed host blood and tissue fluid.
EX:
Ascaris lumbricoides (roundworm),
Trichuris trichiura (whipworm),
Enterobius vermicularis (pinworm),
Ancylostoma duodenale & Necator americanes
(hookworms)
Enterobius vermicularis(Pin worm)
Wuchereria bacncrofti (Filarias)
(Nemathelminths)
Platyhelminths
Trematodes (Flukes)
Ex:-
Blood flukes ( Schistosomiasis)
Liver flukes (Clonorchiasis)
Lung Flukes (Paragonimiasis)
Intestinal flukes(Fasciolopsiasis)
Cestodes( Tape worm)
Ex:-
Beef tape worm (Taenia saginata)
Pork tape warm (Taenia solium)
Fish tape worm (Diphyllobothrum latum)
Dwarf tape warm (Hymenolepis nana)
ROUND WORM Hookworm
filariasis Pin worm male, female
Tapeworm whipworm
Onchocerciasis Fasiola hepatica
Antihelminthic Drugs
Antihelminthics
Anti – against and helminths – worms
May be
Vermicide – Drugs that kill worms
Vermifuge – expel infesting helminthes via Peristaltic movement
of Intestine
Ideal anthelmintics:
Orally effective
Effective in single dose
Inexpensive
Wide safety of margin with highest toxicity to worms, but lesser
toxic to the host
Available Drugs
1) Benzimidazoles – Mebendazole, Albendazole
2) Pyrantel pamoate
3) Piperazine
4) Levamisole
5) Diethyl carbamazine citrate (DEC)
6) Ivermectin
7) Niclosamide
8) Praziquantel
Mebendazole
Synthetic benzimidazole derivative
MOA:
inhibition of microtubule polymerization by binding to “ß-
tubulin”
A range of other biochemical changes are found in
nematodes following BZ exposure, including
inhibition of mitochondrial fumarate reductase,
reduced glucose transport,
and uncoupling of oxidative phosphorylation,
Mebendazole – contd.
Pharmacokinetics: Minimal absorption, 75-90% is passed
unabsorbed in the faeces. Excreted mainly in urine as inactive
metabolite
Adverse effects:
No adverse effects with short term therapy, mild GIT
disturbanes- nausea, diarrhoea and abdominal pain
Allergic reactions, granulocytopenia, loss of hair and
elevation of liver enzymes
Uses: Common indications: 100 mg twice daily for 3 days
Enterobius 100 mg single dose + repeat after 2-3 weeks
Trichinella spiralis – 200 mg twice daily for 4 days
Albendazole
Congener of Mebendazole
Pharmacokinetics: Moderate and inconsistent oral
absorption
Fatty meals enhance absorption
Fraction absorbed is converted to “sulfoxide”
metabolite – active
It is active and penetrates brain with t1/2 of 8-9 Hrs –
BASIS of TISSUE Anthelmintic action
For intesinal worm given in empty stomach and for
tissue action – with fatty meals
Albendazole – Uses and dosage
Available as 400 mg tablet and 200 mg/5ml susp.
Normal dosing: Single dose of 400 mg (200 mg below 2
years).
Tape worm: 400 mg for 3 days
Neurocysticercosis: treatment of choice – 400 mg twice
daily for 8-30 days
Hydatid disease: 400 mg BD for 1-6 months (for children,
15 mg/kg per day with a maximum of 800 mg)
Filariasis: with DEC or Ivermectin – in lymphatic filariasis
Used in mass programmes – yearly dose for
microfilaraemia transmission
Pyrantel pamoate
Originally for thread worm but extended to hook worm and round
worms
MOA:
Activation of nicotinic cholinergic receptors
Persistent depolarization leding to contracture and spastic
paralysis – expelling of worms
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
Dose and Uses: 250 mg tabs and 50 mg/ml susp.
Used in Ascaris, entarobius and ancylostoma – single dose
Piperazine
Highly active drug against Ascaris and Enterobius – but 2nd choice
drug
MOA:
Hyperpolarization of Ascaris muscles GABA agonistic action of
Cl- channel opening
Decreased responsiveness to ACh contractile response –
flaccid paralysis
Does not excite Ascaris for abnormal migration
ADRs: usually well tolerated - nausea, vomiting
Dizziness and convulsion in high doses
Contraindicated in renal insufficiency and epileptics
Uses: Round worm infestation – 4 gm. once a day for 2 days
Safe in pregnants
Diethyl carbamazine citrate (DEC) Drug of choice for the treatment of filariasis, loiasis
Pharmacokinetics:
Rapidly absorbed from gut
It is excreted in urine unchanged
MOA: 2 mechanisms
Alteration of Mf membrane – to be readily phagocytosed by tissue monocytes
DEC compromises intracellular processing and transport of certain macromolecules to the plasma membrane
Uses: Filariasis: 2 mg/kg tds X 7 days – improved
Elephantiasis not affected
Tropical eosinophilia (2-4 mg/kg tds for 2-3 weeks)
ADRs: Nausea, vomiting, loss of appetite etc.
Febrile condition – rash, pruritus, enlargement of lymph nodes
Levamisole and Tetramisole
Effective against any nematodes, but restricted to Ascriasis and
ancylostomiasis
MOA: 2 mechanisms
Tonic paralysis of worms and expulsion of live worms - by
stimulating ganglia of worms
Inhibition of fumerate reductase enzyme: carbohydrate
metabolism interfered
Dose:
Ascariasis and A. duodenale
Immunomodulator
Safe and well tolerated – mass treatment of round worms
Ivermectin
Obtained from Streptomyces avermitilis
Action:
Drug of choice for Onchocercosis volvulus and Strongyloides
and equal to DEC in Filaria
Also efective against ascariasis, scabies and head lice
MOA:
Acts via special type of glutamate gated Cl- channel found only
in invertebrates
Such channels are absent in man, flukes and tape worms – not effective
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
Filaria: single dose 0.2 mg per kg with 400 mg Albendazole
annually for 5-6 years
Strongyloides: 0.2 mg/kg single dose
Replaced DEC in O. volvulous by WHO
ADRs: Pruritus, nausea, abdominal pain and sudden ECG changes
Ivermectin…contd
Niclosamide
Against tape worms – saginata, solium, latum and nana
MOA: Inhibition of oxidative phosphorylation in
mitochondria and interference of anaerobic generation
of ATP
Injured worms are digested or expelled (purgation)
But, problem with T. solium – dangerous visceral
cysticercosis
Regimen:
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 Trematodes, cestodes but not nematodes
MOA:
Rapidly taken up by worms
At the lowest effective concentrations, it causes increased
muscular activity, followed by contraction and spastic paralysis
(influx of intracellular Ca++ ).
At slightly higher concentrations, praziquantel causes
tegumental damage and exposes a number of tegumental
antigens
Pharmacokinetics: Rapidly absorbed and enhanced by food
High first pass metabolism
Phenytoin, carbamazepine and steroids induce metabolism –
failure of therapy
Praziquantel – contd.
ADRs: Bitter in taste, produce nausea and vomiting and
abdominal pain
Headache, dizziness and sedation
Urticaria, rash, fever etc- destroyred flukes
Uses: available as 500 mg/600 mg tabs
First line of drug in all tape worms except
Neurocysticercosis (10-25 mg/kg per day single dose)
First line of drug in all schistosome infestations and
flukes except Fasciola hepatica (50-75 mg/kg/day)
Drug of Choice
Albendazole is DOC of all nematodes except –
Enterobiasis (Mebendazole)
Wuchereria & brugia (DEC)
Oncocerca & Strongyloides (ivermectin)
Dracunculus (Metronidazole)
Drug of Choice
Praziquantel is DOC of all trematodes &
cystodes except –
Fasciola hepatica (Bithionol)
Hydatid disease (Albendazole)
Thank You