Antihelminthics

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