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ANTIHELMINTICS

Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

Antihelmintics

Drugs used to treat parasitic worm infections: helmintic infections

Unlike protozoa, helminths are large and have complex cellular structures

Drug treatment is very specific It is very important to identify the causative worm Done by finding the parasite ova or larvae in

feces, urine, blood, sputum, or tissue

HELMINTHSNEMATELMINTHS(ROUND)

ROUND.W-ASCARIS.L HOOK W-NECATOR A WHIP W-TRICHURIS T THREAD W-

STRONGYLOIDES.S PIN W-ENTEROBIUS V FILARIASIS-W BANCROFTI ONCHOCERCIASIS-

O.VOLVULUS GUINEA W-

DRACANCULUS M

PLATYHELMINTHS

TREMATODES-FLUKES BLOOD F-

SCISTOSOMIASIS LIVER F-CLONORCHIASIS INTESTINAL F-

FASCIOLOPSIASIS LUNG F-

PARAGONIMIASISCESTODESBEEF TW-T.SAGINATPORK TW-T.SOLIUMFISH TW-DIPHYLLOBO

THRIUM DWARF TW-

HYMENOLEPIS.NANA

LIFE CYCLE OF HELMINTHS

Classification

Against Nematodes-ALBENDAZOLE, MEBENDAZOLEPYRANTEL PAMOATE, LEVIMASOLE, PIPERAZINE,

IVERMECTIN, DIETHYLCARBAMAZINE, THIABENDAZOLE, DOXYCYCLINE

Against trematodesMETRIFONATE, OXAMNIQUINE, BITHIONOL,

TRICLABENDAZOLEAgainst CestodesNICLOSAMIDEAgainst trematodes and Cestodes-PRAZIQUANTEL

Against Nematodes

PYRANTEL PAMOATEMOA-Blocks acetylcholine at the neuromuscular

junction, resulting in paralysis of the worms, which are then expelled through the GI tract

P/K-small amount is absorbed, so high levels are achieved in intestinal walls luminal helminths

Uses –round w, hook w, Pin w—10mg/kgS/E-may cause hypersensitivity reactions, neurological

symptoms (including “worm wobble”) and may precipitate epilepsy.

Against Nematodes

Benzimidazoles (ALBENDAZOLE & MEBENDAZOLE )MOA-binds to beta tubulinprevents

polymerisationbreak down of cytoplasmic microtubulesthey Inhibit uptake of glucose and other nutrients, depletion of glycogen stores decrease of ATPleading to autolysis and death of the parasitic worm

Benzimidazoles -Pharmacokinetics

Mebendazole is absorbed after oral – 10% Fatty meal increases absorption Albendazole,

mebendazoleIt is rapidly metabolised, the products being excreted

in the urine and the bile within 24-48 hours. Single dose for threadworm, BD daily for 3 days for hookworm and roundworm

infestations.Thiabendazole is rapidly absorbed orallyAlbendazole is metabolised extensively by first-pass

metabolism to the sulfoxide so has t1/2 -8-10 hrs

Against nematodes

Benzimidazoles-ADR-Well tolerated, less side effectsIf used for >3months as in hydatid diseaseEpigastric distress, alopacia, insomnia, Teratogenic in

animalsThiabendazole inhibits cellular enzymesof susceptible helminths. Inhibits the helminth-

specific enzyme, fumarate reductaseS/E-Gastrointestinal, neurological and hypersensitivity

reactions, liver damage, and crystallurea may be induced.

LEVAMISOLE

It is effective in infections with the common round-worm as well as hook worm

MOA: It has a nicotine-like action, stimulating and subsequently blocking the neuromuscular junctions. The paralysed worms are then expelled in the faeces. Ova are not killed.

Phamacokinetics:The drug is given orally, is rapidly absorbed and is widely distributed. It

crosses the blood-brain barrier. Side effects:They include gastrointestinal disturbances,

Dizziness and skin eruptions. High concentrations can have nicotinic actions on autonomic

ganglia in the mammalian host. There are some reports of encephalopathy

Piperazine

MOA-It reversibly inhibits neuromuscular transmission in the worm

It probably by acting like GABA/GABA-gated chloride channels in nematode muscle. The paralyzed worms are expelled alive

-used for Ascariasis -4g * 2 daysand Pin worm- 4g * 7 daysADR- nausea, vomiting,

rarely neurotoxic and allergic reactionsnitrosamine metabolite-carcinogenic and

teratogenic potentialD/I- should not be used concurrently with pyrantel pamoate

Ivermectin

It is highly effective broad-spectrum antiparasitic First choice of drug for the treatment of filarial infections

and is very effective in onchocerciasisMOA: It kill the worm by opening glutamate-gated chloride

channels (found only in invertebrates) and increasing Cl- conductance; by binding to a novel allosteric site on the acetylcholine nicotinic receptor to cause an increase in transmission, leading to motor paralysis; or by binding to aminobutyric acid receptors.

Ivermectin

Uses :It has also given good results against W. bancrofti, which causes elephantiasis.

A single dose kills the immature microfilariae of O. volvulus- river blindness

The drug also has activity against infections with some roundworms: common roundworms, whipworms, and threadworms

It works best if repeated at 6–12-month intervals.Side effects: skin rashes, fever, giddiness, headaches

and pains in muscles, joints and lymph glands

Diethylcarbamazine

Diethylcarbamazine is a piperazine deri.It is active in filarial infections caused by W. bancrofti It mainly act by make opsonisation of worm that detected

by our immune systemThe drug is absorbed by oral administration and clear from

body within 48 hrsSide effects Fever, headache, anorexia, malaise,urticaria, vomiting, and asthmatic attacks followingthe first dose are due to products of destruction ofthe parasite, and reactions are minimised by slowincrease in dosage over the first 3 days.

Against cestodes- NICLOSAMIDEMOA: Its action has been ascribed to inhibition of the parasite's

mitochondrial anaerobic phosphorylation of ADP which produces usable energy

The scolex and a proximal segment are irreversibly damaged by the drug

The worm separates from the intestinal wall and is expelledThere is negligible absorption of the drug from the

gastrointestinal tract.Taenia solium, the drug is given in a single dose after a light

meal, followed by a purgative 2 hoursUnwanted effects are few, infrequent and transient. Nausea

and vomiting can occur.

Adverse effects Drowsiness, dizziness, Malaise, anorexia, as well as gastrointestinal upsets.

It is contradicted in pregnant women or nursing mothers. Drug interaction:

Enzyme inducers dexamethasone, phenytoin, and carbamazepine increase metabolism

Cimetidine, known to inhibit cytochrome P-450 isozymes, causes increased praziquantel levels.

NICLOSAMIDE

Against trematodes and Cestodes-PRAZIQUANTELPRAZIQUANTEL-It is the drug of choice for all forms of schistos

and for cestode infections like cysticercosis.

MOA: Permeability of the cell membrane to calcium is increased, causing contracture and paralysis of the both adult worms and larvae.

Pharmacokinetics: It is rapidly absorbed after oral administration and distributes into the cerebrospinal fluid.

S/E-It may cause nausea, headache, dizziness, and drowsiness; it cures with a single dose (or divided doses in one day).

Against trematodes

METRIFONATE, OXAMNIQUINE, BITHIONOL, TRICLABENDAZOLE

MIRTIFONATE –organophosphorus compound so is cholinesterase inhibitors. It is safe and coast effective for schistosoma infection.It has good oral absorptionOrally active and t1/2 =1-5 hrsS/E-cholinergic side effects

-diarrhoea, tremors, bronchospasmC/I- pregnancy

Against trematodes

OXAMNIQUINE-tertahydroquinoline dervtUsed against Scistosoma mansoniIt is the drug of choice for all forms of schistosomiasis

-given orallyMOA- flukes esterifies drug to produce reactive

metabolite that alkylates DNA of flukes. It intercalated with parasite DNA and inactivate it

S/E- CNS-drowsiness, dizziness pruritis, urticaria

Against trematodes

BITHIONOL-orally well absorbedDOC-for fascioliasis(sheep liver fluke)

30-50mg for 10-15 days on alternate daysADR- anorexia, nausea, vomiting

avoided in children below 8yrsTRICLABENDAZOLE

narrow spectrum benzimidazoleDOC for treating human fasciola hepatica

Worms (helminths) Drug of choice

Tapeworms (cestodes) Niclosamide or Praziquantel or Albendazole

Roundworms (nematodes)•Enterobius vermicularis (pinworm)•Ascaris lumbricoides•Trichuris trichiura (whipworm)•Trichinella spiralis (trichinellosis)

•Strongyloides stercoralis•Necator americanus (hookworm)•Ancylostoma duodenale

•Onchocerca volvulus (Onchocercosis)•Wuchereria bancrofti (Elephantiasis)

Mebendazole or PyrantelMebendazole or PyrantelMebendazole or AlbendazoleMebendazoleand ThiabendazoleThiabendazoleMebendazole or PyrantelMebendazole, Pyrantel, or AlbendazoleIvermectinDiethylcarbamazine

Flukes (trematodes)•Schistzoma (Schistozomes) Praziquantel

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