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Infection with parasitic worms (helminthiasis) is a global problem with more than 2 billion people estimated to be affected, though tropical countries demonstrate the maximum prevalence. Common worms encountered include nematodes (round worms), trematodes (flukes), and cestodes (tapeworms).
Hookworms, threadworms, whipworms, and guineaworms are also common culprits in India. In some parts of the country filariasis (due to the nematode Wuchereria bancrofti), echino-coccosis or hydatid disease (due to the tapeworm Echinococcusgranulosis), and cysticercosis (due to the larval form of thetapeworm Cysticercus) are occasionally reported.
The following discussion is centred around the common antihelminthic drugs available in India.
These are broad -spectrum antihelminthic agents, the most popular of which include albendazole, cambendazole, meben-dazole, and thiobendazole.
· Benzimidazoles are effective in the treatment of cutaneous larva migrans (creeping eruption), strongyloidiasis (threadworm infestation), hydatid disease, and infestation due to Enterobius (pinworm), Ancylostoma and Necator (hookworms), Ascaris (roundworm), Trichuris (whipworm) and Taenia solium (tapeworm).
· Mebendazole has also been used as a fungicide for controlling spoilage in citrus fruits and Dutch Elm disease. Thiabendazole has also been used as a fungicidal food preservative.
· Common side effects include nausea, vomiting, and vertigo, while ocasionally there may be diarrhoea, headache, rash, fever, haematuria, and intrahepatic cholestasis. Elevated SGOT, SGPT, alkaline phosphatase, and BUN have been reported during therapeutic treatment with mebenda-zole. Colour vision disturbances and tinnitus have been reported during therapeutic use of thiabendazole. Sicca complex occurs rarely during thiabendazole therapy; symptoms include reduced tear production and dry mouth. Neutropenia and leukopenia are rare side effects with high-dose therapy. Mebendazole and albendazole are less toxic than thiobendazole.
· Animal experiments suggest that these drugs are teratogenic and hence should not be administered to pregnant women.
· Symptomatic and supportive measures.
· Activated charcoal/stomach wash may be helpful in the early stages of an overdose.
· Hepatic injury generally responds to supportive care.
· Monitor for fluid and electrolyte replacement.
It is a piperazine derivative and remains the drug of choice for filariasis and tropical pulmonary eosinophilia, more than 50 years after it was introduced into therapeutics. Diethylcarbamazine is also used in the treatment of loiasis,* onchocerciasis, and ascariasis.
Absorption is rapid after oral administration and toxic effects are uncommon with usual therapeutic doses. Peak plasma concentrations are reached in 1 to 2 hours, followed by a rapid decline, then a secondary rise 3 to 6 hours after dosing. The drug does not distribute in the fat and consequently has a volume of distribution, close to that of body water. It is primarily excreted in the urine as unchanged drug, but a relatively small amount is excreted as the N-oxide metabolite.
Most of the severe clinical effects following diethylcar-bamazine ingestion are due to allergic reactions to the protein substance elaborated by the dying microfilariae and not to diethylcarbamazine alone. The most disturbing adverse effect is the Mazotti reaction which is a result of the host response to destruction of parasites, and is characterised by rash, itching, tender lymphadenopathy, fever, arthralgia, and headache. It usually occurs with the first dose and disappears in 3 to 7 days. Rare toxic effects include encephalitis and retinal haemor-rhages (invariably during the course of treatment of loiasis). Corneal opacities, anterior uveitis, visual field restriction, optic atrophy, punctate keratitis, and chorioretinal changes have been observed when diethylcarbamazine has been administered as eye drops (or even orally) in onchocerciasis. Dose-related responses to diethylcarbamazine, when used for therapy of filariasis, include weakness, dizziness, lethargy, anorexia, and nausea. These effects generally occur within 1 to 2 hours following a dose and may persist for several hours.
In a study of almost 300,000 therapeutic administrations of the drug, approximately 29% of the patients experienced adverse reactions. The WHO no longer recommends the use of diethylcarbamazine for onchocerciasis.
There is no antidote for diethylcarbamazine poisoning.
Treatment is symptomatic and supportive.
Niclosamide is a halogenated salicylanilide derivative which is mainly used in the treatment of tapeworm infestation. Unfortunately, while the drug may kill adult worms, ova are usually unaffected, which may result in cysticercosis due to liberation of viable ova into the lumen of the gut following digestion of dead worm segments. However, niclosamide is a very safe drug and is virtually free from serious side effects.
Piperazine is a cyclic secondary amine which is very effective against roundworm, pinworm, and threadworm infestations. It is also used as a corrosion inhibitor, insecticide, and accelerator for curing polychloroprene.
Piperazine is given orally and acts by inducing flaccid muscle paralysis in the worms facilitating their expulsion by peristalsis. In therapeutic doses piperazine is safe, but overdose results in convulsions, hallucinations, and respiratory failure. The problem is that the margin between therapeutic and toxic dose is very narrow. Toxicity has been reported to develop at doses as low as 30 mg/kg/day in patients with renal failure, and 50 to 75 mg/kg/day in patients with normal renal function. Common effects include nausea, vomiting, confusion, muscular weakness, and ataxia. Treatment involves administration of anticonvulsants and symptomatic measures.
It is a pyrazinoisoquinoline derivative and is effective against tapeworms, liver flukes, and schistosomiasis. Praziquantel displays two major effects: it causes spastic paralysis of worms, and (at higher doses) induces tegumental damage which acti-vates host defence mechanisms resulting in the destruction of the worms.
Side effects include abdominal pain, headache, drowsiness, vertigo, urticaria, rash, fever, and arthralgia. They usually respond to symptomatic measures such as administration of analgesics. Praziquantel is contraindicated in ocular cysticer-cosis since the host response can cause irreversible damage to the eye. Concomitant intake of alcohol can aggravate vertigo that is often associated with this drug.
It is a depolarising neuromuscular blocking agent and causes spastic paralysis of pinworm, roundworm, and hookworm. Adverse effects are mild and comprise headache, drowsiness, insomnia, anorexia, nausea, abdominal cramps, diarrhoea, rash, and occasional dizziness. Transient elevations of serum transaminase levels have been reported in a small percentage of patients. It must not be given along with piperazine because both are mutually antagonistic.
This drug is not in use in Western countries because of the risk of agranulocytosis, but still finds a place in India. Levamisole is effective against roundworms and hookworms. Apart from blood dyscrasias, it can cause hepatic damage, GI distress, and olfactory disturbances. Haematologic toxicity has included neutropenia, anaemia, thrombocytopenia, and fatal cases of agranulocytosis have occurred with therapy. Levamisole also has nicotinic and muscarinic effects at cholinergic receptors. Initially there may be stimulation of the ganglionic and skeletal muscle transmission, followed by blockade. CNS depression, clonic convulsions, and dizziness may occur. An encephalop-athy-like syndrome has developed in some patients during chronic therapy; onset of symptoms is variable. Taste perver-sion, salivation, lip licking, and head shaking have occurred with therapeutic doses. Frequent urination and defaecation have been reported.
Treatment is symptomatic and supportive. Do not admin-ister antacids since levamisole may be better absorbed in an alkaline medium. Atropine may help in some cases of levami-sole toxicity.
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