Tiêu đề 17. PHARMACOLOGY OF ANTHELMINTIC DRUGS.pdf ✅

PHARMD GURU Page 1 Anthelmintics are drugs used in the treatment of infestation with helminths in the intestinal tract or tissues of the body (Table 11.27). Anthelmintics that kill worms are called vermicides and those that help to expel the worms are called vermifuges. PHARMACOLOGY OF ANTHELMINTIC DRUGS
PHARMD GURU Page 2 DRUGS USED TO TREAT HELMINTHIASIS:  Mebendazole  Albendazole  Niclosamide  Ivermectin  Pyrantel pamoate  Levamisole  Praziquantel  Diethylcarbamazine citrate MEBENDAZOLE: Mebendazole is a benzimidazole and has a broad spectrum of anthelmintic activity. It binds to β-tubulin and inhibits microtubule polymerization. It also blocks glucose transport into the parasite. As a result, intestinal parasites are immobilized or die slowly. PHARMACOKINETICS: Mebendazole is administered orally, poorly absorbed from the GI tract, highly bound to plasma proteins and metabolized in liver. Most of the oral dose is excreted in faeces. ADVERSE EFFECTS: Systemic toxicity of mebendazole is low because of its poor absorption. It is well tolerated and rarely causes GI side effects – anorexia, nausea, vomiting, diarrhoea and abdominal discomfort. Occasionally, it may cause skin rashes, itching, drug fever, etc. It is contraindicated in pregnancy and children younger than 1 year. USES: Mebendazole is highly effective against intestinal nematodes – roundworm, hookworm, whipworm, pinworm and mixed worm infestations. It is more effective than albendazole in trichuriasis. DOSE AND ADMINISTRATION: Mebendazole 100 mg orally b.d. for 3 days. It does not require fasting or purging, is well tolerated and is relatively cheap.
PHARMD GURU Page 3 ALBENDAZOLE: It is also a benzimidazole and has a broad spectrum of anthelmintic activity. The mechanism of action is similar to that of mebendazole. PHARMACOKINETICS: Albendazole is given orally. It is erratically absorbed – fatty food increases its absorption; it is metabolized in liver. It produces an active metabolite, albendazole sulphoxide, which is widely distributed into various tissues including hydatid cyst. Hence, albendazole is preferred to mebendazole in the treatment of hydatid disease. ADVERSE EFFECTS: Albendazole is very well tolerated. The side effects are rare, but can cause nausea, vomiting, diarrhoea and epigastric distress. During long-term therapy, it may cause hepatic dysfunction, headache, dizziness, fever, weakness, loss of hair and neutropenia. DOSE AND ADMINISTRATION: It can be taken as a single oral dose of 400 mg for adults and children older than 2 years, and as 200 mg single dose for children between 1 and 2 years of age. It is taken at any time of the day, does not require fasting or purging and side effects are rare. USES: 1. Nematodes: Albendazole is highly effective against intestinal nematodes – roundworm, hookworm, whipworm, pinworm and threadworm – and also in mixed worm infestations. It is more effective than mebendazole in trichinosis. 2. Neurocysticercosis: Both albendazole and praziquantel are highly effective in neurocysticercosis. But albendazole is preferred to praziquantel because of the following reasons: (a) It is cheaper. (b)Duration of treatment is shorter. (c) It reaches high concentration in brain and CSF. (d)It is less toxic and better tolerated.
PHARMD GURU Page 4 (e) Glucocorticoids increase plasma levels of albendazole sulphoxide but decrease plasma praziquantel levels. High doses of glucocorticoids are usually given with albendazole or praziquantel to minimize the inflammatory reactions to dying parasites. Drug treatment is contraindicated in ocular cysticercosis – blindness can occur due to inflammatory reaction. 3. Hydatid disease: In hydatid cyst, surgical resection is the treatment of choice, but albendazole is the drug of choice for medical therapy. 4. Filariasis: Single dose of (400 mg) albendazole is given with diethylcarbamazine citrate (DEC) or ivermectin in the treatment of lymphatic filariasis. Albendazole has adjuvant value. Albendazole is also effective in cutaneous larva migrans. THIABENDAZOLE: A benzimidazole, thiabendazole has a broad spectrum of anthelmintic activity and is effective against most of the nematodes. The mechanism of action is similar to that of mebendazole and albendazole. It is rarely used because of high incidence of toxicity. PIPERAZINE: It is effective against roundworm and pinworm. It causes flaccid paralysis of worms that are later expelled by peristaltic movements. It is partly absorbed and most of the drug is excreted unchanged in urine. ADVERSE EFFECTS: The adverse effects include nausea, vomiting, abdominal pain, skin rashes and dizziness. It occasionally produces convulsions and is contraindicated in patients with epilepsy. It is safe for use during pregnancy. LEVAMISOLE: It is effective against roundworm and hookworm infestations. It is an immunomodulator. It is also used as an adjunct in rheumatoid arthritis and cancer chemotherapy.