Helminthiasis

Helminthiasis

1. KARNATAKA COLLEGE OF PHARMACY DRUGS USED FOR TREATMENT OF HELMINTHIASIS SUBMITTED TO SUBMITTED by Mrs Kusu Susan Cyriac Rajahmad N adaf ASSISTANT PROFESSOR 1 ST M.PHARMA DEPARTMENT OF PHARMACOLOGY DEPARTMENT pharmacology

2. Helminthiasis A disease in which part of the body is infested with one or more intestinal parasitic worms such as roundworm, tapeworms or flukes. In human body GIT is the abode of many helmintics ,but some also live in tissues or their larvae migrate into the tissues. They harm the host by depriving him of food ,causing blood loss ,injury to organs ,intestinal or lymphatic obstruction and by secreting toxins . Helminths have a complex life cycle, often involving several host species. Infection may occur in many ways, with poor hygiene a major contributory factor.

3. Symptoms Clinical symptoms arise mainly due to the toxins production . • Acute or chronic blood loss leading to anemia . • Dysentery, Diarrhoea • Abdominal pain • Subcutaneous nodules • Allergic Reactions, Urticaria • Injury to the visceral organs • Intestinal or lymphatic obstruction • Conjunctivitis, Retinitis, Blindness • Hepatosplenomegaly

4. 1)Nemathelminths (round bodied worms) (Nematodes ,roundworms)

5. 2. Platyhelminthes (flat-bodied worms ) (flatworms , tapeworms ) (more intestinal parasitic worms such as roundworm)

6. INTESTINAL WORMS Beef tape worms ( taenia saginata ) Pork tape worms ( taenia solium ) Fish tape worms ( diphyllobothrium latom ) Dwarf tape worms ( hymenolepis nana ) Intestinal roundworms(ascaris lumbricoides)

7. Worms living in other tissues Includes: Blood flukes (schistosomiasis) Liver flukes ( clonorchiasis ) Tissue flukes (trichinella spiralis, filariae- wucherreia bancrofti , loa loa , brugia malayi ) Lung flukes (paragonimiasis) Hydatid tapeworm

8. Life cycle of helminth

9. Anti Helmintics Drugs Classification A. Benzimidazoles: albendazole, mebendazole, thiabendazole B. Pryantel pamoate C. Diethyl carbamazine D. Ivermectin E. Levamisole F. Salicylanilides : Niclosamide G. Praziquantel

10. MEBENDAZOLE : Hook worm (Nectar americanus) Round worm (Ascariasis lumbricoides) Whip worm (Trichuris trichuria ) Pin worm (Enterobius vermicularis) tape worms Moa : Interfere with microtubules synthesis will leads to stop the mitosis & also decreases the glucose uptake. Affected parasites are expelled out from the faeces. P/k Absorption of mebendazole from intestines is minimal; 75–90% of an oral dose is passed in the faeces . The fraction absorbed is excreted mainly as inactive metabolites in urine/ faeces . ADVERSE EFFECTS : Diahorrea , Abdominal pain (nausea). CONTRA INDICATIONS : In(safety ) pregnant woman (not known), because it shown to be embryotoxic & teratogenic in experimental animals. Uses ; multiple infestations Trichinosis Hydatid disease Guinea worm

11. Albendazole Single dose is enough in many cases. Eg : Ascariasis, Hookworm and Enterobiasis . (3 day treatment with mebendazole) Superior to Mebendazole in Strongyloidosis , Hookworm, Hydatid disease. But, inferior in Trichuriasis . MOA: Similar to that of Mebendazole. p/k ; converted by first pass metabolism , distributed in the body, enters brain and is excreted in urine. ADRS : • GI side effects • Dizziness in few cases • headache, fever, alopecia, jundice , neutropenia in prolonged use Note: It should be given in empty stomach for intestinal worms but for cysticercosis , hydatid disease and cutaneous larva margins it should be given with fatty meal. Uses : Ascaris, Hook worm, Enterobius, Trichuris infestations. Tapeworm and strongyloidosis •Neurocysticercosis •Cutaneous Larva migrans •Hydatid disease •Filariasis

12. Thiabendazole polyantihelmintic , practically covers all species of nematodes. Also inhibits development of egg and kills the worm. MOA : as same of mebendazole relief in cutaneous larva migrans and skeletal muscle symptoms produced by migration of Trichinella spiralis larvae to muscles, because it has antiinflammatory action as well. Symptomatic relief also occurs in guinea worm disease. ADRS : thiabendazole is well absorbed from g.i.t. loss of apatite, headache are common. Impaired alertness, interferes with normal activities Itching, abdominal pain, diarrhea Uses: practically against all nematodes infesting the GIT But, because of frequent side effects and poor patient acceptability it isn’t used regularly these days. It is used only when other better tolerated drugs are in effective.

13. Pyrantel pamoate High and comparable efficacy to that of mebendazole against Ascaris, hookworm, Enterobius. But less active against Strongyloids and inactive against Trichuris . MOA : It causes activation of nAch ( nicotinic cholinergic )receptors in worms resulting in persistent depolarization thus slowly developing and spastic paralysis . Worms are then expelled. Because piperazine causes hyperpolarization and flaccid paralysis, it antagonizes the action of pyrantel. But, have very low affinity to human nAch receptors. ADRS: Almost free of side effects. Occasional GI symptoms, headache, dizziness has been reported. Safe during pregnancy. p/k ; Only 10–15% of an oral dose of pyrantel pamoate is absorbed: this is partly metabolized and excreted in urine.) Uses : For Ascaris, Ancyclostoma , and Enterobius; single dose recommended For Necator and Strongyloides ; 3 day course

14. Diethyl Carbamazine Citrate (DEC) Highly selective effects on microfilariae (mf) MOA : The most important action of DEC appears to be alteration of organelle membranes of the Mf promoting cell death. muscular activity of Mf ( microfilariae ) and adult worms is affected so that they are dislodged. p/k ; absorbed after oral ingestion, distributed all over the body, metabolized in liver and excreted in urine. ADRS : Not serious. Nausea, loss of appetite, headache, weakness and dizziness are usual. Rash, pruritus, lymphadenopathy, hypotension may occur d/t mass mf destruction. (If it occurs DEC is temporarily withheld and antihistamine and/or corticosteroids are given) Uses : • Filariasis: produces rapid symptomatic relief, mf disappears form the blood and patient. Becomes noninfective to mosquito in 7 days. Tropical pulmonary eosinophilia .

15. Ivermectin Extremely potent semisynthetic derivative of antinematodal principle obtained from Streptomyces avermitilis . MOA: It is microfilaricidal but not macrofilaricidal, Ivermectin is also highly effective in cutaneous larva migrans and ascariasis It acts through special type of glutamate gated Cl- channe Potentiation of GABAergic transmission in the worms. The ultimate effect is tonic paralysis in worms. p/k ; absorbed orally , distributed in the body, but does not enter CNS , It is metabolized by CYP3A4 ADRS : Mild side effects; Nausea, abdominal pain, constipation, pruritus, lethargy and transient ECG changes More important are d/t degradation products of MF as in DCE. USES : onchocerciasis and strongyloidosis Highly effective in cutaneous larva migrans and ascaris

16. Levamisole Tetramisole (D) and levamisole (L) are optical isomers. They are active against large number of nematodes but their use is restricted to only ascariasis and ancylostomiasis because of poor action against other worms. MOA: They stimulate ganglia in worms and cause tonic paralysis Interfere with carbohydrate metabolism P/K ; well absorbed orally, widely distributed in the body, but does not enter CNS, sequestrated in liver and fat, and has a long terminal t½ of 48–60 hours. It is metabolized by CYP3A4. ADRS : Nausea, abdominal pain, fatigue, drowsiness or insomnia is low. Uses : Ascariasis Ancylostomiasis as adjuvents in malignancies. Recurrent herpes But recurrent use produces reactions , not used now as immunomodulators. A single 10–15 mg (0.2 mg/kg) oral dose of ivermectin

17. Praziquantel Novel antihelmintic , broad range of activity against trematodes (Schistosomes), cestodes but not nematodes. MOA: Rapidly taken by the susceptible worms and causes leakage of intracellular calcium from membrane contracture and paralysis. Lose of intestinal mucosal grip and are expelled. P/K ; absorbed from intestines , metabolism in liver , excreted chiefly in urine ADRS: Bitter taste, nausea, abdominal pain Headache, dizziness and sedation. Uses : Tapeworm infestations Neurocysticercosis Schistosomes

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