Section 9/ Chemotherapy 358 It is mainly indicated in mild intestinal amoebiasis and asymptomatic cyst passers It is also used in combination with tinidazole (TINIBA DF) and metronidazole (ENTAMIZOLE) in the treatment of intestinal amoebiasis, hepatic amoebiasis and other systemic diseases due to E histolytica FURAZOLIDONE It is effective against gram negative bacilli e.g Shigella, Salmonella and also effective against Trichomonas and Giardia It is indicated in bacterial enteritis, diarrhoea, giardiasis and bacillary dysentery Adverse effects include nausea, vomiting, headache and dizziness PAROMOMYCIN It is an aminoglycoside antibiotic used only as luminal amoebicide and has no effect against extra intestinal amoebic infections It is less toxic than other agents, but it should be used cautiously in patients with significant renal disease and with gastrointestinal ulcer LEISHMANIASIS Visceral leishmaniasis (kalaazar) is caused by Leishmania donovani and transmitted by Phlebotomus sandfly In human being, it is found intracellularly within macrophages in the nonflagellate form The important drugs used in leishmaniasis are pentamidine, sodium stibogluconate, antifungal antibiotics (amphotericin B and ketoconazole) and antigout agent (allopurinol) PENTAMIDINE Pentamidine is an aromatic diamidine formulated as an isoethionate salt used parenterally (4 mg/kg IM or slow IV injection) It has activity against trypanosomatid protozoans and against Pneumocystis carinii It probably interacts with kinetoplast DNA and inhibits topoisomerase II It is used in the treatment of pneumocystosis (pulmonary and extrapulmonary disease caused by P carinii), African trypanosomiasis (disease caused by Trypanosoma brucei) and leishmaniasis Systemic pentamidine is highly toxic and can lead to severe hypotension, tachycardia, dyspnea, dizziness, hypoglycemia Other adverse effects are skin rash, metallic taste, gastrointestinal symptoms, thrombocytopenia and cardiac arrhythmias SODIUM STIBOGLUCONATE It is pentavalent antimonial It inhibits –SH dependent enzymes and block glycolytic & fatty acid oxidation pathways It is rapidly absorbed after IM injection and excreted unchanged in urine Used in cutaneous and visceral leishmaniasis It is given parenterally (20 mg/kg/day IM/IV) for three weeks in cutaneous leishmaniasis and for four weeks in visceral and mucocutaneous disease Adverse effects include metallic taste headache, fever, rash, myalgia and ECG changes TRYPANOSOMIASIS It is caused by genus Trypanosoma which is characterized by skin eruptions, sus- Antiamoebic and other Antiprotozoal Drugs tained fever, lethargy and lymphadenitis, progressive brain dysfunction Apart from imidazole derivative e.g metronidazole, tinidazole, nimorazole etc and other agents such as hydroxyquinolines, iodine preparation (povidoneiodine) and antifungal antibiotics e.g clotrimazole (used mainly as vaginal pessaries), there are some other compounds which are mainly used in the treatment of trypanosomiasis They are: Suramin Melarsoprol Eflornithine Nifurtimox g each wk for wks IV or g on day 1, 3, 7, 14, 21 3.6 mg/kg/day IV for 3-4 days 100 mg/kg IV every hrs for 14 days 8-10 mg/kg orally 3-4 months SURAMIN It is a sulfated napthylamine and used as first line therapy for early hemolymphatic African trypanosomiasis (caused by T brucei gambiense) It has very tight protein binding and having short initial half life but terminal half life is about 50 days and is excreted by kidney It is also used for chemoprophylaxis against African trypanosomiasis Adverse effects include nausea, vomiting, fatigue, dermatitis, fever, photophobia, haemolytic anaemia, albuminuria and hematuria MELARSOPROL Chemically it is trivalent arsenical used for advanced CNS African trypanosomiasis It is administered IV in propylene glycol and after administration it is rapidly excreted It is highly toxic and used only in advanced trypanosomiasis when no alternative is there Adverse effects include vomiting, fever, abdominal pain, renal and cardiac 359 disease and encephalopathy characterized by cerebral edema, seizures, coma (even death) EFLORNITHINE It is an inhibitor of ornithine decarboxylase and is used as second line therapy for advanced CNS African trypanosomiasis After oral or IV administration, peak plasma level is reached rapidly and elimination half life is approximately three hours It is effective against advanced T brucei gambiense infection Adverse effects include vomiting, diarrhoea, leukopenia, thrombocytopenia, anaemia and seizures NIFURTIMOX Chemically it is nitrofuran, used for American trypanosomiasis which is commonly known as ‘Chagas disease.’ After oral administration, it is well absorbed and plasma half life is about three hours Adverse effects include nausea, vomiting, fever, rash, abdominal pain, neuropathies and seizures TRICHOMONIASIS It is caused by Trichomonas vaginalis and is mainly associated with vulvovaginitis which is characterized by greenish yellow and cheesy vaginal discharge The various agents used in trichomoniasis are metronidazole, tinidazole and secnidazole which are already described earlier They produce 100% cure Other protozoal infection is giardiasis which is caused by Giardia lamblia and the drug of choice in its treatment are imidazole derivatives This page intentionally left blank r r e e t t p p a CChh 9.10 1.4 Pharmacodynamics Anthelmintic Agents (Mode of Action of Drugs) Anthelmintic agents are used to eradicate (either kill or expel) the infesting helminths The important anthelmintic agents along with their specific uses and dosage are listed in table 9.10.1 MEBENDAZOLE It is a synthetic benzimidazole having a wide spectrum of anthelmintic activity After administration it is poorly absorbed and approximately 90 percent of the drug is passed in faeces Complete clearance of the parasites from the GIT may take up to three days Mebendazole binds to microtubular β tubulin’ of parasite and inhibits protein ‘β its polymerization, thus irreversibly impairing glucose uptake Adverse effects include nausea, diarrhoea, abdominal pain Alopecia and granulocytopenia may occur at high doses Poorly absorbed from the GI tract, oral bioavailability being enhanced when given with a fatty meal (up to fold) Its active sulphoxide metabolite is widely distributed throughout the body and is excreted in urine Adverse effects include nausea, vomiting, epigastric distress, abnormal LFTs, reversible alopecia THIABENDAZOLE Apart from anthelmintic property, thiabendazole also possesses antiinflammatory, analgesic and antipyretic actions It also inhibits development of eggs of worms and kills the larvae It is rapidly absorbed, metabolised by hydroxylation and conjugation to inactive metabolites and excreted through kidney Adverse effects include nausea, vomiting, skin rash, anorexia, giddiness, abdominal pain, diarrhoea, fever and headache ALBENDAZOLE LEVAMISOLE Congener of mebendazole It is given only as single dose It is a synthetic imidazothiazole derivative and is highly effective in Section 9/ Chemotherapy 362 Table 9.10.1: Classification of anthelmintic agents Drug(s) Mebendazole (MEBEX) Albendazole (ZENTEL) Thiabendazole (MINTEZOL) Levamisole (DECARIS) Niclosamide (NICLOSAN) Piperazine (as citrate) Pyrantel pamoate Diethyl carbamazine (HETRAZAN) Ivermectin (IVERMECTOL) 10 Praziquantel (CYSTICIDE) Uses and Dose Ascariasis, ankylostomiasis: 100 mg BD × days; Trichuriasis: 400 mg single dose; Pinworm: 100 mg OD & repeat after & weeks; Intestinal capillariasis: 400 mg/d × 21 days; Taeniasis: 300 mg BD × days Ascariasis, ankylostomiasis and trichuriasis: 400 mg single dose; Taeniasis & strongyloidosis: 400 mg × days; Neurocysticercosis: 15 mg/kg/daily × month; Hydatid disease: 400 mg BD × month (if required repeat after wks) Trichinosis and strongyloidosis: 25 mg/kg/day in two divided doses × days after meal (if required repeat after days) Ascariasis and hook worm infestation: 50-150 mg single dose Taeniasis: 0.5-2 g (After breakfast g to be chewed and swallowed with water followed by g after hr); For H nana infestation: g dose is repeated daily for days Ascariasis: 4.5 g OD × days; in children 0.75 g/year of age (max 4.5 g); Enterobiasis: 4.5 g OD, repeat after weeks For Ascaris, enterobius & ancylostoma: 10-15 mg/kg (max g) single dose; Necator and strongyloides: day course Tropical eosinophilia: 4-6 mg/kg BD-TDS × 7-10 days; Filariasis: 6-12 mg/kg OD-BD × 21 days; Also used in prophylaxis of filaria Onchocerciasis: 150 µg/kg single dose Also used in intestinal nematode infection and enterobiasis For scabies and strongyloidiasis: 200 µg/kg single dose Taeniasis: 10 mg/kg single dose; H nana: 15-25 mg/kg single dose; Neurocysticercosis: 50 mg/kg in divided doses × 15 days; Schistosome and other flukes except Fasciola hepatica: 75 mg/kg/day, can be repeated if needed eradicating ascariasis and ancylostomiasis It acts by stimulating ganglia of the worm which results in tonic paralysis, which are subsequently eliminated from the intestines inhibiting anaerobic phosphorylation of ADP by the mitochondria of the parasite It is devoid of any major toxicity except minor gastrointestinal disturbances Adverse effects include nausea, epigastric discomfort, insomnia, dizziness, weakness and drowsiness PIPERAZINE CITRATE It is an alternative drug for treatment of ascariasis and pinworms It possibly exerts its action by antagonizing the action of acetylcholine thus blocking neuromuscular transmission Hence, flaccid paralysis occurs It is considerably absorbed, partly metabolized If taken along with alcohol, it may produce disulfiram like reaction NICLOSAMIDE It is salicylamide derivative, act by ... after hr); For H nana infestation: g dose is repeated daily for days Ascariasis: 4.5 g OD × days; in children 0 .75 g/year of age (max 4.5 g); Enterobiasis: 4.5 g OD, repeat after weeks For Ascaris,... Suramin Melarsoprol Eflornithine Nifurtimox g each wk for wks IV or g on day 1, 3, 7, 14, 21 3.6 mg/kg/day IV for 3-4 days 100 mg/kg IV every hrs for 14 days 8-10 mg/kg orally 3-4 months SURAMIN It... Adverse effects include nausea, epigastric discomfort, insomnia, dizziness, weakness and drowsiness PIPERAZINE CITRATE It is an alternative drug for treatment of ascariasis and pinworms It possibly