In The Name Of Allah

In The Name Of Allah

Antiprotosoal Drugs By: Dr. M. Minaiyan Dept. of Pharmacology Isfahan University of medical sciences

Amebiasis • The main pathogen of human amebiasis is E. histolytica • Clinical presentation of infection may be changed from asympthomatic intestinal infection to ameoma and liver abscess

Asympthomatic Amebiasis • Only should be treated in non-endemic areas with a luminal amebicide • Standard luminal amebicides are: Diloxanide furoate (10d), Iodoquinol (21d) • Treatment with luminal amebicide is necessary for curing all other forms of infection • 80-96% of carriage are treated by using above mentioned drugs

Amebic Enterocolitis • In mild to moderate colitis : Metronidazole plus Idoquinole • In severe Colitis: Metronidazole plus Idoquinole which Metronidazole could be substituted with emetine • Course of treatment with metronidazole is 10 days

Liver Abscess & Ameboma • Initial treatment include Metronidazole for 10 days concurrent with a luminacidal agent (Diloxanide furoate or Iodoquinol)

Metronidazole • A nitroimmidazole derivative • Effective on trophozoites but not cysts of parasites • Absorption and distribution are well, mainly metabolized in liver and the metabolites are excreted in the urine • Liver impairment necessitate dose adjustment • Nitro group is reduced to reactive species and then interact with DNA of parasite

Clinical Uses • Amebiasis • Giardiasis: the treatment of choice, especially because of lower doses and duration of treatment (5 days) • Trichomoniasis: 2g as single dose (or 250mgTID for one week) and may be repeated and used in combination with topical form • H. pylori (for 2 weeks) and non-aerobic infections

Adverse Drug Reactions • Most common: nausea, vomiting, diarrhea and metallic taste • Disulfiram like reactions • Interaction with lithium and warfarin • It is best to avoid in pregnancy and lactation

Tinidazole • Have similar activity and a better toxicity profile than metronidazole. • Its half life is about twice (12-14hr) than metronidazole • It offers simpler dosing regimens and can be substituted for the indications listed below. • - Giardiasis • - Trichomoniasis • - Amrbiasis

Iodoquinol • A hallogenated hydroxyquine derivative • Only effective on luminal amebiasis • Less than 10% of drug is absorbed from GI • Main adverse effects are: GI disturbances and Neuropathy • It is best avoided in patients with allergy to iodine, thyroid disorders, optic neuropathy and whom experienced prolonged diarrhea

Diloxanide Furoate • It splits to diloxanide and furoic acid within the lumen • About 90% of drug is absorbed and amebicidal effect in the lumen is due to proportion which was not absorbed • Flatulence is the most common adverse effect but other GI symptoms may occur • It should be avoided in pregnancy

Dihydroemetine • It is an alkaloids extracted from Ipecac • They are alternatives for Metronidazole, when the latter drug should not be used or couldn't be tolerated • Because oral absorption is erratic and intolerable, IM or SC injection are used • Its usage should not be exceeded from 10 days • Drugs should not be used in patients with cardiac arrhythmia,sever renal disease and young children

Anti-leishmania Drugs • Stibogluconate sodium (Pentostam) and Meglumine antimonite (Glucantime) are most common drugs • Both are Antimony 5 derivative and are both effective on various forms of Leishmaniasis • They are used IV, IM or intra -lesional for 21-28 days • They have two half lives; first about 2hrs and second about 24 hrs

Adverse Drug Reactions • GI disturbances • Rash and headache • Sterile abscesses • Myalgia and artheralgia • Cardiac arrhythmia

Anthelmintic Drugs By: Dr. M. Minaiyan Isfahan University of Medical Sciences

Albendazole A benzimidazole carbamate derivative acts by inhibiting microtubules synthesis Its absorption is erratic and will be increased in the presence of fatty meal. Its main metabolite is sulfoxide which in turn penetrates well to target tissues including CNS. Albendazole has both larvicidal and ovicidal effects

Indications It is the drug of choice for the treatment of Hydatid disease Cysticercosis Cutaneous and Visceral larva migrans It is also used in the treatment of Pinworm, Hookworm, Ascaris, Trichuris tricura and Strongyloides infections

Dosage Ascaris, Pinworm, Hookworm, Trichuris tricura: Single oral dose of 400 mg before meal. For sever infections repeated doses for 2-3 days are justified. For Pinworm infections; a more single dose of 400 mg, 2 weeks later is recommended. For Hydatid disease; 400mg/bid for 21 days. For neurocycticercosis 400mg/bid for 21 days + Corticosteroid  Praziquantel is recommended.

Adverse drug reactions, Cautions & Contraindications Free of significant adverse effects for single or 2-3 days doses Fever, Fatigue, Alopecia, Increased levels of liver trans-aminases for prolonged treatments hypersensitivity reactions, cirrhosis, pregnancy and children younger than 2 years of age are conditions that the drug administration is best to be avoided

Mebendazole A benzimidazole derivative with broad spectrum of action and low incidence of adverse effects

Kinetics Less than 10% will be absorbed from GI but its absorption might be enhanced in the presence of fatty meal. Its metabolite is inactive and the parent drug as well as its metabolite are excreted mainly in the urine. The efficacy of Mebendazole is affected by GI transit time and intensity of infection

Dosage and Uses Chewable tabs: Single dose of 100mg for Pinworm which should be repeated 2 weeks later 100mg/bid for 3 days for Ascariasis, Trichuriasis and Hookworms. High doses for prolonged time are used for Trichinosis concurrent with corticosteroids

Niclosamide A salicylamide derivative which acts as second line anthelmintic drug against tape worm infections. It is minimally absorbed from GI in which neither the drug nor its metabolite could be recovered from the blood or urine. Mechanism of action consists: 1.Inhibition of oxidative phosphorylation 2. Stimulation of ATPase activity. Adult worms but not ova are rapidly killed in the presence of Niclosamide.

Uses & Doses Taenia saginata, Taenia solium, D. Latum: 2g as single oral dose at the morning and on an empty stomach. For H. nana, praziquantel is quite superior Niclozamide is not effective against cysticercosis and hydatid disease.

Adverse drug reactions, Cautions & Contraindications Mild and transient GI and CNS adverse effects Disulfiram like reactions even by consuming alcohol for one day afterward.

Piperazine Blocks Ach receptors at myoneural junctions and results in paralysis in Ascaris so adult worms will be expelled by normal peristaltism. Rapid absorption from GI with Tmax of 2-4 hours. Most of the drug is excreted unchanged in the urine which will be completed after 24 hours.

Uses & Doses Ascariasis: 75mg/kg (max=3.5g) orally once daily for 2 days. For heavy Ascaris infections, doses should be continued for 3-4 days or repeated after one week. Pinworm infection: 65mg/kg (max=2g) orally once daily which should be repeated after 2 weeks.

Adverse drug reactions, Cautions & Contraindications Mild to moderate GI and CNS adverse effects It should not be given: 1. during pregnancy. 2. to whom with a history of hepatic or renal failure. 3. to whom with a history of epilepsy and chronic neurologic diseases.

Praziquantel Its main mechanism of action is increased Ca++ ion permeability in cell membranes which results in paralysis, dislocation and death.

Drug & Food Interaction of Praziquantel Increased bioavailability Decreased bioavailability Carbohydrate rich foods Anti-epileptic drugs Cimetidine Corticosteroides Albendazole

Clinical Uses Schistosomiasis, Trematodes, Cestodes, and Cysticercosis infections. The tablets should be taken after meal and without chewing due to its extremely bitter taste and vomiting stimulation. It should be used in together with Corticosteroides to prevent fever and sever allergic & inflammatory reactions to died worms in sever infections.

Uses & Doses H. nana: 25mg/kg on the first day which is repeated one week later. Praziquantel is the drug of choice for this indication. Hydatid disease: Praziquantel kills the protoscoleces but not affect the germinal membrane. Concurrent administration of Praziquantel and Albendazole result in enhanced plasma concentration of Praziquantel in addition to additive direct effects. For cysticercosis, Albendazole is the drug of choice but praziquantel has same efficacy

Adverse drug reactions, Cautions & Contraindications Mild to moderate GI and CNS adverse effects. Driving and physical activities need physical coordination should be avoided. Mild and transient elevation of liver enzymes It is contraindicated in spinal and ocular cysticercosis and during pregnancy. Intensity and frequency of adverse effects are dependent to dose of drug.

Pyrvinum Pamoate A cyanid red dye derivative with limited anthelmintic effect Its absorption from GI is negligible. It is effective on pinworm by inhibiting oxidative and non-oxidative (anerobic) metabolic pathways A single oral dose of 50mg/10kg (max 300mg) is enough for treatment however, the dose should be repeated after 2 weeks. Mild GI adverse effects are common. It could be used during pregnancy and lactation.

In The Name Of Allah