ANTHELMINTIC DRUGS

M.Djamaludin.MGDepartement of Pharmacology

Achmad Yani School of Medicine

ALBENDAZOLE

INDICATION1.Ascaris lumbricoides2.Trichuris trichura3.Necator americanus4.Strongilodes stercoralis5.Enterobius vermicularis

DOSE

• Adults and children over 2 years : Single dose 400 mg, orally repeated 2-3 weeks

• Taeniasis : 400 -1200 mg for 3 days• Enterobiasis: 400 mg ingle dose. Repeated after 2 –

4 weeks to prevent reinfection

• Visceral larva migrans• Trichinella spiralis• Wuchereria bancrofti• Capillaria philipinensis• Clonorchis sinensis

Cutaneous larva migrans : 400 mg/day,for 5 days, capillariasis intestinal 10 days, trichuriasis 15 daysCONTRAINDICATIONI:PregnancyBreast feeding

CAUTIONS: Hepatic and renal dysfunctionSIDE EFFECT :Abdominal discomfortDizzinessHeadachePREP:Caplet 400 mgChew captab 100 mgSiruf 200 mg/5 cc,10 cc

MEBENDAZOLE

INDICATION:Ascariasis,OxyuriasisAnkylosttomiasis,trichuraisis,strongiloides stercoralisDOSE: Oxyuriasis : Single dose 100 mgAscariasis :Twice 100 mg/day for 3 days

Taenia saginata: Twice 300 mg/day,for 3 daysTrichuriasis: Twice 100 mg/day, for3-4 daysAnkilostomiasis: Twice 100mg /day,for 3 daysCONTRAINDICATION:Pregnancy

PIPERAZIN HEXAHYDRAT

INDICATION: Ascariasis,oxyuriasis,DOSE:Oxyuris: Adult and children over 6 years, 1 measure spoon,3 times /day Children: 3-6 year: 1 measure spoon twice/dayChildren 1-2 years: ½ measure spoon, twice/day, for 4 days

CONTRAINDICATION:Hepatic and renal dysfunction, epilepticCAUTION : G6PD DefSIDE EFFECT: GIT synndrome,headache, hypersensitivityDRUG INTERACTONI:Pirantel dan phenothiazin

LEVAMISOL (Konimex)

INDICATION:• Ascaris lumbricoides,Ankylostoma duodenaleSIDE EFFECT • GIT syndrome,dizziness,headache.DOSE:• Adult and children over 15 years, 4-6 tablet• Children:12-15 years 3-4 tablet 8-12 years 3 tablet

• Children: 6-8 years :2 tablet• 3-6 years :1 ½ tablet• 1-3 years : 1 tablet• Single dose• Prep: Tablet 25 mg: 4 tablet/strip

DIETHYLCARBAMAZINE (Filarzan)

CHEMISTRY: It is a piperazine derivatedMOA: Imobilization and change surface structure of

microfilaria , to microfilaria from tissue, facilitates the destruction of microfilaria by host defense mechanism

INDICATION:Wuchereria bancrofti, Brugia malayi, Brugia Timori dan Loa’LoaDOSE3 times/day 2 mg/kgBB concommitent with meal, 10-30 days.

SIDE EFFECT:Headache, malaise, anorexia, weakness, nausea, vomitus

IVERMECTIN

INDICATION:Ivermectin is the drug of choice in strongiloidosis and onchoceciasis. It is also an alternative drug for other helminthic infectioni.e. ; Wuchereria bancrofti, Brugia malayi, tropical eosinofilia, and Loa-Loa.

SIDE EFFECT:Fever, headache, nausea, vomitus abdominal pain, and rashDOSE:Single dose: 150 ug/kgBW, effectivity proportional with DEC to microfilaria of tissue, skin, and anterior chamber of eye.

CONTRAINDICATION: • Pre gnancy• Children under 5 years (Safety is not

established) • It is not administered with barbiturat,

benzodiazepine, or valproac acid

PRAZIQUANTHEL

INDICATION : Taenia soliumSingle dose : 10 mg/kgBW

NICLOSAMIDEINDICATION :Taenia soliumDOSE : Twice a day @ 1 gram Children a half dose

THIABENDAZOLE

INDICATION : Drug of Choice for S.stercoralis, cutaneous larva migrans. Not recomended for: Askariasis, trichuriasis, ankylostomiasis and oxyuriasis DOSE: 2x25 mg/kgBW for 2 day.• For hyperinfection syndrome 2x25 mg/kgBW, 5-7

days• For cutaneous larva migrans 2x25 mg/kgBw, 2-5

days

TREATMENT OF SPECIFIK FORM OF AMEBIASIS

A. ASYMPTOMATIC INTESTINAL INFECTION Asymptomatic carriers generally are not treated in

endemic areas but in nonendemic area they are treated with luminal amebicides

A tissue amebicides drug is unnecessary. Standard luminal amebicides are diloxanide furoate, iodoquinol, and paramomycin. Therapy with luminal amebicides is also require in all other forms of amebiasis

B.AMEBIC COLITIS

• Metronidazole plus a luminal amebicide is the treatment of choice for colitis and dycentry

• Tetracyclines and erythromycin are alternative drugs for moderate colitis but are not effective against extraintestinal disease. Dehydroemetine or emetinne can also be used, but these agents are best avoided, because of their toxicity

C.EXTRINTESTINAL INFECTIONS

The treatment of choice is metronidazole plus a luminal amebicide. A 10-day course of metronidazole cures over 95% of uncomplicated liver abscesses. For unusual cases where initial therapy with metronidazole has failed, aspiration of the abscess and the addition of chloroquine to a repeat course of metronidazole should be considered. Dehydroemetine and emetine are toxic alternative drugs.

METRONIDAZOLE

• Metronidazole nitroimidazole is the drug of choice for the treatment of extraluminal amebicides. It kills trophozoites but not cyst of E.hystolytica and effectively erradicates intestinal and extraintestinal tissues

Chemistry and Pharmacokinetics

• Absorbed after oral adminitration permeates all tissues by simple diffusion. Low binding with protein. The drug and its metabolites are excreted mainly in the urine

Mechanism of Action

• The nitro group of metronidazole is chemically reduced in anaerobic bacteria and sensitive protozoans.

• Reactive reduction products appear to be responsible for antimicrobial activity.

Clinical uses

1. Amebiasis2. Giardiasis3. Trichomoniasis

D. Adverse Effects and Cautions

• Nausea, headache, dry mouth, or metallic taste occurs commonly.

• Infrequent adverse effects include and vomiting, diarrhea, insomnia, weakness, dizziness, thrush, rash, dysuria, dark urine, vertigo, paresthesia,and neutropenia. Taking the drugs with meals lessens git irritation

• The rare effects pancreatitis, severe CNS toxicity

• Metronidazole has a disulfiram-like effect, so that nausea and vomiting can occur if alcohol ingested during therapy. The drug should be used with caution in patients with CNS disease.

• Metronidazole has been reported to potentiate the anticoagulant effect of coumarin-type anticoagulant.

IODOQUINOL

• Iodoquinol (iodohydroxyquin) is a halogenated hydroxyquinoline. The MOA of iodoquinol against trophozoites is unknown.

• It is an effective luminal amebicide. But not against trophozaotes in the intestinal wall or extraintestinal tissues.

Infrequent adverse effects include diarrhea, which usually stop after several days-anorexia, nausea,vomitus, abdominal pain, headache, rash, and pruritus.

DILOXANIDE FUROATE

• Diloxanide furoate is a dichloroacetamide derivate. It as an effective luminal amebicide but si not active against tissue trophozoites.

• In the gut diloxanide furoate is split into diloxanide and furoic acid, about 90% of the diloxanide is absorbed.

The unabsorbedis active antiamebic substance. The MOA of diloxanide furoate is unknown. It is usedwith a tissue amebicide, usually metronidazole to treat serious inestinal and extraintestinal infection.

SIDE EFFECTS: Flatulence Nausea RashCONTRAINDICATION: Pregnancy

EMETINE & DEHYDROEMETINE

• Emetin is an alkaloid derived from ipecac, and dehydroemetine, synhhetic analog, are effective against tissue trophozoites of hystolytica. The drug administered parenterally because oral preparation are absorbed erraticaly.

• Dehydroemetine is preffered over emetine because of its somewhat better toxicity profile

• ROA: S.C or I.M but never intravenously. Because of

adverse effects it should not be used more than 10 days.

Serious side effect is cardiac arrythmias, heart failure, and hypertension.

CONTRAINDICATION:1. Cardiac disease2. Renal disease3. Young children4. Pregnancy

AMEBIASIS TREATMENT

•INFECTION DOC ALTERNATIVE DRUGS

Asmp/carier Iodoq. Diloks.fur/ParInt mild-mod Metr...>Iodoq AA lum+T/DE/EInt sev. Metr....>Iodoq AA lum+T/DE/EAbsces Metr....>Iodoq DE/E....klo+AA lum

DOC = Drug of choice ALTERN. DRUGS = Alternative DrugsAsmp = AsymptomaticIodoq. = IodoquinolonDilocs.fur = Dilocsanide furoate Par = Paramomycin

Int mild-mod = Intestinal mild-moderate Metr = MetronidazoleAA lum = Anti amebic luuminalT = TetracyclineDE = dehydro emetineE = emetineInt sev. = Initestinal severe

OTHER ANTIPROTOZOAL DRUGS

PENTAMIDINEClinical uses 1. Pneumocystosis 2. African Trypanosomiasis (Sleeping Sickness) 3. Leishmaniasis

TRYPANOSOMIASIS (SLEEPING SICKNESS)

Pentamidine • Has been used since 1940 as an alternative to

suramin.• The drug can be used with suramin• Pentamidine should not be used to treat late

trypanosomiasis with CNS involvement• DOSE: 2-4 mg/kg daily or on alternate days for a

total of 10-5 doses.• As chemoprophylactixis:v4 mg/kg every 3-6 months

SODIUM STIBOGLUCONATE

First line agents for cutaneous and visceral leishmaniasisROA : I.V or I.M.DOSE : Once daily,20 mg/KgBW for 20 days cutaneous and 28 days in visceral leishmaniasisMOA : ?SE : GIT, fever, headache, myalgia, arthralgia, rash

NITAZOXANIDE

• Nitozoxanide appears to have activity against metronidazole resistent protozo al strains and is well tolerated.

• Free of mutagen effect (not as metronidazole)• Other suceptible to, nitazoxanide:• E.hystolytica, H.pylori, A.lumbricoides, several

tapeworms, and F. hepatica

OTHER DRUGS FOR TRYPANOSOMIASIS & LEISHMANIASIS

• SURAMIN• MELARSOPROL• EFLORNITHINE• NIFURTIMOX• BENZINDAZOLE• AMPHOTERICIN• MILTEFOSINE