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Anti-Helminthics
30 January 08
C. Neurocysticercosis
CHEMOTHERAPY OF HELMINTHIC INFECTIONS ⇒ Therapy most appropriate for
symptomatic parenchymal or
intraventricular cysts
Albendazole
⇒ Corticosteroids + Anthelminthic drugs
decrease inflammation caused by dying
• Broad spectrum oral anthelminthic
organism
• DOC: treatment of hydatid disease and ⇒ Albendazole: DOC because of its shorter
cysticercosis course, lower cost, improved penetration
• Also used in the treatment of pinworm and into the subarachnoid space, and
hookworm infections, ascariasis, trichuriasis, and increased drug levels when administered
strongyloidiasis with corticosteroids
⇒ Dose: 400 mg twice a day for up to 21
Chemistry and Pharmacokinetics days
• Benzimidazole carbamate D. Other Infections
• After oral administration, it is erratically absorbed ⇒ DOC for cutaneous larva migrans (400
(increased with a fatty meal) mg daily for 3 days), for visceral larva
• Rapidly undergoes 1st pass metabolism in the liver migrans (400 mg twice daily for 5 days),
to the active metabolite albendazole sulfoxide for intestinal capillariasis (400 mg
(mostly protein-bound, distributes well to tissues, daily for 10 days), for microsporidial
and enters bile, CSF, and hydatid cysts) infections (400 mg twice daily for 2
• Reaches variable maximum plasma weeks or longer) and for
concentrations about 3 hours after a 400 mg oral gnathostomiasis (400 mg twice daily for
dose 3 weeks)
• Plasma half-life: 8-12 hours ⇒ Also has activity against trichinosis (400
• Excreted in the urine mg twice daily for 1-2 weeks) and
clonorchiasis (400 mg twice daily for 1
week)
Anthelminthic Actions
⇒ Reports of effectiveness in treatment of
• Act against nematodes by inhibiting opisthorciasis, toxocariasis, and loiasis
microtubule synthesis ⇒ Conflicting reports of effectiveness in
• Larvicidal effects in hydatid disease, giardiasis and taeniasis
cystecercosis, ascariasis and hookworm infection ⇒ Included in some programs to control
• Ovicidal effects in ascariasis, ancyclostomiasis, lymphatic filariasis
and trichuriasis
Adverse Reactions, Contraindications, and
Clinical Uses Cautions
• Administered on an empty stomach when used • When used 1-3 days, nearly free of significant
against intraluminal parasites adverse effects
• Administered with a fatty meal when used against • Mild and transient epigastric distress, diarrhea,
tissue parasites headache, nausea, dizziness, lassitude, and
A. Ascariasis, Trichuriasis, and Hookworn and insomia
Pinworm Infections • Long-term use for hydatid disease: well-tolerated
⇒ adults & children > 2 y/o: single dose of but can cause abdominal distress, headaches,
400 mg orally fever, fatigue, alopecia, increases in liver
⇒ repeated for 2-3 days: heavy ascaris enzymes, and pancytopenia
infection and in 2 weeks for pinworm • After long-term therapy: Blood counts and Liver
infections Functions Studies
B. Hydatid Disease • Not for patients with known hypersensitivity to
⇒ Treatment of choice for medical therapy other benzimidazole drugs or to those with
and is a useful adjunct to surgical removal cirrhosis
or aspiration of cysts • Safety in pregnancy and in children < 2 y/o has
⇒ More active against Echinococcus not been established
granulosus than E. multilocularis
⇒ Dose: 400 mg twice daily with meals for 1 Bithionol
month or longer
⇒ Therapeutic strategy: Albendazole + • DOC: Treatment of Fascioliasis (Sheep Liver
Praziquantel to assess response after 1 Fluke)
month or more manage
Marco, farsi, jassie, april, viki 1 of 7
Pharmacology – Anti-helminthics by Dra Dando Page 2 of 7
• May prove to be an important drug for filariasis, ⇒ Used with diethylcarbamazine for the
both for treatment of active disease and in mass control of W. bancrofti, but it does not kill
chemotherapy campaigns adult worms
⇒ In loiasis, although the drug reduces
Ivermectin microfilaria concentrations, it can
occasionally induce severe reactions
• DOC: Strongyloidiasis and Onchocerciasis ⇒ Also effective in controlling scabies, lice,
• Also an alternative drug for a number of and cutaneous larva migrans and in
helminthic infections eliminating a large proportion of ascarid
worms.
Chemistry and Pharmacokinetics
• Semisynthetic macrocyclic lactone Adverse Reactions, Contraindications, and
• Mixture of: Avermectin B1a and B1b Cautions
• Derived from soil actinomycete Streptomyces • In strongyloidiasis, infrequent side effects include
avermilitis fatigue, dizziness, nausea, vomiting, abdominal
• Used only orally and rapidly absorbed, reaching pain, and rashes.
maximum plasma concentration 4 hours after a • In onchocerciasis, the adverse effects are
12 mg dose principally from the Mazotti reaction, due to the
• Has a wide tissue distribution and a volume of killing of microfilariae fever, headache,
distribution of about 50L dizziness, somnolence, weakness, rash, increased
• Half-life: 16 hours pruritus, diarrhea, joint and muscle pains,
• Excretion of drug and its metabolite: feces hypotension, tachycardia, lymphadenitis,
lymphangitis, and peripheral edema starts on
Anthelminthic Actions the 1st day and peaks on the 2nd day of treatment
• Paralyze nematodes and arthropods by • Some develop corneal opacities and other eye
intensifying GABA-mediated transmission of lesions several days after treatment rarely
signals in peripheral nerves severe and generally resolve without
• In onchocerciasis, it is microfilaricidal corticosteroid treatment
• It does not effectively kill the adult worms but • Best to avoid concomitant use of ivermectin and
blocks the release of microfilariae for some other drugs that enhance GABA activity
months after therapy (barbiturates, benzodiazepines and valproic acid)
• With repeated doses, the drug does appear to • Should not be used in pregnancy
have a low-level macrofilaricidal action and to • Safety in children younger than 5 years has not
permanently reduce microfilarial production been established
• Can be taken before or after meals, the tablets • Single oral dose, 7.5-10 mg/kg is given 3 times at
should be chewed before swallowing 14-day intervals
• Pinworm infections: 100 mg once, repeated at 2 • As prophylactic agent when given monthly to
weeks children in a highly endemic area
• Ascariasis, trichuriasis, hookworm and • Used in mass treatment programs
trichostrongylus infections: 100 mg twice daily for • In mixed infections with S. haematobium and S.
3 days (adults and children < 2y/o) mansoni: combined with oxamniquine
• Intestinal capillariasis: 400 mg/d in divided doses
for 21 or more days Adverse Reactions, Contraindications, and
• Trichinosis: efficacy against adult worms in the Cautions
intestinal tract and tissue larvae 3x daily with • Mild and transient cholinergic symptoms
fatty foods, at 200-400 mg/dose for 3 days and nausea and vomiting, diarrhea, abdominal pain,
then 400-500 mg/dose for 10 days bronchospasm, headache, sweating, fatigue,
• For severe infections: with corticosteroids weakness, dizziness, and vertigo
• May begin within 30 minutes and persist up to 12
Adverse Reactions, Contraindications, and hours
Cautions • Should not be used after recent exposure to
• Short-term therapy for intestinal nematodes: pesticides or drugs that might potentiate
nearly free of adverse effects cholinesterase inhibition
• Mild nausea, vomiting, diarrhea and abdominal • Contraindicated in pregnancy
pain
• High-dose therapy: hypersensitivity reactions Niclosamide
(rash, urticaria), agranulocytosis, alopecia, and
elevation of liver enzymes • 2nd line for treatment of most tapeworm infections
• Contraindicated in pregnancy (teratogenic in
animals) Chemistry and Pharmacokinetics
• Caution in children < 2 y/o (convulsions) and • Salicylamide derivative
patients with cirrhosis • Minimally absorbed from the GIT – neither the
• Plasma levels may be decreased with drug nor its metabolites have been recovered
concomitant use of Carbamazepine or from the blood or urine
Phenytoin ; and increased by Cimetidine
Anthelmintic Actions
Metrifonate (Trichlorfon) • Adult worms (but not ova) are rapidly killed,
pesumambly due to inhibition of oxidative
• Safe, low cost, alternative drug for Schistosoma phosphorylation or stimulation of ATPase activity
haematobium infections of worms
• Not active against S. mansoni or S. japonicum
Clinical Uses
• Adult dose: 2 g once, given in the morning on an
Chemistry and Pharmacokinetics
empty stomach
• Organophosphate compound (cholinergic • Tablets must be chewed thoroughly and are then
inhibit acetyl cholinesterase) swallowed with water
• Rapidly absorbed after oral administration A. Taenia Saginata (beef tapeworm), T. solium
• Following the standard oral dose, peak blood (pork tapeworm), Diphyllobothrium latum
levels are reached in 1-2 hours (fish tapeworm)
• Half-life: 1.5 hours ⇒ Single 2 g dose
• Clearance: nonenzymatic transformation to ⇒ Cysticercosis is theoretically possible after
dichlorvos (active metabolite) treatment of T. solium infections, because
• Metrifonate ad dichlorvos: well distributed to viable ova are released into the gut lumen
thetissues and are completely eliminated in 24-48 following digestion of segments
hours
B. Other Tapeworms
Anthelminthic Actions ⇒ H. diminuta and Dipylidium caninum
• Related to cholinesterase inhibition infections are cured with a 7-day course
• Temporarily paralyzes the adult worms, resulting of treatment; a few require a second
in their shift from the bladder venous plexus to course
small arterioles of the lungs, where they are ⇒ Praziquantel is superior for
trapped, encase by the immune system, and die Hymenolepis nana (dwarf tapeworm)
• Not effective against S. haematobium eggs infection
⇒ Not effective against cysticercosis or
hydatid disease
Clinical Uses C. Intestinal Fluke Infections
Pharmacology – Anti-helminthics by Dra Dando Page 5 of 7
but not against migratory stages in the tissues or • For strongyloides infection: treatment is for 2
against ova days
• A neuromuscular blocking agent that causes • For hyperinfection syndrome: standard dose is
release of acetylcholine and inhibition of continued twice daily for 5 -7 days
cholinesterase results in paralysis, which is • For cutaneous larva migrans: cream can be
followed by expulsion of worms applied topically or the oral drug can be given for
2 days (Albendazole preffered, less toxic)
Clinical Uses
• Dose: 11 mg/kg (maximum, 1 g) orally once with Adverse Reactions, Contraindications, and
or without food Cautions
• For pinworm: dose is repeated in 2 weeks • Much more toxic than other benzimidazoles or
• For ascariasis: single dose 85-100% cure rates ivermectin
treatment should be repeated if eggs are found • Common adverse effects: dizziness, anorexia,
2 weeks after treatment nausea and vomiting
• For hookworm infections: single dose is effective • Less frequent problems: epigastric pain,
abdominal cramps, diarrhea, pruritus, headache
against light infections, but not for heavy
and drowsiness, and neuropsychiaitric symptoms
infections, esp. with N. americanus 3-day
• Fatal Steven-Johnson syndrome and irreversible
course is necessary to reach 90% cure rates
liver failure
course treatment can be repeated in 2 weeks
• Limited in children weighing less than 15 kg
Adverse Reactions, Contraindications, and • Not be used in pregnancy or in the presence of
Cautions hepatic or renal disease
• Infrequent, mild and transient nausea,
vomiting, diarrhea, abdominal cramps,
drowsiness, headache, insomnia, rash, fever, and
weakness
• Caution: patient with liver dysfunction because
of low, transient aminotransferase elevations
• Experience with the drug in pregnant women and
children younger than 2 years of age is limited
Thiabendazole
Anthelminthic Actions
• Probably the same as that of other
benzimidazoles
• Has ovicidal effects for some parasites
Clinical Uses
• Dose: 25 mg/kg (maximum 1.5 g) twice after
meals
• Tablets should be chewed