Owen 1-8-08 Anti-Helmithic

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Differentiate the 3 major groups of helminths that infect humans.
Describe the characteristics of and therapy for commonly encountered nematode, trematode and cestode infections.
Delineate drug MA, pharmacokinetics, adverse effects and rationale for use in a particular situation.

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elongated roundworms that possess a complete digestive system, including both a mouth and an anus. They cause infections of the intestine as well as the blood and tissues.

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Nematodes

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(flukes) are leaf-shaped flatworms that are generally characterized by the tissues they infect. For ex., they can be categorized as liver, lung, intestinal, or blood flukes.

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Trematodes

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“true tapeworms” typically have a flat, segmented body and attach to the host’s intestine. Like the trematodes, they lack a mouth and a digestive tract throughout their life cycle.

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Cestodes

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flatworms?

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Trematodes and Cestodes are types of flatworms

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Cause of most helminth infections

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ascaris

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Drugs for the Treatment of Nematodes

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Mebendazole
Pyrantel pamoate
Thiobendazole
Ivermectin
Diethylcarbamazine

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live in tissues of the host

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Wucheria bancrofti / Brugia malayi (Filariasis
Trichinella spiralis
Onchocerca volvulus

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MEBENDAZOLE (VERMOX)

Broad-spectrum use / round (________ lumbricoides)/ hook (_______ americanus and Ancylostoma duodenale) / pin (__________ vermicularis)/ whip (_________ trichiura)
Acts by selectively inhibiting ___________ synthesis and _______ uptake in nematodes.
Affected parasites are expelled with the _____. Slow death of worms. May be expelled alive.
Nonsystemic, ~10% absorbed PO, used for local GI action, usu adm 500 mg once or 100 mg BID x 3 days
Main side effects on GI (can occassionally occur), cramps\diarrhea
___________ potential, contraindicated in pregnancy, used with caution < 2 yrs age
Relatively new, Albendazole indicated for a # worm infections.

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MEBENDAZOLE (VERMOX)

Broad-spectrum use / round (Ascariasis lumbricoides)/ hook (Necator americanus and Ancylostoma duodenale) / pin (Enterobius vermicularis)/ whip (Trichuris trichiura)
Acts by selectively inhibiting microtubule synthesis and glucose uptake in nematodes.
Affected parasites are expelled with the feces. Slow death of worms. May be expelled alive.
Nonsystemic, ~10% absorbed PO, used for local GI action, usu adm 500 mg once or 100 mg BID x 3 days
Main side effects on GI (can occassionally occur), cramps\diarrhea
Teratogenic potential, contraindicated in pregnancy, used with caution < 2 yrs age
Relatively new, Albendazole indicated for a # worm infections.

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PYRANTEL PAMOATE

Acts as a ____________ neuromuscular blocking agent that causes persistent activation of _________ receptors and thus paralysis of the worm. Paralyzed worm then expelled from the host’s intestinal tract.
Effective in the treatment of infections caused by roundworms, pinworms, and hookworms, alternative to ___________ for round-/hook-/whipworm infections
Most drug remains in GI, polar drug
Toxic effects are usually transient & may include nausea, vomiting, headache & rash.

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PYRANTEL PAMOATE

Acts as a depolarizing neuromuscular blocking agent that causes persistent activation of nicotinic receptors and thus paralysis of the worm. Paralyzed worm then expelled from the host’s intestinal tract.
Effective in the treatment of infections caused by roundworms, pinworms, and hookworms, alternative to mebendazole for round-/hook-/whipworm infections
Most drug remains in GI, polar drug
Toxic effects are usually transient & may include nausea, vomiting, headache & rash.

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THIABENDAZOLE (MINTEZOL)

MA similar to ___________ (binds to tubulin & inhibits microtubule polymerization), same drug class (synthetic benzimidazole)
Rapid PO absorption, used for systemic treatments, alternative for treatment of ______________ (threadworm) & ___________ (pork round worm)
Topically use for cutaneous larva migrans (dog/cat hookworm)
Thiobendazole is much more toxic than other Benzimidazoles or Ivernectin, so other agents are now preferred for most indications. Most impt. S. E. : ___ effects – tingling & numbness; GI effects – diarrhea, nausea, vomiting; Reactions caused by dying parasites – fever, chills, & lymphadenopathy, & skin rash.
Contraindicated in pregnancy

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THIABENDAZOLE (MINTEZOL)

MA similar to mebendazole (binds to tubulin & inhibits microtubule polymerization), same drug class (synthetic benzimidazole)
Rapid PO absorption, used for systemic treatments, alternative for treatment of strongyloidiasis (threadworm) & trichinosis (pork round worm)
Topically use for cutaneous larva migrans (dog/cat hookworm)
Thiobendazole is much more toxic than other Benzimidazoles or Ivernectin, so other agents are now preferred for most indications. Most impt. S. E. : CNS effects – tingling & numbness; GI effects – diarrhea, nausea, vomiting; Reactions caused by dying parasites – fever, chills, & lymphadenopathy, & skin rash.
Contraindicated in pregnancy

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IVERMECTIN (MECTIZAN)

DOC for _____ Blindness caused by __________ volvulus & for strongyloidiasis caused by Strongyloides stercoralis (______worm), also used for for cutaneous larva migrans, adm 1-2 days
PO, rapidly abs, widely distributed, not ___
Intensifies gamma –aminobutryic acid (GABA)- mediated neurotransmission in nematodes & causes immobilization of parasites, facilitating their removal by the reticuloendothelial system. Selective toxicity results because in humans GABA is a neurotransmitter only in the CNS, & drug does not cross BBB.
ADRs: fatigue, dizziness, nausea, GI pain, rashes
M______ rx: in treatment onchocerciasis – fever, headache, joint pain, edema, hypotension; can be controlled with NSAIDs & antihistamines

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IVERMECTIN (MECTIZAN)

DOC for River Blindness caused by Onchocerca volvulus & for strongyloidiasis caused by Strongyloides stercoralis (threadworm), also used for for cutaneous larva migrans, adm 1-2 days
PO, rapidly abs, widely distributed, not BBB
Intensifies gamma –aminobutryic acid (GABA)- mediated neurotransmission in nematodes & causes immobilization of parasites, facilitating their removal by the reticuloendothelial system. Selective toxicity results because in humans GABA is a neurotransmitter only in the CNS, & drug does not cross BBB.
ADRs: fatigue, dizziness, nausea, GI pain, rashes
Mazotti rx: in treatment onchocerciasis – fever, headache, joint pain, edema, hypotension; can be controlled with NSAIDs & antihistamines

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DIETHYLCARBAMAZINE (HETRAZAN)

A piperazine derivative that is the DOC for the treatment of filariasis caused by __________ _________. It is also used as an alternative in the treatment of onchocerciasis.
Immobilizes micro_______ by an unknown mechanism, increasing their suseptibility to host defense mechanisms.
Adverse effects include headache, malaise, weakness, & ________. Reactions to proteins released by dying filariae include fever, rashes, ocular damage, joint & muscle pain, & lymphangitis. In onchocerciasis, the M_______ reaction includes most of these symptoms, as well as hypotension, pyrexia, respiratory distress & prostration.

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DIETHYLCARBAMAZINE (HETRAZAN)

A piperazine derivative that is the DOC for the treatment of filariasis caused by Wuchereria bancrofti. It is also used as an alternative in the treatment of onchocerciasis.
Immobilizes microfilariae by an unknown mechanism, increasing their suseptibility to host defense mechanisms.
Adverse effects include headache, malaise, weakness, & anorexia. Reactions to proteins released by dying filariae include fever, rashes, ocular damage, joint & muscle pain, & lymphangitis. In onchocerciasis, the Mazzotti reaction includes most of these symptoms, as well as hypotension, pyrexia, respiratory distress & prostration.

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PRAZIQUANTEL (BILTRICIDE)

Considered DOC for treatment of ______somiasis ( all species), certain ________ infections such as cysticercosis and infections by __________ (flukes).
PO. Rapidly absorbed after administration and distributes readily to ___.
Increases permeability of the cell membrane to calcium, which causes _______ contraction of the muscle and death of the parasite.
Adverse effects: drowsiness, dizziness, nausea, headache.
Not recommended for pregnant women or nursing mothers.
Contraindicated for the treatment of ocular cystercercosis, because destruction of the organism in the eye may damage the organ.

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PRAZIQUANTEL (BILTRICIDE)

Considered DOC for treatment of shistosomiasis ( all species), certain tapeworm infections such as cysticercosis and infections by trematodes (flukes).
PO. Rapidly absorbed after administration and distributes readily to CNS.
Increases permeability of the cell membrane to calcium, which causes tetanic contraction of the muscle and death of the parasite.
Adverse effects: drowsiness, dizziness, nausea, headache.
Not recommended for pregnant women or nursing mothers.
Contraindicated for the treatment of ocular cystercercosis, because destruction of the organism in the eye may damage the organ.

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NICLOSAMIDE (NICLOCIDE)

One of 2 DOCs (with praziquantel) for infections caused by beef, pork & fish ________ infections. However, it is not effective in ___________ ( for which albendazole or praziquantel is used) or hydatid disease caused by ___________ granulosus a( for which albendazole is used). Scoleces & cestode segments are killed, but ___ are not.
Adult worms (but not ova) are rapidly killed, presumably by inhibition of oxidative phosphorylation or by stimulation of ATPase activity.
Purgative adm 2 - 4 hrs later to flush out ova and dead segments before they can be digested
Drug action in GI, poor PO abs.
Infrequent, mild, & transitory adverse effects include n-v-d & abdominal discomfort.

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NICLOSAMIDE (NICLOCIDE)

One of 2 DOCs (with praziquantel) for infections caused by beef, pork & fish tapeworm infections. However, it is not effective in cystercosis ( for which albendazole or praziquantel is used) or hydatid disease caused by Echinococus granulosus a( for which albendazole is used). Scoleces & cestode segments are killed, but ova are not.
Adult worms (but not ova) are rapidly killed, presumably by inhibition of oxidative phosphorylation or by stimulation of ATPase activity.
Purgative adm 2 - 4 hrs later to flush out ova and dead segments before they can be digested
Drug action in GI, poor PO abs.
Infrequent, mild, & transitory adverse effects include n-v-d & abdominal discomfort.

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ALBENDAZOLE (ZENTEL)

Same drug class as mebendazole
MA is unclear. Blocks _______ uptake in both larval & adult parasites, which leads to decreased formation of ATP & subsequent parasite immobilization. Actions may also include inhibition of ___________ assembly, as has been described for mebendazole.
PO inc _____ foods, forms active metabolite (albendazole sulfoxide) with potent anthelmintic activity
Admin on an _____ stomach when used against intraluminal parasites, but with a _____ meal when used against tissue parasites.
DOC for treatment of _____________ & _______ disease. Also used in the treatment of pinworm and hookworm infections, ascariasis, trichuriasis, & strongyloidiasis.
Mild and transient GI disturbances, headache, dizziness; with longer use (for hydatid disease) can cause alopecia, inc liver enzymes, blood dyscrasias, renal dysfunction; teratogenic in animal studies
Safety of drug in pregnancy & in children younger than 2 yrs has not been established.

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ALBENDAZOLE (ZENTEL)

Same drug class as mebendazole
MA is unclear. Blocks glucose uptake in both larval & adult parasites, which leads to decreased formation of ATP & subsequent parasite immobilization. Actions may also include inhibition of microtubule assembly, as has been described for mebendazole.
PO inc fatty foods, forms active metabolite (albendazole sulfoxide) with potent anthelmintic activity
Admin on an empty stomach when used against intraluminal parasites, but with a fatty meal when used against tissue parasites.
DOC for treatment of cysticercosis & hydatid disease. Also used in the treatment of pinworm and hookworm infections, ascariasis, trichuriasis, & strongyloidiasis.
Mild and transient GI disturbances, headache, dizziness; with longer use (for hydatid disease) can cause alopecia, inc liver enzymes, blood dyscrasias, renal dysfunction; teratogenic in animal studies
Safety of drug in pregnancy & in children younger than 2 yrs has not been established.