Antihelmintics
3 general mechanisms
effective against larval forms
1) metabolic energy production
2) cytostkeletal filaments (for division, vesicle transport
3) motility
Antihelminths
Anti-roundworm
4 classes
Benzimidazole
Avermectin
Pyrantel Pamoate
Deithylcarbamazine
Antihelminths
Anti-fluke/tapeworm
1 class
Praziquantal
Benzimidazoles
Albendazole, Mebendazole
indication
primarily for roundworms (nematodes)
kill eggs, larvae, some adult
Benzimidazoles
Albendazole, Mebendazole
mechanism
-inhibits B-tubulin polymerization
-selective for parasite over mammalian
-inhibits mitosis, cellular organelle mvmt
-also inibits glc uptake, ox-phosphorylation,
mitochondrial fumarate reductase
Benzimidazoles
Mebendazole
ADME
- poorly absorbed
- GI tract infections
- no systemic use
- negligible renal excretion
Benzimidazoles
Toxicity
- well tolerated, few sx
- common: gi distress
- uncommon: neutropenia, alopecia, liver fx
- contra’d: PG, <2yo
- P450 interaxns
Benzimidazoles
Albendazole
ADME
- rapid 1st pass metabolism
- absorption enhanced by fat, bile salts
- GI and system infxns
- hyatid cysts
Avermectins
Ivermectin
indications
- onchocerciasis (African river blindness)
- every 6-12 mos for 5-10 yrs
Avermectins
Ivermectin
mechanism
- effective against nematode larvae
- activates invertibrate-specific glu/Cl- channel
- causes flaccid paralysis in nematode
Avermectins
Ivermectin
ADME
- absorbed in GI
- systemic or GI lumen
- Met’d by P450
- small amt crosses BBB
Avermectins
Ivermectin
toxic
- Mazotti rxn (caused by release of bact antigens)
- Contra’d in Pts with impaired blood-brain barrier
- Contra’d Loariasis
Pyrantel Pamoate
indications
- not well absorbed, no systemic indication
- luminal nematodes (pinwormm ascaris, trichostrongylus)
- kills adults, larvae; not eggs
Pyrantel Pamoate
mechanism
- stims nicotinic receptors at neuromusc jxns
- increases ACh at synapse
- spastic paralysis
- worm is expelled from GI tract
Pyrantel Pamoate
ADME
- poorly absorbed
- eliminated in feces
Pyrantel Pamoate
Toxicity
- transient GI discomfort
- major: neuromuscular blockade
Diethylcarbamazine
indications
-nematodes
Diethylcarbamazine
mechanism
- alters surface membranes
- triggers immune response
- worm paralysis
- worm apoptosis
Diethylcarbamazine
ADME
- well absorbed in GI
- systemic and GI infxns
- renal excretion (dose adjust for dysfxn)
Diethylcarbamazine
toxicity
- well tolerated
- anorexia, headache, vomiting
- major: mazzotti and other inflammatory response
- contra’d: onchocerciasis (inflamm resp)
Praziquantel
indications
Trematodes and Cestodes
effective against adult and larvae
Praziquantel
mechanism
- increased Ca++ influx into worm
- increased exposure of antigen, immune response
- spastic paralysis of worm
Praziquantel
ADME
- readily absorbed, met’d by P450
- increased absorprtion with carbs, cimetidine
- competes with phenytoin, steroids
Praziquantel
toxicity
- GI distress, headache, fever, urticaria
- Contra’d: PG
- dosage reduction with cimetidine, hepatic dz
- Contra’d: introcular cysticercosis
