Antihelminthic drugs Flashcards
how popular are worm infections?
25% world is infection
15% in U.S
unique biology of worms
multiple outside of their definitive host in contrast to parasites
-evade immune system-> infections are chronic
most common helminth?
ascaris, hook worms, trichuris
two phyla of worms
flatworms and roundwarms
Flatworms
tapeworm infections:
- ) beef tapeworm (taenia saginata) global distribution
- ) Pork tapeworm (taenia solium) bladder worms
- ) fish tapeworm (diphyllobothruimlatum) robs host vitamine, especially B12
tapeworm life cycle
pig or cattle infection-> penetrate intestine and go into muscle-> humans ingest (undercooked or raw)-> development in human small intestine
Cysticercosis
autoinfection by ingestion of eggs produced by T. Solium
-after ingestion->oncpsheres hatch in intestine-> invade the intestinal wall-> migrate to striated muscle (or brain, liver)-> develop into cysticerci
Flatworms: Dwarf tapeworm
can be transmitted directly between humans
- 3-4cm in length
- found in temperate regions
- children predominantly infected
- infected by ingestion of eggs
- not that serious
flatworms: schistosomiasis (bloodflakes)
can live 5-10 years
-headaches, fatigue, fever, GI problems, hepatic fibrosis, bladder cancer, ascites
hematobium
mansoni
japonicum
Caribbean, south america, africa, middle east
Praziquantel
highly effective
- disrupts calcium homeostasis
- causes muscular contraction follwed by spastic paralysis
- worms dislodge and die
Praziquantel dose
two or three doses
- reduces egg burden in those not cured
- single dose kills 100% of T. saginata, T. solium, and D. latum
- doesn’t kill eggs of T. solium
Praziquantel toxicity
mild
- dizziness/drowsiness-avoid driving
- can get a severe reaction to dead/dying worm
Hookworms
- found in soil
- associated with poor hygeine
- penetrate through skin or by ingestion
- feed on intestinal tissue and blood
- live up to 15 years
- pulmonary lesions, skin reactions, intestinal ulcerations and anemia
Pineworms
temperate regions
- live in GI tract, female migrate to rectum at night
- perianal pruritis
- eggs infect fingers and bed sheets
- eggs remain infective for 3 weeks
- ingestion of eggs starts new infection cycle
Ascariasis round worm:
eggs ingested-> larva hatch in small intestine-> penetrate intestinal wall and migrate to lungs-> re-swallowed-> return to small intestine
whipeworm
eggs passed in feces, can live for 5 years, 5cm in length
colonic mucosa
abdominal pain, diarrhea, distention
Trichinosis
Trichinella spiralis
- undercooked pork
- round replication is in intestines
- progreny throughout body
- diarrhea, abdominal pain, N, muscle pain, edema, weakness
Filarial disease: eyeworm
deer flies
- ocular lesions can cause blindness
- africa
Filarial disease: onchocerca volvulus
female blackflies
-Africa
Benzimidazoles
bind tubulin
- inhibit formation of microtubules-> cap microtubules
- continue to be shortened
Benzimidazoles
mebendazole
thiabenazole
albendazole
Benzimidazoles kinetics
poorly absorbed in GI tract-> fatty meal can increase absoprtion
-luminal parasites-> empty stomach
-tissue infection-> fatty meal
rapidly metabolized
albenazole
drug of choice for cysticercosis
-pineworms, hookworms, ascariasis, trichuriasis and strongyloidiasis
Benzimidazoles toxicity?
Albendazole and mebendazole (teratogenic) well tolerated
thiabendazole more toxic
-dizzness, anorexia, N&V, NOT IF PREGNANT
diethylcarbamazine
drug of choice for filariasis and loiasis
- microcilariae are rapidly killed
- adults killed more slowly
- well absorbed from GI tract
- well tolerated
- reaction to dying worm-> b/c worms have bacterial endosymboint, can get a systemic inflammatory response-> can be treated with doxycycline
Ivermectin
drug of choice for stronglyoidiasis and onchocerciasis
- semisynthetic marcocyclic lactone
- good oral availability
Ivermectin MOA
paralyzes microfilariae
- intensifies GABA mediated transmission of signals in peripheral nerves
- allows host cytotoxic cells to adhere
- DOES NOT kill adult worms
- blocks progeny release
Ivermectine therapeutic use
single dose
treat onchocerciasis
-used in pets-> lack P-glycoprotein transport so can have neurological symptoms
Pyrantel pamoate
Low bioavailability, acts in gut
- treat roundworms and pinworms
- active against adult and immature worms
- not active against migratory worms
Pyrantel pamoate MOA
neuromuscular blocking agent
causes release of acetylcholine and inhibiton of cholinesterase
-worms paralyzed and expelled
clinical use of Pyrantel pamoate
ascariasis-1 dose
pineworms-> drug of choice
tissue nematodes: trichinosis
mebendazole + corticosteroids
tissue nematodes: stronglyoidiasis
mebendazole or albendazole
tissue nematodes: onchocerciasis
ivermectin
tissue nematodes: filariasis
diethyclarbamazine
nematode infections: Filariasis
lymphatic dwelling filaria
- wuchereria bancrofti-> tropical regions
- Brugia malayi-> Asia
- Brugia timori-> indonesia
- mosquitoes transmit
- elephantiasis
antihelminth medication
diethycarbamazine ivermectin mebendazole praziquantel pyrantel pamoate
thiabendazole is no longer preferred why?
toxicity
what is mebendazole used for?
pinworms, hookworms, ascariasis, and trichuriasis