Antihelminthic Flashcards
What are some unique characteristics of parasitic infections?
Worms multiply outside of their definitive host in contrast to other parasites
Evade immune system
Infections are chronic - last lifetime of the host
What parasite has the high infection rate in the world?
Ascaris
Where are anthropod-borne parasites endemic?
tropic and pets in the USA
What are the two phyla?
Flatworms (Platyhelminths) - Tapeworms (Cestodes), Flukes and Schistosomes (Trematodes)
Roundworms (Nematodes)
What are examples of tapeworm infections?
Beef Tapeworm (Taenia saginata) Pork Tapeworm (Taenia solium) Fish Tapeworm (Diphyllobothrium latum)
Facts about T. saginata - cestode
Global distribution
Transmitted by eating undercooked meat
Facts about T. solum - cestode
Global distribution
Bladder worms
Occasionally found in undercooked pork
Facts about D. latum - cestode
Largest tapeworm (10m)
Transmitted by eating undercooked fish
Northern hemisphere
Robs host of nutrients, especial vit. B12
Life cycle of Taenia
Eggs/proglottids pass into environment –> cattle or pig become infected by eating contaminated vegetation –> oncospheres hatch –> penetrate intestinal wall –> circulate to musculature –> oncospheres develop into cysticerci in muscle –> human infected by eating raw or undercooked meat –> taenia use scolex to attack to intestine –> mature into adults –> release proglottids into feces
What is cysticercosis
caused by autoinfection by ingesting eggs produced by T. solium
can go to the brain (instead of the muscle) and cause neurocysticercosis
What is Dwarf Tapeworm - cestode
Hymenolepis nana most common cestode infection can be transmitted directly between humans found in temperate regions worldwide children predominately infected infected by ingesting eggs generally not serious
What is schistosomiasis - trematode
Bloodflukes
3 species: S. hematobium; S. mansoni; S. japonicum
Caribbean, S. America, Africa, Middle East
Can live for 5-10 yrs
Sx due to immune reaction to eggs (headaches, fatigue, fever, GI problems, ascites, hepatic fibrosis, bladder cancer)
What is Praziquantel used for?
Highly effective against cestodes and trematodes
No activity against nematodes
MOA: disrupt calcium homeostasis, causes muscular contraction followed by spastic paralysis, immune response may be involved
Praziquantel therapeutic uses
Drug of choice for all schistosomiasis
dramatically reduces egg burden in those not cured
Single does kills 100% of saginata, solium, and latum
DOES NOT KILL EGGS OF SOLIUM
Toxicity: mild and transient, avoid in pregnancy, and avoid driving(dizziness/drowsiness)
Facts about Hookworms
American hookworm (Necator americanus)
Old world hookworm (Ancyclostoma duodenale)
Found in soil
Infect by penetrating through the skin or ingestion
feed on intestinal tissue and blood
Cause pulmonary lesions, skin reactions, intestinal ulcerations, and anemia
Prevalent in regions w/ temp around 23-33C
Facts about Pinworms - Nematode
Enterobiasis
widespread in temperate regions
most common worm infection in US (household and institutions)
Live in GI tract: females migrate to rectum at night to deposit eggs
Causes perianal pruritus
Eggs infect fingers and bed sheets (infective for 3 wks)
INGESTION OF EGGS STARTS NEW LIFE CYCLE
Facts about Roundworms - nematodes
Ascariasis Common in developing countries Resides in small intestine Life cycle: Ingest eggs --> larva hatch in small intestine --> penetrate intestinal wall --> transported to lungs --> after 10 days pass through lungs to trachea --> re-swallowed --> return to small intestine Associated with poor sanitation
Facts about Whipworm infections - nematode
Trichuriasis
Infections are common in tourists who visit the subtropics and S.E US
Caused by ingesting eggs in contaminated food or liquid
Eggs are passed in feces
Reside in large intestine
Cause irritation and inflammation of colonic mucosa, abdominal pain. diarrhea, and distention
Facts about Trichinosis - nematode
Trichina
Caused by Trichinella spiralis
Infection can be intestinal and systemic
Associated with undercooked pork (also wild boar, bear, and walrus)
Initial round of replication is in intestines
Progeny are distributed throughout the body
Cause diarrhea, abdominal pain, nausea (intestinal stage)
and muscle pain, edema, and weakness (muscular stage)
Facts about Filariasis
lymphatic dwelling filaria include: Wuchereia bancrofti - tropical regions worldwide Brugia malayi - Asia Brugia timori - Indonesia Transmitted by mosquitos Cause elephantiasis
What is Loa Loa
Eyeworm transmitted by deer flies often asymptomatic ocular lesions can cause blindness Primarily found in Africa
What is River blindness
Onchocerca volvulus
Transmitted by female blackflies
Renders parts of Africa uninhabitable
750,000 blinded/impaired
What is the reasonable goal of Tx:
reasonable goal is to reduce the burden of infection
What drugs are used to treat helminth infections:
Diethylcarbamazine Ivermectin Mebendazole or Albendazole Praziquantel Pyrantel Pamoate
What are benzimidazoles
broad spectrum activity
Ex: mebendazole, thiabendazole, albendazole
Thiabendazole most toxic
MOA: binds to tubulin; inhibits formation of microtubules by capping them
Are able to bind to mammalian tubulin
What are the pharmacokinetics of benzimidazoles
poorly absorbed in the GI tract (fatty meal can increase absorption)
luminal parasites –> empty stomach
tissue infections –> admin with fatty meal
Rapidly metabolized in liver
Albendazole –> sulfoxide form (active)
Metabolites of mebendazole and thiabendazole are NOT ACTIVE
Toxicity of benzimidazoles
albendazole and mebendazole well tolerated in short-term treatments
thiabendazole more toxic (dizziness, anorexia, nausea, committing, don’t give during pregnancy)
mebendazole is teratogenic (not used in pregnant women)
Therapeutic uses of benzimidazoles
Albendazole is the drug of choice for cysticercosis (also for pinworms, hookworms, ascariasis, trichuriasis, and strongyloides)
Mebendazole used for pinworms, hookworms, ascariasis, and trichuriasis
Thiabendazole NO LONGER preferred due to toxicity
What is diethylcarbamazine?
MOA unknown
Drug of choice for filariasis and loiasis (elephantiasis and eye worm)
microfilariae are rapidly killed; adults are killed slowly
must be careful in high burden (Mazzotti rxn)
well absorbed in GI tract
Generally well tolerated
reaction to dying worms can be severe –> may lead to systemic inflammation from release of bacterial endosymbiont –> Tx with Doxy
What is Ivermectin?
Drug of choice for strongyloidiasis and onchocerciasis (river blindness)
good oral availability
semisynthetic macrocyclic lactone
MOA: paralyzes microfilariae; intensifies GABA-mediated transmission of signals in peripheral nerves
allows host cytotoxic cells to adhere
Does not kill adult worms
Block release of progeny
affects similar channels in mammalian brain but requires higher concentration –> therefore selective only for parasite
What are the therapeutic uses of Ivermectin
primarily used for onchocerciasis
single dose
Tx must be continues for lifespan of adult worm
Can also be used in Pets (many collies)?
What is pyrantel pamoate
broad spectrum antihelminth
available OTC
bioavailability extremely low, acts in gut
highly effective for treatment of PINWORMS and ASCARIS
moderately effective against hookworms
active against adult and immature worms (not against migratory stages or ova)
What is the MOA and Clinical uses of Pyrantel pamoate
MOA: neuromuscular blocking agent
causes release of Ach and inhibition of cholinesterase
worms are paralyzed and expelled
Clinical uses: Ascaris - 1 dose; Pinworms- drug of choice - 2 doses 2 weeks apart
What drug is used for Trichinosis
Mebendazole + corticosteroids
What drug is used for Strongyloidiasis
Mebendazole or albendazole
What drug is used for Onchocerciasis
Ivermectin
What drug is used for Filariasis
Diethylcarbamazine
