Antihelmintics & Drugs for Ectoparasites ~ PDA

Intestinal Helminth MOA

infectious form = filariform larvae & enter human skin directly and reach pharynx and swallowed → reach small intestine & mature = cause blood loss

Intestinal Helminth SE

Anemia - they’re sucking up th eblood

protein deficiency - growth and mental retardation in kids

Trematodes Treatment

Triclabendazole

Praziquantel

Cestodes Treatment

Albendazole

Praziquantel

General Anti-Helminth Drug Effects

• Paralysis of the worm

• *Damaging the worm leading to partial digestion or rejection by immune mechanisms

• *Rudimentary nervous system → target for therapeutic

• Only a few do not cause significant toxicity (direct toxicity) to host cells

• Drugs may only kill specific forms/stage (adult, larval etc) of the helminth

• Careful consideration for use in pregnant women, some teratogenic or embryocidal

Mazzotti Reaction

a toxicity due to dying/dead worms ~ can be life threatening

TX with steroids and/or antihistamines

have to have 2 or more of following

• fever/chills/ HA

• edema/swollen

• dizziness/hypotension

• tachycardia/rashes

• myalgias

Praziquetal MOA

In Trematodes (Blood-flukes) & Cestodes (tapeworms)

• incr cell membrane permeability to Ca2+ = strong contractions initially, then paralysis of worm musculature = dislodgement of suckers from blood vessel wall = expulsion

• In schistosomes(blood-fluke), also causes disintegration of tegument of worm

  • doesn’t cause mazzoti reaction

Praziquetal Drug of Choice

drug of choice against adult cestodes & trematodes

• including all species of Schistosoma

Pyrantel Pamoate MOA

A nicotinic receptor agonist-stimulates nicotinic receptors present at nematode neuromuscular junction→prolonged activation of excitatory nicotinic acetylcholine (nACh) receptors on body walls→ depolarizing neuromuscular block→paralysis of helminths and release from the intestinal wall

Pyrantel Pamoate Drug of Choice

Drug of choice for the treatment of pinworms caused by Enterobius vermicularis and hookworms ~ nematodes

Benzimidazoles [Albendazole]

inhibit tubulin polymerization

Benzimidazoles [Mebendazole]

inhibits formation of microtubules

Benzimidazoles [Triclabendazole]

inhibit tubulin function [protein synthesis]

Benzimidazole Overall MOA

• disrupting motility & DNA replication of the nematodes

• inhibits mitochondrial reductase→ causes decr glucose uptake in susceptible helminths

Benzimidazole Uses

• Alb & Meb have a broad spectrum of activity of nematodes, including activity against

  • Ancylostoma duodenale

  • Necator americanus (hookworms)

  • Ascaris lumbricoides (roundworms)

  • Enterobius vermicularis (pinworms)

  • Trichuris trichiura (whipworms) in single or mixed infection

Benzimidazole AE

ContraIndication: pregnancy [teratogenic & embryotoxicity]

SE: mainly GI irritation, prolonged use cause more SE past 3 days

Ivermectin MOA

Acts as a selective GABA agonist = binds with glutamate gated chloride channels = incr cell membrane permeability to Cl = Chloride ion influx = hyperpolarization of nerve & muscle cells blocking neuromuscular transmission = paralysis of pharynx and body wall vasculature = immobilization and death = allows its removal

Ivermectin Uses

• roundworm Strongyloides stercoralisis limited to the intestinal stages

• tissue microfilariae of Onchocerca volvulus (African river blindness) but not against adult form = not curative

Ivermectin AE

PO dose [every 6-12mo] tx onchocerciasis

mazzotti rxn is short term and rare

pregnancy & meningitis is a no go

Moxidextin MOA

• binds & activates glutamate-gated Cl channels = worm paralysis

• binds GABA channels

Moxidextin Use

• Tx Onchocerciasis- River blindness (Ivermectin resistant disease)

• Advantage: Poor substrate for P-glycoproteins (P-gps) = won’t get effluxed out

Moxidextin AE

mazzotti rxn

Diethylcarbamazine MOA

• Traditional: acts as an opsonin, sensitizes microfilarie to phagocytosis [immune system]

• Recent: binds to Brugia TRP channels allowing Ca2+entry = paralysis of worm

Diethylcarbamazine Uses

Tx filariasis caused by Wucheria bancrofti, Brugia malayi, Brugia timori [caused by lymph system]

Diethylcarbamazine AE

Mazzotti Rxn ~ VERY common

Scabies [Topical Ectoparasite Infection]

infection w/ sarcoptes scabiei

mites burrow in skin, live there, & lay eggs

spread: skin-skin contact, result= pimple rash

crusted _= contagious atypical form = thick crusted lesions with little/ no itch 

Lice [topical ectoparasite infection]

• Infestation (pediculosis) caused by

  • Pediculus humanus var capitis (head lice)

  • Pediculus humanus var corporis (body lice)

  • Phthirius pubis (crab lice in genital area)

• blood sucking parasites

• spread via close contact

Lice w/ Pediculicides Tx

head infestation

• neurotoxicity = paralysis of louse

• suffocate via “coating” louse

Pyrethrins 1 & 2 MOA

combined with piperonyl butoxide = inhibits the CYP 450 enzyme of the insect = inactivate activity of the pyrethrins by the parasite.

Pyrethrin Use

used for lice ONLY

Permethrin MOA

a pyrethroid which is a synthetic derivative of pyrethrins with increased stability

• not used with a synergist [piperonyl butoxide]

Permethrin Use

used for lice & scabies BOTH

MOA of pyrethrins & permethrin

• Contact poisons = penetrate CNS of insect = paralyzed =  drug metabolized by enzymes 

• Bind insect Na channels & interferes with Na transport channel = delay membrane repolarization = neurotoxicity, paralysis & death of parasite.

Crotamiton [for scabies] MOA

• For eradication of scabies (Sarcoptes scabiei )

• Symptomatic treatment of pruritic skin

• 10% (Eurax®) cream or lotion

• Less effective than pyrethrins or permethrin

  • MOA: unknown-scabicidal and anti-pruritic

Spinosad [tx head lice] MOA

• topical suspension

• Acts as agonist at nicotinic acetylcholine receptors (nAchRs) = prolong hyperexcitation of the insects CNS = involuntary muscle contractions =  paralysis & death

  • more effective than permethrin→ patients showing non-adherence to other therapies

Malathion [tx head lice MOA]

• topical treatment for head lice

• alternative tx for pubic lice when treatment with permethrin and pyrethrins fails

• inhibits acetylcholinesterase activity in lice and ova