pharmacology of anti-parasite drugs Flashcards
what are the two classes of parasites of people?
- Macroscopic parasites:
- Taenia species (tapeworms) - Enterobius (pinworm)
- Pediculus (head louse) - Microscopic parasites:
- Entamoeba (amebiasis)
- Giardia (beaver fever)
- Trichomonas (trichomoniasis)
- Plasmodium (malaria) Prevention:
To what extent can control be achieved without drugs ?
what is Taenia saginata and Taenia solium
Taenia saginata: beef tapeworm - by eating raw beef
Taenia solium: pork tapeworm - by eating raw pork
- flat and segmented
- live in river - will go with the flow until anchored to GI tract
what is the life cycle of Taenia saginata/Taenia solium?
info slide
what are the structures at the anterior end of tapeworm for attachment to wall of small intestine
what are cestocidal drugs?
cestodes = tapeworms
- praziquantel
- niclosamide
praziquantel pharmacokinetics and moa
Chemistry & pharmacokinetics:
- synthetic isoquinoline derivative
- systemic bioavailability ~80% after oral dosing within small intestine
Action: (exact mechanism unknown)
- binds to parasite integument → focal vacuolization
- influx of Ca2+ causes muscle contraction (in seconds)
- impaired function of hooks and suckers at anterior end:
→ paralysis, dislodgement, death
praziquantel clinical uses and adverse reactions
Clinical uses:
- effective against most cestode infections (drug of choice)
- safe and effective as single oral dose
- swallow without chewing (bitter taste → retching/vomiting)
Adverse reactions:
- mild, transient reactions = common (e.g. nausea, headache, abdominal discomfort)
niclosamide pharmacokinetics and moa
Chemistry & pharmacokinetics:
- salicylanilide derivative
- minimally absorbed from gastrointestinal (GI) tract
Action:
- rapidly kills scolex + segments of adult tapeworms
- mechanism of action:
* inhibition of mitochondrial anaerobic phosphorylation of ADP results in ↓ ATP production
niclosamide clinical uses and adverse reactions
Clinical uses:
- second-line choice for treatment of Taenia saginata and Taenia solium
- single oral dose effective
- cheap and readily available in many parts of world
Adverse reactions:
- minor GI complaints rarely encountered - nausea, vomiting, diarrhea
prevention of reinfection of Taenia saginata and Taenia solium
- start cooking your beef
- start cooking your pork
Life cycle of Enterobius vermicularis (pinworm)
what is Enterobius vermicularis transmission and clinical presentation?
- most common nematode infection in temperate countries
Transmission: - female parasite on perianal skin → pruritus
- eggs → hands → ingestion
- eggs sticky + can survive long periods in environment
- contamination of nightclothes / bedding
- eggs → wide dispersal in bedrooms / house
Clinical presentation: - most frequent in school age children
- most infections asymptomatic, high risk of reinfection
- itching → irritability, incontinence, weight loss
how to minimize risk of infection of enterobius vermicularis and drug of choice for treatment?
Minimise risk of infection:
- personal hygiene – handwashing, fingernail cleaning, regular bathing
- keep bedrooms scrupulously clean + dust free
- bed linen / nightclothes – change and launder frequently
Treatment:
- Drugs of choice: mebendazole, pyrantel
mebendazole chemistry and pharmacokinetics and moa
Chemistry & pharmacokinetics:
- benzimidazole (broad spectrum activity against endoparasites)
- administered orally - less than 10% absorbed (want it in the gut)
- tablets should be chewed (maximized dispersion in GIT)
MOA:
- binds to β-tubulin (parasite specific):
* inhibits polymerisation to microtubules:
→ inhibits parasite motility, glucose uptake, cell division
- slow kill → expelled in feces (within day or two)
- efficacy varies with gastro-intestinal (GI) transit time (diarrhea decreases efficacy, transit time is quicker)
mebendazole clinical uses and adverse reactions
Clinical uses:
- approved for pinworms (+ roundworms, whipworms, hookworms)
- for pinworms – treat twice at 2-week interval
Adverse reactions:
- short-term therapy – nearly free of adverse effects (abdominal pain, nausea, diarrhea = infrequent)
- embryotoxic + teratogenic in animals – contraindicated in pregnancy
pyrantel chemistry and pharmacokinetics and moa
Chemistry & pharmacokinetics:
- tetrahydropyrimidine
- poorly absorbed from GI tract activity within GI tract
Action:
- “nicotinic anthelmintic”
- acts selectively at neuromuscular junction of parasite on
nicotinic acetylcholine receptors:
→ release of acetylcholine + inhibition of acetylcholinesterase
→paralysis (very rapid paralysis of parasite)→ expulsion
pyrantel clinical uses and adverse effects
Clinical uses:
- approved for pinworms (+ roundworms, hookworms)
* narrower spectrum of activity than mebendazole
- for adult pinworms only – treat twice at 2-week interval
Adverse reactions:
- adverse effects = mild (rare for this particular drugs), transient: nausea, vomiting, diarrhea
what is pediculus capitis?
head louse - lays eggs on hair called nymph - needs blood from scalp
Life cycle of Pediculus capitis
- entire life cycle on head
- nymphs and adult lice feed on human blood
- egg to 1st nymph = 8-9 days (for eggs to hatch)
- egg to adult = 18-21 days (right in time for 2nd treatment)
- survive <2 days away from scalp at room temperature
Pediculus capitis clinical presentation, transmission and epidemiology
Clinical presentation:
- itchy head – Note: many children = asymptomatic
- adult lice + eggs (nits) on hair
– most easily seen behind ears / back of neck
Transmission:
- mainly by direct head-to-head contact
- uncommon via combs, hairbrushes, hats etc
Epidemiology:
- most common in children in childcare and elementary schools
- not a sign of poor hygiene (affects everyone)
- all socioeconomic groups affected
how do you treat Pediculus capitis?
- Permethrin
- Malathion
Treatment of Pediculus capitis: what is permethrin moa and pharmacokinetics?
- Permethrin:
- drug class = synthetic pyrethroid:
– synthetic derivative of the insecticide pyrethrin (applied topically)
– obtained from Chrysanthemum plant Action and pharmacokinetics:
- causes voltage-gated sodium channels to remain open → membrane depolarisation → rapid paralysis
- absorption through skin = minimal
- rapidly degraded to inactive metabolites in liver (typically pretty safe)
- resistance to permethrin in ~50% head lice in USA
what are some suggestions when treating Pediculus capitis?
- neither drug is significantly ovicidal (i.e. do not kill eggs)
- more than one application is typically required – retreat at
10-11 day interval - treat bed mates at the same time
- examine and treat infested household / close contacts at the same time
- manual removal of nits after successful treatment is helpful, e.g. with fine-toothed nit comb