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Marinelle De Los Santos
CASE 11 Marinelle De Los Santos
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PJ a 4 y/o boy was playing with his friends when he suddenly vomited a large worm. History revealed nocturnal pruritus. What’s your diagnosis? What laboratory examinations will you request? How would you manage this case? Discuss the pharmacokinetics of the drug used.
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What’s your diagnosis? ENTEROBIASIS
The pinworm (Genus Enterobius) is a parasitic roundworm of the phylum Nematoda. also known as the threadworms Enterobius vermicularis
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MORPHOLOGY creamy white colored nematodes
female measuring only approximately 10mm by 0.4mm wide females have a cuticular expansion at their anterior ends, with a long pointed tail male parasites, which are much less numerous than the females, are much smaller, measuring only up to 5mm long, and have a curved tail, with a small bursa like expansion, and a single spicule The head has a mouth with three small lips Two pinworms, captured on emergence from the anus. Markings are 1 mm apart
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PATHOGENESIS Eggs ingested Hatch in the duodenum Mate
Pinworms travel & mature in cecum and ascending large intestine Female migrates to perianal area (usually at night) to lay her eggs Air contact stimulates the female to lay her eggs Eggs become infectious 4-6 hours later Infection causes severe perianal itching Infected individual will scratch the area then reinfect himself or others (hand to mouth) because the hands are now covered with microscopic pinworm eggs Infection is more of a nuisance than dangerous
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2. What laboratory examinations will you request?
SCOTCH TAPE TEST sticky side of a strip of cellophane tape is pressed against the peri-anal skin, then examined under a microscope for pinworm eggs 2) EOSINOPHILIA COUNT NO eosinophiliia because there is NO tissue invasion 3) OBSERVATION At night the larger adult females can sometimes be seen with the unaided eye, crawling across the perineal area
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3. How would you manage this case?
Administer anthelminthics drugs: a) MEBENDAZOLE b) PYRANTEL PAMOATE c) ALBENDAZOLE d) PIPERAZINE (no longer used) To be an effective anthelminthic drug it must: be able to penetrate the cuticle of the worm OR gain access to its alimentary tract Anthelminthic Drugs MOA: Paralysis worm Damaging its cuticle, leading to partial digestion or to rejection by immune mechanims Interfere with metabolism of the worm wash hands before eating (to prevent any pinworm eggs under fingernails from being ingested) wash any area or clothes that have touched or been in the vicinity of the infected areas treating the entire family is often necessary for cure
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4. Discuss the pharmacokinetics of the drug used?
MEBENDAZOLE (DOC) Synthetic Benzimidazole Wide spectrum of anthelminthic activity Low incidence of adverse effects CHEMISTY & PHARMACOKINETICS Less than 10% of orally administered mebendazole is absorbed Absorbtion is increased if ingested with a fatty meal More than 90% of absorbed durg is protein bound Rapidly converted to inactive metabolites (primarily during its first pass in the liver) Half life of 2-6 hours Excreted mostly in urine, principally as decarboxylated derivatives and bile within hours
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MEBENDAZOLE (cont…) USE
Can be taken before or after meals, tablets should be chewed before swallowing DOSE 100mg once, repeated at 2 weeks Cure rate % MOA inhibiting microtuble synthesis, irreversibly impairing glucose uptake
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MEBENDAZOLE (cont…) ADVERSE EFFECTS
Short term mebedazole therapy is nearly free of adverse effects: mild nausea, vomiting, diarrhea and abdominal pain have been reported infrequently High dose therapy: hypersensitivity reactions (rash, urticaria), a granulocytosis, alopecia, elevation of liver enzymes CONTRAINDICATIONS & CAUTIONS Teratogenic therefore, contrainicated in pregnancy Used with caution in children under 2 y/o because of convulsions Plasma levels decreased by concomitant use of carbamazepine or phenytoin & increased by cimetidine
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b) PYRANTEL PAMOATE Broad spectrum anthelmintic
Highly effective for the treatment of pinworm, ascaria, and Trichostrongylus orientalis CHEMISTRY & PHARMACOKINETICS Tetrahydropyrimidine derivative Poorly absorbed from the GIT Active mainly against luminal organisms Peak plasma levels reached in 1-3 hours Over half of the adminstered dose is recovered unchanged in the feces
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PYRANTEL PAMOATE cont…
Nueromuscular blocking agent that causes release of acetycholine and inhibition of cholinesterase Results in paralysis or worm Followed by expulsion of worms USE DOSE 11 mg / kg (maximum 1 g) given orally once with or without food. Repeat dose in 2 weeks Cure rate is 95%
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PYRANTEL PAMOATE (cont…)
ADVERSE REACTIONS Infrequent, mild and transient Nausea, vomiting, diarrhea, abdominal cramps, dizzimess, drowsiness, headache, insomnia, rash, fever & weakness CONTRAINDICATIONS & CAUTIONS Use with caustion in patients with liver dysfunction, since low transient aminotransferase elevations have been noted Experience with the drug in pregnant women and children under 2 years is limited
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c) ALBENDAZOLE Benzimidazole carbamate
Broad spectrum oral anthelmintic DOC for hydatid disease and cysticercosis, also used for pinworm & hookworm infections, ascariasis, trichuriasis, strongyloidiasis CHEMISTY & PHARMACOKINETICS Oral administration Erratically absorbed (increased with a fatty meal) Albendazole is administered on an empty stomach when used against intra luminal parasites but with a fatty meal when used against tissue parasites Rapidly undergoes first pass metabolism in the liver to the active metabolite ALBENDAZOLE SULFOXIDE
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ALBENDAZOLE cont… Reaches variable maximum plasma concentration about 3 hours after a 400mg oral dose The plasma concentration of its active metabolite is 100 times greater that that of mebendazole Plasma half life is 8-12 hours Sulfoxide is mostly protein bound, distributes well to tissues and enters bile, CSF and hydatid cysts. Metabolites excreted in urine MOA inhibiting microtuble systhesis, irreversibly impairing glucose uptake USE DOSE 400 mg orally repeated in 2 weeks
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ALBENDAZOLE (cont…) Adverse Reactions
Short term: Mild and transient epigatric distress, diarrhea, headache, nausea, dizziness, lassitude & insomnia Long term: abdominal distress, headaches, fever, fatigue, alopecia, increases in liver enzymes & pancytopenia (blood counts and liver functions studies should be followed during long term therapy) Contraindications & Cautions Patients with known hypersensitivity to other benzimiazoles drugs Patients with cirrhosis Saftey of albendazole in pregnancy and in children under 2y/o has not been established
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d) PIPERAZINE CHEMISTRY & PHARAMCOKINETICS
Available as hexahydrate and as a variety of salts Given orally & some but not all is absorbed Maximum plasma levels reached in 2-4 hours It is partly metabolized and the remainder is excreted unchanged in the urine in 2-6 hours and the excretion is complete within 24 hours Has been largely superseded by the benzimidazoles MOA Inhibits neuromuscular transmission in the worm, probably acting like GABA, the inhibitory neurotransmitter on GABA chloride channels in the nematode muscle Paralyzed worms are expelled alive
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PIPERAZINE cont… ADVERSE EFFECTS
Occasional mild adverse effects include nausea, vomiting, diarrhea, abdominal pain, dizziness and headache Nuerotoxicity and allergic reactions are rare CONTRAINDICATIONS AND CAUTIONS Pregnant Patients with impaired renal or hepatic function Patients with history of epilepsy or chronic neurological disease
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