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CASE 11

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CASE 11

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  1. CASE 11 Marinelle De Los Santos

  2. 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.

  3. What’s your diagnosis? • ENTEROBIASIS • The pinworm (Genus Enterobius) is a parasitic roundworm of the phylum Nematoda. • also known as the threadwormsEnterobius vermicularis

  4. 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 MORPHOLOGY Two pinworms, captured on emergence from the anus. Markings are 1 mm apart

  5. 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

  6. 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

  7. 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

  8. 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 24-48 hours

  9. 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 90-100% MOA • inhibiting microtuble synthesis, irreversibly impairing glucose uptake

  10. 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

  11. 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

  12. PYRANTEL PAMOATE cont… MOA • 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%

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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