1. Marinelle De Los Santos
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 threadworms Enterobius vermicularis

4. 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

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 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 %
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…
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