Download CASE 11 - Caangay

CASE 11
Marinelle De Los Santos
PJ a 4 y/o boy was playing
with his friends when he
suddenly vomited a large
worm. History revealed
nocturnal pruritus.
1. What’s your diagnosis?
2. What laboratory examinations will
you request?
3. How would you manage this case?
4. Discuss the pharmacokinetics of
the drug used.
1. What’s your diagnosis?
• ENTEROBIASIS
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The pinworm (Genus Enterobius) is a parasitic
roundworm of the phylum Nematoda.
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also known as the threadworms Enterobius vermicularis
MORPHOLOGY
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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
PATHOGENESIS
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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
2. What laboratory examinations
will you request?
1) SCOTCH TAPE TEST
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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
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NO eosinophiliia because there is NO tissue invasion
3) OBSERVATION
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At night the larger adult females can sometimes be
seen with the unaided eye, crawling across the
perineal area
3. How would you manage this
case?
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Administer anthelminthics drugs:
a) MEBENDAZOLE
b) PYRANTEL PAMOATE
c) ALBENDAZOLE
d) PIPERAZINE (no longer used)
To be an effective anthelminthic drug it must:
1) be able to penetrate the cuticle of the worm OR
2) gain access to its alimentary tract
Anthelminthic Drugs MOA:
1) Paralysis worm
2) Damaging its cuticle, leading to partial digestion or to rejection
by immune mechanims
3) Interfere with metabolism of the worm
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wash hands before eating (to prevent any pinworm eggs under
fingernails from being ingested)
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wash any area or clothes that have touched or been in the
vicinity of the infected areas
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treating the entire family is often necessary for cure
4. Discuss the pharmacokinetics
of the drug used?
a) MEBENDAZOLE (DOC)
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Synthetic Benzimidazole
Wide spectrum of anthelminthic activity
Low incidence of adverse effects
CHEMISTY & PHARMACOKINETICS
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Less than 10% of orally administered mebendazole is
absorbed
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Absorbtion is increased if ingested with a fatty meal
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More than 90% of absorbed durg is protein bound
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Rapidly converted to inactive metabolites (primarily
during its first pass in the liver)
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Half life of 2-6 hours
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Excreted mostly in urine, principally as decarboxylated
derivatives and bile within 24-48 hours
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
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
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High dose therapy: hypersensitivity reactions (rash,
urticaria), a granulocytosis, alopecia, elevation of liver
enzymes
CONTRAINDICATIONS & CAUTIONS
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Teratogenic therefore, contrainicated in pregnancy
• Used with caution in children under 2 y/o because of
convulsions
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Plasma levels decreased by concomitant use of
carbamazepine or phenytoin & increased by cimetidine
b) PYRANTEL PAMOATE
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Broad spectrum anthelmintic
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Highly effective for the treatment of pinworm, ascaria, and
Trichostrongylus orientalis
CHEMISTRY & PHARMACOKINETICS
• Tetrahydropyrimidine derivative
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Poorly absorbed from the GIT
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Active mainly against luminal organisms
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Peak plasma levels reached in 1-3 hours
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Over half of the adminstered dose is recovered unchanged in the
feces
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%
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
c) ALBENDAZOLE
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Benzimidazole carbamate
• Broad spectrum oral anthelmintic
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DOC for hydatid disease and cysticercosis, also used for
pinworm & hookworm infections, ascariasis, trichuriasis,
strongyloidiasis
CHEMISTY & PHARMACOKINETICS
• Oral administration
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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
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Rapidly undergoes first pass metabolism in the liver to
the active metabolite ALBENDAZOLE SULFOXIDE
ALBENDAZOLE cont…
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Reaches variable maximum plasma concentration about 3 hours after a
400mg oral dose
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The plasma concentration of its active metabolite is 100 times greater
that that of mebendazole
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Plasma half life is 8-12 hours
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Sulfoxide is mostly protein bound, distributes well to tissues and enters
bile, CSF and hydatid cysts.
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Metabolites excreted in urine
MOA
• inhibiting microtuble systhesis, irreversibly impairing glucose uptake
USE
• DOSE 400 mg orally repeated in 2 weeks
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
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
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