Transcript PHARMACOLOGY

Case 12
Andrea De Mesa
Case Description
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MG, a native from Leyte, was brought to Manila
and admitted to your hospital because of
swelling of both lower extremities and scrotal
edema, noted for the past 2 weeks.
Filariasis
Diagnosis
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Filariasis
Caused by very small worm
* Wuchereria bancrofti
* Brugia malayi
Endemic in the southern part of the country
MOT: skin penetration
ELEPHANTIASIS
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Massive swelling, esp. of the genitalia and lower
extremities, resulting from obstruction of lymphatic
vessels, for example by filarial parasites, malignancies,
neurofibromatosis, or a familial congenital disease
(Milroy's disease). Prolonged swelling can cause an
increase in interstitial fibrous tissue and skin puckering
or breakdown. In patients with parasitic elephantiasis
(i.e, the filarial diseases, which are common in the
tropics), single-dose therapy with ivermectin or
ivermectin plus albendazole destroys immature but not
adult worms
Lymphatic filariasis
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Lymphatic filarial worms
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Wuchereria bancrofti
Brugia malayi & timori
In tropical areas:
SE Asia, India, Indonesia,
China, South Pacific, Central
America, Caribbean
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120 million infected
Vectored by various mosquitoes
Show different periodicity
Larval stages (microfilaria) circulate in blood at
different times, corresponding to times when
vector feeds
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Generalized life cycle
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1st stage larvae
(microfilaria=mf) circulating
in blood of human ingested
as mosquito takes blood meal
Develop over 1-3wks in
mosquito to infective 3rd
stage larvae, deposited onto
skin and enter blood stream
Mature in lymphatics, mate,
produce mff
Morphology
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Adults
Females 80-100 mm long, males half
 White, threadlike, in lymphatics
 Females bear live young (mff)
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Microfilaria
Sheathed
 In blood
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Sheath
Lymphatic Microfilaria
Wuchereria bancrofti
Brugia spp
250-300 μm
Pointed tail
Nuclei stop short of tip
Nuclei discrete, not smudged
175-230 μm
Tapered tail w/nuclei to tip
A constriction separates last 2 nuclei
(subterminal & terminal)
Sheath of B. malayi stains pink w/ Giemsa
Lymphatic Filariasis
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Initially asymptomatic until mechanical damage caused by highly
motile adult worms in lymphatic channels induce an
inflammatory response
Inflammation leads to valve damage, flow inhibition, fibrosis,
collateral channel development
Bancroftian filariasis usually in inguinal, epitrochlear, axillary,
testicular areas
Brugian filariasis usually in inguinal or axillary area, affecting
distal extremities
Early disease
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Retrograde lymphangitis, fever, chills, malaise for 3-15 days, occurring
several times/year
Lymph node abscesses in brugian type
Can get marked eosinophilia (1000->2500 cu mm)
Tropical Pulmonary Eosinophilia
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Sequestration of mff in lungs, no microfilaremia
Allergic response
Recurring episodes of wheezing or nocturnal
paroxysmal cough
Persistent hypereosinophilia (>3000/ cu mm),
high IgE levels, miliary lesions on xray
Lasts for weeks
Tx as for bancroftian filariasis
Chronic disease
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Prolonged infection leads to obstructive disease
Chyluria w/ obstruction of renal lymphatics
Hydrocele most common complaint in genital
area
Lymphadema & elephantiasis most common in
extremities (full leg w/ bancroftian, lower leg w/
brugian)
Elephantiasis of Extremities
LABORATORY
EXAMS
Thick blood Smear
Thick blood smear – most commonly used for
detection of microfilaremia
- taken 8pm-4am (filarial species have nocturnal
periodicity)
 In many chronic infections, microfilariae may not be
demosntrable in the peripheral blood. Among the
reasons include:
a. low intensity infection
b. dead worms
c. obstructed lymphatics
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For low infections, perform filtration using
Nucleopore filter or Knott’s method
Ultrasonography – may be able to demonstate
live worms in the lymphatics
Contrast lymphangiography and
Lymphscintigraphy using radiolabelled
albumin or dextran – may be able to
demonstrate obstructed lymphatics
MANAGEMENT &
PHARMACOKINETICS
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The most useful nonspecific procedure in
swelling of both lower limbs is pressure
bandaging using 6-inch strips of bath toweling,
covering with cotton elastic bandage and an
outer muslin bandage to keep out dirt.
Exercise is required to prevent cyanosis and
hasten reduction of the lymphedema
Diethylcarbamazine
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DEC for treatment of infections with these
parasites, given its high order of therapeutic
efficacy and lack serious toxicity.
Synthetic piperazine derivative, given at dose of
6mg/kg/BW, orally for 12 days, given preferably
in divided doses after meals.
Rapidly absorbed in GIT
Peak plasma level is reached within 1-2 hrs
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Plasma half-life is 2-3 hrs in presence of acidic
urine but about 10 hrs if urine is alkaline.
Drug rapidly equilibrates with all tissue except
fat
It is excreted, principally in the urine unchanged
It immobilized microfilariae (which results in
their displacement in tissues) and alters their
surface structure, making them more susceptible
to destruction by host defense mechanisms.
Mode of action against adult worm is unknowm
Ivermectin
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Semisynthetic macrocyclic lactone
Derived from the soil actinomycete, Steptomyces
avermitilis
Given orally at 200-400μg/kg for 12 days
The drug is rapidly absorbed, reaching maximum
plasma concentration at 4 hrs
Has a wide tissue distribution
Half life is 11 hrs
Excretion is almost exclusively in the feces
Ivermectin
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By opening glutamate-gated chloride channels (found
only in invertebrates) and increasing chloride
conductance
Thru binding to a novel allosteric site on the
acetylcholine nicotinic receptor to cause an increase in
transmission leading to motor paralysis.
Side effects include: skin rashes, fever, giddiness,
headaches and pain in muscles, joints and lymph gland
In general, the drug is well tolerated
THANK YOU FOR
YOUR
ATTENTION.
Enjoy the rest of your day!