Transcript LEISHMANIASIS dec 2010-2011.ppt

LEISHMANIASIS
Dr.Abdul latif Mahesar
Dept.of medical pharmacology
King Saud university
8/6/2016
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Leishmaniasis is a parasitic disease caused by
microsopcopic protozoans of genus leishmania
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It was identified by a British medical officer Sir
William boog leishman.
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It occurs in Mediterranean region, Africa , central
and south America.
The parasite is in blood stream
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It is transmitted from animals to humans and
between humans by the bite of infected sand fly
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It is diagnosed by the presence of parasite in
biopsy from skin lesions
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Its treatment is limited due to toxicities and
failure of the drugs.
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It can cause visceral disease mainly
enlargement of liver and spleen with
anemia and intermittent fever, as well as
cutaneous and mucocutaneous lesions.
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Sodium stibogluconate is a primary drug for all
forms of the disease.
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Cutaneous lesions can also be treated by
fluconazole and metronidazole .
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Mucocutaneous disease can be treated by
amphotericin B
Types of leishmaniasis
a) Cutaneous
b) Mucocutaneous
c) Visceral
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life cycle
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The sand fly transfer the flagellated promestigote
form of protozoa.This is rapidly phagocytized by
macrophages.
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In macrophage the promastigote rapidly changes
to nonflagellated amastigote and multiply ,killing
cell.
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The newly released amastigote are again
phagocytized and the cycle continues
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Treatment
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It is treated by antimonials as conventional
therapy.
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and with pentamidine and amphotericin as
backup therapy.
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SODIUM STIBOGLUCONATE
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Pentavalent antimonials include:
Sodium stibogluconate
Meglumine antimonate
Generally considered as first line agents for
cutaneous and visceral leishmaniasis
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Mechanism of action:
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It is unknown
Evidence for inhibition of glycolysis in
the parasite .
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Pharmacokinetics
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It does not get absorbed orally
It is administered parenterally in a dose of
20mg/kg /day /IM or slow I/V infusion for 20
days for cutaneous leishmaniasis and 28 days
for visceral and mucocutaneous disease.
It can be diluted in 5%dextrose for ease of
administration
 Cardiac monitoring should be performed ,if
central chest pain occurs,drug must be stopped.
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It is distributed in extra vascular compartment
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It is excreted in urine rapidly ,70 % being
excreted with in 6 hours.
Half life ranges between 2 to 24 hours.
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More than one course may be required.
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ADVERSE EFFECTS:
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Pain at the site of injection site
Gastrointestinal upset
Cardiac arrhythmias ,Brdycardia ,hypotension
Myalgia
Fever
Cough
Headache
Arthralgia
serum amylase may increase to 4 time the normal.
Renal and hepatic function should be monitored
regularly
Resistance is frequent
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PENTAMIDINE ISETHIONATE
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It is used as an alternative to Na stibogluconate
for the treatment of visceral leishmaniasis and
sometimes used for cutaneous lesion , but not
routinely.
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It is given in a dose of 2-4 mg/kg Im daily or
every other day up to 15 days
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Pharmacokinetics
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It is not absorbed orally
It is accumulated and eliminated very slowly in
urine
It has a half life of 12 days
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Its mechanism of action is
unknown
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Adverse effects
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Pain at the site of injections
Hypotension
tachycardia
Dizziness
Dyspnea
Pancreatic toxicity
hypoglycemia
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Reversible renal insufficiency
GIT disturbances
Cardiac arrhythmia
Abnormal liver function tests
it can also be used for the treatment of
pneumocystosis and African trypanosomiasis
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MILTEFOSINE
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It is alkylphosphocholine analog
It is used in the treatment of visceral
leishmaniasis
it is orally effective and administered
2.5mg/kg daily for adults
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Adverse effects
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Gastrointestinal disturbances
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Elevation in liver transaminase
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Teratogenic
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Am Amphotericin B photericin B
an antifungal drug which can be used as an
alternative therapy for visceral leishmaniasis.
liposomal form has shown excellent
efficacy.3mg/kg/day on day1-5, 14 and 21.non
liposomal 1mg/kg/day i.v on alternate day for
30 days
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