LEISHMANIASIS

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LEISHMANIASIS

• Dr.Abdul latif Mahesar
• Dept.of medical pharmacology
• King Saud university

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• Leishmaniasis is a parasitic disease caused by
  microsopcopic protozoans of genus leishmania
• It was identified by a British medical officer
  Sir William boog leishman.
• It occurs in Mediterranean region, Africa ,
  central and south America.

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• The parasite is in blood stream
• It is transmitted from animals to humans and
  between humans by the bite of infected sand fly
• It is diagnosed by the presence of parasite in
  biopsy from skin lesions
• 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.
• Cutaneous lesions can also be treated by
  fluconazole and metronidazole .
• Mucocutaneous disease can be treated by
  amphotericin B

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• Types of leishmaniasis
• a) Cutaneous
• b) Mucocutaneous
• c) Visceral

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life cycle

• The sand fly transfer the flagellated
  promestigote form of protozoa.This is rapidly
  phagocytized by macrophages.
• In macrophage the promastigote rapidly changes
  to nonflagellated amastigote and multiply
  ,killing cell.
• The newly released amastigote are again
  phagocytized and the cycle continues

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Treatment

• It is treated by antimonials as conventional
  therapy.
• and with pentamidine and amphotericin as backup
  therapy.

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SODIUM STIBOGLUCONATE

• 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

• It is unknown
• Evidence for inhibition of glycolysis in the
  parasite .

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Pharmacokinetics

• 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 5dextrose 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
• It is excreted in urine rapidly ,70 being
  excreted with in 6 hours.
• Half life ranges between 2 to 24 hours.
• More than one course may be required.

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ADVERSE EFFECTS

• 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

• It is used as an alternative to Na
  stibogluconate for the treatment of visceral
  leishmaniasis and sometimes used for cutaneous
  lesion , but not routinely.
• 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

• 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

• 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

• 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

• Gastrointestinal disturbances
• Elevation in liver transaminase
• 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