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LEISHMANIASIS

Dr.Abdul latif Mahesar

Dept.of medical pharmacology

King Saud university

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.

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 5%dextrose for ease of administration

Cardiac monitoring should be performed ,if central chest pain occurs,drug must be stopped.

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