LEISHMANIASISLEISHMANIASIS

Dr.Abdul latif MahesarDept.of medical pharmacologyKing 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 the Mediterranean region, Africa , central and south America.

Introductions

The parasite is in blood stream

It is transmitted from animals to humans and between humans by the bite of an 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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primary drug for all forms of the disease = Sodium stibogluconate

Cutaneous lesions can also be treated by fluconazole and metronidazole .

Mucocutaneous disease = amphotericin B

Types of leishmaniasis

a) Cutaneous

b) Mucocutaneous

c) Visceral

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Life cycle:Life cycle:

The sand fly transfer the flagellated promastigote form of protozoa. This is rapidly phagocytosed by macrophages.

In the 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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TreatmentTreatmentPentavalent antimonials, such as sodium

stibogluconate

And with pentamidine and amphotericine as a backup therapy.

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SODIUM STIBOGLUCONATESODIUM STIBOGLUCONATE

Pentavalent antimonials include:

1. Sodium stibogluconate.

2. Meglumine antimonate.

Generally considered as first line agents for cutaneous and visceral leishmaniasis

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Mechanism of action:Mechanism of action:

It is unknown Evidence for inhibition of glycolysis in

the parasite at the phosphofructokinase reaction has been found.

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Pharmacokinetics:Pharmacokinetics:

It does not get absorbed orally

It is administered parenterally in a dose of 20mg/kg /day IM or slow IV 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.

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It is distributed in extra vascular compartment

It is excreted in urine rapidly, 70 % being excreted within 6 hours.

Half life ranges between 2 to 24 hours.

More than one course may be required.

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ADVERSE EFFECTS:ADVERSE EFFECTS:Pain at the injection siteGastrointestinal upsetCardiac arrhythmias, Brdycardia, hypotension Cardiac monitoring should be performed, if central

chest pain occurs, the drug must be stopped.Myalgia, ArthralgiaFever, Cough, &HeadacheSerum amylase may increase to 4 times the normal if the

level is raised greater than 4 times the drug must be stopped.

Renal and hepatic function should be monitored regularly

Hemolytic anemiaResistance is frequent

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PENTAMIDINE ISETHIONATEPENTAMIDINE ISETHIONATE

It is used as an alternative to sodium 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:Pharmacokinetics: It is not absorbed orally

It is accumulated and eliminated very slowly in urine

It has a half-life of 12 days

Its mechanism of action is unknown

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Adverse effectsAdverse effects Pain at the site of injections Hypotension Tachycardia Dizziness Dyspnea Pancreatic toxicity hypoglycemia*

* pacreatic enzyme polysaccharide degradation surge absorption

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Reversible renal insufficiency GIT disturbances Cardiac arrhythmia Abnormal liver function testsRash, metallic taste, fever.Hypocalcemia, thrombocytopenia, hallucination.

It can also be used for the treatment of pneumocystis pneumonia and African trypanosomiasis

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MILTEFOSINEMILTEFOSINE

It is an alkylphosphocholine analog

It is used in the treatment of visceral leishmaniasis

It is first orally effective drug, and is administered 2.5 mg/kg daily for adults

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Adverse effectsAdverse effects

Gastrointestinal disturbances

Elevation in liver transaminase and nephrotoxicity

Teratogenic (avoid in pregnancy)

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Amphotericin BAmphotericin B

An antifungal drug which can be used as an alternative therapy for visceral leishmaniasis resistant to sodium stibogluconate.

The liposomal form has shown excellent efficacy. 3mg/kg/day on day1-5, 14 and 21.

Non-liposomal 1mg/kg/day IV on every other day for 30 days.

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