LEISHMANIASIS Dr.Abdul latif Mahesar Dept.of medical pharmacology King Saud university 5/29/2018

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.

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. 5/29/2018

It can cause visceral disease mainly enlargement of liver and spleen with anemia and intermittent fever, as well as cutaneous and mucocutaneous lesions. 5/29/2018

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

Types of leishmaniasis a) Cutaneous b) Mucocutaneous c) Visceral 5/29/2018

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 5/29/2018

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Treatment It is treated by antimonials as conventional therapy. and with pentamidine and amphotericin as backup therapy. 5/29/2018

SODIUM STIBOGLUCONATE Pentavalent antimonials include: Sodium stibogluconate Meglumine antimonate Generally considered as first line agents for cutaneous and visceral leishmaniasis 5/29/2018

Mechanism of action: It is unknown Evidence for inhibition of glycolysis in the parasite . 5/29/2018

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. 5/29/2018

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. 5/29/2018

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 5/29/2018

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 5/29/2018

Pharmacokinetics It is not absorbed orally It is accumulated and eliminated very slowly in urine It has a half life of 12 days 5/29/2018

Its mechanism of action is unknown 5/29/2018

Adverse effects Pain at the site of injections Hypotension tachycardia Dizziness Dyspnea Pancreatic toxicity hypoglycemia 5/29/2018

Reversible renal insufficiency GIT disturbances Cardiac arrhythmia Abnormal liver function tests it can also be used for the treatment of pneumocystosis and African trypanosomiasis 5/29/2018

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 5/29/2018

Adverse effects Gastrointestinal disturbances Elevation in liver transaminase Teratogenic 5/29/2018

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 5/29/2018