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LEISHMANIASIS Dr.Abdul latif Mahesar Dept.of medical pharmacology King Saud university 5/11/20151.

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Presentation on theme: "LEISHMANIASIS Dr.Abdul latif Mahesar Dept.of medical pharmacology King Saud university 5/11/20151."— Presentation transcript:

1 LEISHMANIASIS Dr.Abdul latif Mahesar Dept.of medical pharmacology King Saud university 5/11/20151

2 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

3 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. 5/11/20153

4 primary drug for all forms of the disease = Sodium stibogluconate Cutaneous lesions can also be treated by fluconazole and metronidazole. Mucocutaneous disease = amphotericin B

5 Types of leishmaniasis a) Cutaneous b) Mucocutaneous c) Visceral 5/11/20155

6 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 5/11/20156

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9 Treatment Pentavalent antimonials, such as sodium stibogluconate And with pentamidine and amphotericine as a backup therapy. 5/11/20159

10 SODIUM STIBOGLUCONATE SODIUM STIBOGLUCONATE Pentavalent antimonials include: 1. Sodium stibogluconate. 2. Meglumine antimonate. Generally considered as first line agents for cutaneous and visceral leishmaniasis 5/11/201510

11 Mechanism of action: It is unknown Evidence for inhibition of glycolysis in the parasite at the phosphofructokinase reaction has been found. 5/11/201511

12 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. 5/11/201512

13 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. 5/11/201513

14 ADVERSE EFFECTS: Pain at the injection site Gastrointestinal upset Cardiac arrhythmias, Brdycardia, hypotension Cardiac monitoring should be performed, if central chest pain occurs, the drug must be stopped. Myalgia, Arthralgia Fever, Cough, &Headache Serum 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 anemia Resistance is frequent 5/11/201514

15 PENTAMIDINE ISETHIONATE PENTAMIDINE 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 5/11/201515

16 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 5/11/201516

17 Adverse effects Pain at the site of injections Hypotension Tachycardia Dizziness Dyspnea Pancreatic toxicity  hypoglycemia* * pacreatic enzyme  polysaccharide degradation  surge absorption 5/11/201517

18 Reversible renal insufficiency GIT disturbances Cardiac arrhythmia Abnormal liver function tests Rash, metallic taste, fever. Hypocalcemia, thrombocytopenia, hallucination. It can also be used for the treatment of pneumocystis pneumonia and African trypanosomiasis 5/11/201518

19 MILTEFOSINE 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 5/11/201519

20 Adverse effects Gastrointestinal disturbances Elevation in liver transaminase and nephrotoxicity Teratogenic (avoid in pregnancy) 5/11/201520

21 Amphotericin 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. 5/11/201521

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