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LEISHMANIASIS

LEISHMANIASIS. Dr.Abdul latif Mahesar Dept.of medical pharmacology King Saud university. Pharma Team. Introductions. Leishmaniasis is a parasitic disease caused by microsopcopic protozoans of genus leishmania It was identified by a British medical officer Sir William Boog Leishman .

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LEISHMANIASIS

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  1. LEISHMANIASIS Dr.AbdullatifMahesar Dept.of medical pharmacology King Saud university Pharma Team

  2. Introductions • Leishmaniasis is a parasitic disease caused by microsopcopicprotozoans of genus leishmania • It was identified by a British medical officer Sir William BoogLeishman. • It occurs in the Mediterranean region, Africa , central and south America.

  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.

  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

  6. 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

  7. Treatment • Pentavalent antimonials, such as sodium stibogluconate • And with pentamidine and amphotericine as a backup therapy.

  8. SODIUM STIBOGLUCONATE Pentavalentantimonials include: • Sodium stibogluconate. • Meglumineantimonate. • Generally considered as first line agents for cutaneous and visceral leishmaniasis

  9. Mechanism of action: • It is unknown • Evidence for inhibition of glycolysis in the parasite at the phosphofructokinase reaction has been found.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Adverse effects • Pain at the site of injections • Hypotension • Tachycardia • Dizziness • Dyspnea • Pancreatic toxicity  hypoglycemia* * pacreatic enzyme  polysaccharide degradation  surge absorption

  16. 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

  17. 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

  18. Adverse effects • Gastrointestinal disturbances • Elevation in liver transaminase and nephrotoxicity • Teratogenic (avoid in pregnancy)

  19. 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.

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