anti leishmaniasis by fxz3722

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									  LEISHMANIASIS
Dr.Abdul latif Mahesar
Dept.of medical pharmacology
King Saud university




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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.

    It occurs in the 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 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:

    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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Treatment
   Pentavalent antimonials, such as sodium
    stibogluconate

   And with pentamidine and
    amphotericine as a backup therapy.




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SODIUM 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:
  It is unknown
 Evidence for inhibition of glycolysis in
  the parasite at the phosphofructokinase
  reaction has been found.




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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 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:
 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

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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




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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

   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*

* pacreatic enzyme    polysaccharide degradation  surge
  absorption


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   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

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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




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Adverse effects
   Gastrointestinal disturbances

   Elevation in liver transaminase and
    nephrotoxicity

   Teratogenic (avoid in pregnancy)




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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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