anti leishmaniasis

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LEISHMANIASIS

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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 sandfly.

It is diagnosed by the presence of parasite in biopsy from skin lesions

Its treatment is limited due to toxicities andfailure of the drugs.

It can cause visceral disease mainly enlargementof liver and spleen with anemia and intermittent

fever, as well as cutaneous and mucocutaneouslesions.

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Types of leishmaniasis

a) Cutaneous

b) Mucocutaneous

c) Visceral

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Life cycle:

The sand fly transfer the flagellated promastigoteform of protozoa. This is rapidly phagocytosed bymacrophages.

In the macrophage the promastigote rapidlychanges to nonflagellated amastigote and multiplykilling cell.

The newly released amastigote are again phagocytized and the cycle continues

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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 ( kala – azar)

leishmaniasis

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Mechanism of action:

It is unknown

-SH dependent enzymes are inhibited

Evidence for inhibition of glycolysis and

fatty acid oxidation path ways.

Pentavalent – trivalent.

Efflux of glutathione and thiol.

Resistance

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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 20days for cutaneous leishmaniasis and 28 days forvisceral and mucocutaneous disease.

It can be diluted in 5% dextrose for ease ofadministration.

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It is distributed in extra vascular compartment

It is excreted in urine rapidly, 70 % beingexcreted 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 centralchest pain occurs, the drug must be stopped.

Myalgia, Arthralgia

Fever, Cough, &Headache

Serum amylase may increase to 4 times the normal if thelevel 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 sodiumstibogluconate 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 5 – 15 weeks.

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Anti-protozoal drugs

Active against: Trypanosoma

leshmaniasis

fungus - pneumocystis jiroveci Pentamidine interfere with synthesis

of RNA, DNA and proteins.



Pharmacokinetics:

It is not absorbed orally

It is accumulated and eliminated very slowly in

urine

It has a half-life of 12 days

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Adverse effects

Pain at the site of injections Strong basic – releases histamine

Hypotension

Tachycardia

Dizziness

Dyspnea

Pancreatic toxicity hypoglycemia

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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 Africantrypanosomiasis

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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 analternative therapy for visceral leishmaniasis

resistant to sodium stibogluconate.

Forms micropores. 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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Ketaconazole: inhibits conversion oflanosterol to ergosterol.

Paramomycin: aminoglycoside effective

in SSG resistant cases. Allopurinol: leishmania metabolizes this

into the corresponding nucleotides.

Companion drug toantimonials.

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Trypanosomiasis : Caused byTrypanosoma

African sleeping sickness Tryp brucei gambiense – slow to enter CNS

Tryp brucei rhodesiense – invade CNS early.

American sleeping sickness – Chagas disease -- tryp cruzi - cardiomyopathy




Suramin: Trypanosomiasis

Used in the early treatment and

prophylaxis of Africantrypanosomiasis.

It acts by inhibiting enzymes ofenergy metabolism including glycerolphosphate dehydrogenase – for

trypanocidal activity




Melarsoprol : Trypanosomiasis

Trivalent arsenical

Mainly used to treat trypanosomainfections with CNS involvement.

The drug acts by reacting with SH

groups of various enzymes




Pentamidine Trypanosomiasis

Active against: Trypanosoma

leshmaniasis fungus - pneumocystis jiroveci

Pentamidine interfere with synthesis

of RNA, DNA and proteins. Administered IV or aerosol

Nephrotoxicity is the limitation.




Nifurtimox : Trypanosomiasis Chagasdisease

Used in the treatment of Trypanosomacruzi infection.

It acts by generating superoxide and

hydrogen peroxide radicals –

toxic asthey lack catalase.

Orally well absorbed



Trichomoniasis

Oral

Metronidazole: 400 mg TDS 7 days or 2 gm

single dose

Secnidazole 2 gm single dose

Tinidazole 600mg daily for 7 days or 2 gm

single dose.

nimorazole 2g single dose.

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Intravaginal:

diiodohydroxyquin, quiniodochlor,

clotrimazole, hamycin, natamycin, and

povidone-iodine.

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