Leishmaniasis is caused by protozoan parasites of the genus Leishmania and transmitted by sandfly bites. It manifests as three main forms: visceral, affecting internal organs; cutaneous, causing skin lesions; and mucocutaneous, affecting skin and mucous membranes. Current treatments include pentavalent antimonials as first-line but resistance has emerged, requiring alternatives like amphotericin B, miltefosine, pentamidine, paromomycin, and azole antifungals. New drug development is needed as most treatments are toxic and require hospitalization.

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2.  Leishmaniosis is a dismissed vector-borne tropical contamination thought to be an ailment of
poor people.
 It is a standout among the most ignored tropical sickness as far as medication disclosure and
improvement.
 The administration of the heterogeneous disorders controlled by parasites having a place
with the genus Leishmania is, especially troublesome in created, non-endemic nations
attributable to the newness of doctors with clinical side effects, demonstrative conceivable
outcomes, and accessible treatment choices.
 The flagellate leishmania is transmitted to humans by the bite of the female sandfly of the
genus Phlebotomus.
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4.  Three principal diseases result from infection with Leishmania spp.
 L.donovani causes visceral leishmaniasis;
In visceral leishmaniasis, the protozoan parasitizes the reticuloendothelial cells, and this results
in an enlargement of the lymph nodes, liver, and spleen; the spleen can become massive.
 L.tropica and L.major produce cutaneous leishmaniasis,
Cutaneous leishmaniasis remains localized to the site of inoculation, where it forms a raised
disfiguring ulcerative lesion.
 L.braziliensis causes South American mucocutaneous leishmaniasis
 South American leishmaniasis is variable in its presentation. It is characterized by ulceration of the
mucous membranes of the nose, mouth, and pharynx; some disfiguring skin involvement also is possible.
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5. VISCERAL
MUCOCUTANEOUS
CUTANEOUS
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6.  Most antileishmanial medications are very lethal and introduce resistance issues or require
hospitalization, being along these lines not sufficient to the field.
 As of late changes have been accomplished by blend treatment, decreasing the time, and cost of
treatment. Regardless, new medications are still direly required.
 Chemotherapy is the only compelling approach to treat leishmaniosis.
 Chemotherapy against leishmaniosis is constructed primarily on toxic pentavalent antimonial created
during the main portion of the most recent century .
 The objective for chemotherapy is the intracellular amastigote that survives and partitions in tissue
macrophages whereby bringing about the sickness.
 The requests for new antileishmanial drugs have been bolstered as of late by the exhibit of gained
imperviousness to the pentavalent antimonial medications, the principal line chemotherapy.
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7. Pentavalent antimonials
 Antimonial is essentially used as first-line parenteral treatment for a wide
range of leishmaniosis. Essentially, they are utilized for the treatment of CL
and instinctive leishmaniosis.
 The primary restriction related with pentavalent antimonial is resistance
 Poisonous pentavalent antimonial, which constitutes the backbone of treatment for
leishmaniasis, has practically been deserted in India attributable to the absence of reaction of
L.donovani against glucantime.
Eg Meglumine antimonite (glucantime) and SSG (Pentostam)
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8. Mechanism of action
 The pentavalent antimonials act as prodrugs that are reduced to the more toxic Sb3+ species that kill
amastigotes within the phagolysosomes of macrophages.
 They are activated within the amastigote, but not in the promastigote, by converting to a lethal trivalent
form. Their activation mechanism is not known.
 Antileishmanial activity might be due to action on the host macrophage.
Pharmacokinetics
The drug is given intravenously or intramuscularly; it is not active orally.
Elimination occurs in two phases, the first with a t½ of about 2 h, the second with a much longer half-
time (33–76 h).
The drug is eliminated in the urine.
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9.  The standard course is
20 mg/kg/d for 20 days for cutaneous disease
28 days for visceral leishmaniasis.
o Patients who respond show clinical improvement within 1–2 weeks of initiating therapy.
o Patients infected with HIV often relapse after therapy.
Side Effects
 Chemical pancreatitis in nearly all patients
 Elevation of serum hepatic transaminase levels
 Bone marrow suppression, manifested by decreased red cell, white cell, and platelet counts
 muscle and joint pain
 weakness and malaise; headache; nausea and abdominal pain; and skin rashes.
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10. Polyene macrolide group of antibiotics
Amphotericin B (Amp B)
It is synthesized from actinomycetes microorganisms and compelling against pentavalent antimony-safe
mucocutaneous ailment.
It follows up on sterols and phospholipids in cell films.
 Amp B is at present proposed as an option first-line treatment and is the drug of choice for antimonial-
resistant cases.
 The principle restriction related with Amp B is harmfulness and its toxicity.
Amphotericin B is therapy for cutaneous or mucosal leishmaniasis and is effective for treating
immunocompromise patients.
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11. Mechanism of action
o Leishmania has sterol composition, and amphotericin binds this sterols preferentially over host
cholesterol.
o It complexes with 24-substituted sterols, such as ergosterol in cell membrane, thus causing
pores which alter ion balance and result in cell death.
Pharmacokinetics
 Amphotericin B is poorly absorbed from the gastrointestinal tract.
 It is administered by slow intravenous (IV) infusion.
 Is widely distributed in most tissues, except CSF, vitreous humor, peritoneal fluid, synovial fluid.
 It is mostly metabolized and its metabolites are excreted primarily in the urine over a long period of
time. The serum half-life is approximately 15 days.
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12. Amphotericin B has a low therapeutic index.
The toxicity of amphotericin B can be divided into two broad categories
1. Infusion-related toxicity
 fever, chills, muscle spasms, vomiting, headache, thrombophlebitis, and hypotension.
2. Cumulative toxicity
 Renal impairment can cause decrease in glomerular filtration rate and renal tubular function, renal tubular
acidosis and severe potassium and magnesium wasting.
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13. Phosphocholine analog
Miltefosine (MT):
 MT is an alkyl phosphocholine (ALP) imitative which was previous used as an anticancer drug but
nowadays cast off as antileishmanial drug i.e. operative against both CL and VL (oral treatment).
 It is used in opposition to antimony resistant parasites
 It is likewise utilized for the treatment of CL which is created by Leishmania vienna panamensis.
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14. Mechanism of action
The mechanism of action of miltefosine is not understood.
Studies suggest that the drug may alter:
 ether-lipid metabolism,
 cell signaling, or
 glycosylphosphatidylinositol anchor biosynthesis.
Pharmacokinetics
 Miltefosine is well absorbed orally and distributed throughout the human body.
Detailed pharmacokinetic data are lacking, with the exception that miltefosine has a long t½(1–4 weeks).
Plasma concentrations are proportional to the dose for Leishmaniasis,
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15. o Vomiting and diarrhea are reported as frequent side effects, in up to 60% of patients.
o Elevations in hepatic transaminases and serum creatinine also have been reported.
 It has teratogenic potential, miltefosine is contraindicated in pregnant women.
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16. Diamidine Derivative; Pentamidine isethionate (pentam 300)
Pentamidine
 It is considered as second-line treatment for instances of lethargy to antimony, in VL and CL.
 Diverse creators have told distinctive system of activity of this medication.
 It has broad spectrum activity.
 Mechanism of action
 The mechanism of action of the diamidines is unknown
 It is accumulated by the parasite; effects include binding to kinetoplast DNA.
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17. Pharmacokinetics
Pentamidine is administered IM or IV. Equivalent blood levels are achieved with both routes.
The drug is extensively bound in tissues. Penetration to the brain and cerebrospinal fluid is poor.
Between 50% and 65% of each dose is excreted rapidly in the urine.
Adverse Effect
 Pentamidine can produce serious side effects when given IM or IV.
 Sudden and severe hypotension occurs in about 1% of patients.
 The fall in blood pressure may cause tachycardia, dizziness, and fainting.
 Hypoglycemia and hyperglycemia have occurred.
 Intramuscular administration is painful.
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18. Broad spectrum antibiotics: Aminoglycoside antibiotics
Paromomycin sulfate:
It is the main aminoglycoside with clinically essential antileishmanial movement.
 Paromomycin is currently in phase IV clinical trials against leishmaniasis
 Paromomycin in methylbenzethonium chloride ointment is utilized as a topical treatment for Leishmania
major and Leishmania mexicana.
 It can be conjugated with antimonials to reduce the number of injections.
Mechanism of Action
 Inhibit protein synthesis by binding to 30s units of ribosome, causing misleading and premature
termination of mRNA translation.
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19. Pharmacokinetics
 The drug is not absorbed from the GI tract; thus, the actions of an oral dose are confined to the GI tract,
with 100% of the oral dose recovered in the feces
Side Effect
 The main side effect is inflammation and pigmentation
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20. Nucleoside analogs
The azoles (ketoconazole, fluconazole, and itraconazole) are dynamic option drugs, offering an appealing
plausibility for the treatment of VL.
Ketoconazole
 Ketoconazole acted by interferes with cellwall biosynthesis, inhibiting the 14 alpha-demethylation of
lanosterol to ergosterol.
Fluconazole
 Fluconazole is utilized orally. Inhibiting the cytochrome P-450-mediated 14 alpha-demethylation of
lanosterol, blocking ergosterol synthesis, and causing accumulation of 14 alpha-methyl sterols.
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21. Macrolide antibiotics
Azithromycin
 Azithromycin is a macrolide antitoxin utilized for more than 40 years in numerous irresistible conditions,
particularly those that influence the respiratory tract and in sexually transmitted sicknesses.
 In vitro, it has additionally demonstrated viability against L. amazonensis, L. (V.) brazililensis, and L.
chagasi in the focus 150 µg/ml
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