PRESENTATION

ANTIPROTOZOAL DRUG AND

THEIR MODE OF ACTION
PRESENTEDTO:-
Dr. MURTAZ

PRESENTED BY:-

14-ARID-2022

PMAS FAISAL SHAHZAD SOMROO

ANTIPROTOZOAL DRUG:
DEFINATION:
 Antiprotozoal drugs are used to treat a variety of
diseases caused by protozoa.
 Anti protozoal drug use for fallowing protozoal
diseases are
 Amebiasis
 Malaria
 Trypanosomiasis
 Leishmaniasis
 Giardiasis
AMEBIASIS:
 Amebiasis is an infection of the intestinal tract
that occurs due to ingestion of foods or water
contaminated with Entameba Histolytica cysts
which cause dysyntery associated with invasion
of the intestinal wall,rarely of the liver.
 Organism may present in the motile ,invasive
form or as a cyst .
LUMEN AMEBICIDES

 Acts on the parasites in the lumen of the bowl.

Include
 Diloxanide Furoate
 Iodoquinol
 Antibiotics
- Paromomycin
- Tetracyclines
- Erythromycin
TISSUE AMEBICIDES (SYSTEMIC)
 Acts on the intestinal wall and liver (or any other
extra--intestinal tissue).
 Used for treatment of systemic form of the disease
(intestinal wall infection or liver abscesses).
 Emetine
 Dehydroemetine
 Chloroquine (liver only)
MIXED AMEBICIDES

 Effective against both luminal and systemic forms of

the disease
 Metronidazol
 Tinidazole, ornidazole and nimorazole are similar
drugs.
 DILOXANIDE FUROATE
 Direct amoebicidal action against luminal.
 is active against non-invasive forms
MECHANISM OF ACTION:
 Unkown mechanism of action
 This agent destroys the trophozoites of E. histolytica
that eventually form into cysts. The cysts are then
excreted by persons infected with asymptomatic
amebiasis.
IODOQUINOL:
 Lumen amoebicide.
MECHANISM OF ACTION
 Clear mechanism Unknown
 Effective against organisms in GIT only not
intestinal wall or liver.
 Iodoquinol acts against the trophozoites of
Entamoeba histolytica . Iodoquinol produces its
amebicidal effect at the site of infection, since it is
poorly absorbed from the gastrointestinal tract and
can reach high concentrations in the intestinal
lumen.
PARAMOMYCINE:
 Luminal amoebcidial
MECHANISM OF ACTION:
 Direct amebicidal action (causes leakage by its
action on cell membrane of parasite).
 Indirect killing of bacterial flora essential for
proliferation of pathogenic amoebae.
EMETINE &DEHYDROEMETINE:
 Tissue or systemic amoebicide
 MECHANISM OF ACTION:
Act on tissue trophozoites causing irreversible block
of protein synthesis by blocking movement of
ribosomes along mRNA.
METRONIDAZOLE
 Mixed amoebicide.
 Drug of choice for intestinal &
extraintestinal amoebiasis.
MECHANISM OF ACTION:
 Acts on trophozoites.
 Has no effect on cysts.
 Nitro group of metronidazole is reduced by protozoan
leading to cytotoxic reduced product that binds to DNA
and proteins resulting into parasite death.
 is active against the invasive form in gut and liver.
 The metronidazole metabolites are taken up into bacterial
DNA, and form unstable molecules. This function only
occurs when metronidazole is partially reduced.This
reduction usually happens only in anaerobic cells
LUMINAL AMEBIASIS DILOCANIDE FUROATE ,
IODOQUINOL FUROATE,
PAROMOMYCIN

MILD MODERA MILD- METRONIDAZOLE + LUMINAL

INTEINTESTINAL INFECTION AMEBICIDE

METRONIDAZOLE + LUMINAL
SEVERE INTESTINAL AMEBICIDE
INFECTION DEHYDROEMETINE +
LUMINAL AMEBICIDE

METRONIDAZOLE OR
LIVER ABSCESS DEHYDROEMETINE OR
CHLOROQUINE PLUS
LUMINAL AMEBICIDE
ANTIMALARIAL DRUG
QUININE………………….Con
 Parasite feeds on haemoglobin - Breaks down globin
proteins into a.a. in lysosomes - haeme converted to
a non-toxic product by parasite
 Quinine accumulates in lysosome of parasite in RBC
 Quinine binds to haeme and inhibits conversion of
haeme to non- toxic product
 Haeme-quinine complex highly toxic to parasite
 May function by disrupting lysosome membrane
QUININE:
 QUININE complex with double stranded DNA to
prevent strand sepration.
 Block replication of DNA and transcription to RNA.
 CHLROQUINE…………….Con
 Systemic or tissue amebcidese
 Antimalarial drug
 Used in combination for amebic liver diseases
 MECHANISM OF ACTION:
 The parasite produces the toxic and soluble molecule
heme. The parasite biocrystallizes heme to form
hemozoin, a non-toxic molecule. Hemozoin collects in the
digestive vacuole as insoluble crystals
 Chloroquine enters the red blood cell, inhabiting parasite
cell
 Chloroquine caps hemozoin molecules to prevent further
biocrystallization of heme.
 Chloroquine binds to heme to form Chloroquine
complex; this complex is highly toxic to the cell and
disrupts membrane function.
 Action of the toxic Chloroquine complex results in cell
lysis and ultimately parasite cell autodigestion.
CHLROQUINE:
 It cause the inhibition of parasite digestive enzymes.
 It decreased parasite growth.
 inhibits digestion of haemoglobin.
MEFLOQUINE:

 Blood schizonticidal agents.

MECHANISM OF ACTION:
 Inhibiting the parasite's haem polymerase, thus
interferes with the transport of host material into the
parasite’s food vacuole.
 Interferes with the transport of haemoglobin and
other substances from erythrocytes to the food
vacuoles of the malaria parasite.
 Affects only the asexual form of the parasite, with no
effect on gametocytes.
 Inhibition of protein synthesis by effects on
ribosomal subunits.
ARTIMISININ:
 very rapidly acting schizonticides.
MECHANISM OF ACTION:
 React with heme, causing free-radical damage to
parasite membranes.
 Kill trophozoites of erythrocytes.
 Parasites consumes hemoglobin within its digestive
vacuole, liberating free heme, an iron-porphyrin
complex. The iron reduces the peroxide bond in
artemisinin generating high-valent iron-oxo species,
resulting in a cascade of reactions that produce
reactive oxygen radicals which damage the parasite
leading to its death.
PRIMAQUINE:
 Active against gametocytes.
 Insignificant activity against the asexual blood forms
of the parasite
MECHANISM OF ACTION:
 Mechanism unclear.
 Acting by generating reactive oxygen species.
PYRIMETHAMINE:
 Act slowly against premature schizonts of erythrocytic
stage.
• No action against gametocytes, but can inhibit
development of plasmodium in mosquito.
MECHANISM OF ACTION:
 interferes with folic acid synthesis by inhibiting
the enzyme dihydrofolate reductase (DHFR).
Folic acid is needed for DNA and RNA synthesis
in many species, including protozoa
CHEMOTHERAPY FOR
TRAYPNOSOMIOSIS:
MELARSOPROL:
MECHANISM OF ACTION:
 The primary action of melarsoprol is to disrupt parasite
glycolysis.
 Disruption of energy generation in the trypanosome
parasite due to the high affinity of melarsoprol for
sulfhydryl groups .The trypanosome eventually dies as a
result of diminished energy production.
 Sulfhydral group form active site of many enzyme and
involve in maintainence of primary and secondary
structure of proteins.
NIFURTIMOX:

MECHANISM OF ACTION:
 The ability of this agent to form a nitro-anion radical
metabolite, which reacts with the nucleic acids of the
parasite, causing a significant breakage in the
deoxyribonucleic acid (DNA).
 The production of superoxide anions, and hence,
hydrogen peroxide (both of which are very toxic to
the parasite) and inhibition of trypanothione
reductase, which is a parasite-specific antioxidant
defense enzyme. Lack of these enzymes leads to
the accumulation of hydrogen peroxide to cytotoxic
levels, resulting in death of the parasite.
PENTAMIDINE:
MECHANISM OF ACTION:
 The mode of action of pentamidine is not fully
understood.
 Drug interferes with nuclear metabolism producing
inhibition of the synthesis of DNA, RNA,
phospholipids, and proteins.
 Inhibitor of nucleic acid biosynthesis .
SURAMIN:

Mechanism Of Action:
 Suramin works by blocking various growth processes
within the parasites. Specifically, the drug blocks
insulin growth, NADH oxidation enzyme, epidermal
growth, and platelet-derived growth, which limits cell
production and migration. When this happens, the
parasites become immobile and eventually die.
CHEMOTHERAPY FOR
LEISHMANIASIS
SODIUM STIBOGLUCONATE:
MECHANISM OF ACTION:
 The mode of action of sodium stibogluconate is
unknown.
 Inhibit parasite glycolysis and fatty acid oxidation,
leading to decreased energy and reduction in ATP
(adenosine triphosphate) and GTP (guanosine
triphosphate) synthesis contributes to decreased
macromolecular synthesis.
 Decrease in parasite DNA, RNA protein.
CHEMOTHERAPY FOR
TOXOPLASMOSIS
PYRIMETHAMINE:
• No action against gametocytes.
MECHANISM OF ACTION:
 interferes with folic acid synthesis by inhibiting
the enzyme dihydrofolate reductase (DHFR).
Folic acid is needed for DNA and RNA synthesis
in many species, including protozoa
CHEMOTHERAPY FOR GIARDIASIS
METRONIDAZOLE:
MECHANISM OF ACTION:
 Metronidazole metabolites are taken up into bacterial
DNA, and form unstable molecules.
 This function only occurs when metronidazole is
partially reduced.
 Nitro group of metronidazole is reduced by protozoan
leading to cytotoxic reduced product that binds to DNA
and proteins resulting into parasite death