PRESENTATIONANTIPROTOZOAL 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-INTEINTESTINAL INFECTION

METRONIDAZOLE + LUMINAL AMEBICIDE

SEVERE INTESTINAL INFECTION

METRONIDAZOLE + LUMINAL AMEBICIDE DEHYDROEMETINE + LUMINAL AMEBICIDE

LIVER ABSCESS METRONIDAZOLE OR 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 parasiteMECHANISM 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