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Antiamoebics-Shahare HV

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Amoebicidal drugs eradicate the parasitic species of amebae in animals or humans. Classification, Chemistry, Mode of action, Side effects....

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Mr. Hitesh Vishwanath Shahare Assistant Professor Dept. Ph. Chem. SNJBs Shriman Sureshdada Jain Coll. Ph. Chandwad ANTIIAMOEBIC DRUGS
Learners will be able to know; 1. Introduction 2. Classification 3. SAR & MOA 4. Marketed Preparations 4 3 2 1
Protozoal Infection Unicellular protozoal cells have metabolic processes closer to human cells than bacteria Protozoal infections are less easily treated than bacterial infections: Protozoal Infections Malaria Amoebiasis Leishmaniasis Trypanosomiasis Trichomoniasis Giardiasis
Amoebiasis Causative agent: Protozoal parasite Amoebiasis: Infection of Large Intestine : Entamoeba histolytica Cyst Tropozoites - Not active - Survive outside of Host Body -Tissue lysis of wall of intestine Diarrhoea Dysentery -Presence of Blood & mucous in stools -Abdominal Pain Parasite invade to blood vessels & Causes problems in Liver & Brain: Leads to death of Host Exist in 2 Forms
Life Cycle of Amoeba 5
Classification 6
Chemical Classification 7
Nitroimidazole derivatives 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethanol Metronidazole 8
Binds to proteins and DNA, resulting in cell death Metronidazole is a Prodrug that is reduced in the cytoplasm by a Nitroreductase enzyme; resulting toxic intermediates disrupt nucleic acid structure. 9
Metabolism: In the liver, metabolism of metronidazole leads to two major metabolites, hydroxylation of the 2-methyl group to 2- hydroxymethyl metronidazole and oxidation to metronidazole acetic acid (MAA) 10
Side effects Uses 11
Synthesis of Metronidazole 12
Mechanism of action is similar to that of Metronidazole Used in the treatment of intestinal and hepatic Amoebiasis Greater efficacy than Metronidazole . Tinidazole 1-Chloro-3-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ol Ornidazole 1-(2-ethylsulfonylethyl)-2-methyl-5-nitro-imidazole
Dichloroacetamide Derivatives Mechanism of Action: Side effects: Flatulence, Vomitting Effective in Intestinal, Luminal and local Amoebiasis Diloxanide Furoate 4-[(Dichloroacetyl)(methyl)amino]phenyl furan-2-carboxylateDiloxanide
2,2-Dichloro-N-[[4-[[(2,2-dichloroacetyl)-(2- ethoxyethyl)amino]methyl]phenyl]methyl]-N-(2- ethoxyethyl)acetamide 2,2-dichloro-N-(2-ethoxyethyl)-N- [4-(4- nitrophenoxy)benzyl]acetamide Teclozan Etofamide 15
Alkaloids Emetine Dehydroemetine Differ only in a double bond next to the ethyl substituent Alkaloid derived from Cephaelis ipecacuanha Synthetic analog Less side effects Parenterally administered (IM/SC), by oral route cause vomiting MOA: Inhibiting intra-ribosomal translocation of tRNA-amino acid complex Inhibition of Protein Synthesis
1. Emetine Possesses a skeleton with two Tetrahydoisoquinoloine ring system and a Terpenoidal portion. 2. Psychotrine is a phenolic. It gives Emetine on reduction followed by methylation. 3. Emetine is non Phenolic moiety. 4. N-5 and C-9 are critical positions : Essential for Biological activities Chemistry 17
1. Local stimulation: Pain and tenderness in the area of injection 2. Gastrointestinal tract discomfort: Nausea, vomiting CTZ (oral and IV) 3. Diarrhoea and abdominal cramps 4. Neuromuscular blockade: Muscle weakness and discomfort 5. Cardiac toxicity: Arrhythmias, congestive heart failure, hypotension, ECG changes Contraindication: Not be used in patients with cardiac or renal disease, in pregnancy Emetine Adverse Effects
8-Hydroxyquinolines Quinoline ring: Basic nucleus Effectiveness limited to bowel luminal organism -Not effective against intestinal wall/extraintestinal tissue tropozoites Poor Absorption Interfere with Thyroid functions: decreases 131I uptake SE: On long term use-Goiter Neurotoxicity Green stools 5-Chloro-7-iodo-quinolin-8-ol 5,7-diiodoquinolin-8-ol Iodoquinol Clioquinol
Broad-spectrum Antiparasitic and Antiviral drug used in medicine for the treatment of various helminthic, protozoal and viral infections. SE: Stomach pain, headache, vomiting, discolored urine, excessive urinating, skin rash, itching MOA: Interference with the Pyruvate: Ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic energy metabolism Tizoxanide is an active metabolite of Nitazoxanide Nitrothiazolidines Nitazoxanide [2-[(5-Nitro-1,3-thiazol-2-yl)carbamoyl]phenyl]ethanoate
(RS)-N'-(7-chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine Chloroquine Effective in tissue or hepatic Amoebiasis Very effective in combination with Dehydroemetine or Emetine in amebic liver abscess 4-Aminoquionolines
Antibiotics Paromomycin Aminoglycoside antibiotic Use in Amoebiasis, Leishmaniasis MOA: Cause leakage in cell membrane of parasite SE: Abdominal distress and Diarrhea Administered as by IM and in capsule dosage form 22
Marketed Preparations 23
24
2525 shahare.hvcop@snjb.org Thank You! SNJBs Shriman Sureshdada Jain Coll. Ph. Chandwad

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Antiamoebics-Shahare HV

  • 1. Mr. Hitesh Vishwanath Shahare Assistant Professor Dept. Ph. Chem. SNJBs Shriman Sureshdada Jain Coll. Ph. Chandwad ANTIIAMOEBIC DRUGS
  • 2. Learners will be able to know; 1. Introduction 2. Classification 3. SAR & MOA 4. Marketed Preparations 4 3 2 1
  • 3. Protozoal Infection Unicellular protozoal cells have metabolic processes closer to human cells than bacteria Protozoal infections are less easily treated than bacterial infections: Protozoal Infections Malaria Amoebiasis Leishmaniasis Trypanosomiasis Trichomoniasis Giardiasis
  • 4. Amoebiasis Causative agent: Protozoal parasite Amoebiasis: Infection of Large Intestine : Entamoeba histolytica Cyst Tropozoites - Not active - Survive outside of Host Body -Tissue lysis of wall of intestine Diarrhoea Dysentery -Presence of Blood & mucous in stools -Abdominal Pain Parasite invade to blood vessels & Causes problems in Liver & Brain: Leads to death of Host Exist in 2 Forms
  • 9. Binds to proteins and DNA, resulting in cell death Metronidazole is a Prodrug that is reduced in the cytoplasm by a Nitroreductase enzyme; resulting toxic intermediates disrupt nucleic acid structure. 9
  • 10. Metabolism: In the liver, metabolism of metronidazole leads to two major metabolites, hydroxylation of the 2-methyl group to 2- hydroxymethyl metronidazole and oxidation to metronidazole acetic acid (MAA) 10
  • 13. Mechanism of action is similar to that of Metronidazole Used in the treatment of intestinal and hepatic Amoebiasis Greater efficacy than Metronidazole . Tinidazole 1-Chloro-3-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ol Ornidazole 1-(2-ethylsulfonylethyl)-2-methyl-5-nitro-imidazole
  • 14. Dichloroacetamide Derivatives Mechanism of Action: Side effects: Flatulence, Vomitting Effective in Intestinal, Luminal and local Amoebiasis Diloxanide Furoate 4-[(Dichloroacetyl)(methyl)amino]phenyl furan-2-carboxylateDiloxanide
  • 16. Alkaloids Emetine Dehydroemetine Differ only in a double bond next to the ethyl substituent Alkaloid derived from Cephaelis ipecacuanha Synthetic analog Less side effects Parenterally administered (IM/SC), by oral route cause vomiting MOA: Inhibiting intra-ribosomal translocation of tRNA-amino acid complex Inhibition of Protein Synthesis
  • 17. 1. Emetine Possesses a skeleton with two Tetrahydoisoquinoloine ring system and a Terpenoidal portion. 2. Psychotrine is a phenolic. It gives Emetine on reduction followed by methylation. 3. Emetine is non Phenolic moiety. 4. N-5 and C-9 are critical positions : Essential for Biological activities Chemistry 17
  • 18. 1. Local stimulation: Pain and tenderness in the area of injection 2. Gastrointestinal tract discomfort: Nausea, vomiting CTZ (oral and IV) 3. Diarrhoea and abdominal cramps 4. Neuromuscular blockade: Muscle weakness and discomfort 5. Cardiac toxicity: Arrhythmias, congestive heart failure, hypotension, ECG changes Contraindication: Not be used in patients with cardiac or renal disease, in pregnancy Emetine Adverse Effects
  • 19. 8-Hydroxyquinolines Quinoline ring: Basic nucleus Effectiveness limited to bowel luminal organism -Not effective against intestinal wall/extraintestinal tissue tropozoites Poor Absorption Interfere with Thyroid functions: decreases 131I uptake SE: On long term use-Goiter Neurotoxicity Green stools 5-Chloro-7-iodo-quinolin-8-ol 5,7-diiodoquinolin-8-ol Iodoquinol Clioquinol
  • 20. Broad-spectrum Antiparasitic and Antiviral drug used in medicine for the treatment of various helminthic, protozoal and viral infections. SE: Stomach pain, headache, vomiting, discolored urine, excessive urinating, skin rash, itching MOA: Interference with the Pyruvate: Ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic energy metabolism Tizoxanide is an active metabolite of Nitazoxanide Nitrothiazolidines Nitazoxanide [2-[(5-Nitro-1,3-thiazol-2-yl)carbamoyl]phenyl]ethanoate
  • 21. (RS)-N'-(7-chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine Chloroquine Effective in tissue or hepatic Amoebiasis Very effective in combination with Dehydroemetine or Emetine in amebic liver abscess 4-Aminoquionolines
  • 22. Antibiotics Paromomycin Aminoglycoside antibiotic Use in Amoebiasis, Leishmaniasis MOA: Cause leakage in cell membrane of parasite SE: Abdominal distress and Diarrhea Administered as by IM and in capsule dosage form 22
  • 24. 24
  • 25. 2525 shahare.hvcop@snjb.org Thank You! SNJBs Shriman Sureshdada Jain Coll. Ph. Chandwad