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Intestinal infection - Entamoeba histolytica
 Ingested cysts through food water
 Poor environmental sanitation
 Low socio-economic status
 Many patients are asymptomatic
 Characterized by diarrhea, weakness

Luminal Phase
Cysts in Faeces – propagation of
disease.
 Tissue phase
Ulcer /dysentery
Abscess
 Extra intestinal
Lung, Spleen, Kidney, Brain

Classification
 Tissue Amoebicides
 Extra intestinal & Intestinal
Nitroimidazoles Metronidazole
Tinidazole

Secnidazole
Ornidazole
satranidazole
Alkaloids
Emetine
Hydroemetine
 Extra intestinal amoebiasis only
SHOULD always be followed by Luminal
Chloroquine
amoebicide to eradicate source of infection


Luminal amoebiasis
Amide
8-Hydroxy quinolones

Antibiotics

Diloxanide furoate
Quinidochlor
Diiodohydroxyquin
Tetracycline
Metronidazole
Nitroimidazole group, Prototype drug
introduced in 1959
 It active aganist amoebae, anaerobic
bacteria and certain helminthis
 PK:- Oral & parental
 Absorption occurs in proximal intestine
 Well distribution, therapeutic level it found in
vaginal, seminal fluid, CSF, saliva and milk
 Metabolized by oxidation and glucuronidation
 t½-8hrs.
 Not given pregnancy

MOA:
Enters micro-organism by diffusion
PFOR enzyme act as electron removal
(Pyruvate ferrodoxin oxido reductase)

Nitro group serves as electron acceptor reduced
Cyto toxicity
DNA Damaged
Clinical uses
DOC for tissue amoebiasis
 Cysts passers Metroindazole + Diloxanide furoate
 Moderate intestinal amebiasis 400mg orally TDS 5-7days
 Amoebic dysentry , liver abcess 800mg TDS for 7days
 Giradiasis- 200mg TDS for 7days
 Trichomonas vaginitis -400mgTDS for 7days
 Anaerobic bacterial infections brain abscess, endocarditis
 Psudomembranous colitis – 500mg TDS
 Ulcerative gingivitis, Stomatitis- Metro+ tetracycline
 Guinea worm , eradicating H.Pylori

Adverse Drug Reactions
 Frequent
○ Anorexia, nausea
○ Metallic taste, abdominal cramps
○ Dark red brown urine

• Less frequent
○ Headache, dry mouth,
○ dizziness, rashes
○ neutropenia



On prolonged administration
○ Peripheral neuropathy, CNS effects
Contraindications
 Neurological diseases, blood dyscrasias,
 First trimester, Chronic alcoholism(ADH Inhibition)
Drug Interactions







Disulfiram reaction
Enzyme inducers - Rifampicin -↓therapeutic
effect
Cimetidine - ↓metronidazole metabolism reduce
dose
Metronidazole ↓renal elimination of Lithium
Warfarin ↓renal elimination
Tinidazole
Slower metabolism – longer duration action –
Given OD
 Better tolerated
 Use in amoebiasis – 600mg BD X 7 days
 Trichomoniasis, Giardiasis 600mg for 7days
Secnidazole – longer duration
 2g single dose
 Less side effects

Emetine








Alkaloid from Cephaelis ipecacuanha
MOA: Protein synthesis inhibitor
Potent directly acting amoebicide (trophozoites)
Does not kill cysts
Toxicity high –Seldom used
Reserve drug – not responding/intolerant to
metronidazole
Luminal amoebicide follows emetine to eradicate cysts

Dihydroemetine =effective but less toxic
 Preferred over emetine
Chloroquine











Kills trophozoites
Concentrates in liver Used in hepatic amoebiasis
Rx duration longer 500mg x 21days
Relapses more frequent than emetine
Resistance doesn’t develop
Luminal amoebicide must always be given with or
after Chloroquine to abolish luminal cycle
Dose in liver abcess -600 mg(base) X
2days,300mg X 2-3 weeks
Reserved drug only used metronidazole is not
tolerated
Diloxanide furoate
Highly effective luminal amoebicide
 Directly kills trophozoites
 No anti bacterial action
 Drug of Choice for mild intestinal/
asymptomatic amoebiasis
 Given after tissue amoebicide to eradicate
cysts
 Given in combination with metronidazole OR
tinidazole
 ADRs – pruritis, urticaria, flatulance

8-hydroxy quinolone
Once widely used luminal amoebicide
 Rarely now because neuritis & optic damage
 Uses: luminal amoebicide, giardiasis
 Locally for monilial/trichomonas vaginitis,
fungal & bacterial infections
 ADR:- green colored stool
 Prolong use case iodine overload (Goiter)
 Not safer drug for pregnancy and children

Tetracycline
 Directly inhibit amoebae but only at high
concentration.
 ↓bacterial flora
 Used along with other luminal agents
 Adjuvant in chronic difficult to treat cases
GIARDIASIS











Giardia lamblia, Pear shaped
Two nuclei and four flagella
Attach to intestinal mucosa
From they absorb nourishment & interfere
absorption
Characterized by watery diarrhea & malabsorption
Metroindazole 200mg TDS 7days
Tinidazole 600mg daily 7days
Secnidazole 2g single dose
TRICHOMONIASIS


Gential infection produced by Trichomonas
vaginalis



Metroindazole 400mg TDS 7days or 2g single
dose
Tinidazole 600mg daily 7days or 2g single dose
Secnidazole 2g single dose
Nimorazole 2g single dose with meals





* Repeat course may given after 6 weeks
TRYPANANOSOMIASIS
Africian Trypnosmiasis :- T. brucei
Two stages –


Haemolymphatic – enlargement of lymph node
 Meningo encephalopathic – mental distrubance,
diziness (Sleeping
sickness)
 Early- Sumarin or pentmidine
 Late CNS – Melarsoprol

American trypanosomiasis(Chagas’
disease)
 T.Cruzi
Cardiomyopthy


Mega colon- mega esophagus &
gastrointestinal lesions
Nifurtimox: MOA: free radical generator
Toxoplasmosis
Toxoplasma gondii
 Pyrimethamine+ Clindamycin+ Folinic
acid
 Pyrimethamine + sulfadiazine

Thank

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12. anti amoebiais

  • 1.
  • 2. Intestinal infection - Entamoeba histolytica  Ingested cysts through food water  Poor environmental sanitation  Low socio-economic status  Many patients are asymptomatic  Characterized by diarrhea, weakness 
  • 3.
  • 4. Luminal Phase Cysts in Faeces – propagation of disease.  Tissue phase Ulcer /dysentery Abscess  Extra intestinal Lung, Spleen, Kidney, Brain 
  • 5. Classification  Tissue Amoebicides  Extra intestinal & Intestinal Nitroimidazoles Metronidazole Tinidazole Secnidazole Ornidazole satranidazole Alkaloids Emetine Hydroemetine  Extra intestinal amoebiasis only SHOULD always be followed by Luminal Chloroquine amoebicide to eradicate source of infection
  • 6.  Luminal amoebiasis Amide 8-Hydroxy quinolones Antibiotics Diloxanide furoate Quinidochlor Diiodohydroxyquin Tetracycline
  • 7. Metronidazole Nitroimidazole group, Prototype drug introduced in 1959  It active aganist amoebae, anaerobic bacteria and certain helminthis  PK:- Oral & parental  Absorption occurs in proximal intestine  Well distribution, therapeutic level it found in vaginal, seminal fluid, CSF, saliva and milk  Metabolized by oxidation and glucuronidation  t½-8hrs.  Not given pregnancy 
  • 8. MOA: Enters micro-organism by diffusion PFOR enzyme act as electron removal (Pyruvate ferrodoxin oxido reductase) Nitro group serves as electron acceptor reduced Cyto toxicity DNA Damaged
  • 9. Clinical uses DOC for tissue amoebiasis  Cysts passers Metroindazole + Diloxanide furoate  Moderate intestinal amebiasis 400mg orally TDS 5-7days  Amoebic dysentry , liver abcess 800mg TDS for 7days  Giradiasis- 200mg TDS for 7days  Trichomonas vaginitis -400mgTDS for 7days  Anaerobic bacterial infections brain abscess, endocarditis  Psudomembranous colitis – 500mg TDS  Ulcerative gingivitis, Stomatitis- Metro+ tetracycline  Guinea worm , eradicating H.Pylori 
  • 10. Adverse Drug Reactions  Frequent ○ Anorexia, nausea ○ Metallic taste, abdominal cramps ○ Dark red brown urine • Less frequent ○ Headache, dry mouth, ○ dizziness, rashes ○ neutropenia  On prolonged administration ○ Peripheral neuropathy, CNS effects
  • 11. Contraindications  Neurological diseases, blood dyscrasias,  First trimester, Chronic alcoholism(ADH Inhibition) Drug Interactions      Disulfiram reaction Enzyme inducers - Rifampicin -↓therapeutic effect Cimetidine - ↓metronidazole metabolism reduce dose Metronidazole ↓renal elimination of Lithium Warfarin ↓renal elimination
  • 12. Tinidazole Slower metabolism – longer duration action – Given OD  Better tolerated  Use in amoebiasis – 600mg BD X 7 days  Trichomoniasis, Giardiasis 600mg for 7days Secnidazole – longer duration  2g single dose  Less side effects 
  • 13. Emetine        Alkaloid from Cephaelis ipecacuanha MOA: Protein synthesis inhibitor Potent directly acting amoebicide (trophozoites) Does not kill cysts Toxicity high –Seldom used Reserve drug – not responding/intolerant to metronidazole Luminal amoebicide follows emetine to eradicate cysts Dihydroemetine =effective but less toxic  Preferred over emetine
  • 14. Chloroquine         Kills trophozoites Concentrates in liver Used in hepatic amoebiasis Rx duration longer 500mg x 21days Relapses more frequent than emetine Resistance doesn’t develop Luminal amoebicide must always be given with or after Chloroquine to abolish luminal cycle Dose in liver abcess -600 mg(base) X 2days,300mg X 2-3 weeks Reserved drug only used metronidazole is not tolerated
  • 15. Diloxanide furoate Highly effective luminal amoebicide  Directly kills trophozoites  No anti bacterial action  Drug of Choice for mild intestinal/ asymptomatic amoebiasis  Given after tissue amoebicide to eradicate cysts  Given in combination with metronidazole OR tinidazole  ADRs – pruritis, urticaria, flatulance 
  • 16. 8-hydroxy quinolone Once widely used luminal amoebicide  Rarely now because neuritis & optic damage  Uses: luminal amoebicide, giardiasis  Locally for monilial/trichomonas vaginitis, fungal & bacterial infections  ADR:- green colored stool  Prolong use case iodine overload (Goiter)  Not safer drug for pregnancy and children 
  • 17. Tetracycline  Directly inhibit amoebae but only at high concentration.  ↓bacterial flora  Used along with other luminal agents  Adjuvant in chronic difficult to treat cases
  • 18. GIARDIASIS         Giardia lamblia, Pear shaped Two nuclei and four flagella Attach to intestinal mucosa From they absorb nourishment & interfere absorption Characterized by watery diarrhea & malabsorption Metroindazole 200mg TDS 7days Tinidazole 600mg daily 7days Secnidazole 2g single dose
  • 19. TRICHOMONIASIS  Gential infection produced by Trichomonas vaginalis  Metroindazole 400mg TDS 7days or 2g single dose Tinidazole 600mg daily 7days or 2g single dose Secnidazole 2g single dose Nimorazole 2g single dose with meals    * Repeat course may given after 6 weeks
  • 20. TRYPANANOSOMIASIS Africian Trypnosmiasis :- T. brucei Two stages –  Haemolymphatic – enlargement of lymph node  Meningo encephalopathic – mental distrubance, diziness (Sleeping sickness)  Early- Sumarin or pentmidine  Late CNS – Melarsoprol 
  • 21. American trypanosomiasis(Chagas’ disease)  T.Cruzi Cardiomyopthy  Mega colon- mega esophagus & gastrointestinal lesions Nifurtimox: MOA: free radical generator
  • 22. Toxoplasmosis Toxoplasma gondii  Pyrimethamine+ Clindamycin+ Folinic acid  Pyrimethamine + sulfadiazine 
  • 23. Thank

Editor's Notes

  1. Parasite adhere to intestine by lactin proteins. Tropozoites invades the host cell cause cell lysis histolytica
  2. Cysts live outside the body at least one week
  3. Flatulance excessive gas in stomach & intestine