1. ANTIAMOEBIC DRUGS
PRESENTED BY: Group 8 (PRIST) Sneha Kulkarni Vinita Pillai Snehal Khedekar Urvashi Rajput Vijay Bansode

2. Amoebiasis
Amoebiasis is an infection of the intestine, liver, or other tissues caused by a one-celled parasite called Entamoeba histolytica.
Amoebiasis is most prevalent in tropical and subtropical countries
Poverty, ignorance, overcrowding, poor sanitation and malnutrition favour transmission
It is acquired by ingesting food or water contaminated by infected feces.

4. Symptoms Mostly they are quite mild and can include loose stools
stomach pain
abdominal cramps
Amoebic dysentery – severe form
bloody stools
fever
jaundice
anorexia
weight loss
Rarely the parasite invades liver and forms an abscess and spread to other parts of the body, such as lungs or brain

5. Diagnosis of Amoebiasis
Medical history, physical examination, lab tests and stool examination
Blood test to reveal antibodies against the organism
Sigmoidoscopy to evaluate the intestinal wall
Radiological studies including ultrasound and CT scans to detect liver abscesses

6. Treatment of Amoebiasis
The choice of drug depends on the severity of the symptom
Drugs include
Metronidazole
Emetine
Chloroquine
Diloxanide furoate
8 - hydroxyquinoline
Tetracycline

7. Classification Tissue amoebicides
For both intestinal and extra intestinal amoebiasis:
Nitroimidazoles: Metronidazole, Tinidazole, Secnidazole, Ornidazole, Satranidazole.
Alkaloids: Emetine, Dehydroemetine
For extraintestinal amoebiasis only:
Chloroquine
Luminal amoebicides
Amide: Diloxanide furoate
8-Hydroxyquinolines: Quiniodochlor, Diiodohydroxyquin
Antibiotics: Tetracycline

8. Metronidazole MOA Prototype nitromidazole.(1959)
Highly active amoebicide.
Broad spectrum cidal activity against protozoa.
It is selectively toxic to anaerobic microorganism.
MOA
Nitro group is reduced to highly reactive nitro radical that causes damage to DNA and other critical biomolecules by cytotoxicity
It disrupts energy metabolism
DNA helix destabilization and strand breakage are observed
Found to inhibit cell mediated immunity to induce mutagenesis and to cause radiosensitization

9. Pharmacokinetics ADR Completely absorbed from small intestine
Metabolized in liver by oxidation and glucoronide conjucation
Excreted in urine
Plasma t1/2 is 8hrs
ADR
Frequent- Anorexia, Nausea, Metallic taste, Abdominal cramps
Less frequent-Headache, Glossitis, Dizziness, Rashes
Peripheral neuropathy and CNS effects
Seizures
Thromboflebitis

10. Uses Amoebiasis Giardiasis Trichomonas vaginitis
Anaerobic bacterial infections
Pseudo membranous enter colitis
Ulcerative gingivitis, trench mouth
Peptic ulcer

11. Tinidazole Secnidazole Equally efficacious as metronidazole
Metabolism is slower, t1/2 approx.12hrs
Better tolerated
Lower incidence of side effects
ADRs- Nausea, Rash, Metallic taste
Secnidazole
Congener of metranidazole
Same spectrum of activity and potency
Absorption rapid after oral administration
Slow metabolism (17-29hrs)

12. Ornidazole Satranidazole Activity similar to metronidazole
Slowly metabolized (12-14hrs)
Dose and duration resemble those for Tinidazole
Side effect profile is also similar
Satranidazole
Longer t1/2 (14hrs)
Better tolerability
No nausea, vomiting or metallic taste, absence of neurological diseases

13. Contradictions Neurological diseases Blood dyscrasia
First trimester of pregnancy
Chronic alcoholism

14. EMETINE MOA: Alkaloid from Cephalis ipecacuanha.
Potent directly acting amoebicide (trophozoites).
Does not kill cysts.
Inhibiting protein synthesis in amoebae.
Cannot given orally, administered by s.c or i.m injection.

15. ADR: Cumulative toxicity high
It is an irritant; pain, stiffness, eczematous lession at site of injection.
Nausea and vomiting, abdominal cramp and diarrhoea, Weakness and stiffness of muscle
Hypotension, tachycardia, ECG change, mayocarditis.
Contraindicated in presence of cardiac or renal disease and during pregnancy.

16. USES:
Seldom used as Reserve drug in intestinal and extra intestinal amoebiasis
Patients not responding / intolerant to metronidazole.
Luminal amoebicide follows emetine to eradicate cysts.
Also effective in liver fluke infestation.
Dihydroemetin = effective but less toxic.
Preferred over emetine.

17. Chloroquine
MOA
By accumulating in the acidic vesicle of amoeba it raises the vesicular PH interfere with degradation of haemeoglobin by parasitic lyzosomes.
PHARMACOKINETICS
Oral absorbtion
Have the high affinity for melanin and nuclear chromatin
Partly metabolised in liver
50% bound in the plasma

18. Side effects Uses Anorexia Epigastric pain
Loss of vision due to retinal damage
Loss of hearing
Mental disturbance
Uses
Rhematoid arthritis
Lepra reaction
Photogenic reaction

19. Diloxanide furoate MOA Luminal amoebicidal
Furoate ester hydrolysed in intestine
Then released diloxanide which gets largely absorbed
Diloxanide is weaker amoebicide than furoate ester.
Pharmacokinetics
Its is metabolised by glucoronidation.
Excreted in urine.

20. Uses Mild intestinal/asymptomatic amoebiasis
Combined with metroniadazole or tinidazole.
ADR
Occasional nausea
Itching
Rarely urticaria

21. 8-Hydroxyquinolines PHARMACOKINETIC MOA Widely employed in past.
Active against ENTAMOEBA
Kill cyst forming tropozoids in intestine
Eradicate cyst from asymptomatic carrier
PHARMACOKINETIC
Absorption from intestine (10-30%)
Absorbed fraction conjugate in liver with glucoronic acid.
Excreted in urine.
½ life is 12 hour.

22. Uses ADR Giardiasis Trichomonas Vaginitis Non specific diarrhoea
Dietry indiscretion.
Fungal and bacterial skin infection
ADR
SMON-sub acute myelo optic neuropathy in Japan
Goitre
Transient loose and green stool

23. TETRACYCLINE Directly Inhibit amoebae at high concentration.
Older tetracycline is incompletely absorbed in the small intestine which reaches colon and inhibits bacterial flora along with Entamoeba living symbiotically.
USES:
It is adjuvant in chronic, difficult to treat cases
Tetracycline lessen risk of opportunistic infection, perforation, peritonitis.
When given along with systemic amoebicide.
Not good for acute dysentery and for hepatic amoebiasis.

24. RECENT RESEARCH Drugs for treating amoebic colitis
This review compares different drugs used against amoebic colitis, alone or in combination, and also assesses single-dose regimens versus longer regimens. Thirty-seven trials with 4487 participants were included, and only one was of high methodological quality. Tinidazole reduced clinical failure compared with metronidazole and was associated with fewer adverse events. Combination therapy resulted in fewer parasitological failures than metronidazole alone. Tinidazole appears more effective at reducing clinical failures than metronidazole and has fewer associated adverse events. There is insufficient evidence to draw conclusions regarding the efficacy of the other antiamoebic drugs. The choice of antiamoebic drugs would depend largely on the availability and accessibility of drugs.

25. References Essential of medical pharmacology by K. D. Tripathi
Journal of Ethano pharmacology

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