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AMEBIASIS
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I. Emetine group : e.g. Emetine, dehydroemetine and its resinate.
II. Quinoline derivatives: Halogenated hyroxyquinolines:
Diiodohydroxyquinoline, iodochloroquine 4 – aminoquinolines: Chloroquine.
III. Imidazole derivatives: Metronidazole, tinidazole, secnidazole, ornidazole
IV. Antibiotics: Tetracyclines, paromomycin.
V. Miscellaneous: Diloxanide furoate and kurchi.
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Metronidazole:
Reductive activation by intracellular transport proteins
Reduced by the pyruvate:ferredoxin oxidoreductase system in the mitochondria of obligate anaerobes, which alters its chemical structure.
Reduced intermediate particle interacts with intracellular targets — Cytotoxic intermediate particles interact with host cell DNA, resulting in DNA strand breakage and fatal destabilization of the DNA helix
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Metronidazole
• Mechanism of action: – Enters bacteria via cell diffusion– Activated via single reduction step by bacteria
forms radicals reacts with nucleic acid cell death
• Spectrum of activity:– Anaerobic bacteria– Microaerophilic bacteria– Protozoa
• Resistance:– Rare– Mechanism: decreased activation (↓ red ox
reaction) of drug
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Metronidazole
• Indications:– Anaerobe infections – C. difficile– H. pylori– Bacterial vaginosis– Trichomonas vaginitis– Amebiasis– Giardiasis
• Drug interactions:– Ethanol– Antacids– CyA/tacrolimus– Lithium– Phenytoin– Rifampin– Warfarin
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Metronidazole:
Uses:
1)T vaginalis 2g single dose, 0.7% gel, 500mg – 1g
suppository
2) Amoebiasis
3) Giandaisies
4) Anerobic infections – Bactericides, clostridium,
fusobacterium, peptococcus, peptosirgstococcus,
Eubacterium, H. pyloris.
5) Polymicrobial infections.
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6) Prophylaxis of postop mixed bacterial infection
7) Bacterial vaginosis
8) Pseudomembranous colitis
9) Crohns disease with perianal fistulas
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Metronidazole•Distribution into tissue•Therapeutic levels:•PMNs•Unobstructed biliary tract•Pancreas•CSF •Empyema fluid•Peritoneal fluid•Hepatic abscess•Pelvic tissues•Vaginal/seminal fluid
•Adverse Effects:–GI: N, V, epigastric distress
–Metallic taste–Darkening of urine–Peripheral neuropathy
–Pancreatitis–Hepatitis–Fever–Reversible neutropenia
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IODOQUINOL
EMETINE & DEHYDROEMETINE
PAROMOMYCIN SULFATE
DILOXANIDE FUROATE
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Asymptomatic Intestinal Infection
Diloxanide 500 mg tid x 10d
or-
Iodoquinol 650 mg tid x 21d
or-
Paromomyin 10 mg/kg tid x 7d
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Mild to Moderate Intestinal Infection
Metronidazole 750mg tid x 10d
or-
Tinidazole 2g od x 3d
Plus-
Luminal agent
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Mild to Moderate Intestinal Infection
Alternative: Luminal agent
Plus either-
Tetracycline 250mg tid x 10d
or-
Erythromycin 500 mg qid x 10d
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Severe Intestinal Infection
Metronidazole 750mg tid (500mg IV every 6 h)
or
Tinidazole plus
Luminal agent
Alternative:
Luminal agent plus either
Tetracycline or
Dehydroemetine 1mg /kg SC/IM x 3-5d
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Hepatic / Extra intestinal
Same as above
Alternative:
Dehydroemetine 1mg /kg S.C/IM x 3-5d
Followed by (liver abscess only) Chloroquine 500mg bd x 2d, then 500mg od x21d
Plus
Luminal agent
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PENTAMIDINE:
Pnenmocytosis sleeping sickness leishmaniasis
Parenteral
omebahized powder,
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LEISHMANIASIS:-
1) Liposonal anyrhotencin
2) Pentroalent antimonish. Sodium
stibozhconate meglumine antimonite
3) Miltefosine
4) Pent amidine isethionate
5) paromorycin
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CUTANEOUS:
1) Pentacalant antimoniab
2) As above
3)Antifungals, allopunol
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TOPICAL:
1) Iutratesional antimony
2) Paromomycin oint
3) Cryotherapy
4) local heat
5) surgical removal
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SODIUM STIBOGLUCONATE:-
IV / IM.
Iutial t1/ 2 – 2 h
Terminal t1/ 2 – 24 h
20 mg / kg 1d x 20 d
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ADR:
G.I headache, arthralgia, rash
- IM – Stenile abscers
- ECG
- Hemolytic anemia
- LFT, renal effects,
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NITAZOXANIDE:
General. Lanbia C. Parvum
E. histohytica A. Iumbricoides
Several tapumorns
Increase Tizoxamide
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MILTEFOSINE:-
- 2.5mg / kg / d x 28 d
- Single dose amp B + 7 – 14 d miltepoine
- G. I.
- Decrease LFT
- Not in Pregnancy
- Resistance is a problem. Combination
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PAROMOMYCIN:-
11mg / kg x 21 d IM
- ADR as with AGI