12. anti amoebiais
TRANSCRIPT
ANTIAMOEBIC
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 MetronidazoleTinidazole
Secnidazole
Ornidazole
satranidazole
Alkaloids Emetine
Hydroemetine Extra intestinal amoebiasis only
ChloroquineSHOULD always be followed by Luminal amoebicide to eradicate source of infection
Luminal amoebiasis
Amide Diloxanide furoate
8-Hydroxy quinolones Quinidochlor
Diiodohydroxyquin
Antibiotics 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
CardiomyopthyMega colon- mega esophagus &
gastrointestinal lesions
Nifurtimox: MOA: free radical generator
Toxoplasmosis
Toxoplasma gondii Pyrimethamine+ Clindamycin+ Folinic
acid Pyrimethamine + sulfadiazine
ThankQ