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