drugs for amoebiasis, giardiasis, trichonomiasis, leishmaniasis ( kala azar) ,

1. ANTIAMOEBIC DRUGS

4. NITROIMIDAZOLES
Metronidazole
• prototype nitroimidazole
• amoeba , Trichonomas vaginalis, anaerobic protozoa (Giardia lamblia)
• Many anaerobic bacteria, Bacteroids fragilis, Fusobacterium,
Clostridium perfringens, Cl. difficile, helicobacter pylori,
Campylobacter;
• spirochetes and anaerobic Streptococci
• does not affect aerobic bacteria.

5. NITROIMIDAZOLES
Metronidazole
Mechanism of action
• nitro group of metronidazole is reduced by certain redox proteins
present only in anaerobic microbes to a highly reactive nitro radical
which exerts cytotoxicity
• metronidazole acts as an electron sink which competes with the
biological electron acceptors of the anaerobic organism for the
electrons generated by the pyruvate : ferredoxin
oxidoreductase(PFOR) enzyme pathway of pyruvate oxidation.
• Aerobic environment does not cause reduction of nitro group no
activation

6. NITROIMIDAZOLES
Metronidazole
pharmacokinetics
• Almost completely absorbed from the small intestines
• widely distributed in the body ( semen, saliva, vaginal secretion, CSF)
• Metabolism occurs in liver (oxidation and glucuronide conjugation)
• renal excretion
• t½ is 8 hrs

7. NITROIMIDAZOLES
Metronidazole
Adverse effects
• Anorexia, nausea, metallic taste and abdominal cramps (most
common)
• headache, glossitis, dryness of mouth
• flushing, heat, itching, rashes and fixed drug eruption
• Peripheral neuropathy and CNS effects ( c/I in neurological diseases)
• mutagenic potential ( c/I in pregnancy )
• Disulfiram like reactions in alcoholics ( inhibit acetaldehyde
dehydrogenase ). C/I in blood dyscrasias

8. NITROIMIDAZOLES
Metronidazole
Drug interactions
• Enzyme inducers- reduce effects
• Cimetidine- reduce metabolism
• Inhibits metabolism of warfarin
• Decrease renal excretion of Li

9. NITROIMIDAZOLES
Metronidazole
Uses
• Amoebiasis: Metronidazole is a first line drug
• Giardiasis
• Trichomonas vaginitis
• Anaerobic bacterial infections after colorectal or pelvic surgery,
appendicectomy, etc
• Pseudomembranous enterocolitis caused by Cl. Difficile
• Acute necrotizing ulcerative gingivitis (ANUG/ trench mouth) :
Metronidazole/ tinidazole are the drugs of choice ; caused by mixed flora
of anaerobes like fusobacteria, spirochetes and bacteroides.
• Helicobacter pylori gastritis/peptic ulcer

10. NITROIMIDAZOLES
Tinidazole
Similar to metronidazole except:
• Metabolism is slower; t½ is ~ 12 hr;
• Duration of action is longer;
• dosage schedules : once daily therapy/ single dose
• Higher cure rates in amoebiasis
• better tolerated

11. NITROIMIDAZOLES
Secnidazole
Similar to metronidazole except:
• Metabolism is slower; t½ of 17- 29 hours

12. NITROIMIDAZOLES
Ornidazole
Similar to metronidazole except:
• Metabolism is slower; t½ ( 12-14 hr).

13. NITROIMIDAZOLES
Satranidazole
Similar to metronidazole except:
• Metabolism is slower; t½ ( 14 hr).
• better tolerability

14. • potent and directly acting amoebicide
• MOA: inhibiting protein synthesis in amoebae by arresting
translocation Act on trophozoites.
• administered by s.c. or i.m. injection
• ADR: local irritant and has high systemic toxicity, viz, nausea, vomiting
(due to CTZ stimulation and gastric irritation), abdominal cramps,
diarrhoea, weakness, ECG changes and myocarditis
• Use: only in patients not tolerating metronidazole.
ALKALOIDS
Emetine

15. • equally effective
• Less toxicity overall and less toxic to the heart
ALKALOIDS
Dehydroemetine

16. Chloroquine
• kills trophozoites of E. histolytica and is highly concentrated in liver.
Therefore, it is used in hepatic amoebiasis only.
• Completely absorbed from GIT, no intestinal or luminal effect.
• Poorly tolerated
• Use: amoebic liver abscess– emetine or metronidazole f/b CQ or
alternative to emetine

17. LUMINAL AMOEBOCIDE
Diloxanide furoate
• kills trophozoites responsible for production of cysts
• No systemic antiamoebic activity is evident despite its absorption.
• metabolized by glucuronidation and is excreted in urine
• No/less action on bacteria, invasive amoebic dysentery
• ADR: very well tolerated; flatulence, occasional nausea, itching and
rarely urticaria.
• Use: mild intestinal and asymptomatic amoebiasis/cyst passers
• given after or along with any tissue amoebicide

18. LUMINAL AMOEBOCIDE
Nitazoxanide
• protozoa including E. histolytica, T vaginalis, giardia
• helminths- Ascaris, H. nana,
• MOA: inhibitor of PFOR enzyme that is an essential pathway of
electron transport energy metabolism in anaerobic organisms.
• ADR: Abdominal pain, vomiting and headache

19. LUMINAL AMOEBOCIDE
8-HYDROXYQUINOLINES- quiniodochlor,
diiohydroxyquin
• Entamoeba, Giardia, Trichomonas, some fungi ( dermatophytes,
Candida) and some bacteria.
• Less effective than diloxanide
• Liver glucuronide conjugation excreted in urine; t½ is ~ 12 hours
• rarely prescribed now, except in some poor localities ( inexpensive)
• ADR: nausea, transient loose and green stools, pruritus
• lodism (furunculosis, inflammation of mucous membranes) and goiter
may develop on prolonged intake.
• Prolonged/repeated use of relatively high doses cause a neuropathic
syndrome called ·subacute myelo-optic neuropathy' (SMON)

20. LUMINAL AMOEBOCIDE
Tetracyclines
• MOA: inhibit the bacterial flora with which Entamoebae live
symbiotically. Thus, they indirectly reduce proliferation of
entamoebae in the colon
• Use: chronic cases who have only the luminal cycle with little
mucosal invasion; adjuvant role ( used with a more efficacious
luminal amoebicide)

21. LUMINAL AMOEBOCIDE
Paromomycin
• Entamoeba, Giardia,, Trichomonas, leishmania and some tape worms,
• Aminoglycoside, closely resembles neomycin
• Orally administered paromomycin acts only in the gut lumen. It is
neither absorbed nor degraded in the intestine and is eliminated
unchanged in the faeces. free from systemic toxicity.
• similar or even better clearance of cysts from stools compared to
diloxanide furoate

22. Treatment
Acute amoebic dysentery
• Metronidazole/tinidazole are the drugs of choice kill the
trophozoites in 5- IO days.
• followed by a course of luminal amoebicide to ensure
eradication
• Metronidazole 800 mg oral TDS x 7-1 0 days/Tinidazole 2.0
g oral daily x 3-6 days
+ Diloxanide furoate 500 mg TDS x 5-10 days

23. DRUGS FOR GIARDIASIS
DOC:
• Metronidazole 400mg TDS x 5-7 days or
• Tinidazole 0.6 g daily x 7 days or
• Secnidazole 2 g single dose
• Nitazoxanide 500 mg BDx 3 days
• Quiniodochlor 250 mg TDS x 7 days ( less effective)
• Furazolidone 100 mg TDS x 7 days ( less effective)

24. DRUGS FOR TRICHOMONIASIS
• Metronidazole 400 mg TDS x 7 days OR Tinidazole 600 mg OD x 7 days
or Secnidazole 2 g single dose
IV:
• Diiodohydroxyquin 200mg intravaginally at bed time x 1-2 weeks
• Quinidochlor 200 mg intravaginally at bed time x 1-3 weeks
• Povidine – iodine 400 mg intravaginally at bed time x 2 weeks

25. DRUGS FOR LEISHMANIASIS
• Leishmania donovani
• Kala azar= visceral L
• Sandfly- phlebotomus
• Promastigote
• Amastigote

26. DRUGS FOR LEISHMANIASIS
SODIUM STIBOGLUCONATE
• Antimonial
• East Africa, central asia, South America
• Not used in INDIA and NEPAL
MOA:
Pentavalent-SB
Trivalent-Sb
Efflux of glutathione/reduced thiol
from parasite
Oxidative stress to parasite
Reductase in Amastigote

27. DRUGS FOR LEISHMANIASIS
SODIUM STIBOGLUCONATE
• Rapidly absorbed ( im / iv injection)
• Excreted unchanged in urine
• Remains stored in tissues
• Accumulation in macrophages prolonged effect
ADRS
• Tolerated well
• Nausea, vomiting, metallic taste, cough, abdominal pain
• Stiffness at injection site, sterile abscess
• QT prolongation, arrythmia, shock, death

28. DRUGS FOR LEISHMANIASIS
AMPHOTERICIN B ( AMB)
• Antifungal
• deoxycholate (AMB DOC)- older,
cheaper
• liposomes (L-AMB) newer, expensive
• AMB is the most effective drug with
highest cure rate up to 99%
• leishmania has high percentage of
ergosterol

29. DRUGS FOR LEISHMANIASIS
AMPHOTERICIN B ( AMB)
• high toxicity and need for prolonged hospitalization, monitoring and
repeated slow i. v. infusions  2nd line treatment of VL under
NVBDCP,
• WHO recommends it as the drug of choice
• AMB is the drug of choice in pregnant women and breast feeding
mothers.
• Liposomal AMB delivers the drug inside the reticuloendothelial cells
in spleen and liver where the amastigotes live- high cost
• Also used for mucocutaneous and dermal leishmaniasis

30. DRUGS FOR LEISHMANIASIS
MILTEFOSINE
• SSG resistance in Bihar and neighbouring areas, NVBDCP is now using
miltefosine as the 1ST line treatment of VL in India
MOA
• not known.
• may be interfering with lipid metabolism of the parasite or
• prevent synthesis of some critical cell surface anchor molecules,or
• alter signal transduction.

31. DRUGS FOR LEISHMANIASIS
MILTEFOSINE
• rapidly absorbed after oral medication,
• and widely distributed
• a long acting drug with biphasic elimination. In the early phase, t½ is
~7 days while the terminal t½ ~ 4 weeks.
ADR
• Anorexia, vomiting and diarrhoea are the commonest
• Skin allergy
• rise in hepatic transaminases
• Reversible kidney dysfunction with rise in serum creatinine
• Teratogenic. It is contraindicated in pregnant

32. DRUGS FOR LEISHMANIASIS
PAROMOMYCIN
• aminoglycoside antibiotic with antiamoebic action
• For intestinal protozoal infections,
• it is used by the oral route and remains confined to the gut.
• in India for use in VL by the i.m. route
• As an alternative to miltefosine, lower efficacy

33. DRUGS FOR LEISHMANIASIS