Antiamoebic and antiprotozoal drugs

pharmacology 2nd year MBBS theory class

1. ANTI AMOEBIC DRUGS

2. Antiamoebic Drugs
Drugs useful in infections caused by the protozoa
Entamoeba histolytica (E. histolytica)
E. histolytica, a protozoal parasite causative agent of
amoebiasis

3. E. HISTOLYTICA –
PATHOGENESIS
•Water-borne pathogen transmitted by fecal-oral route
•Exists in 2 forms:
1.Cyst or dormant form INFECTIVE & can survive
outside the body
2.Trophozoite or dividing form Non-infective and
do not persists outside the body but invasive

4. E. HISTOLYTICA –
PATHOGENESIS
•Two stages of development 
Ingested cyst reaches colon transform to trophozoites
May live as
commensals
Form cysts that
pass on to stool
1.Multiply & invade to ulcerate the
mucosa of large intestine
2.Form amoebic ulcers (acute
dysentery
3.Chronic amoebic dysentery
(vague symptoms, amoeboma)

5. PATHOGENESIS OF E. HISTOLYTICA
• Late stage extra intestinal
• Trophozoites enter  blood stream and travel to other parts
most commonly liver, sometimes lungs or brain  abscesses.
• In tissues, only trophozoites are present

6. AVAILABLE DRUGS
1.Tissue amoebicides:
a)Intestinal and extra-intestinal:
Nitroimidazoles – Metronidazole, Tinidazole, Secnidazole,
Ornidazole, Satranidazole
Alkaloides – Emetine and Dihydroemetine
a)Extra-intestinal – Only Chloroquine
2.Luminal amoebicides:
Amides – Diloxonide furoate, Nitazoxamide
8-Hydroxyquinolines – Quinodochlor, Diiodohydroxyquin
Antibiotics - Tetracycline

7. METRONIDAZOLE –
PROTOTYPE
Originally discovered and used for Trichomoniasis in
1959
Broad spectrum cidal activity against  Protozoa – E.
histolytica, T. vaginalis, G. lamblia
Anaerobic bacteria – B.fragilis, C.perfringes, H.pylori, Cl.
difficile
Resistance – no significant resistance for E. histolytica till
now, but developed for T. vaginalis
G. lambliaT. vaginalis

8. METRONIDAZOLE –
MOA
•Selective Toxicity to anerobic microorganisms
•Anaerobic protozoan parasites ( including amoebae),possess an
enzyme, pyruvate –ferrodoxin oxido –reductase involved in energy
production and other metabolic functions through electron transfer
reactions.
•This enzyme is not found in mammalian cells.
•The nitro group in metronidazole serves as an electron
acceptor.
•Reduced metronidazole is cytotoxic to anaerobic
bacteria/protozoa and disrupts replication , transcription and
repair process of DNA  results in cell death.

9. METRONIDAZOLE
Pharmacokinetics:
Well absorbed from small intestine
Widely distributed in body secretions – vaginal secretions, saliva and
CSF
Metabolized in liver by oxidation and glucoronidation
Half life – 8 Hrs
ADRs:
Most common - Nausea, Vomiting, abdominal cramps and metallic
taste , dark brown urine
Less frequent – headache, glossitis, rashes and dryness of mouth
Prolonged administration – Peripheral neuropathy and CNS effects
 Seizures at high dose

10. METRONIDAZOLE
•Contraindications:
–First trimester of pregnancy
–Neurological diseases and Blood dyscrasias
–Chronic alcoholism
•Interactions:
–Disulfiram-like intolerance
–Symptoms  flushing, burning sensation, throbbing
headache, dizziness, vomiting, visual disturbance, mental
confusion, fainting and circulatory collapse
–Enzyme inducers like Phenobarbitone and Rifampicin
(reduced therapeutic effect)

11. METRONIDAZOLE -DOSE
1.The recommended dose regimen :
2.For moderate intestinal amoebiasis 400 mg orally TDS for 7
days
3.For amoebic dysentry and liver abscess  800 mg TDS for 7
days
4.Giardiasis  200 mg TDS for 7 days
5.Trichomonas vaginitis  400 mg TDS orally for 7 days (male
partner also be treated )
6.Pseudomembraneous colitis  500 mg TDS
7.Anaerobic infections  15 mg/kg IV infusion over 1 hr
followed by 7.5 mg/kg IV infusion every 6 hrs till oral therapy
could be started . (400 mg TDS for another 7 days )

12. METRONIDAZOLE - USES
1.Ameobiasis – Kills E. histolytic trophozoites but not cysts.
2.Giardiasis
3.Trichomonas vaginalis – both partners
4.Anaerobic infections
5.Pseudo-membranous enterocolitis
6.Ulcerative gingivitis
7.Helicobacter pylori

13. OTHER NITROIMIDAZOLES
•Tinidazole, Secnidazole, Ornidazole, Satranidazole
•Tinidazole:
–Slower metabolism, duration of action (t 1/2 12 hrs) – single dose
–Higher cure rates (600 mg BD for 5-7 days )
–Better tolerated – lesser incidence of side effects
•Ornidazole: t ½ 12 -24 hrs
•Secnidazole: Rapid absorption, but slower metabolism – t ½ 17-29
hrs)
•Satranidazole: t ½ 14 hrs – better tolerated ; no nausea, vomiting
metallic taste . ( no disulfiram like reaction or neurological
symptoms )
• (300 mg BD for 5 days-amoebiasis ) (600 mg orally single dose for giardiasis
and trichomoniasis

14. EMETINE AND DEHYDROEMETINE
Emetine, alkaloid derived from Cephaelis ipecacuanha
 Dehydroemetine , a synthetic analog, are effective against
tissue trophozoites of E histolytica
•MOA 
•Inhibiting intra ribosomal translocation of t RNA-amino acid
complex → inhibiting elongation of peptide chain → inhibiting
protein synthesis

15. EMETINE AND DEHYDROEMETINE
•Action Effects on trophozoites (but not on cysts)
•Potent and rapid action – symptomatic relief in 1-3 days, but
not curative
Administered s/c (preferred) or i.m. (but never i.v.)
Uses: Seldom used now. (Cardiac toxicity)
 Dehydroemetine is preferred over emetine.
DOSE 60 mg IM once daily for 3-5 days .

16. EMETINE - ADRS
Local stimulation pain and tenderness in the area of
injection
GIT discomfort nausea, vomiting, diarrhoea and abdominal
cramps
Neuromuscular blockade muscle weakness and discomfort
Cardiac toxicityarrhythmias, congestive heart failure,
hypotension, ECG changes
C/I  cardiac or renal disease, in young children & pregnancy

17. CHLOROQUINE
Highly concentrated in liver & Kills trophozoites of E.
histolytica
– used in hepatic amoebiasis
Completely absorbed from upper intestine – not effective in
invasive or luminal dysentery
Effective in amoebic liver abscess , extra intestinal amoebiasis
Not effective against cyst form– so a luminal amoebicide must
be added after chloroquine to abolish luminal cycle
Dose  600mg stat and next day & 300mg for 2-3 days

18. DILOXANIDE FUROATE (DF)
•Highly effective luminal amoebicide
•Kills trophozoites responsible for production of cyst
•MOA: Oral DF F hydrolyzed and D is freed 90% D is
absorbed remaining 10% reaches Large intestine and exerts
effects
•Absorbed D – low serum level – no therapeutic effects

19. •Uses: Mild tissue amoebiasis/asymptomatic cyst passers,
Tissue amoebiasis and liver abscess with Metronidazole
•ADRs: Well tolerated, only flatulence, nausea, itching and
rarely urticaria
 DOSE500 mg TDS for 5–10 days
children 20 mg/kg/day.

20. NITAZOXANIDE
•Newer Drug for Giardiasis
•Also effective in E. Histolytica, T. Vaginalis, H. Pylori etc.
•Converted to Tizoxanide after absorption
MOA: inhibitor of PFOR (pyruvate ferrodoxin oxido reductase)
enzyme , an essential pathway of electron transport energy
metabolism in anaerobic organisms.
•Uses: Giardiasis, amoebiasis as luminal amoebicide
Abdominal pain, vomiting and headache are mild and
infrequent side effects.
•Dose: 500 mg BD for 3 days

21. 8-HYDROXYQUINOLINES
•Drugs – Iodoquinol and Iodochlorohydroxyquin
•Act against Entamoeba, Giardia, Trichomanas, some fungi and
Bacteria
kill the cyst forming amoebic trophozoites in the intestine, but
do not have tissue amoebicidal action.
•Absorbed very less amount (10-30%)
•conjugated and excreted in urine
•Once a popular drug – but less now because of ADRs

22. 8-HYDROXYQUINOLINES
•ADRs
•Subacute myelo-optic neuropathy (SMON) - the inflammation
of the optic nerve causing a complete or partial loss of vision
and also peripheral neuropathy
•Uses: Alternative to DF in amoebiasis, Giardia, local treatment
of vaginal Trichomonas , fungal and bacterial infections.
•250 to 500 mg tds

23. TETRACYCLINES
•direct inhibitory action on Entamoeba.
• incompletely absorbed in the small intestine, reach the colon in
large amounts and inhibit the bacterial flora
•Added as the third drug along with a nitroimidazole +
•a luminal amoebicide in the treatment of amoebic dysentery

24. PAROMOMYCIN
•aminoglycoside antibiotic active against many protozoa like
Entamoeba, Giardia, Cryptosporidium, Trichomonas,
Leishmania
•mechanism of antiprotozoal action of paromomycin
• same as its antibacterial action  binding to 30S ribosome and
interference with protein synthesis.
•Orally administered paromomycin acts only in the gut lumen. It
is neither absorbed nor degraded in the intestines, and is
eliminated unchanged in the faeces.

25. PAROMOMYCIN
•Paromomycin is an efficacious luminal amoebicide.
•Given along with metronidazole in acute amoebic dysentery
and in hepatic amoebiasis to eradicate the luminal cycle.
•Paromomycin is an alternative drug for giardiasis, especially
during 1st trimester of pregnancy when metronidazole and
other drugs are contraindicated.
•Topically, it may used in trichomonas vaginitis and dermal
leishmaniasis

29. THANK U

30. OTHER ANTI-PROTOZOAL
DRUGS

31. GIARDIASIS
Giardia lamblia – flagellate protozoan
Intestinal commensal
Invades mucosa – acute watery diarrhoea
Faeco-oral transmission

32. TREATMENT
Metronidazole – 400mg TDS 5-7 days
Tinidazole – 0.6g daily 7 days
Nitazoxanide – 500mg BD 3 days
Quiniodochlor – 250mg TDS 7 days
Furazolidone

33. TRICHOMONAS VAGINITIS
Microaerophilic flagellate protozoan
Vulvovaginitis
Common STD

34. TRICHOMONAS VAGINITIS
TREATMENT
Metronidazole – 400 mg tds for 7 days or 2
gm single dose, or
Tinidazole 600 mg BD for 7 days or 2 gm
single dose
Repeat after 6 weeks
Additional intravaginal treatment for
refractory cases
Resistance have been reported
Both partners should be treated
Local application drugs: Quinodochlor,
Clotrimazole, Natamycin, Povidone Iodine
etc.

35. •Drugs for
Leishmaniasis
•Visceral leishmaniasis or kala-azar caused by
Leishmania donovani
•Transmitted by bite of female sand fly of genus
phlebotomus
•Amastigote and Promastigote

36. AVAILABLE DRUGS
Antimonial – Sodium stibogluconate (SSG)
Diamide – Pentamidine
Antifungal – Amphotericin B (AMB),
Ketoconazole (KTZ)
Others – Mifepristone, Paromomycin and
Allopurinol

37. SODIUM STIBOGLUCONATE (SSG)
The drug of choice in Leishmaniasis – some resistance
Water soluble pentavalent antimonial compound – 1/3
rd

antimony by weight
MOA: Not clear
-SH dependent enzymes are inhibited – bioenergetics of the
parasite
Blocks glycolytic and fatty acid oxidation pathways
Enzyme in leishmania converts SSG to trivalent compound –
causes efflux of glutathione and thiols – oxidative damage
Not metabolized – excreted unchanged in urine after IM
injection
Dose: 20-30 mg/kg deep IM daily in buttock for 20-30 days
or more – depends on response – also IV
Response in Bone marrow and splenic aspirates
Should be give on alternate days I poor health patients

38. SSG - ADRS
All antimonials are toxic
Pentavalent compounds are less toxic and better
tolerated
Nausea, vomiting, metallic taste, cough and pain
abdomen
Stiffness and abscess in injected muscles
Pancreatitis, liver and kidney damage etc.
Rarely shock and death

39. PENTAMIDINE
•MOA: Not clear, inhibits Topoisomerase II or
interferes with aerobic glycolysis
•Dose: 4 mg/kg IM or slow IV for 1 Hr on
alternate days for 5-15 weeks
•Not metabolized but stored in kidneys and liver –
slowly released
•Toxicity: Histamine release – acute reactions
–Sharp fall in BP, dyspnoea, palpitation, fainting,
vomiting and rigor etc. – supine position
–Other reactions - rashes, mental confusion, kidney and
liver damage
–Cytolysis of pancreatioc beta cells – initially insulin
release – hypoglycaemia, but later IDDM

40. PENTAMIDINE – USES
SSG failure cases as salvage therapy - AMB is
preferred now
Leishmaniasis with Tuberculosis
Pneumocystis jiroveci pneumonia in AIDS
patients
Other drugs AMB and
Paromomycin etc. – shall be
discussed elsewhere!

41. DID YOU SLEEP DURING LAST 45
MIN. ?
If yes, no problem – just have to go
and read Metronidazole and SSG
If No, enjoy today - for knowing
Metronidazole and SSG

42. THANK YOU