Presentation for theory class of MBBS 2nd year

1. Antiprotozoal agents
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Assistant Professor, Maharajgunj Medical College
2 July 2019 (17 Asar 2076), Tuesday

2. By the end of the class, B Pharm
3rd year students will be able to:
List the common protozoal infections in humans
Understand the life cycle of common protozoa
Explain the pharmacotherapeutic management of
amoebiasis and giardiasis

3. Common Protozoal infections
in humans
Condition Infecting agent
Amoebiasis Entamoeba histolytica
Giardiasis Giardia Lambia
Trichomoniasis Trichomonas vaginalis
Malaria Plasmodium sps.
Leishmaniasis Leishmania donovani
Toxoplasmosis Toxoplasma gondii
Trypanosomiasis T. cruzi, T. brucei gambiense, T.
brucei rhodesiense

4. Life cycle of E. histolytica

5. Life cycle of G. lambia

6. Life cycle of T. vaginalis

7. Classification: Anti-amoebic
drugs
Tissue amoebicides Luminal amoebicides
For intestinal and
extraintestinal
amoebiasis
For extraintestinal
amoebiasis
Nitroimidazole
s
Metro-, Tini- Secni-,
Satrani-dazole
Alkaloids
(Dehydro)Emetine
Chloroquine

8. Classification: Anti-amoebic
drugs
Tissue amoebicides Luminal amoebicides
Amides Diloxanide furoate, Nitazoxanide
8-
hydroxyquinolines
Quiniodochlor,
Iodoquinol
Antibiotics
Tetracycline,
Paromomycin

9. Drugs Used in Giardiasis
Nitroimidazole
Metronidazole, Tinidazole, Secnidazole
Amides
Nitazoxanide
8-hydroxyquinolones
Quiniodochlor

10. Drugs used in Trichomonasis
Drugs used orally
Nitroimidazoles
•Metronidazole, Tinidazole, Secnidazole
Drugs used intravaginally
Diiodohydroxyquin
Quiniodochlor
Povidone-iodine

11. Nitroimidazoles
Metronidazole, Tinidazole, Secnidazole
Mechanism of action:
Enters cells and gets reduced to highly reactive
nitro radical
Competes for electrons with electron acceptors
generated by pyruvate-ferredoxin oxidoreductase
(PFOR)
•Acts as electron-sink
Energy metabolism disrupted  Cytotoxic effect

12. Metronidazole: Adverse effects
Most common:
Anorexia, nausea, metallic taste and abdominal
cramps, looseness of stool
Urticaria, flushing, heat, itching, rashes and
fixed drug eruption occur in allergic subjects

13. Metronidazole: Indications
Amoebiasis
Giardiasis
Trichomonas vaginitis
Anaerobic bacterial infections
Pseudomonas enterocolitis
Acute necrotizing ulcerative gingivitis (ANUG)
Helicobacter pylori gastritis/peptic ulcer

14. Alkaloids
Emetine, Dehydroemetine
Potent and directly acting amoebicides
Kills trophozoites
Cysts not affected
Acts by inhibiting intra-ribosomal translocation of
tRNA-amino acid complex
Administered by s.c. or i.m. injection

15. Alkaloids
Emetine: side effects
Local irritant
Systemic toxicity:
•Nausea,vomitting, abdominal cramps, diarrhoea
•Weakness, stiffness of muscles, myositis
•Hypotension, ECG changes, myocarditis
Dehydroemetine: less toxic

16. Alkaloids
Acute amoebic dysentery and amoebic liver abscess
In patients not tolerating metronidazole
Followed by luminal amoebicide

17. Chloroquine
Active against trophozoites of E. histolytica and
gets highly concentrated in liver
Completely absorbed in upper intestine
Longer duration of treatment required
Higher relapse rate

18. Chloroquine
Uses:
Amoebic liver abscess
600mg (base) for two days, followed by 300mg
base daily for 2-3 weeks
•Should be combined with luminal amoebicides
Side effects:
Nausea, vomitting, anorexia
Difficulty in accommodation, headache

19. Diloxanide furoate
Highly effective luminal amoebicides
Kills trophozoites
Diloxanide furoate (DF) is more effective
Unabsorbed fraction reaching the intestine
responsible for therapeutic effect
DF  hydrolysed by esterases into diloxanide
Absorbed, no therapeutic activity seen
Glucuronide conjugated, eliminated by kidneys

20. Diloxanide furoate
Uses:
Intestinal amoebiasis
Asymptomatic cyst passers
After or along tissue amoebicides
Adverse effects:
Flatulence, occasional nausea, itching and rarely
urticaria

21. Nitazoxanide
Prodrug
Active form- tizoxanide
Acts by inhibiting Pyruvate: ferredoxin
oxidoreductase (PFOR)
Is active against:
Protozoans- E. histolytica, T. vaginalis, G.
lambia, Cryptosporidium
Helminthes- A. lumbricoides, H. nana

22. Nitazoxanide
Indications:
Cryptosporidium infection
Giardiasis (metronidazole resistant as well)
E. histolytica (luminal amoebicide)
Side effects:
Abdominal pain, vomitting, headache

23. Quiniodochlor
Luminal agents (8-hydroxyquinolines)
Active against:
Protozoa
Fungi (Candida)
Bacteria
Active against the cysts present in the lumen

24. Quiniodochlor
Indications:
Intestinal amoebiasis
Giardiasis
Monilial and trichomonas vaginitis (local
treatment)
Fungal and bacterial skin infection

25. Quiniodochlor
Adverse effects:
Nausea, transient loose and green stools
Pruritis
Iodism, goiter
Acute reactions: fever with chills, angioedema,
cutaneous haemorrhage
Prolonged/continuous use:
•Subacute myelo-optic neuropathy (SMON)

26. Tetracycline
Adjuvant role
Modest direct inhibitory action on E. histolytica
Older tetracyclines reaches colon in large amounts
Inhibit bacterial flora (symbiotic relation with E.
histolytica)
Indirect inhibition of E. histolytica
Uses: chronic amoebiasis with only luminal
infection

27. Paromomycin
Aminoglycoside antibiotic
Active against protozoa and helminths as well
For intestinal amoebiasis, should be given orally
No absorption
No metabolism
Eliminated unchanged in faeces

28. Paromomycin
Uses:
Amoebiasis
Giardiasis
Cryptosporidiosis
Leishmaniasis
• 500mg three times
a day for 7 days
• Children 10mg/kg

29. Treatment: Amoebic infections
Acute amoebic dysentery
Either:
•Tab. Metronidazole 800mg, oral, three times a day
for 7-10 days
•Inj. Metronidazole 500mg, i.v., four times a day till
oral therapy can be instituted
•Tab. Tinidazole 2g, oral, once a day for 3-6 days
And:
•Tab. Diloxanide furoate 500mg, oral, three times a
day for 5-10 days

30. Treatment: Amoebic infections
Mild intestinal amoebic dysentery
Either:
•Tab. Metronidazole 400mg, oral, three times a
day for 5-7 days
•Tab. Tinidazole 2g, oral, once a day for 2-3 days
And:
•Tab. Diloxanide furoate 500mg, oral, three times
a day for 5-10 days

31. Treatment: Amoebic infections
Amoebic liver abscess
Either:
• Tab. Metronidazole 800mg, oral, three times a day for 10 days
• Inj. Metronidazole 500mg, i.v. infusion, four times a day for
10days
• Tab. Tinidazole 2g, oral, once a day for 2-3 days
• Inj. Tinidazole 800mg, i.v., daily for 6 days or till oral can be
given
And:
• Tab. Diloxanide furoate 500mg, oral, three times a day for 5-
10 days

32. Treatment regimens in
Giardiasis
Metronidazole 400 mg, three times a day for 5-7
days OR 2g, once daily for 3 days
Children 15mg/kg/day in three divided doses
Tinidazole 2g single oral dose OR 600 mg once
daily for 7 days
Secnidazole 2g, single oral dose

33. Treatment regimens in
Giardiasis
Nitazoxanide:
500 mg, twice daily for 3 days
•Children 7.5mg/kg
Quiniodochlor:
250 mg, three times a day for 7 days

34. Treatment regimens for
Trichomoniasis
Oral regimen:
Either:
•Metronidazole 400 mg three times a day for 7 days
•Tinidazole 600 mg once daily for 7 days
•Secnidazole 2g single oral dose
Resistant cases- higher doses
Courses can be repeated after 6 weeks
Treatment of partners may be necessary

35. Treatment regimens for
Trichomoniasis
Intravaginal regimen:
Either:
•Diiodohydroxyquin 200mg intravaginally at bed
time for 1-2 weeks
•Quiniodochlor 200mg intravaginally at bed time
for 1-3 weeks
•Povidone-iodine 400mg intravaginally at bed
time for 2 weeks

36. Conclusion
Though there are plenty of protozoal infections, only few are
known to cause disease in humans
Depending on the species, protozoa can have intestinal as well as
extra-intestinal stages in their life cycles
Important pharmacotherapeutically
Luminal amoebicides are important for amoebiasis
Three groups of drugs are available for the treatment of giardiasis
Nitroimidazole is the treatment of choice for giardiasis
Trichomoniasis in females can be treated locally as well

37. Thank you