This document discusses antiprotozoal agents used to treat common protozoal infections in humans. It begins by listing common protozoal infections such as amoebiasis, giardiasis, malaria, and toxoplasmosis. It then covers the life cycles of Entamoeba histolytica and Giardia lambia. The document classifies antiamoebic drugs as tissue amoebicides or luminal amoebicides. It provides details on nitroimidazoles, alkaloids, chloroquine, diloxanide furoate, and other drugs. For giardiasis, it recommends nitroimidazoles like metronidazole and tinid
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Antiprotozoal for MBBS 2021
1. Antiprotozoal agents
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Assistant Professor, Maharajgunj Medical College
14 November 2021 (28 Kartik 2078), Sunday
2. By the end of the class, MBBS 2nd
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
8. Drugs Used in Giardiasis
Nitroimidazole
Metronidazole, Tinidazole, Secnidazole
Amides
Nitazoxanide
8-hydroxyquinolones
Quiniodochlor
9. 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
10. 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
12. Antiprotozoal agents- II
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Assistant Professor, Maharajgunj Medical College
17 November 2021 (1 Mangsir 2078), Wednesday
13. 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
15. 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
16. 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
18. 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
19. 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
20. 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
22. 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
26. 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)
27. 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
30. 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
31. 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
32. 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
33. 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
35. 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
Tissue as well as 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
Aerobic environment attenuates cytotoxicity of metronidazole by inhibiting its reductive activation
O2 competes with nitro radical of metronidazole for the free electrons generated by PFOR
Mechanism of resistance: deficient in generation of nitro radical, lower levels of PFOR
Relatively frequent and unpleasant, but mostly non serious
Urticaria, flushing, heat, itching, rashes and fixed drug eruption occur in allergic subjects, warrant discontinuation of the drug and preclude future use of nitroimidazoles.