describe about different protozoal infection and drug used for the treatment and mechanism of actions.

1. Drug used in protozoal infections
Praveenkumar.s
M.pharm2nd semester
Department of pharmacology
PSG College of pharmacy

2. Contents
• Protozal infections and protozoa
• Anti-amoebic drugs
• Drugs for Giardiasis
• Drugs for Trichomoniasis
• Drugs for Leishmaniasis
• Chagas disease and African trypanosomiasis.
• Antimalarial drugs.
• Bibilography.

3. Protozoal infections
• Protozoal infections are characterized by hyperproliferation of the
infectious agent independent of the parasites living intracellularly or
extracellularly of their respective host cells.
1. Amoebiasis
2. Malaria
3. Giardiasis
4. Trichomoniasis
5. Leishmaniasis
6. Trypanosomiasis

4. Protozoa
• The term protozoa implies ‘first animals’.
• As the primary hunters of the microbial world, protozoa help in
continuing the equilibrium of bacterial, algal and other microbial life
forms.
• Protozoa are single-celled organisms without cell walls.
• Protozoa vary in size and shape.
• Their sizes range from 10 to 55 micrometers, but they can be as large
as 1 mm.

5. • Protozoa are,
1. Amoeboids.
2. Flagellates.
3. Ciliates.
4. Sporozoans.

6. Anti-amoebic drugs
• These are the drugs useful in infection caused by the anaerobic
protozoa ‘Entamoeba histolytica’
• Amoebiasis has a wordwide distribution (over 50million people suffer
invasive disease, but many more harbour it).
• Poor environmental sanitation and low socio-economic status are the
important factors in the spread of disease,occurs by fecal
contamination of food and water.

7. Life cycle

8. Classification of anti-amoebic drugs

9. Nitroimidazoles
Metronidazole
• Is a nitroimidazole, is a powerful amoebicide.it is amoebicidal,
kills the trophozoites and is effective in both intestinal and
extraintestinal amoebiasis.
• It also inhibits Trichomonas vaginalis,Giardia lamblia and
Balantidium coli.

10. Mechanism of action

11. Adverse effects
Side effects metronidazole are relatively frequent and unpleasant,but
mostly unserious.
• Most common- Anorexia,nausea,metallic taste and abdominal cramps.
• Occasional- Loosening of stool.
• Less frequent- headache, glossitis,dryness of mouth and impairment
concentration.
• Discontinuation drug- Urticaria, flushing,heat,rashes.
• Prolonged administration- peripheral neuropathy,seizures.
• Thrombophlebitis.

12. Uses
1. Amoebiasis
2. Trichomonas vaginitis
3. Giardiasis
4. Anaerobic infections
5. H.pylori infections.
6. Pseudomembranous colitis.
7. Acute ulcerative gingivitis

13. Emetine and dehyroemetine
• Emetine is an alkaloid,derived from ipecac (Brazil root).
• Dehyroemetine is a semisynthetic analog.
• Mechanism: directly affect the trophozoites but not cysts.
• Can be used only in severe amoebiasis for 3-5 days in patients,but
generally not preferred due to toxicity.
Adverse effects:
• Thrombophlebitis
• Nausea,vomiting and diarrhoea.
• Cardiotoxicity including arrythmiasis (drugs should be avoided in patients
with cardiac dysfunction).

14. Diloxanide furoate
• Is directly amoebicidal.
• Highly effective luminal amoebicide, which directly kills trophozoites
responsible for production of cysts.
• It spilt in the intestines to diloxanide and furoic acid,it acts on the parasite
intestines but not in the tissues.
Uses
• Is used along with nitroimidazole for the cure of amoebiasis.
• Eradication of cysts.
ADR
Flatulence,nausea and occassionally abdominal cramps and rashes can occur.

15. Nitazoxamide
• Is a congener of niclosamide effective against
E.histolytica,T.vaginalis,Giardia and some intestinal helminths like
Ascaris and H.nana.
• Mechanism: nitazoxamide and it’s active metabolite interfere with
the PFOR enzyme- depandent electron transfer reaction in anaerobic
metabolism.
• It is well tolerated as adverse effects are rare.it imparts greenish tint
to the urine should avoided in pregnancy.

16. Iodoquinol and quiniodochlor
• These 8-hydroxyquinolines are directly acting luminal amoebicide.
• Exact mechanism is not known.
• They kill the cyst forming amoebic trophozoites in the intestine.
• Is an inexpensive these drugs widely and injudiciously used for
prophylaxis and treatment of nonspecific diarrhoea, traveller’s
diarrhoea, dietary indiscretion.
• Side effects-nausea, transient loose and green stools,pruritus.
• Iodism (furunculosis, inflammation of mucous membranes) and
goiter-prolonged intake.

17. Paromomycin
• Aminoglycoside antibiotic given orally.
• Is an intestinal amoebicide (luminal amoebicide)
• ADR; mild diarrhoea and abdominal discomfort.
Tetracyclines
• Older tetracyclines,like chlortetracycline are not well absorbed and
large amounts reach colon-These are useful in intestinal amoebiasis.
• They Inhibit the intestinal flora and break symbiosis Between them
and amoebae.
• Tetracyclines used as adjuvants in chronic cases.

18. Treatment of different forms of amoebiasis
1. Acute intestinal amoebiasis:
• Metronidazole 400-800 mgTDS for 5-7 days or 2.4 g OD for 3 days.
• Tinidazole 2g OD for 3 days.
• Secnidazole 2g single dose.
2.Chronic amoebiasis and asymptomatic cyst passers:
• Diloxanide furoate 500mg TDS for 10 days or tetracycline 250mg qid
for 10 days.
• Alternatives iodoquinol (650mg TDS for 21 days ).

19. 3.Hepatic amoebiasis;
• Requires intensive treatment for complete eradication of the
parasite from the liver in order to avoid relapses.
• Metronidazole 600-800mg TDS for 10 days+chloroquine given to
ensure complete destruction of liver forms.
• Diloxanide furoate 500mg TDS for 10days eradicate the cysts.

20. Giardiasis
• Giardia lamblia – flagellate
protozoon.
• It infects children and adults
by oro-faecal contamination
and mostly lives as a
commensal in intestine.
• It invades the mucosa and
cause acute watery diarrhoea
with foul smelling stools,gas
and abdominal cramps.

21. Giardiasis life cycle

22. Drugs for Giardiasis
1. Metronidazole: 400mg TDS (children 15 mg/kg/day)for 5-7 days or
2g daily for 3 days
2. Tinidazole 0.6 g daily for 7days or 2g single dose.
3. secnidazole 2g single dose.
4. Nitazoxamide prodrug PFOR enzyme inhibitor for treatment of
diarrhoea and dysentery caused by Giardia lamblia, E.histolytica.
5. Quiniodochlor
6. Furazolidone nitrofuran compound against salmonella, shigella and
giardia.dose 100mg TDS for 5-7 days.

23. Trichomoniasis
• Trichomonas Vaginalis –
microaerophilic flagellate
protozoon causes
vulvovaginitis.
• Sexually transmitted
disease affecting ~10%
sexually active women.
• Several drugs are partly
effective by vaginal
application,but may not
entirely clear the infection.

24. 1. Drugs used orally
• Metronidazole 400mg TDS for 7days or 2g single dose or
• tinidazole 600mg daily for 7days or 2g single dose or
• Secnidazole 2g single dose are the drug of choice.
• Vaginitis due to nitroimidazole resistant t.vaginalis is being reported.
• Additionally intravaginal treatment require only in refractory cases.
• Repeate course can be given after six weeks
• In some cases recurrences are due to reiinfection from male partner
who harbours the parasites in the seminal vesicles but remain
asymptomatic,such cases both partner should be treated
concurrently.

25. 2 .Drug used intravaginally
1. Diiodohydroxyquin 200mg inserted intravaginally at bed time 1 to 2
weeks.
2. Quiniodochlor 200mg inserted intravagina every night for 1 to 3
weeks
3. Povidone-iodine 400mg inserted in the vagina daily at night for 2
weeks

26. Leishmaniasis
• Visceral Leishmaniasis (VL; kala-azar) caused
by Leishmania donovani (Other Leishmania
species) occurs in several tropical and
subtropical regions of the world.
• In india,leishmaniasis is prevalent in bihar,
West Bengal, Jharkhand and eastern UP. (Bihar
which contributes 50% of cases that occur
world over).
• Is transmitted by bite of female sandfly
phlebotomus

27. Lifecycle:

28. Drugs for Leishmaniasis
1. Sodium stibogluconate (SSG)
2. Amphotericin B(AMB)
3. Miltefosine.
4. Paramomycin.

29. Mechanism of action

30. HAT /African sleeping sickness
• HAT, also known as African sleeping sickness, it affects 70 million people in 36 countries.
• HAT is a vector-borne disease caused by the protozoa parasite
Trypanosoma brucei .
• It is transmitted through the bite of an infected tsetse fly or passed from an infected
mother to her child through the placenta.
• This disease has two stages:
1. The first stage involves parasite-included seizures of the hemolymphatic system,
2. Second, involves the transmission of the parasites into the central nervous system
(CNS) across the blood–brain barrier ,Infection of the CNS leads to a number of
symptoms including mental impairment, severe headaches, fever, chronic
encephalopathy, and eventual death.
• Drugs, suramin, pentamidine, and melarsoprol

31. Life cycle

32. Chemotherapy of malaria
• Malaria caused by protozoa of the genus plasmodium is the most
commonly transmitted through the bite of a female Anophales
mosquito,through malaria transmitted by blood transfusion and
vertically from mother to foetus across placenta.
• Five species of malarial parasite,
1. Plasmodium falciparum
2. Plasmodium vivax
3. Plasmodium ovale
4. Plasmodium malariae
5. Plasmodium knowlesi

33. Life cycle of malaria

34. Drugs for treatment of malaria
A) Therapeutic classification:
1. Causal prophylactics:(Primary tissue schizonticides)
Destroy parasite in liver cells and prevent invasion of
erythrocytes.
Eg: primaquine,pyrimethamine.
2. Blood schizonticides:
Suppressives, destroy parasites in the RBC and terminate clinical
attacks of malaria.
Eg: chloroquine,quinine,artemisinin,mefloquine,
pyrimethamine,atovaquone .

35. 3. Clinical cure(erythrocytic schizonticide):
used to terminate an episode of malarial fever.
Fast acting (high efficacy):
Eg; artemisinin, chloroquine,amodiaquine,quinine.
Slow acting (low efficacy):
Eg: proguanil, pyrimethamine, sulfonamide, tetracycline.
4.Radical curative:
Eradicate all forms p.vivex,p.ovale from the body
Drugs: suppressive drugs+hypnozoiticidal drugs.
For p.vivax : primaquine 15 mg daily for 14 days.

36. 5. Gametocidal
Destroy gametocytes and prevent the transmission.
Eg:. Primaquine, artemisinin- against all plasmodium.
Chloroquine, quinine derivatives- p.vivex
Proguanil, pyrimethamine –prevent development of
sporozoites.

37. B) Chemical classification
1. 4-aminoquinolines
. Eg: chloroquine, amodiaquine
2. 8- aminoquinolines
. Eg: primaquine,bulaquine
3. Quinoline methanols
eg: quinine,quindine,mefloquine.
4. Sesquiterpine lactones
. Eg; artemisinin,artesunate,artemether
5. Folate antagonists
. Eg: proguanil,sulfadoxine, pyrimethamine.
6. Phenanthrene methanol:
Eg:. Halofantine,lumefantrine
7. Naphthaquinone
Eg: Atovaquone.
8. Antibiotics
Eg: Tetracycline,
doxycycline,ciprofloxacin

38. Quinolines

39. Uses
• Highly effective for malaria.
• Extraintestinal amoebiasis.
• Rheumatoid arthritis.
• Photogenic reactions.
• Lepra reaction.
• Discoid lupus erythematosus

40. Other actions of quinine
• Mild analgesic and antipyretic activity.
• Quindine –arrythmiasis.
• Local anaesthetic properties
• Skeletal muscle relaxant.
• Stimulate uterus-abortifacient.

41. Halofantrine and lumefantrine
MOA:simliar to chloroquine (inhibits haeme polymerase).
Uses:
• Lumefantrine is combined with artemisinin in the treatment of MDR
falciparum malaria.
The combination is well tolerated with side effects like gastrointestinal
disturbances, headache, dizziness.
Lumefantrine 120mg+Artemether 20mg -4tabs BD for 3 days.

42. Primaquine

43. Uses
• Radical cure of p.vivax and p.ovale.
• Gametocidal effects.
• Terminal prophylaxis.
• Pneumocystis jiroveci.

44. Folate antagonists
• Pyrimethamine, proguanil, sulfonamides.
MOA

45. Uses
• Pyrimethamine+sulfadoxine: treatment of malaria.
• Toxoplasmosis.
• Pneumocytosis.

46. Atovaquone
• Is effective against the erythrocytic forms of plasmodium, combined
with proguanil,synergism effect.
MOA:
• Inhibits the mitochondrial electron transport leading to collapse of
mitochondrial membrane potential in malarial parasite.
• Also interfere with pyrimidine synthesis in the parasite.

47. Artemisinin and derivatives
• Is an sesquiterpine lactone obtained from plant artemisia annua.
MOA:
• Interact with haem resulting in the generation of free radicals that
bind to the macromolecules and membrane proteins that damage the
parasite membrane.
• It also inhibit calcium ATPase in the parasite.
Actions: potent, rapidly acting, erythrocytic schizonticide effective
against all the plasmodial species.

48. Antibiotics in malaria
• Tetracycline – weak activity against erythrocytic forms of malaria
parasites.
• Doxycycline – chemoprophylaxis of malaria.
• Clindamycin- activity against erythrocytic forms of malarial parasite.

50. References
• Essential medical pharmacology by KD Tripathi.
• Medical pharmacology padmaja Uday Kumar.
• Image sources:jaypee digital book, Wikipedia,indian journal of
dermatology,mpmp.huji.ac.in, WWW.malariasite.com, e -medicine
medscape.com, WWW.cdc gov.in , WWW.ejid.org ,
WWW.researchgate.in

51. Thank you