presentation comprising knowledge about various protozoal infections and therapy options available for the treatment of those infections. various different drugs used in the therapy with their proposed mechanism of action. Hope it will be useful for understanding the pharmacology of antiprotozoals.

1. Antiprotozoal Drugs
Department Of Pharmaceutical
Sciences And Technology,
Maharaja Ranjit Singh Punjab
Technical University (Bathinda)
PRESENTED BY:-GAGANDEEP JAISWAL
(M. PHARM. PHARMACOLOGY)

2. Contents:-
Introduction to protozoa and its several types
Various protozoal diseases and their treatment:-
oAntimalarial drugs
oAntiamoebic drugs
oDrugs for Giardiasis
oDrugs for Trichomoniasis
oDrugs for Leishmaniasis

3. Protozoa.....The first animals?
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 do not have a cell wall and
therefore can have a variety of shapes. Protozoa vary in size and shape. Their sizes range from
10 to 55 micrometers, but they can be as large as 1 mm. The largest protozoa are called
xenophyophores, which can measure up to 20 centimeters in diameter.

4. 1.Amoeboids:-An amoeboid (ameba or amoeba)
is a type of cell or organism that is capable of
changing its shape, mainly by extending and
retracting pseudopods. They are normally found
in the soil and in aquatic habitats. They move by
using pseudopods. They typically ingest their
food by phagocytosis.
2.Flagellates :- Flagellates are organisms which
have one or more whip-like organelles called
flagella. Parasitic forms live in the intestine or
bloodstream of the host. An example of a
parasitic flagellate is Trypanosoma. Some
flagellates are autotrophic while others are
heterotrophs.
Flagellates are divided into two classes:
Phytomastigophorea
Zoomastigophorea
Amoeba
Euglena

5. 3.Ciliates:- The ciliates are a group of
protozoans which possesses hair-like
organelles called cilia. Cilia are used in
swimming, crawling, attachment, feeding.
Most ciliates are heterotrophs. They eat
organisms such as bacteria and algae. There
are three types of ciliated protozoa. They are
free-swimming ciliates, crawling ciliates, and
stalked ciliates. All of them use cilia for
locomotion and capturing food.
Paramecium
4.Sporozoans:- Sporozoans are non-motile,
unicellular protozoa, usually parasites. These
protozoans are also called intracellular
parasites. An example is Plasmodium vivax,
that causes malaria in humans. The earlier
stage sporozoan forms show some movement.
They do not possess locomotor organelles in
their later stage. Four main groups of sporozoa
include:
Apicomplexa
Microsporidia
Ascetosporea
Myxosporidia Plasmodium

6. Antiprotozoal Drugs
Anti-
malarial
Drugs
Anti-
amoebic
Drugs
Anti-
giardiasis
Drugs
Anti-
trichomoni
asis Drugs
Anti-
leishmanias
is Drugs

7. Malaria and Anti-Malarial Drugs
Malaria is a protozoal disease caused by one of the 4 species of protozoal parasite plasmodium
i.e. P. vivax , P. ovale , P. falciparum , P. malariae.
LIFE CYCLE
OF
MALARIAL
PARASITE

8. CLASSIFICATION
Chemical classification:-
1. 4-Aminoquinolines:- chloroquine, amodiaquine
2. 8-aminoquinoline:- primaquine
3. Quinoline methanols:- quinine,quinidine,mefloquine
4. Antifolates:-pyrimethamine, sulphadoxine ,dapsone ,proguanil
5. Antibiotics:- tetracycline,doxycycline,clindamycin
6. Hydroxynaphthoquinone:- atovaquone
7. Quinghaosu compounds:- artemisnin, artemether, artesunate
Clinical classification:-
A. Based on the stage of the parasite they affect:-
I. Tissue schizontocidals:- acts on pre erythrocytic and exoerythrocytic stages. Eg. Primaquine,
proguanil
II. Blood schizontocidals:- acts on erythrocytic phase . Eg. Chloroquine, artemisnin,
mefloquine.
III. Gametocidals:- kill gametocytes of plasmodia in blood. Eg. Primaquine, chloroquine
B. Based on clinical indication for use:-
I. Drugs used for causal prophylaxis:- acts on pre erythrocytic stage of plasmodium. Eg.
Proguanil, primaquine etc.
II. Drugs used for clinical and suppressive cure:- blood agents are used to completely eliminate
the parasites from the body. Eg. Rapidly acting like chloroquine, artemisnin and slow acting
like proguanil, pyrimethamine etc.
III. Drugs used to prevent relapse:- acts on latent tissue forms i.e. Hypnozoites. Eg. primaquine

9. iv. Drugs used to prevent the transmission of infection to anopheles mosquito(gametocidal
agents):- primaquine is effective against all the 4 types whereas chloroquine and quine are
effective only against P. Vivax and P. Malariae.

10. 4-Aminoquinolines
Chloroquine
Effective and rapidly acting blood schizontocide.
MOA:- its a basic drug, taken up by acidic food vacuoles of plasmodia and inhibits the
conversion of heme to hemozoin. Drug-heme complex is toxic and kills the parasite
Hemoglobin
Heme (toxic)
Chloroquine, Quinine, - - - + + Heme
Mefloquine polymerase
Hemozoin(non toxic to plasmodium)
Pharmacokinetics:- can be given through oral i.m. And i.v. Routes. Well absorbed oral and
parentral administration. Gets concentrated in liver and kidney. Metabolized in liver and slowly
excreted in liver. Early plasma t ½ varies from 3-10 days. Dose....... 500/250/150 mg tablets
ADR:- skin rashes, itching, headache, visual disturbances, confusion etc.
8-Aminoquinolines
Primaquine
Synthetic compound, effective against hepatic stages. Highly effective against gametocites and
hypnozoites.
MOA:- unknown

11. Pharmacokinetics:- Readily absorbed orally. Metabolized in liver . Plasma t ½ is of 3-6 hrs.
Excreted in urine within 24 hours. Dose...... 26 mg tablet
ADR:- g.i. Upset, abdominal pain, uneasiness in chest etc.
Quinoline methanols
Quinine and Quinidine
Both are obtained from cinchona bark
MOA:- similar to chloroquine
P’cokinetics:- readily absorbred from gut or i.m. Site. Metabolized in liver and excreted in urine
ADR:- cause dose dependent toxiccities like hypoglycemia, hypotension, deafness, visual
disturbances etc.
Antifolates
Pyrimethamine
slow acting blood schizontocide. Greater affinity for plasmodial DHF reductase. Always use din
combo with dapsone/sulphadoxine.
MOA:- PABA DHFA THFA ( PABA to DHFA through Folate
Synthetase and DHFA to THFA
-- - - - - - - - - through DHF Reductase)
Sulphadoxine, Pyrimethamine,
Dapsone Proguanil

12. P’cokinetics:- good absorbed orally, accumuulates in liver, kidney, lungs. Long plasma t ½ of 80-
90 hrs. Doses.......pyrimethamine(25 mg) + sulphadoxine(500 mg)/ dapsone(100 mg)
ADR:- urticarea, anemia, teratogenic effects etc.
Quinghaosu Compounds
Artemisnin and its derivatives
Derived from leaves of Chinese herb ‘qing hao’ , rapidly acting blood schizontocide.
Exact MOA isn’t clear. However, they may damage the parasite membrane by generation of
organic free radicals.
P’cokinetics:- available for oral and parentral administration. Artesunate and artemether
derivatives of artemisnin are actually prodrugs and gets converted into dihydroartemisnin which
is responsible for antimalarial activity.
ADR:-Animal studies shown to produce toxicity of CNS, liver, bone marrow, foetus.
Antibiotics
Tetracyclines
Slow acting blood schizontocide, don’t affect hepatic stages.
Usually used in combo with quinine for the treatment of multidrug resistant falciparum.
MOA:- Inhibits protein synthesis by binding to 30 S ribosomes. As a result, peptide chain fails
to grow and inhibition of translation occurs.
P’cokinetics:- widely distributed in the body(Vd >1 L/Kg). Accumulates in liver, spleen. Excreted
in urine through glomerular filtration.
ADR:- liver damage, phototoxicity, antianabolic effect etc.

13. Anti-Amoebic Drugs
Amoebiasis is a protozoal infection caused by Entamoeba histolytica, which is transmitted
through faecal-oral route. Amoebiasis can be present with no, mild, or
severe symptoms. Symptoms may include abdominal pain, diarrhea or bloody diarrhea.

14. CLASSIFICATION
1. Luminal amoebicides:- poorly absorbed after oral administration, attain high concentrations
in the bowel. Acts on cysts and trophozoites present close to the mucosa
a) Amide:- diloxanide furoate
b) Halogenated hydroxyquinolines:- iodoquinol, iodochlorhydroxyquin [now anned due to
SMON(subacute myelo-optic neuropathy)]
c) Antibiotics:- tetracyclines, paromomycin, erythromycin
2. Tissue amoebicides:- attain high concentrations in blood following oral and parentral
administration.
a) Nitroimidazole:- metronidazole, tinidazole
b) Emetine group:- emetine
c) 4- aminoquinoline:- chloroquine
Some of the mostly drugs (in detail) are as follows:-
Metronidazole
Highly effective against anaerobic bacteria and several protozoa such as E. Histolytica
 MOA:- metronidazole enters into microorganismnitro group is reduced in the cytoplasm
by a nitroreductase enzyme and by ferredoxins breaks and damages microbial DNA 
death of organism
 P’cokinetics:- It is widely distributed in the body, attaining therapeutic concentration in
vaginal secretion, semen, saliva and CSF. It is metabolized in liver primarily by oxidation and
glucuronide conjugation, Plasma t½ is 8 hrs. dose…200/400 mg tablet

15. ADR:- Anorexia, nausea, metallic taste and abdominal cramps are the most common. Less
frequent side effects are—headache, dryness of mouth, dizziness, rashes and transient
neutropenia.
Emetine and Dehydroemetine
 Emetine is a potent and directly acting amoebicide—kills trophozoites but has no effect on
cysts.
MOA:- It acts by inhibiting protein synthesis in amoebae by arresting intraribosomal
translocation of tRNA-amino acid complex.
P’cokinetics:- Emetine cannot be given orally because it will be vomited out. It is administered
by s.c. or i.m. injection: 60 mg OD
ADR:- Abdominal cramps and diarrhoea, weakness and stiffness of muscles, hypotension,
tachycardia etc.
 Dehydroemetine is less toxic to the heart. Thus, it is preferred over emetine by most
physicians. Dose: 60–100 mg s.c./i.m.OD
Diloxanide furoate
It is a highly effective luminal amoebicide
MOA:- Directly kills trophozoites responsible for production of cysts (luminal amoebicide).
Splits into diloxanide and furoic acid. Diloxanide moiety is partly absorbed and unabsorbed
portion in gut exerts anti-amoebic activity.
P’cokinetics:- primarily metabolized by glucuronidation and is excreted in urine. Dose: 500 mg
TDS for 5–10 days; children 20 mg/kg/ day.
ADR:- flatulence, occasional nausea, itching and rarely urticaria

16. Drugs for Giardiasis
Giardia lamblia is a flagellate protozoon which mostly lives as a commensal in the intestine. It
sometimes invades the mucosa and causes diarrhoea requiring treatment. Many drugs useful in
amoebiasis are also effective in giardiasis. Drugs used for the therapy are as follows
 Metronidazole:- 200 mg TDS (children 15 mg/ kg/day) for 7 days or 2 g daily for 3 days or
tinidazole 0.6 g daily for 7 days may be considered as the drugs of choice.
 Furazolidone:- It is a nitrofuran compound active against many gram-negative bacilli
including Salmonella and Shigella, also Giardia and Trichomonas. Mechanism of action is not
clear. But it is believed that it interfere with several bacterial enzyme systems. For giardiasis
its dose is 100 mg TDS for 5–7 days.
 Quiniodochlor:- 250 mg TDS for 7 days is a somewhat less effective alternative.
 Nitazoxanide:- an inhibitor of PFOR (pyruvate:ferredoxin oxido reductase) enzyme that is an
essential pathway of electron transport energy metabolism in anaerobic organisms has
recently become available for the treatment of diarrhoea and dysentery caused by Giardia
lamblia, E. histolytica. Dose…… 500 mg (children 7.5 mg/kg) twice daily for 3 days.

17. DRUGS FOR TRICHOMONIASIS
Trichomonas vaginalis is another flagellate protozoon which causes vulvovaginitis (inflammation
of the vagina and possible vulva. It can result in discharge, itching and pain, and is often
associated with an irritation or infection of the vulva. Infected women may also be
asymptomatic). Drugs used for treatment are as follows
Metronidazole:- 400 mg TDS for 7 days or 2 g single dose, or Tinidazole 600 mg daily for 7
days. They produce >90% cure.
Nimorazole: It is another orally effective nitroimidazole; 2 g single dose taken with meals has
produced satisfactory response in trichomonas vaginitis. Dose….250 mg tablet
 Povidone-iodine:- 400 mg inserted in the vagina daily at night for 2 weeks; BETADINE
VAGINAL 200 mg pessaries.
Natamycin:- inhibits transport of amino acids and glucose across the plasma membrane 25 mg
nightly intravaginal application for 10 days; NATAMYCIN 25 mg vaginal tab
Clotrimazole:- causes breakdown of cellular nucleic acids and accelerated potassium efflux.
100 mg dose inserted highup in vagina every night for 6–12 days; SURFAZ 100 mg vaginal tab

18. DRUGS FOR LEISHMANIASIS
Visceral leishmaniasis (kala-azar) caused by Leishmania donovani occurs in several tropical and
subtropical regions of the world. Leishmaniasis is transmitted by the bite of the female sandfly
phlebotomus. Characterized by skin ulcers, fever, low red blood cells, and enlarged spleen and
liver.
Some of the mostly drugs (in detail) are as follows:-
Sodium stibogluconate
 mechanism of action and the basis of selective toxicity to the leishmania amastigotes is
unclear; probably -SH dependent enzymes are inhibited and bioenergetics of the parasite is
interfered with. It is thought to be acting by blocking glycolytic and fatty acid oxidation
pathways.
 rapidly absorbed from the site of i.m. injection and excreted unchanged in urine within 6–12
hrs. Dose: 20 mg/kg (max. 850 mg) daily by i.m. (in buttocks)
Adverse effects :- Metallic taste, cough, pain abdomen, pain and stiffness of injected muscle,
sterile abscesses, mental symptoms, pancreatitis, liver and kidney damage often occur.

19. Pentamidine
Their mechanism of action is not properly understood. Pentamidine probably interacts with
kinetoplast DNA and inhibits topoisomerase II, or interferes with aerobic glycolysis and/or
utilization of polyamines.
After absorption from the site of injection it is rapidly taken up by tissues, especially liver and
kidney and stored for months, during which time it is slowly excreted in urine. Dose: 4 mg/kg
deep i.m.
ADR:- causes histamine release, sharp fall in BP, cardiovascular collapse, dyspnoea, palpitation
Amphotericin B (AMB):- Like fungi, leishmania has high percentage of ergosterol and is
susceptible to this antifungal antibiotic. It forms transmembrane channels leading to alterations
in cell permeability through which monovalent ions (NA+, K+, H+, and CI-) leak out of the cell
resulting in cell death.
 Dose: 0.5–1.0 mg/kg/day slow i.v. infusion till 15–20 mg/kg is administered.