2. Introduction
• Parasite: - a living organism that survives at the
expense of another host organism
• Effects of parasitic diseases on human hosts vary
from minor to major and life threatening
• Anti-parasitic agents to be discussed include:
Antiprotozoal drugs
Antihelminthic drugs
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7. • Amoebiasis - protozoal infection caused by
Entamoeba histolytica.
• Amoeba found in 2 forms:
a) Cysts (non-invasive) – intraluminal (living
in lumen of GIT)
b) Trophozoites (invasive):
Penetrate intestinal wall causing
ulceration of mucosa of large intestine
Cause extra-intestinal amoebiasis e.g.
hepatic or pulmonary amoebiasis
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9. 27-Mar-24 9
Amebiasis
Amebiasis also called amebic dysentery it
is the infection of the intestinal tract
caused by entamoeba histolytica.
Can cause acute or chronic diseases
Diagnosis is established by isolating
E.histolytica in fresh feces.
10. Amebicidal
Therapeutic agents are classified as
luminal, systemic or mixed(luminal and
systemic)
Luminal drugs work on parasites in the
lumen of the bowel, systemic are effective
against those in intestinal wall
Mixed are able to treat or clear out
parasites in both sites.
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12. Clinical forms of Amoebiasis
and their treatment
1. Asymptomatic intestinal carriers:
• Should be treated immediately
• May become symptomatic or sources of
infection;
• D.o.C: Diloxanide furoate
• Alternative: Iodoquinol
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13. 2. Mild to moderate intestinal amoebiasis:
• Combination of Metronidazole +
Diloxanide furoate or Tetracyclines
3. Severe intestinal amoebiasis:
• Combination of Metronidazole +
Diloxanide furoate or Tetracyclines
• Fluid and electrolyte replacement
• Emetine can be used in severe resistant
cases
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14. 4. Extra-intestinal amoebiasis:
• Two tissue amoebicides must be
used
• E.g. Metronidazole + Chloroquine for
14 days followed by Diloxanide.
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15. Metronidazole
MOA:Some anaerobic protozoan
parasites(amebas) posses ferrodoxin-like,low
redox-potential, electron transport proteins
that participate in metabolic electron
removal reactions. The nitro group of
metronidazole is able to serve an electron
acceptor, forming reduced cytotoxic
compounds binds to protein and DNA,
resulting in cell death.
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16. Iodoquiol: ahalogenated 8-hydroxyquinolone,
it is effective against luminal trophozoite and
cyts forms.
Side effects: rash, diarrhea, and dose related
peripheral neuropathy ,including rare optic
neuritis.
Diloxanide furoate: useful for luminal
abecides, it is hydrolyzed in the intestinal
mucosa, resulting into free
Side effects;flatulence,pruritus,dry mouth.
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17. Paromomycin: it is an aminoglycosides and
effect against intestinal lumen and tape
worms because it is not significantly
absorbed. It is analternative agent for
cryptosporidiosis.
• Its amebicidal been linked to membrane
interaction, causing leakage
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18. GIADIASIS
Giadia lambia is the most commonly
diarrhea disease diagnosed throughout the
whole world.
G.intestinalis can cause asymptomatic
colonization or acute diarrheal illness.
Ingestion ,usually from contaminated
drinking water, leads to infection, then the
trophozoites exist in the small intestines
and divide by binary fission
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19. Occasionally cysts are formed that pass out in
the stool.
Although some are asymptomatic, severe
diarrhea can occur.
This diarrhea can be very serious in
immunosuppressed.
treatment
Metronidazole most used agent,
Tinidazole-overperfomed albedazole
Mebendazole
In pregnancy paromomycin
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20. Trychomoniasis
It is sexually transmitted infection(STI)
caused by the motile parasitic protozoan
Trichomonas Vaginalis.
One of the most common STIs in the world
Treatment
Metronidazole 2g Start, but 500mg BD for 7
days in HIV-positive individuals.
Tinidazole,secnidazole(2021-approved)
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21. QUESTIONS
1. The drug of choice for non-symptomatic
amoebiasis is
a. Tetracycline
b. Metronidazole
c. Emetine
d. Diloxanide
2. Resistant cases of amoebiasis is treated :
a. Tetracycline and Diloxanide
b. Metronidazole and Diloxanide
c. Emetine
d. Diloxanide
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23. Most important types of Plasmodium
targeted:
• P. falciparum-common and more virulent
• P. malariae,
• P. vivax, and
• P. Ovale
• P knowlesi
Transmitted by female anopheles mosquito
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24. Classification of Antimalarial
Drugs
1. According to anti malarial
activity:
• Tissue or blood
schizonticides
• Gametocytocides
• Sporontocides
(oocystocides)
2. According to chemical
structure:
• Peroxides (e.g. Artemisinin
derivatives)
• Aryl amino alcohols (e.g.
Quinine, mefloquine,
halofantrine)
• 4-aminoquinolines (e.g.
Chloroquine, amodiaquine),
etc
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26. Combination Therapy for
Malaria
Rationale
• Synergism & Potentiation Increased
therapeutic efficacy;
• Short duration of treatment;
• Increase compliance;
• Decrease risk of resistant parasites, and
• Prevent transmission & recrudescence
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27. Combination Therapy for Malaria
Combination Advantages Disadvantages
Artemether + Lumifantrine
(Co-artemether, Coartem)
Very effective, better
tolerated; No
serious ADR documented
Cost; Not recommended for
use in pregnancy and lactating
women
Sulfadoxine-pyrimethamine
(Fansidar)
Single dose; Cheap Drug resistance; Serious
adverse effects
Atovaquone + Proguanil
(Malarone)
Synergistic activity; Good
safety and tolerability
High cost; Restricted
availability; Hypersensitivity
Artesunate + Amodiaquine Better efficacy (>90% cure
rates); Well tolerated
Pharmacokinetic mismatch
Piperaquine +
Dihydroartemisinin +
Trimethoprim (Artecom)
>93% Efficacy; Affordable Animal toxicology studies
indicate additive toxicity; No
human ADR reported
Chlorproguanil + Dapsone +
Artesunate (Lapdap plus)
High cure rates reported No adequate data available
yet
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29. Tissue shizonticide: Primaquine-8-
aminoquinoline
Eradicates exoerythrocytic forms of
P,falciparum and Pvivax.
It’s the only agent that can lead to radical
cures of P.vivax and P.ovale .
It has gametocide effect.
MOA: It disrupts plasmodium mitochondria
Side effects: hemolytic anemia, abdominal
discomfort
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30. QUINOLONES
Quinine,Chloroquine,Lumefantrine,amodiaquin
e,mefloquine
These are effective against erythrocytic
forms.
MOA: They are basic in nature and
concentrate more in cells, inside infected
cells ,they prevent the conversion of hematin
to hemozoin, thus increasing intracellular
concentration of a toxic hematin
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31. Artemisinin
MOA: These drugs are inactive when given,
they are activated by heme forming carbon
centered-free radicals which kill parasites.
Examples: artemether,atesunate
Side effects: Prolongation of QT interval,N/V.
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33. Mode of Action
I. Drugs acting on neuromuscular
transmission :causing worm paralysis:
1) Levamisole - Depolarizing neuromuscular
blocker and immunostimulant
2) Metrifonate: - Anti-choline esterase
3) Diethyl-carbamazine: - Neuromuscular
blocker; produces paralysis and death of
the worm by host defensive mechanism
4) Praziquantel: - Increases Ca2+ entry
through cells thereby causes spastic
paralysis. Destroys integumental membrane
5) Pyrantel: - helminthic nAChR agonist;
causes tetanic receptor stimulation
paralysis
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34. II. Drugs acting by other mechanisms:
1. Mebendazole, Flubendazole: - Inhibits
microtubular system
2. Thiabendazole: - Inhibits microtubular
system
3. Niclosamine: - Inhibits oxidative
phosphorylation leading to scolex loosening
and worm expulsion
4. Oxamniquine: - Intercalates DNA and shift
of worm from mesentery to liver where
autolysis occurs
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35. Antihelminthic Drugs
Drug Clinical Uses Common Adverse
Effects
Mebendazole,
Flubendazole
Albendazole
Ascariasis;
Ancylostoma;
Oxyuriasis;
Trichuriasis
Minimal GIT side
effects
Thiabendazole Strongyloides;
Trichinella; Larva
migrans
GIT upset & Allergy;
CNS effects;
Leucopenia;
Crystalluria
Levamisole Broad spectrum of
Nematodes
(Roundworms)
GIT upset; Allergy;
CNS effects
Niclosamine Cestodes (Flat
worms)
Minimal due to
minimal
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37. Clinical Management of
Helminthic Infections
1. Ascariasis:
• Drug of choice: - Mebendazole PO
500mg single dose or 100mg bd for 3
d;
• Alternative drug: - Flubendazole PO
100mg bd for 3d;
• Alternative drug: - Levamisole PO
150mg single dose.
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38. 2. Ankylostomiasis:
• Drug of choice: - Mebendazole PO
500mg single dose or 100mg bd for 3
d;
• OR Flubendazole PO 100mg bd for 3
d.
• Alternative drug: - Levamisole PO or
Thiabendazole PO.
• Iron supplements for associated
anaemia
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39. 3. Enterobiasis:
• Drug of choice: - Mebendazole PO 500mg
single dose or Flubendazole PO 100mg
single dose; repeat after 2 and 4 weeks.
• The whole family must be treated at the
same time;
• Promote general hygienic measures;
• White precipitate ointment local application
around anal canal
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40. 4. Strongyloides:
• Drug of choice: - Thiabendazole PO
25mg bd for 5d.
• Alternative drug: - Mebendazole or
Flubendazole
5. Taenia saginata:
• Drug of choice: - Niclosamine PO 2g
single dose on empty stomach;
• Alternative drugs: - Praziquantel or
Mebendazole or Flubendazole.
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41. 6. Taenia solium:
• Therapy similar to Taenia saginata;
• Laxative given prior to oral admin of
Niclosamine to purge bowel of all dead
segments in order to prevent digestion and
liberation of ova which may lead to
Cysticercosis.
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42. 7. Neurocysticercosis:
• D.o.C: - Praziquantel PO 50mg/kg for 15
days plus Corticosteroid to reduce
cerebral edema.
• Albendazole 400mg bd for 28 days
N.B: - Praziquantel is contraindicated in
Ocular Cysticercosis because parasite
destruction in the eye causes ocular
damage.
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43. 8. Hymenolepsis nana:
• Drug of choice: - Niclosamine or
Praziquantel
9. Schistosomiasis:
• D.o.C: - Praziquantel is effective against
all species of Schistosoma and many
other trematodes and cestodes.
(Advantages: - High efficacy, safe, Easy administration
orally in a single dose or one day treatment)
• Oxamniquine; specific for Schistosoma
mansoni.
• Metrifonate; specific for Schistosoma
hematobium.
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44. Chemotherapy for trypanosomiasis
Trypanosomiasis refers to the two chronic and
eventually fatal diseases caused by species of
trypanosome: African sleeping sickness and
American sleeping sickness
African sickness cause are trypanosoma
brucei gambiense and trypanosome brucei
rhodiense,initially live and grow in blood.
American sleeping sickness (Chagas’ disease)
is caused by trypanosome cruzi-south America
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45. Melarsoprol
Limited for treatment of trypanosome
infections –usually in late stage(CNS)
MOA: It reacts with sulfhydryl groups of
various substances, including enzymes in the
organism and host.
There is evidence that mammalian cells are
less permeable.
Indication: African trypanosomiasis, covers
both species
Side effects: CNS most serious effects,
encephalopathy may appear soon after the
first course, hypersensitivity reactions may
occur ,GIT disturbance; severe vomiting and
abdominal pain-reduced in fasted state.
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46. Pentamidine isethionate
Active against variety of protozoal infections
including T.brucei gambiense, for Rx and
prevention hematological disease. However
some trypanosome including T.cruzi are
resitant.
MOA: T.brucei concentrates pentamidine by
energy-dependent system. Its exact
mechanism not known by evidence exists that
it binds to parasites DNA and interferes with
RNA, phospholipids and protein of the
parasites.-IM or aerosol
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47. Side effects: Renal dysfunction, hypotension,
dizziness, rash and toxicity to Beta cells of
the pancreas
Nifurtimox
Only used in T.cruzi infections,it is
suppressive ,not curable.
MOA: it undergoes reduction and form oxygen
free radicals, such as superoxides and
hydrogen peroxide-these are toxic to parasite
which lack catalase
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48. Nifrtimox: administered orally and excreted
in urine.
Adverse effects: hypersensitivity, peripheral
neuropathy,GIT and CNS.
SURAMIN
It is used in the earth Rx and prophylaxis of
African trypanosomiasis. Its very reactive
and inhibit many enzymes among those
involved in energy metabolism.
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49. Suramin must be injected intravenously. It
binds to plasma proteins and remain there for
long time, accumulate in liver and proximal
tubular cells.
-Patients needs to be followed due to toxicity;
side effects; N/V, shock, loss of
consciousness,acute
urticarial,photophobia,edema(eye lids)
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50. Principles of therapy.....
1. Antiparasitic drugs should be used along
with personal and public health control
measures to prevent spread of parasitic
infestations. Specific measures vary
according to the type of organism,
environment, and host factors;
2. Many antiparasitic drugs are quite toxic and
should be specifically used only when
clearly indicated (i.e, laboratory
confirmation of specific parasitic infection).
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