Antiparasitic Agents

DR FIRMALINO

ANTI PROTOZOA
ANTIHELMINTHIC
Antiprotozoal Agents
Sporozoans
Malaria:
species of plasmodium that cause human malaria,
transmitted by anopheles mosquito bite
(P. falcifarum, P. vivax, P. malariae, P. ovale;
P. knowlesi)
life cycle: liver/tissue phase and blood phase
radical cure - eliminate both hepatic and erythrocytic
stages
suppressive cure - complete elimination of parasite from
the body by continued therapy
clinical cure - terminate clinical attack
DRUGS
1. Tissue schizonticide - eliminate developing or dormant
liver forms
a. Primaquine
2. Blood schizonticide - act on erythrocytic parasite
a. Chloroquine
b. Quinine
c. Mefloquine
d. Inhibitors of folate synthesis
e. Tetracycline, Doxycycline, Clindamycin
f. Halofantine
3. Gameticide - kill sexual stages
a. Quinine
b. Primaquine
4. Causal prophylactic drugs - capable of
preventing erythrocytic infection
a. Chloroquine
b. Mefloquine
c. Inhibitors of folate synthesis
d. Doxycycline, Azithromycin
 Chloroquine
Blood schizonticide effective for all
specie
Inactive to liver parasite of vivax &
ovale ( so Primaquine must be used)
Resistance common w/ falciparum
Also used in combination w/
metronidazole for amebic liver
abscess
AE agranulocytosis
Safe in pregnancy and children
II. Amodiaquine
- same mechanism of action as Chloroquine (not
available in the Phils)
low cost; limited toxicity; effective against
chloroquine-resistant strains in certain areas
Tx for chloroquine resistant strains of P.
falcifarum
Not for chemoprophylaxis
AE: agranulocytosis
 III. Quinine, Quinidine
Used for treatment of severe Falcifarum malaria
and chloroquine resistant strains
Blood schizonticide for all specie but not to liver
stage
Gametocidal to vivax & ovale but not falciparum
Also for Babesiosis if combined w/ Clindamycin
MOA: inhibits plasmodium hgb polymerase
AE: cinchonism (tinnitus, headache, nausea,
dizziness, flushing, visual disturbance),
hemolytic anemia/ blackwater fever (hemolysis
& hemoglobinuria)
IV. Melfloquine
chemically related to Quinine
- chemoprophylaxis and blood schizonticide for
chloroquine-resistant strains of P. falcifarum
- inactive to liver stage & gametocyte
- given only orally; severe local irritations if parenteral
- MOA: swelling of parasitic food vacuoles
- considered safe for young children; safe in pregnancy
but limited experience in 1st trimester
- AE: confusion, psychosis (lessened by splitting the
dose)
 Primaquine
- drug of choice for the eradication of
dormant liver forms of all specie
- MOA: : - unknown mechanism of action
- swelling of parasitic food vacuoles
- gametocidal (4 strains)
- check G6PD status (risk for hemolysis)
- oral, not parenteral
- C/I: pregnancy
- Other uses: pneumocystis carinii infection
- AE: hemolytic anemia, agranulocytosis,
arrythmia, methhemoglobinemia
Inhibitors of folate synthesis
- selectively inhibit plasmodial dihydrofolate reductase
1. Pyrimethamine + sulfadoxine (Fansidar)- safe in
pregnancy, for chloroquine resistant falciparum
also toxoplasmosis, pneumocystosis
2. Proguanil (Chloroguanide)- safe in pregnancy; for
treatment and prophylaxis (safe alternative to
mefloquine; (+) chloroquine 500mg weekly and
proguanil 200mg daily
 Adverse effects of folate
inhibitors
Proguanil alopecia, mouth ulcer
Fansidar erythema multiforme,
steven johnsons, toxic epidermal
necrolysis
Maloprim agranulocytosis
Pyrimathamine teratogenic in
animals but not noted in humans
VII. Antibiotics - Unclear mechanism of
action (?inhibits cell wall synthesis)
- Tetracycline & doxycycline
(schizonticide for malaria, inactive for liver
forms )
- Clindamycin, Azithromycin,
quinolones, spiramycin (for malaria, also
for toxoplasmosis, pneumocystosis,
babesiosis

VIII. Atovaquone combined w/ Proguanil &

called Malarone
- antimalaria & P. carinii pneumonia
 VIII. Halofantrine
- limited use because of irregular
absorption and cardiac toxicity,
embryotoxic
- C/I: pregnancy
- erythrocytic only, not for liver stage
or gametocyte
- preparation: (not available in the
Phils)
IX. Artemisinin (qinghaosu)
- only drug reliably effective against
quinine-resistant strains
- antipyretic & antimalaria
- schizonticide, not for liver form
- analogs artesunate, artemether,
dihydroartemisinin
- Co artem = artemether + lumefantrin for
falciparum
= artesunate + amodiaquine
- neurotoxic, avoid in pregnancy
 AMEBIASIS
Entamoeba histolytica
Asymptomatic intestinal infection
Colitis,
Dysentery
Ameboma
Liver abscess
Pulmonary or brain abscess
Amoeba Life Cycle:
Drugs used for Amoebiasis
Classification:

I. Tissue amoebicide
I. Dehydroemetine,
II. Emetine
III. Chloroquine.
II. Luminal amoebicide
a. Halogenated hydroxyquinolines
1. Diiodohydroxyquin* ( iodoquinol)
2. Iodochlorhydroxyquin
3. Dibromohydroxyquinoline

b. Dichloroacetamide
1. Diloxanide furoate*
2. Clefamide
3. Teclozan
4. Etofamide
c. Antibiotic
1. Paramomycin

III. Tissue and Luminal amoebicide

a. Nitroimidazole
1. Metronidazole
2. Tinidazole
3. Ornidazole
4. Secnidazole
b. Niridazole
Amebicidal Agents:
I. Metronidazole - drug of choice for the treatment of
extraluminal amebiasis
- kills trophozoites but not cysts
- for anaerobic bacteria and sensitive protozoas
- Tinidazole, a related drug has better toxicity profile
- tissue amoebiasis, giardiasis, trichomoniasis
- AE: nausea, headache, dry mouth, metallic taste,
disulfiram-effect (severe vomiting if taken w/ alcohol)
- Drug interaction: anticoagulants, phenytoin,
phenobarbital
II. Iodoquinol - effective luminal
amoebicide
- unknown mechanism of action
III. Diloxanide furoate - drug of choice
for asymptomatic luminal infections
(carrier)
- unknown mechanism of action
IV. Paramomycin sulfate - an aminoglycoside used only
as a luminal amebicide

V. Emetine and Dehydroemetine - has limited use, given

SC or IM, not IV, analog derived from ipecac
AE: pain and tenderness; diarrhea, nausea and
vomiting
C/I: patients with cardiac or renal disease; children and
pregnancy
Other anti-Protozoal Agents:
I. Pentamidine - only administered parenterally (IV),
and aerosol inhalation powder for pulmonary
infection
- used in Pneumocystosis pneumonia
- Trypanosomiasis (African sleeping sickness from
Tsetse fly bite) early hemolymphatic stage but not
late CNS stage,
- alternative to stibogluconate for cutaneous &
Visceral Leishmaniasis
- unknown mechanism of action
- AE hypotension, hallucination, dyspnea,
arrythmia
 cutaneous leishmaniasis

visceral leishmaniasis

anemia
enlarged liver and spleen
fever
weaker inflammatory response
(due to the loss of phagocytes)
weight loss.
 II. Sodium Stibogluconate &
Meglumine
- 1st line agents against cutaneous
and visceral Leishmaniasis
- unknown mechanism of action
- AE: GI upsets, sterile abscess,
hemolytic anemia
III. Nitazoxanide for Giardiasis,
ameba, cryptosporidium, H. pylori,
ascaris, tapeworm, fasciola hepatica
IV. Other Drugs for Trypanosomiasis
a. Suramin - for African trypanosomiasis,but do not
enter the CNS
- unknown mechanism of action
b. Melarsoprol - 1st line therapy for advanced CNS
East African Trypanosomiasis, very toxic
(cerebral edema)
c. Eflornithine - an inhibitor of ornithine decarboxylase
- a 1st line therapy for advanced CNS west African
trypanosomiasis
d. Nifurtimox - most common drug used for American
Trypanosomiasis (Chagas disease- kissing bug bite,
swollen lymph node, heart failure)
AE- neuropathies, seizure
e. Benznidazole - for the treatment of acute Chagas
disease
toxicities: peripheral neuropathy, rash, GI symptoms,
myelosupression
f. Amphotericin alternative tx to visceral & cutaneous
leismaniasis
g. Miltefosine first effective oral drug for visceral
leishmaniasis
h. Paromomycin also for visceral leishmaniasis
.
Antihelminthic Agents
 Enterobius vermicularis
Ascaris lumbricoides
Rectal prolapse in
Trichuris trichiuria
pinworm/treadworm/seatworm
whipworm
Sheep liver fluke/ Fasciolasis
Filariasis, Wuchereria bancrofti,
Brugia malayi/timori, Loaloa
Strongyloidiasis
Pork tapeworm
Fish tapeworm
Schistosomiasis
Antihelminthic Drugs:
I. Albendazole - drug of choice for the treatment
of hydatid disease, neurocysticercosis and
cutaneous larva migrans ,

MOA: act by inhibiting microtubule synthesis in

nematodes, thus irreversibly impairing glucose
uptake & immobilize the parasite; also has
larvicidal effects in hydatid disease,
cysticercosis, ascariasis and hookworm
infection and ovicidal effects in ascariasis,
ancylostomiasis and trichuriasis
Availability: Zentel 400mg tab and 200mg/5ml
toxicity - agranulocytosis, pancytopenia
II. Mebendazole - same MOA as Albendazole
- used in ascariasis, trichuriasis and hookworm
and pinworm infection( choice)
- MOA: act by inhibiting microtubule synthesis in
nematodes, thus irreversibly impairing glucose
uptake & immobilizes the parasite;
- also has larvicidal effects in hydatid disease,
cysticercosis, ascariasis and hookworm infection

- ovicidal effects in ascariasis, ancylostomiasis

and trichuriasis
Non carcinogenic, non tertogenic
III. Thiabendazole
- alternative drug for the
treatment of strongyloidiasis and
cutaneous larva migrans
- same MOA as Albendazole
- a chelating agent
- has anti-inflammatory
properties, has immunomodulating
effects on T cell function
- AE steven johnson syndrome in
children
IV. Bithionol
- drug of choice for the treatment of
fascioliasis (sheep liver fluke)
- alternative to pulmonary
paragonimiasis
- AE: abdominal cramps; hematotoxic,
hepatotoxic, caution in children

Emetine = alternative drug

V. Diethylcarbamazine Citrate

- drug of choice for the treatment of

filariasis, Loiasis and tropical eosinophilia
- MOA: immobilizes the microfilariae and
alters their surface structure, making
them more susceptible to destruction by
host defense mechanism
- mazzoti reaction (give antihistamines)
 MAZZOTI REACTION
AN ALLERGIC REACTION DUE TO THE
DEATH OF THE PARASITE IN THE SKIN
PRURITUS, FEVER, HEADACHE,
DIZZINES, SOMNOLENCE, WEAKNESS,
DIARRHEA, JOINT PAIN, EDEMA,
LYMPHANGITIS, LYMPHADENITIS,
BRONCHOSPASM
 VII. Ivermectin
- drug of choice in strongyloidiasis (Strongyloides stercoralis
roundworm) Loefflers synd in pulm stage , w/ skin & diarrhea
symptoms
- and onchocerciasis (river blindness or rivers dis) Onchocerca
volvulus, a roundworm transmitted by black fly bite in africa,
when the worm die in humans, it release a bacteria Wolbachia
w/c triggers an immume response causing blindness
- an alternative drug for scabies and bancroftian filariasis,
cutaneous larva migrans
- no known toxic effects in humans because it does not cross
the blood brain barrier
- MOA: modulates GABA-mediated neurotransmission, avoid
using w/ barbiturates, benzodiazepine, valproic acid
- AE: mazzoti reaction
 VIII. Levamisole
- highly effective in eradicating
ascaris
and trichostrongylus and
moderately
effective against both species of
hookworm
- used as an immunomodulating
agent as adjunct therapy with
fluorouracil after surgical resection in
patients with colon cancer.
IX. Metrifonate - a safe, low cost alternative drug
for the treatment of Schistosoma haematobium
infections only, not mansoni or japonocum
- MOA: cholinesterase inhibition (an
organophosphate)
X. Niclosamide - choice for most tapeworm scolex
& cystodes infections but not ova ( Taenia
saginata, solium, diphylobotrium latum,
hymenolepes nana)
- MOA: inhibition of oxidative phosphorylation or
to its ATPase stimulating property.
 Oxamniquine
Choice for schistosoma mansoni
( acute katayama syndrome)
No effect on japonicum, hematobium
XII. Oxantel Pamoate/Pyrantel Pamoate

- MOA: depolarizing muscular blocking

(Ach) agents
- pyrantel: ascaris and hookworm,
pinworm, trichostrongtlus orientalis,
oxantel: trichuriasis
XIII. Piperazine citrate - alternative drug in the
treatment of ascariasis
- MOA: causes paralysis of ascaris by
blocking acetylcholine at the myoneural junction
- AE: seizures
 XIV. Praziquantel
- effective in the treatment of schistosome
infection of all species and most other
trematode and cestode infections,
flukes, tapeworm, including cysticercosis
- not in fasciola or hydatid cyst
- MOA: drug increases cell membrane
permeability to calcium, resulting
vacuolization, marked contraction,
paralysis, dislodgement, and death

END