Antiparasitic Drugs

Overview

Antimalarial drugs
Anti-amebiasis drugs and Antitrichomoniasis drugs
Anti-schistosomiasis drugs and Antifilariasis drugs
Anthelmintic drugs

Malaria
Malaria is caused by plasmodium whose

sporozoites was inoculated to initiate

human infection by anopheline mosquito.
Four species of plasmodium cause human
malaria:
Plasmodium falciparum responsible for

nearly all serious complications and deaths.

P vivax
benign
P malariae
malaria
P ovale seldom

Parasite Life Cycle

Asexual stage in human:

I.

Primary exoerythrocytic stage: sporozoites invade

liver cells schizonts incubation period
Asexual erythrocytic stage: merozoites invade
erythrocytes, trophozoites schizonts, rupture host
erythrocytes repeated cycles cause clinical
illness
Secondary exoerythrocytic stage: In P vivax and P
ovale infections, a dormant hepatic stage,
hypnozoite relapses

Sexual stage in anopheline mosquito:

II.

Sexual stage gametocytes also develop in

erythrocytes before being taken up by mosquitoes,
where they develop into infective sporozoites.

Drug Classification

Classified by their selective actions on

different phases of the parasite life cycle:
Tissue schizonticides: eliminate
developing or dormant liver forms.
2. Blood schizonticides: act on erythrocytic
parasites.
3. Gametocides: kill sexual stages and
prevent transmission to mosquitoes.
1.

No one available agent can reliably effect

a radical cures.

Control
symptoms

Chloroquine
A synthetic 4-aminoquinoline formulated

as the phosphate salt for oral use.

Pharmacokinetics
Rapidly and almost completely absorbed from

the gastrointestinal tract.

Very large apparent volume of distribution of
100-1000 L/kg.
Necessitate the use of a loading dose to rapidly
achieve effective serum concentrations.
Slowly released from tissues and metabolized.
Principally excreted in the urine.

Pharmacological Effects
1.

Antimalarial action: highly effective blood schizonticide.

Moderately effective against gametocytes of P vivax, P
ovale, and P malariae but not against those of P
falciparum. not active against liver stage parasites.

2.
3.

Mechanism: plasmodium aggregates chloroquine.

chloroquine incorporated into DNA chain of plasmodium
inhibit proliferation. chloroquine prevents the
polymerizationof the hemoglobin breakdown product, heme,
into hemozoin and thus eliciting parasite toxicity due to the
buildup of free heme. pH plasmodium protease
activity
Resistance: very common among strains of P falciparum and
uncommon but increasing for P vivax. The mechanism of
resisitance to chloroquine is resistant strains excretes drug
more rapidly.

Killing Amibic trophozoites : chloroquine reaches high

liver concentrations.
Immunosuppression action:

Clinical Uses
Treatment: nonfalciparum and sensitive
falciparum malaria. Primaquine must be
added for the radical cure of P vivax and P
ovale, because chloroquine does not
eliminate dormant liver forms of these
species.
2. Chemoprophylaxis: for without resistant
falciparum malaria in malarious regions.
3. Amebic liver abscess: not effective in the
treatment of intestinal or other extrahepatic
amebiasis.
1.

Adverse Effects and Cautions

Usually very well tolerated, even with prolonged
use.
Pruritus is common.
Nausea, vomiting, abdominal pain, headache,
anorexia, malaise, blurring of vision, and
urticaria are uncommon.
Dosing after meals may reduce some adverse
effects.
Rare reactions include hemolysis in G6PDdeficient persons, impaired hearing, confusion,
psychosis, seizures, hypotension, ECG changes.
teratogenesis

Control
symptoms

Quinine
Quinine and quinidine remain first-line

therapies for falciparum malariaespecially

severe disease.
Quinine is an alkaloid derived from the bark of
the cinchona tree, a traditional remedy for
intermittent fevers from South America.
Quinine is the levorotatory stereoisomer of
quinidine.
Rapidly absorbed after oral administration.
Metabolized in the liver and excreted in the
urine.

Pharmacological Effects
Highly effective blood schizonticide against the

four species of human malaria paresites.

Gametocidal against P vivax and P ovale but not
P falciparum.
Not active against liver stage parasites.
Depressing cardiac contractility and conduction,
lengthening refractory period, exciting uterine
smooth muscle, depressing central nervous
system, little antipyretic-analgesic effect.

Clinical Uses: mainly for chloroquine-

resistant falciparum malaria, especially for

cerebral malaria.
Parenteral treatment of severe falciparum

malaria
Oral treatment of falciparum malaria
Malarial chemoprophylaxis
Babesiosis

Adverse Effects and Cautions

Cinchonism: tinnitus, headache, nausea,
dizziness, flushing, visual disturbances
2. Cardiovascular effects: severe hypotension
and arrhythmia can follow too-rapid
intravenous infusion.
3. Idiosyncrasy: hemolysis with G6PD deficiency.
4. Others: hypoglycemia through stimulation of
insulin release, stimulate uterine contractions
1.

Control
symptoms

Mefloquine
A synthetic 4-quinoline methanol that is

chemically related to quinine.

Pharmacokinetics

Only be given orally because severe local

irritation occurs with parenteral use.

Well absorbed.
Highly protein-bound, extensively distributed in
tissues, and eliminated slowly. t1/2 is 20 days.
Pharmacological Effects:
Strong blood schizonticidal activity against P
falciparum and P vivax, but not active against
hepatic stages or gametocytes.

Clinical Uses
Chemoprophylaxis:
Treatment: mainly for chloroquine-resistant

falciparum malaria.
Adverse Effects and Cautions
Nausea, vomiting, diarrhea, abdominal pain

dose-dependent
Neuropsychiatric toxicities: dizziness, headache,
behavioral disturbances, psychosis, seizures.

Control
symptoms

Malaridine
Developed by China.
blood schizonticidal activity.
Treatment for all types malaria, including

chloroquine-resistant falciparum malaria.

Mechanism: destroy parasite compound
membrane and food vacuoles.

Control
symptoms

Artemisinin
Extracted from yellow flower mugwort.
Kill trophozoites of erythrocytes.
quick and effective. maybe kill earlier

period trophozoites.
Through blood-brain barrie, treatment for
cerebral malaria.
recurrence rate is high.
Resistence.
Interaction with others antimalarial drugs:

Control
symptoms

Artemether and

Artesunate
Dihydroartemisinin

Control
relapse and

Primaquine

transmission

Synthetic 8-aminoquinoline.
Pharmacological Effects
Against hepatic stages of malaria parasites.
The only available agent active against the

dormant hypnozoite stages of P vivax and P

ovale.
Also gametocidal against the four human
malaria species.

Clinical Uses
Therapy (Radical Cure) of Acute Vivax and Ovale
Malaria: chloroquine + primaquine
Terminal Prophylaxis of Vivax and Ovale Malaria:
prevent a relapse
Chemoprophylaxis of Malaria: protection against
falciparum and vivax malaria. But potential toxicities
of long-term use limited its routinely administration.
Gametocidal Action: A single dose of primaquine (45
mg base) can be used as a control measure to render
P falciparum gametocytes noninfective to
mosquitoes. This therapy is of no clinical benefit to
the patient but will disrupt transmission
Pneumocystis carinii infection: clindamycin
+primaquine mild to moderate pneumocystosis

Adverse Effects and Cautions

Nausea, epigastric pain, abdominal cramps,

headache.
Hemolysis or methemoglobinemia,
especially in persons with G6PD deficiency
or other hereditary metabolic defects.

Etiological
factor

Pyrimethamine

prophylaxis

Pharmacokinetics
Slowly but adequately absorbed from the

gastrointestinal tract.
Slowly eliminated and excreted from urine.
Pharmacological Effects
Kill schizonts of primary exoerythrocytic stage.
Act slowly against premature schizonts of
erythrocytic stage.
No action against gametocytes, but can inhibit
development of plasmodium in mosquito.
Inhibit plasmodial dihydrofolate reductase
inhibiting breeding of plasmodium.

Adverse Effects and Cautions

Gastrointestinal symptoms, skin rashes.
Interfering folic acid metabolism in human

megalocyte anemia, granulocytopenia.

Acute intoxication
Teratogenesis

Etiological
factor

prophylaxis

Sulfonamides and Sulfone

Competing dihydropteroatesye synthase with

PABA inhibiting to form dihydrofolic acid

inhibiting production of purines and synthesis
of nucleic acids.
Only inhibiting plasmodial of exoerythrocytic
stage
Not used as single agents for the treatment.
Combination with other agents.

Rational Use of Antimalarial

Drugs
1.

Choice of Antimalarial Drugs:

2.

Control symptoms: chloroquine

Cerebral malaria: chloroquine phosphate, quinine
bimuriate, artemisinin injection
Chloroquine-resistant falciparum malaria: quinine,
mefloquine, artemisinin
Dormant hypnozoite stages : pyrimethamine +
primaquine
Prophylaxis: pyrimethamine, chloroquine

Combination therapy:

chloroquine + primaquine: symptom stages

pyrimethamine + primaquine: dormant hypnozoite
stages
Combination of drugs with different mechanisms:
therapeutic effect, resistance

Anti-amebiasis Drugs
Amebiasis is infection with Entamoeba

histolytic.
Amebiasis is transmitted through
gastrointestinal tract.
Ameba has two stages of development:
cyst and trophozoite.

cysts (colon) asymptomatic intestinal

Cysts
small
intestine
little trophozoites
infection
, source
of infection
(ileocecum)
big trophozoites (tissues of intestine)
intestinal amebiasis extraintestinal infection

Metronidazole
A nitroimidazole. The nitro group of

metronidazole is chemically reduced in

anaerobic bacteria and sensitive
protozoans. Reactive reduction products
appear to be responsible for antimicrobial
activity.
Pharmacokinetics
Oral metronidazole is readily absorbed and

permeates all tissues by simple diffusion.

Protein binding is low (<20%)
Through blood brain barrier
Metabolizing in liver.
Excreted mainly in the urine.

Pharmacological Effects and Clinical Uses

Anti-amebiasis: kills E histolytic trophozoites
but not cysts. Treatment of all tissue
infections with E histolytic. No effection
against luminal parasites and so must be
used with a luminal amebicide to ensure
eradication of the infection.
2. Anti-trichomoniasis:
3. Anti-anaerobic bacteria:
4. Anti-giardiasis:
1.

Adverse Effects and Cautions

Nausea, headache, dry mouth, a metallic taste

in the mouth.
Infrequent: vomiting, diarrhea, rash, insomnia,
neutropenia,
Rare: severe central nervous system toxicity
( ataxia, encephalopathy, seizures)drug
withdrawal
Has a disulfiram-like effect, so that nausea and
vomiting can occur if alcohol is ingested during
therapy.

Emetine and
Dehydroemetine

Emetine, an alkaloid derived from

ipecac, and dehydroemetine, a synthetic

analog, are effective against tissue
trophozoites of E histolytic .
Because of major toxicity concerns they
have been almost completely replaced
by metronidazole.
Administered subcutaneously (preferred)
or i.m. (but never i.v.) because oral
preparations are absorbed erratically.

Pharmacological Effects and Clinical Uses

kills E histolytic trophozoites of histolytic

tissues but no effection against luminal

trophozoites. a luminal amebicide should also
be given.
Rapidly alleviate severe intestinal symptoms,
used to treat amebic dysentery for the
minimum period because of toxicity.
Occasionally as alternative therapies for
amebic liver abscess.

Mechanisms
Inhibiting peptidyl-tRNA transposition

inhibiting elongation of peptide chain

inhibiting protein synthesis interfering
cleavage and breeding of trophozoites

Adverse Effects and Cautions

1.
2.
3.
4.

low selection also inhibiting protein synthesis

of eukaryocyte.
Toxicity increase with length of therapy.
Cardiac toxicity: arrhythmias, congestive heart
failure, hypotention, ECG changes
Neuromuscular blockade: muscle weakness and
discomfort
Local stimulation: pain and tenderness in the
area of injection.
Gastrointestinal tract discomfort: nausea,
vomiting
Not be used in patients with cardiac or renal
disease, in young children, or in pregnancy.

Diloxanide
Diloxanide furoate is a dichoroacetamide

derivative.
Effective luminal amebicide but is not active
against tissue trophozoites.
The unabsorbed diloxanide in the gut is the
active antiamebic substance.
Effective for asymptomatic luminal infections.
It is used with a tissue amebicide, usually
metronidazole.
Adverse Effects: flatulence, nausea,
abdominal cramps, rashes, abortion.

Paromomycin
Aminoglycoside antibiotic.
Not significantly absorbed from the

gastrointestinal tract.
Only as a luminal amebicide and has no
effect against extraintestinal amebic
infections.
inhibiting protein synthesis kill
trophozoites;
inhibiting symbiosis flora indirectly
inhibiting ameba protozoa.

Chloroquine
Chloroquine reaches high liver
concentrations treatment of amebic
liver abscess.
Not effective in the treatment of
intestinal or other extrahepatic
amebiasis.

Anti-trichomoniasis Drugs
Metronidazole
Acetarsol

Anti-schistosomiasis Drugs
Schistosoma including:
Schistosoma japonicum (epidemic in China)
Schistosoma mansoni
Schistosoma haematobium

Antimony potassium tartrate inhibition

of phosphofructokinase treatment of
schistosomiasis. But greater toxicity, long
treatment course, i.v. limit its uses.

Praziquantel
A synthetic isoquinoline-pyrazine derivative.
Pharmacological Effects
Effective in the treatment of schistosome

infections of all species and most other

trematode and cestode infections, including
cysticercosis.
Against adult worms and immature stages.
Mechanisms
Increases cell membrane permeability to calcium

vacuolization, marked contraction, spastic

paralysis, dislodgement, death.

Clinical Uses
Schistosomiasis
Clonorchiasis and Opisthorchiasis
Paragonimiasis
Taeniasis and Diphyllobothriasis
Neurocysticercosis
Hydatid disease
Other parasites: fasciolopsiasis, metagonimiasis,
heterophyiasis

Adverse Reactions
Mild and trainsient.
Headache, dizziness, drowsiness, lassitude
low-grade fever, pruritus, and skin rashes

(macular and urticarial)due to the release

of foreign protein from dying worms.

Anti-filariasis Drugs
Epidemic in China:
Wuchereria bancrofti
Brugia malayi

Parasitize in lymphatic system.

Diethylcarbamazine
A synthetic piperazine derivative. Rapidly

absorbed from the gastrointestinal tract;

excreted rapidly in the presence of acidic
urine.
Pharmacologic Effects and Mechanisms
Immobilizes microfilariae(which results in

their displacement in tissues) and alters their

surface structure, making them more
susceptible to destruction by host defense
mechanisms.
Adult parasites are killed more slowly.
Against adult worms is unknown.

Clinical Uses
The drug should be taken after meals.
1. Wuchereria bancrofti, Brugia malayi, Brugia
timori, and Loa loa
2. Tropical Eosinophilia

Adverse Reactions
Drug-induced Reactions: mild and transient,
headache, malaise, anorexia, nausea,
Reactions induced by Dying Parasites: release
of foreign proteins. Eosinophilia and
leukocytosis. Papular rash, muscle or joint
pains.

Anthelmintic Drugs

Classification of Helminth
Roundworms (nematodes) epidemic in
China
Tapeworms
Flukes (trematodes)

Mebendazole
A synthetic benzimidazole that has a

wide spectrum of anthelmintic activity

and a low incidence of adverse effects.
Pharmacokinetics
Oral absorption 10
First pass elimination is high.
Protein-binding 90
Excreted mostly in the urine, a portion of

absored drug and its derivatives are excreted

in the bile.
Absorption is increased if the drug is ingested
with a fatty meal.

Pharmacologic Effects
Inhibits microtubule synthesis in nematodes,
thus irreversibly impairing glucose uptake.
Intestinal parasites are immobilized or die slowly.
Kills hookworm, ascaris, and trichuris eggs.
Clinical Uses
Pinworminfection
Ascaris lumbricoides, Trichuris trichiura ,

Hookworm, and Trichostrongylus

Other infections: intestinal capillariasis,
trichinosis, taeniasis, strongyloidiasis,
dracontiasis, et al.

Adverse Effects and Cautions

Low-dose: nearly free adverse effects.
Diarrhea, abdominal pain is infrequent.
High-dose: pruritus, rash, eosinophilia,

reversible neutropenia, musculoskeletal pain,

fever, transient liver function abnormalities,
alopecia, glomerulonephritis, agranulocytosis

Albendazole
A benzimidazole carbamate
A broad-spectrum oral anthelmintic for

treatment of hydatid disease and

cysticercosis, pinworm infection, ascariasis,
trichuriasis, strongyloidiasis, and infections
with both hookworm species.
Effect better than Mebendazole.

 Clinical Uses
Administered on an empty stomach when

1.
2.
3.
4.
5.

used against intraluminal parasites but with a

fatty meal when used against tissue
parasites.
Ascariasis, Trichuriasis, and Hookworm and
Pinworm infections.
Strongyloidiasis
Hydatid Disease
Neurocysticercosis
Other infections: cutaneous larva migrans,
gnathostomiasis

Piperazine
Treatment of ascariasis.
No longer recommended for treatment of

pinworm infection, because a 7-day

couse of treatment is required.
Not useful in hookworm infection,
trichuriasis, or strongyloidiasis.
Causes flaccid paralysis of ascaris by
blocking acetylcholine at the myoneural
junction.
Neurotoxic adverse effects.

Levamizole
A synthetic imidazothiazole derivative and

the L isomer of D,L-tetramisole.

Highly effective in eradicating ascaris and
trichostrongylus and moderately effective
against both species of hookworm.
Inhibiting succinic dehydrogenase
energy flaccid paralysis
Immunomodulating effect.

Pyrantel
A tetrahydropyrimidine derivative.
A broad-spectrum anthelmintic
Highly effective for the treatment of pinworm,

ascaris, and Trichostrongylus orientalis

infections.
Moderately effective against both species of
hookworm but less so against N americanus.
Not effective in trichuriasis or strongyloidiasis .
Oxantel, an analog of pyrantel, is effective
against in trichuriasis; the two drugs have been
combined for their broad-spectrum
anthelmintic activity.

Effective against mature and immature

forms of helminths within the intestinal tract

but not against migratory stages in the
tissues or against ova.
Inhibition of cholinesterase a
depolarizing neuromuscular blocking agent
spastic paralysis
Used with caution in patients with liver
dysfunction.
No combination with piperazine because of
antagonistic action.

Pyrvinium Embonate
A dye.
Not absorb orally.
treatment of pinworm
Selectively interfering energy metabolism

enzymatic system
Inhibiting glucose-transporting enzymatic
system
Red feces

Niclosamide
A salicylamide derivative
Treatment of most tapeworm infection.
Pharmacologic Effects
Scoleces and segments of cestodes but not

ova are rapidly killed on contact with

nicolsamide due to the drugs inhibition of
oxidative phosphorylation or to its ATPasestimulating property.
With the death of the parasite, digestion of
scoleces and segments begins.

Clinical Uses
Given in the morning on an empty stomach.
The tablets must be chewed thoroughly and
are then swallowed with water.
Niclosamide can be used as an alternative
drug for the treatment of intestinal fluke
infections.
Adverse Effects and Cautions
Infrequent, mild and transitory.
Nausea, vomiting, diarrhea, and abdominal

discomfort.

Praziquantel
Effective in the treatment of schistosome

infections of all species and most other

trematode and cestode infections, including
cysticercosis.
A first choice in the treatment cestodiasis.