FARMAKOLOGI

ANTIPARASIT

Protozoal infections
Amebiasis

Protozoal infections
1.
2.

3.
4.
5.
6.

Difficult to be treated than bacterial infections.

Protozoal cells (Eukaryotes) have metabolic
processes closer to human host than
prokaryotic bacterial pathogens.
Many of antiprotozoal drugs cause toxic effects
on the host.
Cells with high metabolic processes in the host
are susceptible.
Examples: bone marrow stem, renal tubular
cells, intestinal & neuronal cells.
Antiprotozoal are not safe during pregnancy.

Amebiasis
Amebiasis is a protozoal infection of the
intestinal tract that occurs due to ingestion
of foods or water contaminated with
Entameba Histolytica cysts

LIFE CYCLE

Clinical Presentations
Asymptomatic Intestinal infection

ANTIAMOEBIC DRUGS

LUMEN AMOEBICIDES
Acts

on the parasites in the lumen of

the bowl.
used for treatment of asymptomatic
amebiasis.
Include
Diloxanide Furoate
Iodoquinol
Antibiotics
- Paromomycin
- Tetracyclines
- Erythromycin

Tissue Amoebicides (systemic)

acts on the intestinal wall and liver (or any other
extra-intestinal tissue).
Used for treatment of systemic form of the disease
(intestinal wall infection or liver abscesses).
Emetine
Dehydroemetine
Chloroquine (liver only)

Mixed amoebicides

Effective against both luminal and systemic

forms of the disease. Although luminal
concentration is too low for single drug
treatment.

Metronidazol

Tinidazole

METRONIDAZOLE
Mixed amoebicide.
Drug of choice for intestinal

&

extraintestinal amoebiasis.
Acts on trophozoites.
Has no effect on cysts.
Nitro group of metronidazole is reduced by
protozoan leading to cytotoxic reduced product
that binds to DNA and proteins resulting into
parasite death.

Pharmacokinetics
Given orally or IV.
Absorption is rapid and complete.
Due to rapid absorption from GIT, not reliably
effective against luminal parasites.
Wide distribution to all tissues and body fluids
(CSF, saliva, milk).
Plasma protein binding is low ( < 20%).
Plasma half life is 8 h

Pharmacokinetics
Metabolized in liver by mixed function
oxidase followed by glucouroidation.
Excreted in urine as unchanged drug plus
metabolites.
Clearance is decreased in liver impairment.
Tinidazole has longer duration, simpler
dosing regimen, less toxicity, than
metronidazole, but is equally active.

Clinical Uses
Extraluminal

amoebiasis (combined with

luminal amebicide).
Giardiasis
Trichomoniasis
Broad spectrum of Anaerobic bacteria e.g.,
Helicobacter pylori infection
Pseudomembranous colitis (Clostridium
defficile).

Adverse effects
1. GIT:
Nausea
Vomiting
Dry mouth
Metallic taste
Diarrhoea
Oral Thrush (Moniliasis, yeast infection).

Adverse effects
2. CNS: Neurotoxicological effect
Insomnia, dizziness
peripheral neuropathy, paresthesia
encphalopathy, convulsion ( IV infusion, rare).
3. Dysuria, dark urine.
4. Neutropenia
5. Disulfiram-like effect if taken with alcohol.

disulfiram like -effect

When metronidazole is given with alcohol
abdominal distress, nausea, vomiting, flushing, or
headache, tachycardia, hyperventilation
alcohol
dehydrogenase
Ethanol

aldehyde
dehydrogenase

Acetaldehyde

Acetate

Adverse effects of
metronidazole

Drug interactions:
Enzyme

inhibitors (cimetidine, ketoconazole)

increase duration of action of metronidazole
Inducers (phenytoin and phenobarbitone).
inhibits CYP family 2C9 & 3A4
potentiate anticoagulant effect of warfarin.
potentiates lithium toxicity.

CONTRAINDICATIONS / PRECAUTIONS:
Pregnancy and nursing women
Alcohol intake
CNS diseases
Severe hepatic disease
Severe renal disease

Anthelmintic Drugs

Anthelmintics

The major

Benzimidazoles (BZAs)
thiabendazole, mebendazole, and albendazole
Mechanism of action
inhibition of microtubule polymerization by
binding to -tubulin
Drug resistance in nematodes may involve
expression of a mutated -tubulin

Mechanisme of action mebendazole and other

Benzimidazole

PK/PD
Thiabendazole
Absorbed rapidly after oral ingestion. A
fatty meal enhances absorption
Reaches peak plasma concentrations
after 1 hour
Excreted in the urine within 24 hours as 5hydroxythiabendazole, conjugated either
as the glucuronide or the sulfate

Mebendazole
Tablet formulations of mebendazole are poorly
and erratically absorbed, and plasma
concentrations are low
The low systemic bioavailability (22%) of
mebendazole results from a combination of poor
absorption and rapid first-pass hepatic
metabolism

THERAPEUTIC USES
Thiabendazole generally has been replaced by
newer agents
Mebendazole always is taken orally, and the same
dosage schedule applies to adults and children >2
years of age. For treatment of enterobiasis, a
single 100-mg tablet is taken, repeated after 2
weeks

 For

control of ascariasis, trichuriasis, or

hookworm infections, the recommended
regimen is 100 mg of mebendazole taken in the
morning and evening for 3 consecutive days (or
a single 500-mg tablet administered once)
If the patient is not cured 3 weeks after
treatment, a second course should be given.
The 3-day mebendazole regimen is more
effective than single doses of either
mebendazole (500 mg) or albendazole (400 mg)

Albendazole

For treatment of enterobiasis, ascariasis, trichuriasis,

and hookworm, taken as a single oral 400-mg dose by
adults and children >2 years of age.
In children between the ages of 12 and 24 months, the
WHO recommends a reduced dose of 200 mg.
Cure rates for light-to-moderate Ascaris infections
typically are >97%, although heavy infections may
require therapy for 23 days. A 400-mg dose of
albendazole appears to be superior to a 500-mg dose
of mebendazole for curing hookworm infections.

TOXICITY, SIDE EFFECTS

Thiabendazole

is hepatotoxic and should be used

with caution in patients with hepatic disease
Mebendazole Transient symptoms of abdominal
pain, distention, and diarrhea have occurred with
massive infestation and expulsion of GI worms.
Rare side effects in patients treated with high
doses of mebendazole include allergic reactions,
alopecia, reversible neutropenia, agranulocytosis,
and oligospermia

The most common side

effect is an increase in serum
aminotransferases, which return to
normal upon drug cessation; rarely
jaundice or cholestasis may occur
Liver function tests should be monitored
during protracted albendazole therapy,
and the drug is not recommended for
patients with cirrhosis
Albendazole

Use in Pregnancy
Both

albendazole and mebendazole are

embryotoxic and teratogenic in rats
A review of the risk of congenital
abnormalities from BZAs concluded that
their use during pregnancy is not associated
with an increased risk of major congenital
defects; nonetheless, it is recommended
that treatment should be avoided during the
first trimester of pregnancy.

Use in Young Children

The WHO concluded that the BZAs may be used to treat children past

Praziquantel
a

pyrazinoisoquinoline derivative
Mechanism of Action
low concentrations, it causes increased muscular
activity, followed by contraction and spastic
paralysis
At slightly higher concentrations, praziquantel
causes tegumental damage, which exposes a
number of tegumental antigens. The tegument of
schistosomes seems to be the primary site of
action; the drug causes an influx of Ca2+ across
the tegument via unknown mechanisms

Mechanism of Action Praziquantel

PK/PD
Readily

absorbed after oral administration, and

maximal levels in human plasma occur in 12 hours
The drug is ~80% bound to plasma proteins
Its plasma t is 13 hours but may be prolonged in
patients with severe liver disease, including those
with hepatosplenic schistosomiasis
About 70% of an oral dose of praziquantel is
recovered as metabolites in the urine within 24
hours; most of the remainder is metabolized in the
liver and eliminated in the bile

THERAPEUTIC USES
FDA approved

for therapy of schistosomiasis and

liver fluke infections, but also is used to treat
infections with many other trematodes and
cestodes
Praziquantel is the drug of choice for
schistosomiasis caused by all Schistosoma
species. Although dosage regimens vary, a single
oral dose of 40 mg/kg or three doses of 20 mg/kg
each, given 46 hours apart, generally produce
cure rates of 7095% and consistent reductions
(>85%) in egg counts.

TOXICITY AND SIDE

EFFECT
Abdominal

discomfort, nausea, diarrhea, headache,

dizziness, and drowsiness may occur shortly after taking
praziquantel; these direct effects are transient and doserelated
In neurocysticercosis, inflammatory reactions to
praziquantel may produce meningismus, seizures,
mental changes, and CSF pleocytosis. These effects
usually are delayed in onset, last 23 days, and respond
to symptomatic therapy such as analgesics and
anticonvulsants.
High doses of praziquantel increase abortion rates in rats

kontraindikasi
Praziquantel

Pyrantel Pamoate
a

broad-spectrum anthelmintic directed

against pinworm, roundworm, and
hookworm infections.
Mechanism of Action :
depolarizing neuromuscular blocking agent
that opens nonselective cation channels
and induces marked, persistent activation
of nicotinic acetylcholine receptors, which
results in spastic paralysis of the worm

PK/PD

Side effect, Precaution

Transient

and mild GI symptoms occasionally

are observed, as are headache, dizziness,
rash, and fever.
Pyrantel pamoate use in pregnant patients and
children <2 years of age is not recommended.
Because pyrantel pamoate and piperazine are
mutually antagonistic in their neuromuscular
effects on parasites, they should not be used
together.

DIETHYLCARBAMAZINE
Diethylcarbamazine

is a first-line agent for control and

treatment of lymphatic filariasis and for therapy of
tropical pulmonary eosinophilia caused by W. bancrofti
and Brugia malayi
Mechanism of action :
Diethylcarbamazine appears to exert a direct toxic
effect on W. bancrofti microfilariae; it also kills worms
of adult L. loa and probably adult W. bancrofti and B.
malayi. Diethylcarbamazine may impair intracellular
processing and transport of certain macromolecules to
the helminth plasma membrane.

PK/PD
Absorbed

rapidly from the GI tract.

Peak plasma levels occur within 12
hours, and the plasma t1/2 varies from 2
to 10 hours, depending on urinary pH.
Metabolism is rapid and extensive
Dosage reduction may be required in
people with renal dysfunction or sustained
alkaline urine.

THERAPEUTIC USES
W. Bancrofti, B. Malayi, and B. Timori
The standard regimen for LF has been a 12-day, 72mg/kg
(6 mg/kg/day) course of diethylcarbamazine. A single dose
of 6 mg/kg had comparable macrofilaricidal and
microfilaricidal efficacy to previous regimens. Single-dose
therapy may be repeated every 612 months, as necessary.
Diethylcarbamazine remains the best drug for therapy of
loiasis. Treatment is initiated with test doses of 50 mg (1
mg/kg in children) daily for 23 days, escalating as tolerated
to daily doses of 9 mg/kg in Three doses for a total of 23
weeks.

TOXICITY AND SIDE

EFFECTS
At

<810 mg/kg/daycarbamazine,
including anorexia, nausea, headache,
and vomiting, are rarely severe and
usually disappear within a few days
despite continued therapy

Ivermectin
Mechanism of action :
Avermectins affect a group of glutamategated Cl channels found in nematode
nerve or muscle cells, causing
hyperpolarization and paralysis by
increasing Cl permeability of the cell
membrane

PK/PD
Peak

plasma levels of ivermectin are

achieved 4-5 H
Ivermectin is ~93% bound to plasma
proteins. The drug is extensively
converted by hepatic CYP3A4 to at least
10 metabolites, mostly hydroxylated and
demethylated derivatives.

THERAPEUTIC USES
Onchocerciasis
Single oral doses of ivermectin (150 g/kg) given every
612 months are considered effective, safe, and practical
for reducing the number of circulating microfilariae in
adults and children 5 years of age or older
Lymphatic Filariasis
Single annual doses of ivermectin (400 g/kg) are
effective and safe for mass therapy of infections with W.
bancrofti and B. malayi.
Ivermectin is as effective as diethylcarbamazine for
controlling lymphatic filariasis and can be used in regions
where onchocerciasis, loiasis, or both are endemic.

cutaneous larva migrans

Taken as a single 200-g/kg oral dose,
ivermectin is a first-line drug for treatment of
cutaneous larva migrans
Infections with Intestinal Nematodes
The finding that a single dose of 150200
ivermectin can cure strongyloidiasis is
encouraging, because this drug also is
efcoexisting ascariasis, trichuriasis, and
enterobiasis

Toxicity, Side Effects, and

Precautions
After

treatment of O. volvulus infections with

ivermectin, side effects usually are limited to
pruritus and swollen, tender lymph nodes
Rarely, more severe reactions include high fever,
tachycardia, hypotension, prostration, dizziness,
headache, myalgia, arthralgia, diarrhea, and
edema; these may respond to glucocorticoids
Because of its effects on GABA receptors in the
CNS, ivermectin is contraindicated in conditions
associated with an impaired bloodbrain barrier
(e.g., African trypanosomiasis and meningitis)

Infecting Organism

Drug of Choice

Alternative Drugs

Ascaris lumbricoides
(roundworm)

Albendazole or pyrantel
pamoate or mebendazole

Ivermectin, piperazine

Trichuris trichiura
(whipworm)

Mebendazole or
albendazole

Ivermectin

Necator americanus
(hookworm); Ancylostoma
duodenale (hookworm)

Albendazole or
mebendazole or pyrantel
pamoate

Strongyloides stercoralis
(threadworm)

Ivermectin

Albendazole or
thiabendazole

Enterobius vermicularis
(pinworm)

Mebendazole or pyrantel
pamoate

Albendazole

Trichinella spiralis
(trichinosis)

Mebendazole or
albendazole; add
corticosteroids for severe
infection

Roundworms
(nematodes)

Infecting Organism

Drug of Choice

Alternative Drugs

Roundworms
(nematodes)

Albendazole

Trichostrongylus species

Pyrantel pamoate or
mebendazole

Albendazole

Cutaneous larva migrans

(creeping eruption)

Albendazole or ivermectin

Thiabendazole (topical)

Visceral larva migrans

Albendazole

Mebendazole

Angiostrongylus
cantonensis

Albendazole or
mebendazole

Wuchereria bancrofti
(filariasis); Brugia malayi
(filariasis); tropical
eosinophilia; Loa loa
(loiasis)

Diethylcarbamazine

Onchocerca volvulus
(onchocerciasis)

Ivermectin

Dracunculus medinensis
(guinea worm)

Metronidazole

Thiabendazole or
mebendazole

Capillaria philippinensis
(intestinal capillariasis)

Albendazole

Mebendazole

Ivermectin

Infecting Organism

Drug of Choice

Alternative Drugs

Schistosoma haematobium
(bilharziasis)

Praziquantel

Metrifonate

Schistosoma mansoni

Praziquantel

Oxamniquine

Schistosoma japonicum

Praziquantel

Clonorchis sinensis (liver

fluke); Opisthorchis species

Praziquantel

Albendazole

Paragonimus westermani
(lung fluke)

Praziquantel

Bithionol

Fasciola hepatica (sheep

liver fluke)

Bithionol or triclabendazole

Fasciolopsis buski (large

intestinal fluke)

Praziquantel or niclosamide

Heterophyes heterophyes;
Metagonimus yokogawai
(small intestinal flukes)

Praziquantel or niclosamide

Flukes (trematodes)

Infecting Organism

Drug of Choice

Alternative Drugs

Taenia saginata (beef

tapeworm)

Praziquantel or niclosamide

Mebendazole

Diphyllobothrium latum (fish

tapeworm)

Praziquantel or niclosamide

Taenia solium (pork

tapeworm)

Praziquantel or niclosamide

Cysticercosis (pork
tapeworm larval stage)

Albendazole

Praziquantel

Hymenolepis nana (dwarf

tapeworm)

Praziquantel

Niclosamide, nitazoxanide

Echinococcus granulosus
(hydatid disease);
Echinococcus multilocularis

Albendazole

Tapeworms (cestodes)

TRIMETHOPRIM
SULFAMETHOXAZOLE
ANTIBACTERIAL SPECTRUM

Synergism between trimethoprim and

sulfamethoxazole on the inhibition of growth of
Escherichia coli

Inhibition of tetrahydrofolate synthesis by sulfonamides and

trimethoprim

ABSORPTION,DISTRIBUTION,AND
EXCRETION
After

a single oral dose of the combined

preparation, peak blood concentrations of
trimethoprim 2 hours, peak concentrations
of sulfamethoxazole require 4 hours
The half-lives are ~11 and 10 hours
The drug readily enters CSF and sputum.
High concentrations of each component also
are found in bile. About 65% of
sulfamethoxazole is bound to plasma
protein

 About

60% of administered trimethoprim

and from 25% to 50% of administered
sulfamethoxazole are excreted in the
urine in 24 hours.
Two-thirds of the sulfonamide is
unconjugated. Metabolites of
trimethoprim also are excreted.
The rates of excretion and the
concentrations of both compounds in the
urine are reduced significantly in patients
with uremia.

Administration and fate of the

cotrimoxazole

Gastrointestinal Infections

Typical therapeutic applications of co-trimoxazole

(sulfamethoxazole plus trimethoprim)

Some adverse reactions to

cotrimoxazole

Drug interactions:
Prolonged

Quinolones block bacterial DNA synthesis by inhibiting

bacterial topoisomerase II (DNA gyrase) and
topoisomerase IV.

Fluoroquinolon

Summary of antimicrobial spectrum of

quinolones

Typical therapeutic applications of ciprofloxacin

Adverse reactions to

SEKIAN
TERIMA KASIH !!

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