Dept.

Pharmacology & Therapeutic

School of Medicine

Universitas Sumatera Utara

Mechanisms for treatment-I

Attack a unique enzyme found in parasite
Folate synthesis blocked by sulfonamide
(Folate- dihydrofolate reductase - FH2
dihydrofolate reductase FH4
Deoxythymidylic acid Methionine.
Allopurinol riboside is phosohorylated and
is added to 5-O position in purines and is
non functional, all protozoa especially
Leishmainaia.

Mechanism II
Drug affect enzyme system found in both
host / parasite but is indispensable for
parasite.
Trypansomebrucic lack krebs cycle
Salicyl hyroxamic acid (SHAM) forces
parasite into anaerobic condition,
glycolysis is blocked by glycerol causing
rapid lysis.

Mechanism III
Common biochemical functions found in
host / parasite but have different
pharmacological properties
Ivermectin affects synaptic transmission by
increasing inhibitory transmitter (GABA) increase
inhibition causes flaccid paralysis.
does not cross mammalian blood / brain barrier
. Drug can act as a GABA agonist causing
increased muscular contaction e.g Levamisol

Antiprotozoal drugs
Chemotherapy of Amebiasis
Chloroquine, Dehydroemetine, Diloxanide furoate,
Emetine, Metronidazole, Paramomycin.
.

Chemotherapy of Malaria
Chloroquine, Mefloquine, Primaquine, Pyrimethamine,
quinine/ quinidine.

Chemotherapy of Tyrpanosomiasis
Melarsoprol, Nifurtimox, Pentamidine, Suramin.

Antiprotozoal drugs (contd)

Chemotherapy of Leishmaniasis
Sodium stibogluconate

Chemotherapy of Toxoplasmosis
Pyrimethamine.

Chemotherapy of Giardiasis
Quinacrine

Drugs used in leishmaniasis and

trypanosomiasis
Leishmaniasis may occur as a skin infection or as an infection
of the viscera. Metronidazole is used for the former, and
sodium stibogluconate given parenterally for the latter.
Trypanosome species cause sleeping sickness in Africa and
chagas diseasein south america .Drugs used are suramin given
i.v and pentamidine i.m.

Anthelminthic Drugs
An anthelminthic drug may act by causing narcosis or
paralysis of the worm, or by damaging the
cuticle,leading to partial digestion or to rejection by
immune mechanisms. Anthelminthic drugs may also
interfere with the metabolism of the worm, and
since the metabolic requirements of these parasites
vary greatly from one species to another , this may
be the reason why drugs that are highly effective
against one type of worm are ineffective against
others.

Nematoda (roundworms)

1st choice

2nd choice

Ascaris lumbricoides
(roundworm)

Albendazole/
Piperazine
Pyrantel pamoate/
Mebendazole

Trichuris trichiura
(whipworm)

Mebendazole/
Albendazole

Necator americanus
(hookworm);
Ancylostoma duodenale
(hookworm)

Pyrantel pamoate/
Mebendazole/
Albendazole

Strongyloides stercoralis
(threadworm)

Ivermectin

Thiabendazole,
Albendazole

Enterobius vermicularis
(pinworm)

Mebendazole/
Pyrantel pamoate

Albendazole

Trichinella spiralis
(trichinosis)

Mebendazole

Albendazole

(+kortikosteroid untuk
infeksi berat)

(+kortikosteroid untuk
infeksi berat)

Trichostrongylus species

Oxantel/
Pyrantel pamoate

Pyrantel pamoate/ Albendazole

Mebendazole

1st choice

2nd choice

Cutaneous larva migrans

(creeping eruption)

Albendazole/
Ivermectin

Thiabendazole
(topikal)

Visceral larva migrans

Albendazole

Mebendazole

Thiabendazole

Albendazole/
Mebendazole

Angiostrongylus cantonensis

Wuchereria bancrofti (filariasis);

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

Diethylcarbamazi Ivermectin
ne

Onchocerca volvulus
(onchocerciasis)

Ivermectin

Suramin

Dracunculus medinensis (guinea Metronidazole

worm)

Thiabendazole/
Mebendazole

Capillaria philippinensis
(intestinal capillariasis)

Mebendazole/
Thiabendazole

Albendazole

Trematoda (flukes)

1st choice

2nd choice

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/
Triclabendazole

Fasciolopsis buski
(large intestinal fluke)

Praziquantel/
Niclosamide

Heterophyes heterophyes
Metagonimus yokogawai
(small intestinal flukes)

Praziquantel/
Niclosamide

Cestoda (cacing pita)

Taenia saginata
(beef tapeworm)
Taenia solium
(pork tapeworm)
Diphyllobothrium latum
(fish tapeworm)
Cysticercosis
(pork tapeworm larval stage)
Hymenolepis nana
(dwarf tapeworm)
Echinococcus granulosus
(hydatid disease);
Echinococcus
multilocularis

1st choice
Praziquantel/
Niclosamide
Praziquantel/
Niclosamide
Praziquantel/
Niclosamide
Albendazole

2nd choice
Mebendazole

Praziquantel

Niclosamide

Albendazole

Praziquantel

Mekanisme kerja anthelmentic

Obat

Mekanisme
Kerja

Efek
Spesifik

Piperazine

Memparalisis
otot cacing

Memblokir myoneural junction;

agonis gated chloride channels
hiperpolarisasi paralisis flasid

Ivermectin

Memparalisis
otot cacing

Memblokir transmisi sinyal-sinyal saraf

dengan berinteraksi dengan glutamate
gated chloride channels

Pyrantel

Memparalisis
otot cacing

Agonis reseptor asetilkolin nikotinik &

menghambat kolinesterase
depolarisasi & paralisis spastik

Memparalisis
otot cacing

Menginaktivasi asetilkolinesterase &

mempotensiasi efek-efek kolinergik
inhibitori

Memparalisis
otot cacing

Meningkatkan permeabilitas membran

terhadap Ca2+ memaparkan proteinprotein membran diserang antibodi

Menghambat
produksi energi

Menghambat fosforilasi oksidatif

Metrifonate
(Trichlorfon)

Praziquantel
Bithionol

Mekanisme kerja anthelmentic

Obat

Mekanisme
Kerja

Efek
Spesifik

Menghambat
produksi energi

Menghambat fosforilasi oksidatif

anaerobik dalam mitokondria cacing
sintesa ATP

Menghambat
produksi energi

Berikatan dengan tubulin & menghambat

polimerisasi

Menghambat
produksi energi &
fungsi protein

Menghambat fumarat reduktase &

sintesa ATP; berikatan dengan tubulin

Menghambat
produksi energi

Menghambat enzim-enzim otot yang

berkait dengan glikolisis & konsumsi
oksigen

Oxamniquine

Mengesterifikasi &
mengikat DNA

Menghambat sintesa asam nukleat &

protein

Diethylcarbamazine

Mempermudah
fagositosis &
eliminasi

Meningkatkan kesensitifan mikrofilaria,

memerangkap mikrofilaria dalam sistem
retikuloendotelial

Niclosamide
Mebendazole
Thiabendazole

Suramin

Farmakoterapi
Obat-obat pilihan adalah
benzidimazole (BZA):

albendazole (dosis tunggal 400

mg, 200 mg: anak-anak 12-24 bulan) /

mebendazole (100 mg 2x/hari

untuk 3 hari (dewasa & anak >2 tahun) /

levamisole (dosis tunggal 2,5

mg/kg) /

pyrantel pamoate (dosis tunggal

11 mg/kg, tetapi 1 g)
(WHO 2002)

Migrasi larva A. lumbricoides

bisa menyebabkan

pneumonia hemoragik.

Drugs used in amoebiasis

Amoebiases is due to infection with Entamoeba
histolytica, which causes dysentery associated with
invasion of the intestinal wall and, rarely, of the liver. The
organism may be present in motile, invasive form, or as
a cyst.
Metronidazole: given orally,is active against the invasive
form in gut and liver but not the cyst.Unwanted effects,
which are rare, include GI upsets and CNS symptoms.
Diloxanide: given orally with no serious unwanted
effects, active while unabsorbed against the non invasive
form.
Chloroquine: used for hepatic amoebiasis.

Classification of anti-amoeba
Tissue Amoebiasis
*Both intestinal & extra intestinal
Nitroimidazoles
Metronidazole, Tinidazole, Secnidazole, Ornidazole

Alkaloids
Emetine, Hydroemetine

* Extra intestinal amoebiasis only

Chloroquine
Luminal amoebiasis
Amide (Diloxanide furoate)
8-Hydroxy quinolones (Quinidochlor)
Antibiotics (Tetracycline)

Anti-Amoeba
Anti-amoeba
Chloroquine

Indication

MoA

ADR

Amebic liver
abscess

Metronidazole Intestinal &

Disruption of
extra-intestnal DNA synthesis
& nucleic acid
synthesis

Metallic taste,
nausea,
vomiting,
diarrhea,
abdominal
cramps

Iodoquinol

Intestinal

Directly kills the

protozoa

N/V, diarrhea,
anorexia,
agranulocytosis

Paramomycin

Intestinal

Inhibiting protein N/V, diarrhea,

synthesis
stomach
cramps,
ototoxic, tinnitus

5-nitroimidazoles
Metronidazole, tinidazole, ornidazole,
nimorazole.
Active on anaerobic bacteria and protozoa.
Entamoeba (not invariably the cysts) ,
Trichomonas, Giardia, Blastocystis, ...
Disulfiram-like effects, mutagenic in bacteria.
Pearson R.D. 2005. Chapter 41, In Mandell G.L. et al.

Metronidazole
Prototype drug introduced in 1959
Bactericidal against
Giardia lamblia, anaerobic bacteria,
Bacteroides fragilis, Fusobacterium,
Clostridium perfringes, Helicobacter
pylori, Anaerobic Streptococci

Metronidazole (MoA)
Not clearly understood
Enters micro-organism by diffusion
Nitro group reduced DNA damaged
Cytotoxicity
High selective anaerobic action
interference with electron transportation from
NADPH or other reduced substrates
Also inhibits cell mediated immunity
Induce mutagenesis
Cause radio-sensitization

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.

Metronidazole
Mechanism of Action
Mechanism of action
Disruption of DNA synthesis as well as nucleic acid synthesis
Bactericidal, amebicidal, trichomonacidal
Used for treatment of trichomoniasis, amebiasis,
giardiasis,and antibiotic-associated pseudomembranous
colitis
Also has anthelmintic activity
Adverse Effects:
Metallic taste, nausea, vomiting, diarrhea,
abdominal cramps, many others

Metronidazole
Contraindications
Neurological diseases, blood dyscrasias,
First trimester, Chronic alcoholism
Drug Interactions
Disulfiram reaction
Enzyme inducers - Rifampicin -therapeutic effect
Cimetidine - metronidazole metabolism - reduce
dose
Metronidazole renal elimination of Lithium

Emetine
Alkaloid from Cephaelis ipecacuanha
Potent directly acting amoebicide (trophozoites)
Does not kill cysts
Cumulative toxicity high Seldom used
- Because of major toxicity concerns they have been
almost completely replaced by metronidazole.
Reserve drug not responding/intolerant to
metronidazole
Luminal amoebicide follows emetine to eradicate cysts
Administered subcutaneously (preferred) or i.m. (but
never i.v.) because oral preparations are absorbed
erratically
Dihydroemetine =effective but less toxic
Preferred over emetine

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.

Notice !

Treatment with tissue

amoebicide SHOULD always be
followed by Luminal
amoebicide to eradicate
source of infection

Anti-trichomoniasis Drugs
Metronidazole
Acetarsol

Approaches to antimalarial therapy

Drugs used to treat the acute attack of malaria (clinical cure)
act on the parasites in the blood; they can cure infections with
parasites which have no exo-erythrocytic stage.e.g quinine,
chloroquine
Drugs used for chemoprophylaxis, i.e to prevent malarial
attacks when in a malarious area, act on merozoites emerging
from liver cells. e.g quinine, chloroquine
Drugs used for radical cure are active against parasites in the
liver e.g primaquine.
Drugs act on gametocytes and prevent transmission by the
mosquito e.g primaquine.

Anti malarial drugs

Chloroquine: Drug of choice for both chemoprophylaxis
and treating the acute attack . It is given orally; it is
concentrated in the parasite. Unwanted effects include GI
tract upsets, dizziness, urticaria; given i.v. it can cause
dysrhythmias.

Quinine: Drugsfor treating the acute attack are quinine,

given orally; it can be given i/v in emergency. Unwanted
effects include GI tract upsets, tinnitus, blurred vision and
with large doses,dysrhythmias and CNS disturbances.

Anti malarial drugs

Primaquine:
It is effective against the liver hypnozoites, and is also active
against gametocytes. Given orally . Unwanted effects are
mainly GI tract upsets and, with large doses,
methaemoglobinaemia. Haemolysis is produced in individuals
with genetic deficiency of erythrocyte glucose 6 phosphate
dehydrogenase.

Classification of anti-malaria

Classified by their selective actions on

different phases of the parasite life cycle:
1. 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.

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:
Schizonticide gametocyte
Not active against liver stage
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.
Mechanism:
plasmodium aggregates chloroquine.
chloroquine incorporated into DNA chain of plasmodium inhibit
proliferation.
chloroquine prevents the polymerization of 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.

1. Killing Amibic trophozoites : chloroquine reaches high liver

concentrations.
2. Immunosuppression action:

 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 malaria
especially 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.

Quinine
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

1. 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

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

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 transmission

Primaquine

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

Primaquine
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
prophylaxis

Pyrimethamine

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.

Pyrimethamine
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:

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

2.

Combination therapy:

chloroquine + primaquine: symptom stages

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

Antimalarial Drugs
Attack the parasite during the asexual phase,
when it is vulnerable
Erythrocytic phase drugs: chloroquine,
hydroxychloroquine, quinine, mefloquine
Primaquine: kills parasite in both phases
May be used together for synergistic or additive
killing power

Antimalarials:
Mechanism of Action
4-Aminoquinoline derivatives:
chloroquine and hydroxychloroquine
Bind to parasite nucleoproteins and interfere with
protein synthesis; also alter pH within the parasite

Interfere with parasites ability to metabolize and use

erythrocyte hemoglobin
Effective only during the erythrocytic phase

Antimalarials:
Mechanism of Action
4-Aminoquinoline derivatives:
quinine and Mefloquine (Lariam)
Alter pH within the parasite
Interfere with parasites ability to metabolize
and use erythrocyte hemoglobin
Effective only during the erythrocytic phase

Antimalarials:
Mechanism of Action
Diaminopyrimidines
(pyrimethamine & trimethoprim)
Inhibit protein synthesis essential for growth and
survival
Only effective during the erythrocytic phase
These drugs may be used with sulfadoxine or
dapsone or synergistic effects

Antimalarials:
Mechanism of Action
Primaquine
Only exoerythrocytic drug (works in both phases)
Binds and alters parasitic DNA

Sulfonamides, tetracyclines, clindamycin

Used in combination with antimalarials to
increase protozoacidal effects

Antimalarials
Drug Effects
Kill parasitic organisms
Chloroquine and hydroxychloroquine also have
antiinflammatory effects
Indications
Kills Plasmodium organisms, the parasites that cause malaria
The drugs have varying effectiveness on the different malaria
organisms
Some drugs are used for prophylaxis against malaria
2 weeks prior and 8 weeks after return

Chloroquine is also used for rheumatoid arthritis and systemic

lupus erythematosus

Antimalarials
Adverse Effects
Many adverse effects for the various drugs
Primarily gastrointestinal: nausea, vomiting,
diarrhea, anorexia, and abdominal pain

Dirgahayu negeriku
Dirgahayu FK USU

KEBANGGAAN INDONESIA UNTUK DUNIA

Mebendazole
A synthetic benzimidazole that has a wide spectrum
of anthelmintic activity and a low incidence of
adverse effects.
Pharmacokinetics
Oral absorption 10, Absorption increases with fatty
meal
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. It is
converted to inactive metabolites rapidly in liver.
It has half life of 2-6 hours

 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
Pinworm infection
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
used with caution under 2ys of age may
cause convulsion in this group.
enzyme inducers and inhibitors affect plasma
level of the drug.
hepatic parenchymal disease

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.

Albendazole con;d
Mechanism of action:
It inhibits microtubule synthesis in
nematodes(intestinal round worms) that irreversibly
impairs glucose uptake, intestinal parasites are
immobilized and die slowly.
It is larvicidal in hydatid, cysticercosis, ascariasis and
hook worm infection.
Also ovicidal in ascariasis, ancyclostomiasis
(hookworm), tricurasis
63

Pharmacokinetics (Albendazole)
it is adminstered orally , and absorbed
erratically (unpredictable) , absorption
can be increased with fatty meal
It is metabolized in the liver rapidly to
active metabolite albendazole sulphoxide
It has a plasma half life of 8-12 hours
Sulphoxide is mostly protein bound ,
distributes well to tissues and enters bile,
CSF, hydated cyst
Metabolites are excreted in urine
64

 Clinical Uses
Administered on an empty stomach when used
against intraluminal parasites but with a fatty
meal when used against tissue parasites.
1. Ascariasis, Trichuriasis, and Hookworm and
Pinworm infections.
2. Strongyloidiasis
3. Hydatid Disease
4. Neurocysticercosis
5. Other infections: cutaneous larva migrans,
gnathostomiasis

Albendazole cond
Adverse effects:
In short term: use no significant adverse effects.
In long term use : as used in hydatid cyst and
cysticercosis, abdominal distress, headache ,fever ,
fatigue, alopecia , increased liver enzymes ,
pancytopenia. Blood counts and LFT should be
followed.
Not given during pregnancy and in hypersensitive
people.

66

Piperazine
Only recommended for the treatment of ascariasis.
No longer recommended for treatment of pinworm
infection, because a 7-day course 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.

Piperazine cond
pharmacokinetics :
it is readily absorbed orally and excreted unchanged in
urine.
75 mg /kg/day for 2 days once daily
treatment is continued for 3-4 days or repeated after
one week in case of heavy infections.
Adverse effects:
GI disturbance, Neurotoxicity ,allergic reactions serum
sickness like syndrome
Contraindications
Epilepsy, Impaired liver or kidney functions, pregnancy,
Malnutrition

68

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 PAMOATE
A tetrahydropyrimidine derivative.
A broad-spectrum anthelmintic, but it is not
effective against tricuriasis (whip worms), and
trichostrongylus orientalis infections. Oxantel
pamoate is more effective
Pharmacokinetics:
It is poorly absorbed orally ,
Half of the drug is excreted unchanged in the
feces.
Mechanism of action:
It is a depolrazing neuromuscular blocking agent
that causes release of acetylcholine and
inhibition of cholinestrase leads to spastic
70
paralysis of worms.

Pyrental pamoate cond

Adverse Effects .
Infrequent mild transient GI disturbance
drowsiness , headache ,insomnia.
Rash ,fever
Contraindciations
Should not be used in liver diseases.
Pregnancy
and child under 2 years of age
71

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.

Benzimidazoles

Albendazole, mebendazole, thiabendazole

Inhibit glucose absorption
Poorly absorbed (PO).
Active against nematodes (drugs of choice).
Leder K. & Weller P. 2003. In ASM Manual of CM.

Write the pharmacological action and side

effects of the following drugs

Chloroquine
Metronidazole
Melarsoprol
Primaquine
Mebendazole
Praziquantel
Niclosamide
Pyrantel pamoate
Thiabendazole

Books & sites

Basic and clinical Pharmacology by B.G. Katzung
Pharmacological basis of therapeutics by Goodman and
gillman
Pharmacology by Rang and Dale
www.pharmacology2000.com
www. medicalstudents.com