JSS College of Pharmacy - Mysuru: Anthelmintics Drugs Classification and Mechanism of Action

JSS College of Pharmacy - Mysuru
CHEMOTHERAPY OF ANTIHELMINTICS AND
ANTIAMOEBIC DRUGS
SUBMITTED BY
NARASIMHAMURTHY M
1ST M PHARM
DEPARTMENT OF PHARMACOLOGY
JSSCP, MYSURU

Helminthiasis
 Infections with helminths, or parasitic worms,
affect more than two billion people worldwide.
 In regions of rural poverty in the tropics, where
prevalence is greatest, simultaneous infection with
more than one type of helminth is common. The
relative incidence of common helminthic
infections in humans.
 Worms pathogenic for humans are Metazoa and
can be classified into roundworms (nematodes)
and two types of flatworms, flukes (trematodes)
and tapeworms (cestodes).

Classification of helminths

Roundworms (Nematodes)
The roundworms essentially comprise of the following seven species which shall be
discussed briefly vis-a-vis the disease they produce in humans in the sections that follows :
(a) Hookworm : These are of two types, namely :
(i) American Variety. Necator americanus
(ii) European Variety. Ancylostoma duodenale.
They are found to attach themselves to the mucosa of the duodenum and subsequently
obtain their nourishment (for survival) by sucking blood from the surrounding blood vessels.
(b) Roundworm : The most prevalent human helminths belonging to this category is Ascaris
lumbricoides. It is observed to inhabit in the upper segment of the small intestine ; and,
therefore, it is vomitted up quite often.
(c) Whipworm : It exactly resembles a tiny whip and the causative species in Trichuris
trichiura. It is mostly inhabitated in the cecum, but is also located in the lower segment of
the ileum and the appendix.
(d) Pinworm (Threadworm) : It is only 1.5 to 3mm long, Enterobius vermicularis, and resides
mostly in the small intestine, cecum and colon.

(e) Strongyloides stercoralis : It inhabits in the duodenum mostly but may also be located
in various other parts, for instance : biliary passages, pancreatic ducts, stomach, various
segments of the intestinal passage.
(f) Trichinella spiralis : The infection usually caused with T. spiralis is known as trichinosis
i.e., a condition which comes into being due to the ingestion of partially cooked pork meat
profusely infested with the larvae of the worm. The intake of such meat allows the cysts to
dissolve, the parasites get matured which eventually gives rise to a new crop of larvae that
not only develops but also penetrates right into the intestinal mucosa and ultimately lodge
in the muscles.
(g) Wuchereria bancrofti : It is one of the most vital filarial worms that is particularly
transmitted by the bite of the mosquito. The prevailing symptoms are the blocking of the
lymphatic ducts with the adult worms.

Flat worms
The flatworms are normally of two kinds, namely
(a) Segmented (cestodes)
(b) non segmented (trematodes).
(i) Cestodes : They include the ‘tapeworms’, which are of four categories commonly found in
humans viz., beef tapeworm (Taenia saginata) ; pork tapeworm (Taenia solium) ; fish
tapeworm (Diphyllobothrium latum) ; and dwarf tapeworm (Hymenolepis nana). In reality,
the larval stage of all the four tapeworms is invariably spent in the muscles of the
intermediate host, and human infection usually takes place by means of eating partially
(improperly) cooked meat and fish.
(ii) Trematodes : They mostly include the flukes ; and in man they occur in three varieties
that solely inhabit the blood stream thereby causing prominently schistosomiasis. These
blood flukes are, namely : S. haematobium ; S. mansoni ; S. mekongi ; and S. japonicum.
Importantly, all these human parasites predominantly produce epigastric distress, abdominal
pain, anorexia, diarrhea with blood and mucus in the stools, pyrexia, enlarged and tender
liver, and ascites. It has been established that the intermediate host is either a freshwater
snail or a freshwater mollusk. The usual mode of transmission in humans is on account of
drinking contaminated water.

Anthelmintics
• Anthelmintics are drugs that either kill (vermicide) or expel (vermifuge)
infesting helminths.
• Helminthiasis is prevalent globally (1/3rd of world’s population harbors
them), but is more common in developing countries with poorer personal
and environmental hygiene.
• Multiple infestations in the same individual are not infrequent. In the
human body, g.i.t. is the abode of many helminths, but some also live in
tissues, or their larvae migrate into tissues.
• They harm the host by depriving him of food, causing blood loss, injury to
organs, intestinal or lymphatic obstruction and by secreting toxins.
Helminthiasis is rarely fatal, but is a major cause of ill health.

Classification of Anthelmintic drugs

Mebendazole
• It is a benzimidazole introduced in 1972. This congener of
thiabendazole became very popular because it retained the broad-
spectrum anthelmintic activity but not the toxicity of its predecessor.
• It has produced nearly 100% cure rate/reduction in egg count in
roundworm, hook worm (both species), Enterobius and Trichuris
infestations, but is much less active on Strongyloides. Upto 75% cure
has been reported in tapeworms, but H. nana is relatively insensitive.
• It expels Trichinella spiralis from intestines, but efficacy in killing larvae
that have migrated to muscles is uncertain. Prolonged treatment has
been shown to cause regression of hydatid cysts in the liver. Treatment
after resection of the cyst may prevent its regrowth.

Mechanism of action
• Mebendazole probably acts by
inhibiting microtubule synthesis. Its
bind with parasite ‘β-tubulin’ and
inhibit its polymerization. In addition
mebendazole probably blocks glucose
uptake in parasite and depletes its
glycogen stores.
• Efficacy of the drug varies with
gastrointestinal transit time, with
intensity of infection, and perhaps with
the strain of parasite.

Pharmacokinetics :
 Absorption of mebendazole from intestines is minimal.
 Less than 10% of orally administered mebendazole is absorbed. The absorbed drug is protein-bound (> 90%), rapidly
converted to inactive metabolites (primarily during its first pass in the liver), and has a half-life of 2-6 hours.
 75 – 90% of oral dose passed in the faeces.
Adverse effects
 Mild nausea, vomiting, diarrhea, and abdominal pain have been reported infrequently.
 Rare side effects, usually with high-dose therapy, are hypersensitivity reactions (rash, urticaria), agranulocytosis, alopecia,
and elevation of liver enzymes.
 Mebendazole is teratogenic in animals and therefore contraindicated in pregnancy.
 It should be used with caution in children younger than 2 years of age because of limited experience and rare reports of
convulsions in this age group.
Uses :
 Mebendazole is highly effective against intestinal nematodes-roundworm, hookworm, whipworm, pinworm and
mixedworm infections.
 Mebendazole is more effective than albendazole trichuriasis.

Albendazole
• Albendazole, a broad-spectrum oral anthelmintic
agent.
• It is the drug of choice for treatment of hydatid
disease and cysticercosis and it is also used in the
treatment of pinworm and hookworm, round
worm, whip worm, and thread worm infections.
• One dose treatment is effective against round
worm, pin worm and hook worm infections
which are comparable to 3 days treatment with
mebendazole.
• Three days treatment is necessary for tapeworms
including H. nana. It has weak microfilaricidal
action.

Pharmacokinetics:
 Albendazole is erratically absorbed after oral administration, but absorption is
enhanced by a high-fat meal.
 Its metabolized in liver and primarily excreted in urine and t½ = approx. 8.5 hours.
Adverse effects :
 Mild and transient epigastric distress, diarrhea, headache, nausea, dizziness, lassitude,
and insomnia can occur.
 In long-term use for hydatid disease, albendazole is well tolerated, but it can cause
abdominal distress, headaches, fever, fatigue, alopecia, increases in liver enzymes, and
pancytopenia.
 It has exhibited embryotoxicity in animals, use in pregnant women is contraindicated.
It should be given with caution to patients with hepatic or renal disease.
Uses :
 It is used in the treatment of Ascariasis, trichuriasis hook worm and pin worm
infections.
 Neurocysticercosis.

Thiabendazole
Thiabendazole is synthetic benzimidazole, it is potent broad spectrum anthelmintic agent.
Current use of thiabendazole is limited to the topical treatment of cutaneous larva migrans
(creeping eruption). Because of its toxic effects, it has been largely replaced by other agents
for many clinical applications.
Pharmacokinetics :
insoluble in water but readily available for oral absorption. It is hydroxylated in the liver and
excreted in urine.
Adverse effects :
Nausea, vomiting, loss of appetite, headache, giddiness are most common
Uses :
Thiabendazole has anti-inflammatory, analgesic and antipyretic actions. These may
contribute to its effect in cutaneous larva migrans and other inflammatory conditions
produced by larvae or worms in tissues.

Praziquantel
 Praziquantel (BILTRICIDE, DISTOCIDE) is a
pyrazinoisoquinoline derivative developed after this
class of compounds was discovered to have
anthelmintic activity in 1972. The (–) isomer is
responsible for most of the drug’s anthelmintic activity.
 The drug shows useful activity against most cestodes
and trematodes that infect humans, whereas
nematodes generally are unaffected.
 The drug is best studied and most commonly used for
treatment of schistosomiasis, caused by S. mansoni, S.
haematobium, and S. japonicum.

Mechanism of action
 It is rapidly taken up by susceptible worms and appears to act by causing leakage
of intracellular calcium from the membranes → contracture and paralysis.
 Selectivity of action of praziquantel on tapeworms and flukes may be dependent
on the presence of a specific variant of Ca2+ channel sensitive to praziquantel in
these worms. The tapeworms lose grip of the intestinal mucosa and are expelled.
Flukes and schistosomes are also dislodged in tissues and veins.
 Praziquantel is active against adult as well as juvenile and larval stages of
tapeworms. At relatively higher concentrations, it causes vacuolization of the
tegument and release of the contents of tapeworms and flukes followed by their
destruction by immune mechanisms of the host. This action appears to be more
important in cases of schistosomes and flukes.

Pharmacokinetics :
 Praziquantel is rapidly absorbed from intestines; absorption is enhanced if it is ingested
with food. High first pass metabolism in liver limits its systemic bioavailability.
 Phenytoin, carbamazepine and dexamethasone induce praziquantel metabolism and
further decrease its bioavailability.
 Patients of neurocysticercosis are mostly receiving these drugs which may contribute to
therapeutic failure of praziquantel. It crosses blood-brain barrier and attains therapeutic
concentrations in the brain and CSF. The plasma t½ is short (1.5 hours). Metabolites are
excreted chiefly in urine.
Adverse effects :
 praziquantel has exhibited no systemic toxicity. It tastes bitter: can produce nausea and
abdominal pain.
 Other side effects are headache, dizziness and sedation. When used for schistosomes and
visceral flukes, symptoms like itching, urticaria, rashes, fever and bodyache occur as a
reaction to the destroyed parasites.
 Destruction of cysticerci in the brain may produce neurological complications.

Uses :
• Praziquantel is used in the treatment of Schistosomiasis,
Tapeworms, Neurocysticercosis.
• Praziquantel is the drug of choice for all schistosome and fluke
infestations except Fasciola hepatica. The flukes respond to 75
mg/kg single day treatment in most cases, and on two occasions
in the remaining.

Pyrantel pamoate
 It was introduced in 1969 for pin worm infestation
in children; use soon extended to roundworm and
hookworm as well.
 Efficacy against Ascaris, Enterobius and
Ancylostoma is high and comparable to that of
mebendazole. Lower cure rates (about 60%) have
been obtained in case of Necator infestation.
 It is less active against Strongyloides and inactive
against Trichuris and other worms.

Mechanism of action
• Pyrantel causes activation of nicotinic cholinergic receptors in the worms resulting in
persistent depolarization neuromuscular blocker, slowly developing contracture and
spastic paralysis.

Pharmacokinetics :
o Pyrantel pamoate is given orally but absorbed poorly , about80-90%
of oral dose is excreted in faces.
Adverse effects :
o Adverse effects are mild and include nausea, vomiting, and diarrhea
and it is contraindicated in infants.
Uses :
o Pyrantel is used as a single oral dose ( 11mg/kg ) in the treatment of
roundworm , hookworm and pinworm infections.
o For pinworm, the dose is repeated after 2 weeks.

PIPERAZINE CITRATE
 Introduced in 1950, it is a highly active drug
against Ascaris and Enterobius; achieves 90–100%
cure rates. However, because of the availability at
more convenient and better tolerated
albendazole/mebendazole.
 It is now considered a second choice drug.

Mechanism of action
 Piperazine causes hyperpolarization of Ascaris muscle by a GABA agonistic action
opening Cl¯ channels that causes relaxation and depresses responsiveness to
contractile action of ACh. Flaccid paralysis occurs and worms are expelled alive.
 They recover if placed in piperazine free medium. Therefore, often a purgative
(Senna) is given with it, but is not necessary. No fasting or patient preparation is
required. Piperazine does not excite Ascaris to abnormal migration. It does not
affect neuromuscular transmission in man.
Pharmacokinetics :
 A considerable fraction of the oral dose of piperazine is absorbed. It is partly
metabolized in liver and excreted in urine.

Adverse effects :
 Piperazine is safe and well tolerated.
 Nausea, vomiting, abdominal discomfort and urticaria are
occasional.
 Dizziness and excitement occur at high doses; toxic doses produce
convulsions; death is due to respiratory failure. It is contraindicated
in renal insufficiency and in epileptics, but is safe in the pregnant.
Uses :
 It have been employed profusely in therapeutic treatment of
roundworm and pinworm infections.

Diethylcarbamazine (DEC)
 Diethylcarbamazine (DEC) is a first-line agent for control
and treatment of lymphatic filariasis caused by Wuchereria
bancrofti and Brugia malayi and for therapy of tropical
pulmonary eosinophilia, an uncommon manifestation of
lymphatic filarial infection.
 DEC is also the drug of choice for treatment of loiasis,
caused by infection with the filarial parasite L. loa.
However, caution must be used in treatment of high-grade
L. loa infection because the rapid killing of large numbers
of microfilariae can cause life-threatening post-treatment
complications.

Mechanism of action
The mechanism of action of DEC against susceptible filarial species is
not well understood, but the drug appears to exert a direct effect on
W. bancrofti microfilariae by causing organelle damage and
apoptosis.
The mechanism of filaricidal action of DEC against adult worms is
unknown. Some studies suggest that DEC compromises intracellular
processing and transport of certain macromolecules to the plasma
membrane. The drug also may affect specific immune and
inflammatory responses of the host by undefined mechanisms.

Pharmacokinetics :
 DEC is absorbed rapidly from the GI tract. Peak plasma levels occur within 1-2 hours after a single oral
dose, and the plasma t1/2 varies from 2-10 hours, depending on the urinary pH.
 DEC is excreted by both urinary and extra-urinary routes; >50% of an oral dose appears in acidic urine
as the unchanged drug, but this value is decreased when the urine is alkaline. Therefore, dosage
reduction may be required for people with renal dysfunction or sustained alkaline urine.
Adverse effects :
 These are common but generally not serious. Nausea, loss of appetite, headache, weakness and
dizziness are the usual complaints.
 A febrile reaction with rash, pruritus, enlargement of lymph nodes and fall in BP may occur due to
mass destruction of Microfilaria and adult worms. This is usually mild, but may be severe.
Uses :
 Diethylcarbamazine is used in the treatment of filariasis because of its ability to immobilize
microfilariae and render them susceptible to host defence mechanisms.
 Combined with albendazole , diethylcarbamazine is effective in the treatment of Wuchereria bancrofti
and Brugia malayi infections.
 Used in the treatment of tropical eosinophilia, Loa loa infections.

Ivermectin
 It is an extremely potent semisynthetic derivative of
the antinematodal principle obtained from
Streptomyces avermitilis. Ivermectin is the drug of
choice for single dose treatment of onchocerciasis
and strongyloidosis, and is comparable to DEC for
bancroftian and brugian filaria.
 It is microfilaricidal but not macrofilaricidal.

Mechanism of action
 Ivermectin acts by paralyzing the worms by
binding to glutamate-gated chloride
channels and also enhancing GABA activity.
 It binds to the channels and enhances the
permeability of the cell membranes to
chloride ions leading to hyperpolarization
and paralysis.
 It also enhances the GABAergic transmission
in the nerves of the nematodes.

Pharmacokinetics :
 Ivermectin is well absorbed orally, widely distributed in the body, but does not enter CNS,
sequestrated in liver and fat, and has a long terminal t½ of 48–60 hours. It is metabolized
by CYP3A4, but no drug interactions related to this isoenzyme are known.
Adverse effects :
 Side effects have been mild—pruritus, giddiness, nausea, abdominal pain, constipation,
lethargy and transient ECG changes, but more important are the reactions due to
degeneration products of the Mf, which are similar to those occurring after DEC. Safety of
ivermectin in pregnant women and young children is not established.
Uses :
 Ivermectin is used in the treatment of Onchocerciasis, Lymphatic filariasis,
Strongyloidiasis.
 Ivermectin is also useful in cutaneous larva migrans, ascariasis, in scabies and lice
infestations in a single dose of 200µg/kg.

NICLOSAMIDE
 Niclosamide is a highly effective drug against cestodes infesting man—Taenia
saginata, T. solium, Diphyllobothrium latum and Hymenolepis nana, as well as pin
worm.
Mechanism of action :
 The drug appears to act by inhibiting oxidative phosphorylation in mitochondria
and interfering with anaerobic generation of ATP by the tapeworm.
Pharmacokinetics :
 Injured by niclosamide, the tapeworms are partly digested in the intestine. In cases
of T. solium, digestion of the dead segments can be hazardous, because the ova
released from them may develop into larvae in the intestine, penetrate its wall and
cause visceral cysticercosis.

Adverse effects :
Niclosamide is tasteless and nonirritating. It is minimally absorbed from
g.i.t.—no systemic toxicity occurs. It is well tolerated; minor abdominal
symptoms are produced occasionally. Malaise, pruritus and light
headedness are rare.
 Niclosamide is safe during pregnancy and in patients with poor health.
Uses :
Niclosamide is an alternative drug in infestations by tapeworms like
T.solium, T.saginata, H.nana and D.latum and in intestinal fluke
infestations.

AMOEBIASIS
 Amebiasis (also called amebic dysentery) is an infection of intestinal tract caused by
Entamoeba histolytica. The disease can be acute or chronic, with the patients
showing varying degrees of illness, from no symptoms to mild diarrhea to
fulminating dysentery (Dysentery in which the symptoms are intensely acute,
leading to prostration, collapse, and often death).
 The diagnosis is established by isolating E. histolytica from fresh feces. Therapy is
aimed not only at the acutely ill patients but also at those who are asymptomatic
carriers, because dormant E. histolytica may cause future infections in the carrier
and be a potential source of infections for others.
 Protozoal infections are common among the people in underdeveloped topical and
subtropical countries, where sanitary conditions, hygienic practices and control of
vectors of transmission are inadequate.

Life cycle of Entamoeba histolytica
Entamoeba histolytica exists in two forms:
1. Cysts form (That can survive out side the body).
2. Trophozoites form (That are labile and don’t persist outside the body).
Life cycle
Life cycle consists of following steps:
1.Ingestion of cysts
Cysts are ingested through feces, contaminated food or water.
2. Formation of trophozoites
Cysts are passed into the lumen of intestine, where the trophozoites are
liberated.

3. Penetration and multiplication of trophozoites
Trophozoites are penetrated in intestinal wall and multiply within
colon wall. They either invade and ulcerate the mucosa of large
intestine or simply feed on intestinal bacteria.
4.Systemic invasion
Large numbers of trophozoites within the colon wall can also lead to
systemic invasion and caused liver abscess.
5. Cysts discarded
The trophozoites within the intestine are slowly carried toward the
rectum, where they return to cyst form and are excreted in feces.

ANTIAMOEBIC DRUGS
These are drugs useful in infection caused by the anaerobic protozoa Entamoeba
histolytica. Other Entamoeba species are generally non-pathogenic.

Site of action of antiamoebic drugs

Metronidazole
 Metronidazole , a nitroimidazole, is a powerful
amoebicidal. It is amoebicidal, kills the trophozoites and
effective in both intestinal and extraintestinal
amoebiasis. Apart from this, it also inhibits Trichomonas
vaginalis, Giardia lamblia and Balantidium coli.
 Anaerobic bacteria are also sensitive to metronidazole.
Other actions include-radio sensitization, mutagenesis
and depressed CMI.

Mechanism of action
 Metronidazole is a prodrug. Susceptible microorganisms
including anaerobic bacteria and certain protozoa
reduce the nitro group of metronidazole by a
nitroreductase and convert it to a cytotoxic derivative.
 This derivative binds to DNA and inhibits protein
synthesis. Aerobic bacteria lack this nitro reductase and
are, therefore, not susceptible to metronidazole.

Pharmacokinetics :
• Metronidazole is well-absorbed, is widely distributed, penetrates all
tissues and reaches adequate concentrations in the CSF.
• It has a plasma t½ of 8 hours.
• It is metabolised in the liver by oxidation and glucuronide conjugation.
Adverse Drug Reactions :
• Frequent - Anorexia, nausea, METALLIC TASTE, abdominal cramps,
disulfiram reaction.
• Less frequent - Headache, glossitis, dry mouth, dizziness, rashes,
transient neutropenia.
• On prolonged administration – Peripheral neuropathy, CNS effects.

Uses :
Broad spectrum cidal action for protozoa
1. Anti-amoebiasis: kills E histolytic trophozoites but not cysts.
Treatment of all tissue infections with E histolytic . No effect against
luminal parasites and so must be used with a luminal amoebicide to
ensure eradication of the infection.
2. Anti-trichomoniasis
3. Anti-anaerobic bacteria
4. Anti-giardiasis
Pseudomembranous colitis, Ulcerative gingivitis, H.pylori, Peptic
ulcer disease, Guinea worm infestation.

Tinidazole
 long t ½ ,slower metabolism, long duration of action, OD dosing.
 Higher cure rates in amoebiasis.
 Lower side effect  metallic taste ,nausea, rash.
USES :
 Amoebiasis – 2g od X 3 d
 Tricho, giardiasis- 2g single dose
 Anaerobic infection –
Px -2 g single dose for colorectal surgeries
 H pylori- 500 mg bd X 2 weeks in triple therapy

Secnidazole : longest t ½ [17-29 hrs]
2 g single dose but for hepatic amoebiasis 1.5 gm od X5 days
Ornidazole –long t ½ ,similar to Tinidazole
 Satranidazole – better tolerability
No disulfiram reaction
No acetamide metabolite [weak carcinogen]

Emetine and Dehydroemetine
Emetine is an alkaloid from Cephaelis ipecacuanha. Emetine is a
potent and directly acting amoebicide—kills trophozoites but has
no effect on cysts.
Dehydroemetine is a semisynthetic analog it is equally effective but
less cumulative and less toxic to the heart. Thus, it is usually
preferred over emetine.
They are effective against tissue trophozoites of E.histolytica .

Mechanism of action :
 Inhibiting peptidyl-tRNA translocation → inhibiting elongation of
peptide chain → inhibiting protein synthesis → interfering cleavage
and breeding of trophozoites
 No action on cysts.
Pharmacokinetics :
 Emetine cannot be given orally because it will be vomited out.
 Administered s/c (preferred) or im. (but never i.v.)

Adverse Effects :
o low selectivity → also inhibits protein synthesis of eukaryote.
o Toxicity increase with length o ftherapy.
1. Local irritant: pain and tenderness in the area of injection.
2. GIT : nausea, vomiting (central and direct),abdominal cramps ,diarrhoea
3. Cardiac toxicity: arrhythmias, congestive heart failure, hypotension, ECG
changes–to avoid strict bed rest during therapy, no exercise X 2mnths
4. Neuromuscular blockade: muscle weakness and discomfort– myositis like
o Not be used in patients with cardiac or renal disease, in young children, or
in pregnancy.

Uses :
kills E histolytic trophozoites of histolytic tissues but no effect against
luminal cysts -- + luminal amoebicide.
Rapid action.
Given only till a/c sx subside ( not> 10 days)
Cumulative in liver, kidney, spleen, lungs– 2nd course only after 6
weeks
Reserve drug for severe cases or metronidazole resistant or
intolerant.
Also for liver fluke infection.

Chloroquine
 Kills trophozoites .
 Chloroquine reaches high liver concentrations
→ treatment of amoebic liver abscess.
 Not effective in the treatment of intestinal or other extrahepatic
amoebiasis.
 nor in controlling the luminal cycle (cyst passers). Completely
absorbed from the upper Intestine.

 Efficacy similar to emetine, but duration of treatment is longer and
relapses frequent.
 No resistance detected.
 Dose for amoebic liver abscess: 600 mg (base) for 2 days 300 mg
daily for 2-3 weeks.

DILOXANIDE
Diloxanide furoate is a dichloroacetamide derivative.
Highly effective luminal amoebicide: directly kills trophozoites
responsible for production of cysts
Diloxanide furoate is split in the intestines to diloxanide and furoic acid.
It acts on the parasite in the intestines but not in the tissues.
Hydrolysed in intestine released Diloxanide is absorbed. Diloxanide(
weaker amoebicide): no systemic antiamoebic activity despite its
absorption.
primarily metabolized by glucuronidation  urine.

 Effective for asymptomatic luminal infections and cyst passers.
 used with a tissue amoebicide, usually metronidazole.
Adverse Effects:
 flatulence, nausea, abdominal cramps, rashes etc.

NITAZOXANIDE
 Nitazoxanide is a congener of niclosamide.
Spectrum
 Cryptosporidium parvum
 G. intestinalis , E. histolytica , and T. vaginalis , other protozoans.
 Intestinal helminths: Hymenolepis nana, Trichuris trichiura, Ascaris
lumbricoides, Enterobius vermicularis, Ancylostoma duodenale,
Strongyloides stercoralis , and the liver fluke Fasciola hepatica.
 Anaerobic bacteria, including Clostridium spp. and H. pylori .
 Antiviral activity  now undergoing clinical trials for the treatment of
hepatitis C.

Pharmacokinetics :
 Nitazoxanide and its active metabolites interfere with the PFOR
enzyme dependent electron transfer reaction in anaerobic
metabolism.
 Given orally, nitazoxanide is rapidly converted to tizoxanide which is highly
protein bound (>99%) and is metabolized in the liver.
Uses :
 Amoebic dysentery as luminal amoebicide
 Giardiasis, Cryptosporidiosis
Adverse effect :
 Abdominal pain, vomiting, head ache.

PAROMOMYCIN
 Paromomycin is an Aminoglycoside antibiotic.
It is given orally and not significantly absorbed from the GIT.
Only as a luminal amoebicide and has no effect against extra
intestinal amoebic infections.
inhibiting protein synthesis → kill trophozoites.
inhibiting symbiosis flora → indirectly inhibiting amoeba protozoa.

Uses :
 DOC for treating intestinal colonization with E. histolytica.
 Giardiasis in pregnant women, especially during the first trimester, when
metronidazole is contraindicated and as an alternative agent for
metronidazole-resistant isolates of G. intestinalis .
Dose - 500 mg orally three times daily for 10 days
 6.25% cream has been used to treat vaginal trichomoniasis in patients
who had failed metronidazole therapy or could not receive
metronidazole.
Adverse effects :
 abdominal pain and cramping, epigastric pain, nausea and vomiting,
steatorrhea, and diarrhea. Rarely, rash and headache.

8-HYDROXYQUINOLINES
 against Entamoeba, Giardia, Trichomonas, some fung
(dermatophytes, Candida) and some bacteria.
Uses :
 Intestinal amoebiasis as alternatives to Diloxanide furoate.
 Other uses are--giardiasis; local treatment of monilial and
trichomonas vaginitis, fungal and bacterial skin infections.
 Diarrhoeal diseases
 Di iodohydroxyquine safer drug.

Adverse effects :
Nausea, transient loose and green stools, pruritus etc. Goiter 
prolonged medication.
Iodism (furunculosis, inflammation of mucous membranes) --due to
chronic iodine overload.
Prolonged/repeated use of high doses of quiniodochlor caused a
neuropathic syndrome called 'subacute myelo-optic neuropathy' (SMON)
India banned only for pediatric patients, [blindness]. Banned in other
countries.

Tetracyclines
Directly inhibit amoebae at high concentrations.
Older tetracyclines are incompletely absorbed in the small intestine,
reach the colon in large amounts and inhibit the bacterial flora with
which Entamoebae live symbiotically.
 Thus, they indirectly reduce proliferation of entamoebae in the
colon and are used in chronic, difficult to treat cases with only the
luminal cycle and little mucosal invasion.

 They are not good for acute dysentery and for hepatic amoebiasis
Tetracyclines lessen risk of
 opportunistic infections
 perforation
 peritonitis
when given along with systemic amoebicide

TREATMENT OF AMOEBIASIS
1. Invasive intestinal amoebiasis
Metronidazole/ Tinidazole are DOC
 Secnidazole, ornidazole,satranidazole are the alternatives.
 Adjuvant measures for diarrhea and abdominal pain
 Dehydroemetine is rarely used for most severe cases -> faster symptomatic relief.
Discontinued as soon as acute symptoms are controlled (2-3 days) and
metronidazole started.
 Emetine may also be needed when metronidazole is contraindicated or produces
rashes/neurotoxicity.
 This should be followed by a luminal amoebicide to eradicate and to prevent
carrier (cyst passing) state.

2. Chronic intestinal amoebiasis/asymptomatic cyst passers
Diloxanide furoate –DOC
Metronidazole/ Tinidazole- cure any latent hepatic infection.
A single course of a hydroxyquinoline not > 2 weeks may be used as
third choice.
A tetracycline with tissue amoebicide in cases which fail to clear
completely.

3. Hepatic amoebiasis
Complete eradication of trophozoites from the liver is essential to
avoid relapses.
Metronidazole / Tinidazole are the first choice drugs.
Dehydroemetine is to be used only if metronidazole cannot be given
for one reason or the other.
Abscess  aspirated.
A luminal amoebicide must be given later to finish the intestinal
reservoir of infection.

THANK YOU

JSS College of Pharmacy - Mysuru: Anthelmintics Drugs Classification and Mechanism of Action

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