Transcript Antihelminth

ANTHELMINTIC DRUGS
DR.ABDUL LATIF MAHESAR
Department of Medical Pharmacology
KSU
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‫تنبيه‬
‫في هذه الساليدات قمنا بما يلي‪:‬‬
‫•حذف المقدمة في كيفية انتقال العدوى واشكالها واالكتفاء فقط‬
‫بأسماء الديدان وأصنافها‬
‫•حذف الجرعات من ناحية الكمية وفترة استخدامها‬
‫يمكنكم العودة لساليدات الدكتور للحصول على المعلومات السالفة‬
‫الذكر‬
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Trematodes
Flat worms
Cestodes
Helminth
Tissue type
Round worms
(Nematodes)
Intestinal type
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Nematodes
A) INTESTINAL ROUND WORMS
 Ascaris lmubricoides (common round worm)
 Enterobius vermicularis (pinworm)
 Trichuris trichuria (whipworm)
 Strongyloids stercoralis (threadworm)  Strongyloidiasis
 Ancylostoma duodenale & Necator americanus
(hookworm)
B) TISSUE ROUND WORMS
Trichinella spiralis. (Trichinosis)
Dracunculus medinensis (guineaworm)  Dracunculiasis
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Other round worms
FILARIAE,
includes:
Wuchereria bancrofti (filariasis)
2.
Loa loa (loiasis)
3.
Onchocerca volvulus (onchocerciasis)
River blindness.
4.
Brugia malayi and B. timori
1.
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Cestodes (tape worms)
1.
2.
3.
4.
5.
Tenia saginata (Beef tapeworm)
Tenia solium (Pork tapeworm),
Cysticercosis (Pork tapeworm larval stage)
Hymenolepis nana (Dwarf tapeworm)
Diphyllobothrium latum (Fish tapeworm)
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Hydatid tape worm

Echinococcus species
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TREMATODES/FLUKES (leaf-like)
Schistosoma mansoni
 Schistosoma hematobium
 Schistosoma Japonicum
 Paragonimus species  Paragonimiasis
 Fasciolopsis buski
 Fasciola hepatica
 Clonorchis sinensis

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ANTIHELMINTIC DRUGS
BENZIMIDAZOLEs
1.ALBENDAZOLE:
 It possess broad-spectrum activity . It is the drug of
choice for treatment of
1. Hydatid disease and
2. Neurocysticercosis.
 It is also a major drug the treatment of (intestinal
nematodes) :
1. Ascariasis,
2. Trichuriasis,
3. Strongyloidiasis,
4. Enterobius vermicularis (pinworm),
5. Nector americanus, & Ancylostoma duodenale
(Hookworms) infections.
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Albendazole cont’d
Mechanism of action:

Inhibits microtubule synthesis and glucose uptake

It has larvicidal effects on hydatid disease, cysticercosis,
ascariasis, and hookworm infection.

Also, ovicidal in ascariasis , ancylostomiasis (hookworm),
trichuriasis
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Pharmacokinetics of Albendazole:

It is a benzimidazole carbamate

It is administered orally, and absorbed
erratically (unpredictable), absorption can be
increased with fatty meal.

It is metabolized in the liver rapidly to its
active metabolite albendazole sulphoxide. (1st
pass metabolism)
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Contnued
 It has a plasma half life of 8-12 hours


Sulphoxide is mostly (80%) protein bound ,
distributed to the tissues and enters the bile,
cerebrospinal fluid, and the hydatid cyst.
urinary excretion
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Clinical uses of albendazole:

It is administered on empty stomach when used
against intraluminal parasites but with fatty meal
when against tissue parasites.
1.
Ascariasis, trichuriasis, hookworm, pin worm
infection (intestinal):
Acheives 100% cure in pinworm infection and high
cure rates for others or marked reduction in eggs
counts.
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2. Hydatid diseases:
Drug of choice, with meals.
Bone cyst may require treatment for 1 year.

If patients are to be treated surgically, both
albendazole and praziquantel are used
preoperatively for one month to reduce cyst fluid
leakage. After surgery albandazole should be
continued for a whole month.
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Albendazole cont’d
Neurocysticercosis: It is the drug of choice.
It is effective for symptomatic parenchymal and
interventricular cysts. Less effective in arachnoid cyst.
It is superior to Praziquantel for neurocysticercosis for the
following:
3.

1.
2.
3.
4.
5.
4.
Shorter course of treatment.
It is cheaper
It is co-administeration with steroid increases its absorption
It is better in penetration arachnoid space..
It is also effective for ocular cysts.
Other infections: Drug of choice in cutaneous and visceral
larvea migrans , intestinal cappillariasis, microsporidial
infections, gnathostomiasis, trichinosis, clonorchiasis,
opisthorchiasis, toxocariasis, and loiasis.
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It is used along with cotricosteroid to decrease the
inflammation caused by dying organism, and it also
reduces the duration of course
 During the acute phase of cysticercotic
encephalitis, albandazole is contraindicated and
corticosteroid is indicated instead.
N.B:In intestinal nematodes, treatment in days
But in hydatid disease & Neurocysticercosis, the
treatment take longer duration

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Albendazole con’d
Adverse effects:

In short term use there is no significant adverse
effects.
In long term use: abdominal distress, headache,
fever, fatigue, alopecia , increased liver enzymes ,
pancytopenia. Blood counts and LFT should be
carried out regularly.
 Not given during pregnancy and in hypersensitive
people.
 Safety in children is not established in children
below 2 years of age.

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MEBENDAZOLE (Vermox)
it is a synthetic benzimidazole
 it has wider spectrum and is safe

Mechanism of action: Similar to albendazole
Effecacy influenced by: GI transit time, intensity
of infection, and strain of parasite.
It is also used to kill hook worm, pin worm , ascaris
and trichuris eggs.
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Mebendazole con’t
Pharmacokinetics:
Less than 10% of orally administered drug is absorbed
2. Absorption increases with fatty meals
3. Absorbed drug is 90% protein bound
4. It is converted to inactive metabolites rapidly in liver.
5. It has half life of 2-6 hours
6. It is primarily excreted in bile.
1.
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Mebendazole con’t
Clinical uses:

It is taken orally before or after meal, tablets should be
chewed before swallowing.

Ascaris lumricoides , trichuris trichura , hookworm and
trichstrongylus; It is useful drug in case of mixed infection
by these parasites.

in adults and children over 2 years cure rate is 90-100 %
except hookworm but a marked reduction in worm burden
occurs
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Mebendazole cont’d
Intestinal cappilliaris
 Trichinosis: It has limited efficacy against adult
worm.
 Corticosteroids coadministered in sever infection.

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Mebendazole con’d
Adverse effects and precautions:
1.
No adverse effects in short term therapy except for mild GI
disturbances.
2.
With high dose hypersensitivity reactions, agranulocytosis ,
alopecia, elevation of liver enzymes.
3.
Contraindicated in pregnancy.
4.
Used with caution under 2 years of age may cause convulsion in
this group.
5.
carbamazepine or phneytoin  ↓ conc. Cimetidine  ↑ conc.
6.
used with caution in cirrhosis
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Thiabendazole


It is benzimidazole. It is tasteless and insoluble in water.
It is a chelating agent and forms stable complexes with
metals including iron but does not bind with calcium.

It is rapidly absorbed orally

It has half life of 1.2 hrs

It is completely metabolized in liver and 90% is excreted in
urine

It can also get absorbed through the skin. Thus, could be
applied in creams.
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Thiabendazole con’d:

Mechanism of action: similar to other benzimidazoles.
It is ovicidal for some parasites.
 It also possesses immunosuppressive, antipyretic, and mild
antifungal and scabicidal (destroying the itch mite causing
scabies ) effects.

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Clinical uses:

Should be given after meals and tablets should be
chewed
For strongyloides (threadworms) infections:cure rate is
93%
 For cutaneous larval migrans thiabendazole cream is
effective and applied topically or given orally
 Also effective for intestinal capillariasis and scabiasis.

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Thiabendazole cont’d

1.
2.
3.
4.
5.
6.
Adverse reactions and contraindications:
It is more toxic than other benzamidazoles
GI disturbances
Pruritus, headache, drowsiness, neuropsychiatric symptoms
rarely may cause tinnitus, bradycardia, hypotension,
hyperglycemia, convulsions, neutropenia and other adverse
effects may occur.
Irreversible live failure.
Fatal Stevens–Johnson syndrome (inflammation of the skin)
Not used in children below the weight of 15 kg, during
pregnancy, hepatic and renal diseases.
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PYRANTEL PAMOATE







It is a broad-specturm antihelminthic
It is not effective against trichuriasis (whipworms) and
trichostrongylus orientalis infections, yet oxantel
pamoate is considered effective against trichuriasis. Both
drugs can be combined for their synergistic effect.
Pharmacokinetics:
It is poorly absorbed orally. Active mainly against
luminal organisms.
Half of the drug is excreted unchanged in the feces.
Mechanism of action:
It is a depolarizing neuromuscular blocking agent that
causes release of acetylcholine and inhibition of
cholinesterase leading to the paralysis of worms
followed by their expulsion from the GIT.
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Pyrantel pamoate (cont’d)
Efficacy and clinical uses:

it is very effective against mature and immature luminal
organisms, but not effective against migratory stages in
the tissues or against ova

Enterobius vermicularis (pinworm).

Ascaris lumbricoids (common roundworm)

Ancylostoma duodenale (hookworm) single dose for
light infection but a 3-day course is necessary for heavy
infection especially N americanus infection.
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Pyrantel pamoate cont’d:

Adverse effects are infrequent and mild.
GI disturbance
2. Drowsiness, headache ,insomnia.
3. Rash, fever
 Contraindications:
1. Should not be used in liver diseases.
2. Pregnancy
3. In children under 2 years of age
1.
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PIPERAZINE
Only used for the treatment of ascariasis.
 It is readily absorbed orally and excreted in urine


Mechanism of action:
It causes paralysis of ascaris by blocking
acetylcholine at the myoneural junction, expelling
the live worm by normal peristalsis.
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Piperazine cont’d

Treatment is continued for 3-4 days or
repeated after one week in case of heavy
infections.
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Piperazine cont’d
Adverse effects:
1. GI disturbances
2. Neurotoxicity, allergic reactions serum sickness
like syndrome
 Contraindications
1. Epilepsy or chronic neurologic disease
2. Impaired liver or kidney functions
3. Pregnancy
4. Malnutrition

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Drugs used for treating human intestinal nematodes
(single dose unless otherwise stated
Ascariasis
Hookworm
enterobius
tricuris
strongyloides
Piperazine
++
+
++
-
-
Pyrantel pa
++
++
++
-
-
Albendazole
++
++
++
+
+
Mebendazole
++
++
++
+
+
Thiabendazole
n/a
n/a
n/a
n/a
++
Ivermectin
n/a
n/a
n/a
n/a
++
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Drug treatment for tape worm(cestodes)
infection
Niclosamide
 Praziquantel
 Albendazole

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NICLOSAMIDE


It is useful for the treatment of adult tape worm
(cestodes) infestation
Mechanism of action:
Adult worm is rapidly killed by inhibition of the
oxidative phosphorylation or stimulation of ATPase
activity.
 has no effect on ova


Pharmacokinetics:
It is not absorbed from the gut
 Neither drug nor its metabolites are found in the
blood or urine.

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Niclosamide cont’d

A.





Clinical uses:
T. Saginata (Beef tape worm),T. solium (pork tapeworm), Diphyllobothrium
latum (fish tapeworm)
In case of T. solium after 2 hrs of treatment, purge of magnesium sulphate should be
given to eliminate all
mature segments.
Not effective against cysticercosis or hydatid disease. b/c
it’s not absorbed from the gut
Hymenolepis nana
H diminuta and Dipylidium caninum
Alternative for Fasciolopsis buski, Heterophyes heterophyes, Metagonimus
yokogawi.
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Niclosamide cont’d
Adverse effects:
 Mild, infrequent and transitory GI
disturbances
 Alcohol consumption should be avoided
 Not indicated in children under 2 years of
age or pregnancy.

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Diethylcarbamazine

The drug of choice for the treatment of filariasis,
loiasis and tropical eosinophilia.

Pharmacokinetics:

It is a synthetic derivative of piperazine
Rapidly absorbed from the gut
It has a half life of 2-3 hours which increases in
alkaline urine up to 10 hours.
Equilibrates with all tissues except fat
It is excreted in urine unchanged.
Dosage is reduced in urinary alkalosis and renal
impairment.





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DIETHYLCARBAMAZINE con’d
Mechanism of action:
 It immobilizes microfilariae in tissues and alters its
surface structure, making them more susceptible to
destruction by host defense mechanism




Unknown mechanism against adult worms
It also possesses an immunosuppressive effects
It has no teratogenic effects on experiment animals
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DIETHYLCARBAMAZINE con’d

It is a drug of choice for the treatment tissue cestodes,
W. bancrofti, B. malayi, B. timori, and Loa loa.

Microfiliariae are rapidly killed. Adult worms are killed
slowly requiring several courses of treatment. Adult worms
are either killed or sterilized.

It is highly effective against L. loa.
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DIETHYLCARBAMAZINE con’d

Anti histamines and corticosteroids are given in allergic
manifestations.

Complete Cure may be require several courses of treatment over 1-2
years.
The drug may be used in prophylaxis for loiasis, bancroftian, and
Malayan filariasis
 Tropical (pulmonary) eosinophilia
 Mansonella streptocerca

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DIETHYLCARBAMAZINE con’d
Drug induced/ Reactions induced by
Dying parasites:
 Fever , malaise, papular rash, headache,
GI disturbance, cough, chest, muscle, joint
pain
 Leukocytosis, proteinurea, ↑ eosinophilia
 Retinal hemorrhage
 Encephalopathy
 Lymphangitis and lymphadenopathy.

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DIETHYLCARBAMAZINE con’d

1.
2.
3.
4.
Contraindications and cautions
Hypertension
Renal disease
Patient suspected of having malaria
Patients with lymphangitis
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IVERMECTIN
It is the drug of choice for treatment of
strongyloidasis and onchocerciasis
 It is a macrocyclic lactone
 It is used orally and is rapidly absrobed,
possesses wide volume of distribution
about 50 L.
 It has a half-life of 16 hrs
 It is exclusively excreted in feces

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IVERMECTIN cont’d
Mechanism of action:
 It intensifies GABA –mediated
transmission of signals in peripheral
nerves  paralyzing the worm.
 In onchocerciasis it is microfilaricidal. It
does not kill the adult worm

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IVERMECTIN cont’d
Clinical uses:
 Onchocerciasis: with the 1st treatment,
patients with microfilariae in the cornea or
anterior chamber may be treated with
corticosteroid.

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IVERMECTIN cont’d
Strongyloidiasis: in immunosuppresed
patient, repeated treatment is often
needed.
 Bancrofti filaricidal: as it is mirofilaricidal
 It is also used for scabies, lice, and
cutaneous larva migrans.
 Eliminates adcarid worms
 Reduces microfilariae in Brugia malayi
and M ozzardi.

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IVERMECTIN cont’d

1.
2.
3.

1.
2.
3.
Adverse effects:
Fatigue
dizziness,
GI disturbance
In Onchocerciasis:
Mazotti reaction: fever, headache, dizziness,
somnolence (state of being drowsy), weekness,
rash ,diarrhea, arthralagia, hypotension,
lymphadenitis, peripheral edema due to killing of
microfiliariae, for this steroids may be necessary
for several days
Swelling and abscess at site of adult worm
Punctuate corneal opacities.
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IVERMECTIN con’d

1.
2.
3.
4.
Contraindication:
other drugs that enhance GABA activity
e.g Barbiturates, bnezodiazepines,
valproic acid.
pregnancy
Impaired blood brain barrier
Children under 5 years of age.
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BITHIONOL

It is the drug of choice for the treatment of
fascioliasis (sheep liver fluke)
It is also used as an alternative for praziquantel
in treating pulmonary paragonimiasis
 Repeat doses in case of cerebral
paragonimiasis.

Pharmacokinetics:
 It is orally administered and excreted in urine.

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BITHIONOL

1.
2.
3.

1.
2.
3.
Adverse effects:
GI disturbance
Dizziness,headache
Pruriuts ,urticaria,Leucopenia
Contraindications and precautions:
hepatitis,
leucopenia
Used with caution under 8 years of age.
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