ANTIHELMINTHICS AND

ANTIAMOEBIC CHEMOTHERAPY
BLOCK 11 | LECTURE 2 by Dr. J. Abellar | 12/03/19

I. MYTHS, BELIEFS, FACTS •

•
Vomiting
Dizziness
A. MYTHS AND BELIEFS
• Hallucination
• Do not deworm during full moon, bad weather or rainy days
• Convulsions
• Patients to be dewormed at night will not be allowed to eat
• Cholestasis
prior
CASE STUDY
B. FACTS
• Do not deworm when patient is weak or having febrile illness
• Ipil-ipil seeds, pineapple and papaya have deworming
properties
• Some studies have shown that they are effective
• Routine deworming without fecalysis can be done starting 1
year of age in endemic areas

II. ANTIHELMINTHICS
• Anthelmintics or antihelminthics
→ group of antiparasitic drugs that expel parasitic worms
(helminths) and other internal parasites from the body by
either stunning or killing them and without causing
significant damage to the host
→ In developing world, goal is to:
o control infection,
o eliminate most parasites,
o alleviate disease symptoms, • The skin condition above is known as cutaneous larva migrans.
o decrease transmission of infection • One of the presentations of strongyloidiasis.
→ In some cases, goal is completely eradicate the disease • From cats or dogs
• Refer to Appendix for table on Drugs for the Treatment of • Management is primarily through the use of thiabendazole.
Major Helminthic Infections
B. MEBENDAZOLE
A. THIABENDAZOLE • Synthetic benzimidazole
• Benzimidazole compound • Wide spectrum drug with low incidence of adverse effects
• First line drug for (DOC): • First line drug for:
→ Strongyloides → Trichuris
→ Creeping Eruption → Enterobius (Pinworm)
→ Toxocara (Visceral Larva Migrans) o Nocturnal itchiness is pathognomonic for
• Although from Katzung: enterobiasis
→ Alternative drug to Ivermectin or Albendazole for: → Ascaris
o Strongyloides → Trichinella
o Creeping Eruption o Administered together with steroids
▪ (topical thiabendazole or the oral drug can be → Capillaria
given for 2 days) → Hookworm
• Contraindicated in: pregnancy, liver or renal diseases → Mixed parasitism
• Ovicidal and kills both larvae and adult worms
MECHANISM OF ACTION • Not given to pregnant women and children 2 years old and
Suppresses microtubule assembly below because of its teratogenic effect
↓
Inhibits secretion of parasite acetylcholinesterase Mechanism Of Action
↓ • Inhibits microtubule synthesis (Katzung)
Dislodgement of worm
Depletes energy stores
Side Effects ↓
• Anorexia Disrupts cytoskeletal transport
• Headache

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Side Effects • Monitor blood counts and liver function for prolonged
• Not significant because of poor absorption treatment (abdominal distress, fever, fatugue, alopecia,
• Transient abdominal pain and diarrhea in massive infestation pancytopenia, increase in liver enzymes)
• In high doses: • Absorption erratic:
→ Systemic manifestation → If tissue parasite, taken with fatty meal because there is
o Allergic reactions enhanced drug distribution to tissues
o Alopecia → If against intraluminal parasites, taken on empty stomach
o Agranulocytopenia
o Neutropenia Clinical Uses
o Hypospermia • Heavy Ascaris infection
→ 400 mg single dose for 2-3 days
Case Study • Pinworm infection
→ 400 mg single dose for 2 weeks
• Echinococcus granulosis and multilocularis
→ 400 mg twice daily (with meals) for 1 month
• Trichuriasis
→ 400 mg thrice daily
• Useful adjunct for surgical removal/aspiration of cyst
• Controversial and may exacerbate disease in
neurocysticercosis
→ 400 mg twice daily for 21 days

FROM DVS TRANS

Basic Pharmacology
• A benzimidazole carbamate
• Erratically absorbed
• Metabolized in liver to active metabolite albendazole
sulfoxide that enters bile, cerebrospinal fluid, and hydatid
cysts
• Excreted in urine
• Plasma level peaks in 3 hours (400-mg dose)
• Half-life is 8–12 hours
• Inhibits microtubule synthesis
• The rectal exam shows rectal prolapse in a child with massive • Larvicidal in:
trichuriasis → Hydatid disease, cysticercosis, ascariasis, and hookworm
• Also seen on the prolapsed rectum are numerous male and infection
female Trichuris clinging to the rectal mucosa • Ovicidal in:
• Management of the condition is primarily surgical and is → Ascariasis, ancylostomiasis, and trichuriasis
coupled with Mebendazole.
Side Effects
C. ALBENDAZOLE • Free of adverse effects
• A broad-spectrum oral antihelminthic → 1-3 days
• First line of drug for: • Hydatid disease:
→ Neurocysticercosis → Well-tolerated, abdominal distress, headaches, fever,
o For symptomatic parenchymal or interventricular fatigue, alopecia, increases in liver enzymes, and
cysts with steroid pancytopenia
o Superior to praziquantel • Not preferred in pregnancy or children <2 years old
o If mutlple cysts – albendazole + praziquantel • Not used in benzimidazole hypersensitivity or cirrhosis
→ Echinococcosis
o Medical therapy and adjunct to surgical removal or
aspiration cysts
D. PYRANTEL POMOATE
• According to Katzung, this drug also treats:
• A tetrahydropyrimidine derivative
→ Pinworm and hookworm infestation
• Indicated for:
→ Ascariasis, trichuriasis, strongyloides
→ Hookworm
→ Cutaneous and visceral larva migrans → Pinworm
→ Roundworm
Reactions
→ Trichostrongylus
• Mild and transient: epigastric distress, diarrhea, headache,
• Must be used with Oxantel to be effective against Trichuris
nausea, dizziness, lassitude and insomnia

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Mechanism Of Action → Approach should be:

Depolarizing neuromuscular blocking agent by release of o Pretreatment with steroids or slowly increasing the
acetylcholine and inhibition of cholineterase dosage to desired level or discontinue temporarily
↓
FROM DVS TRANS
Spastic paralysis
DIETHYLCARBAMAZINE CITRATE
↓
• Drug of choice in:
Detachment from host
→ Filariasis
↓
o Commonly causes enlargement of testes in
Expulsion by host peristalsis
males
→ Microfilariae of Onchocerca
• Not used together with piperazine because of antagonistic
o Not used in adult worm
action
o Commonly affects the eyes
→ Piperazine causes hyperpolarization that leads to
• Kills adult worms of Loa loa and Wuchereria
relaxation
Basic Pharmacology
Side Effects
• A synthetic piperazine derivative
• Poorly absorbed, headache, dizziness, rash, fever, mild GI
• Marketed as citrate salt
symptoms
• Rapidly absorbed
• Used with caution in those with liver dysfunction
• Plasma level peaks in 1-2 hours
• Limited experience in pregnant and < 2 y.o
• Half-life is 2-3 hours in acidic urine
• From DVS trans:
• Half-life is 10 hours in alkaline urine
→ Headache
→ Henderson-Hasselbalch trapping effect
→ Dizziness
• Excreted in urine as unchanged drug and N-oxide
→ Rash
metabolite
→ Fever
→ Mild gastrointestinal symptoms
Clinical Uses
• Given after meals
E. DIETHYLCARBAMAZINE CITRATE
• Given in the quiescent period in W. bancrofti or Brugia
• A synthetic piperazine derivative
malayi infection
• Drug of choice for:
• Dosage:
→ Filariasis
→ 50 mg or 1 mg/kg in children for day 1
→ Loiasis
→ 50 mg thrice for day 2
→ Trophical eosinophilia
→ 100 mg or 2 mg/kg in children for day 3
• Has been replaced by Ivermectin in the treatment of
→ 2 mg/kg thrice for W. bancrofti, B. malayi, B. timori
onchocerciasis (Katzung).
and L. loa
→ 2 mg/kg thrice daily for 7 days for tropical
MECHANISM OF ACTION
eosinophilia
• Immobilizes microfilariae → decrease in muscular activity
• Chemoprophylaxis:
• Alters surface membranes rendering destruction by host
→ 300 mg weekly or 300 mg in 3 successive days per
defense mechanism
month for loiasis
• Kills microfilaria of all species in the blood but not in the
→ 50 mg monthly for bancroftian/malayan filariasis
nodules of Onchocerca
• Kills adults worms but slowly needing several courses
Side Effects
• Leukocytosis is common
SIDE EFFECTS
• Mild in W. bancrofti
• Rapidly absorbed
• More intense in B. malayi
• Reduce doses in patients with renal impairment
• Severe in L. loa
• Reactions:
• Adverse effects are from dying microfilariae or adult
→ Mild and transient headache, malasie, anorexia, vomiting,
• worms
weakness, dizziness
• Days 3-12:
→ To microfilariae: fever, malasie, joint pain, muscle pai,
→ Lymphangitis with localized swellings in W. bancrofti
cough, chest pain, leukocytosis, eosinophilia
and B. malayi
• Antihistamines limit allergic reactions
→ Small wheals in L. loa
• Presence of severe reactions:
→ Use corticosteroids or lower/ interrupt doses F. IVERMECTIN
• Associated with MAZOTTI REACTION • Best against Onchocerciasis and Strongyloides
→ Intense itching, skin rashes, enlargemnet and tenderness • Kills microfilariae but little harm to adult worm
of nodes, fever, tachycardia, and arthralgia that occurs → Surgical incision of Onchocerca nodules is
within a few hours after treatment of onchocerciasis with recommended before treatment
diethylcarbamazine due to massive destruction of worms
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• Used with corticosteroids fort those with microfilariae in the
cornea and anterior chamber to avoid inflammatory reaxcion
• Used in mass treatment
Mechanism Of Action
• Toxic paralysis by release and binding of GABA
Side Effects
• Neurotoxicity in patients with renal dysfunction, mild
gastrointestinal upset, transient neurologic effects, and
urticarial
• Contraindicated in pregnant, impaired renal/liver function,
history of epilepsy or chronic neurologic diseases

Side Effects I. PRAZIQUANTEL

• Reactions: • An isoquinoline-pyrazine derivative
→ For strongyloidiasis: mild • Choice for all forms of Schistosomiasis and other
→ For onchocerca: fever, headache, diziness, rash, muscle/ trematodes and cestodes
joint pain, somnolence lymphangitis, hypotension • From DVS trans:
lymphadenitis, tachycardia → Better cure rate than niclosamide for Hymenolepsis nana
• Avoid use with barbiturates, benzodiazepines and valproic → Vacuolization and vesiculation of the parasites’ tegument
acid leads to destruction

G. NICLOSAMIDE Mechanism Of Action

• Drug of choice for: • Alters integumental permeability to Calcium → muscular
→ Cestodes spasticity→ dislodgement
→ Tapeworms • Effective against adult worms, immature stage and
• Use in T. solium predisposes the patient to cysticercosis prophylactic effect against cercaria
→ Digestion of dead segments liberates walled ova into the • Use of corticosteroids limits inflammatory response from
lumen dying worms
→ Niclosamide does not kill the ova
• Cysticercosis can be prevented by: Side Effects
→ Adequate purging within 3-4 hours after giving the drug • Should be swallowed not chewed + bitter taste
which clears the bowel of the dead segments before • Leads to wretching/ vomiting
being digested • Reactions: transient abdominal pain, nausea, malasie,
→ Use of praziquantel rather than niclosamide headache, urticaria, arthalgia, and dizziness
→ When treating cysticercus cellulosae, Przaiquantel or • Several days after intake: fever, rashes, eosinophilia, pruritus
Albendazole si the drug of choice due to proteins from dying worms
• If not used in conjuction with steroids:
Mechanism Of Action → Neurologic abnormalities have been observed (headache,
• Inhibits anaerobic phosphorylation of mitochondria seizure, metal changes)
• Kills proximal worm segments and scolex but not the ova → THO CONTROVERSIAL because steroids decrease level of
praziquantel
Side Effects
• Well tolerated except for mild gastrointestinal upset J. OXAMNIQUINE
• Alternative drug of praziquantel for Schistosoma mansonii
H. PIPERAZINE CITRATE • Not effective for:
• Choice for intestinal obstruction secondary to Ascariasis → S. japonicum
• Useful for ascariasis and pinworms → S. haematobium
• Decompression and maintenance fluids and electrolytes must
also be done K. BIOTHIONOL
• Alternative for paragonimiasis (lung fluke) and fascioliasis
Mechanism Of Action (liver flukes)
• Advantage in ascariasis: • Mild reaction
Hyperpolarization
↓ L. METRIFONATE
Relaxation • It inhibits cholinesterases (organophosphate)
↓ • Effective only for Schistosoma haematobium
Flaccid paralysis • Mixed infection of S. haematobium and S. mansoni =
↓ metrifonate + oxamniquine
Decreased motility
↓
Prevents erratic migration
III. IMPORTANT POINTS ON
• NOTE: Pyrantel pamoate causes spastic paralysis HELMINTH INFECTIONS
→ Possible erratic migration • Ascariasis
→ In highly prevalent areas, deworming can be done 3 times
a year or every 4 months
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•
→ Single dose is effective
Enterobiasis
VI.CHEMOTHERAPY FOR AMEBIASIS
A. LUMINAL AMEBICIDES
→ Tendency for familial occurrence
• Drugs effective in luminal infections only
→ All members of household should be treated if there is
• Dichloroacetamides
reinfection or if another member is symptomatic
→ Diloxanide furoate
→ Treatment should be repeated after 2 weeks because
→ Etofamide
eggs are hatched
• Halogenated hydroxyquinolines
o There is danger of autoinfection
→ Idoquinol (diiodohydroxyquine)
• Hookworm infection
• Antibiotics
→ Blood loss of 0.5 ml/worm
→ Tetracyclines
→ Treat for possible anemia (hypochromatic, microcytic)
→ Paromomycin
• Trichuriasis
• Oral bismuth salt
→ Also consider possible anemia although blood loss is not
→ Emetine bismuth iodide
as severe as in hookworm infection
• Dracuncolosis
Diloxanide Furoate
→ Manual removal of worm + metronidazole
• Drug of choice for asymptomatic cyst passers
• Polyparasitic or Mixed infection
• Destroys the trophozoites of E. hystolytica that eventually
→ Mebendazole/albendazole/ pyrantel
form into cysts
• Laboratory follow up is needed to ensure total eradication
→ Stool exam is done 2 weeks after deworming
Etofamide
• Preventive measures
• Acts principally on the bowel lumen with actions and uses
→ Hygiene
similar to diloxanide furoate
→ Handwashing
• Adverse drug reactions:
→ Avoid street foods
→ Flatulence
→ Cover food against insects
→ Vomiting
→ Proper food sanitation and handling
→ Urticarial
→ Use of clean toilet
→ Pruritus

IV. CHARACTERISTICS OF AN IDEAL FROM DVS TRANS

ANTIPARASITIC AGENT • Adverse drug reactions:
→ Flatulence (common)
• Safe at high therapeutic doses
→ Nausea
• Easily given preferably by oral route in single or divided doses
→ Abdominal cramps
on the same day
→ Rashes
• Chemically stable for long periods under climatic conditions
of use
• Ineffective as an inducer of drug resistance
• Inexpensive Iodoquinol
• Recommended as an intestinal amebicide and for
asymptomatic carriers
V. PHILIPPINE DEWORMING SOCIETY • Caused an epidemic of subacute myelooptic neuropathy
RECOMMENDATION ON
Tetracycline
DEWORMING • Avoid using in children less than 8 years old
• Routine deworming at 1 year of age and above at least every • Can cause staining of teeth
6 months
→ Mebendazole 500 mg for 1 year and above Paromomycin
→ Albendazole 200 mg for 1-2 years old • An aminoglycoside
→ Albendazole 400 mg for older than 2 years • Not significantly absorbed
→ Diethylcarbamazine + albendazole for mass • Alternative drug for diloxanide in asymptomatic carriers
treatment of filariasis
o Eradication program starts at children 2 years of age Mechanism of Action
• Contraindications • Amebicidal by causing leakage of cell membrane and by
→ Abdominal pain reducing population of intestinal flora like Tetracycline
→ Profuse diarrhea → Intestinal flora gives food to the amoeba-causing
→ Severe malnutrition microbes
→ High grade fever
→ Previous hypersensitivity reaction to antihelminthic drug
→ Serious illness

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B. EXTRA-LUMINAL AMEBICIDES
FROM DVS TRANS
• Systemic or tissue amebicides (not effective for luminal
amebicides) • Side effects:
→ Chloroquine → Nausea
→ Emetines: Emetine, Dehydroemetine → Vomiting
• Mixed amebicides → Epigastric distress
→ Drugs effective in systemic and intestinal amebiasis (not → Abdominal cramps
reliably effective against luminal infections as luminal → Metallic taste
concentrations are too low for single drug treatment) → Dizziness/vertigo
→ Nitroimidazoles → Numbness
o Metronidazole
o Tinidazole
o Seconidazole CASE STUDY #3
• If you have extraluminal amoebiasis, there is a high chance • A 3 year-old boy was admitted because of diarrhea for 3 days.
that you also have luminal amoebiasis. The stool was described as watery, foul smelling, greenish,
mucoid and admixed with blood streaks. There was associated
Chloroquine abdominal pain, fever, vomiting and tenesmus. PE revealed
• Used to eliminate trophozoites in liver abscesses like emetine sunken eyeballs, cold skin and diffuse abdominal tenderness.
and dehydroemetine → Yellowish to greenish, foul-smelling, blood-streaked,
• Effective for extra-intestinal amebiasis mucoid stools are usually indicative of amoebiasis
→ Microscopic examination may reveal macrophages that
Emetine and Dehydroemetine look similar with amoeba
• Alternative agents → The presence of blood is suggestive of possible ulceration
• Mechanism of action: inhibit protein synthesis by blocking which means that an inflammatory form of dysentery may
translocation of peptide chain be present
• Intramuscular is the preferred route → Tenesmus means that evacuation is gradual and not
• Used in amebic abscess explosive
• Emetine → Metronidazole is the drug of choice
→ Concentrates in the liver and persists for a month after a o Both luminal and systemic, together with emetine,
single dose dehydroemetine and fluoroquine
→ Limited use due to toxicity o Some are resistant to metronidazole already so we
• Dehydroemetine must know the alternative drugs
→ Less toxic o We must have an idea of what to give if it is only a
• Adverse drug reactions: luminal or extraluminal infection
→ Pain at injection site
→ Nausea CASE STUDY #4
→ Cardiotoxicity
• A 25 year-old man was seen at the ER because of right upper
→ Neuromuscular weakness
quadrant pain for a week. He had on-and-off fever associated
→ Dizziness
with weight loss and poor intake. PE revealed tender and
→ Rashes
enlarged liver with slight icteresia. UTZ of hepatobiliary area
showed an echo-free area at the right lobe of the liver.
Metronidazole
→ An anchovy sauce presentation indicates that the stool is
• Toxic for amoeba, anaerobic organisms, giardia and
dark brown or similar to chocolate in color
trichomonas
o Based on the presentation, it is most likely amoebic
• Choice for symptomatic and invasive amebiasis although
→ The presence of an abscess can lead to rupture of the
effective against cysts and trophozoites
lungs and pleural effusion
→ Amoeba can go to the liver causing colitis, diarrhea or
Mechanism of action:
dysentery symptoms
• Nitro group serves as an electron acceptor and binds to → Drug of choice is metronidazole
protozoan’s ferrodoxin (electron transport proteins)
→ Reduced product is cytotoxic Tinidazole
→ Targets DNA and other biomolecules/proteins resulting in • A second generation nitroimidazole
cell death • Congener of metronidazole
• Impairs the ability of DNA to function as a template → Similar in spectrum of activity, mode of action,
o Distributed well throughout the body tissues and absorption, A/E, D/I
fluids • Effective against cysts of E. hystolytica
• Longer acting (once daily dose)
• Short course – 2 mg daily, single dose—for 3 days

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Metronidazole or Tinidazole 6. Mode of action paralysis by release and binding of GABA

• A nitroimidazole a. Ivermectin
• Drug of choice for extraluminal amebiasis b. Praziquantel
c. Albendazole
• Kills trophozoites but not cysts
d. Niclosamide
• Acute intestinal amebiasis/ amebic colitis with dysentery
→ 10 day course with luminal amebicide (not reliability 7. It is low cost and safe alternative drug for Schistosoma
against parasites in lumen) haematobium infections
• Hepatic amebiasis a. Praziquantel
→ 10 day course cures 95% cases b. Diethylcarbamazine citrate
→ If initial therapy fails, aspiration of abscess and addition of c. Metrifonate
chloroquine/ dihydroemetine or emetine d. Niclosamide
• Readily absorbed and permeate all tissues
• Side effects: 8. Mode of action is thru inhibition of microtubule synthesis
→ Nausea, vomit, epigastric distress, abdominal cramps, except
diarrhea, metallic taste, dizziness, vertigo, numbness, dark a. Mebendazole
b. Praziquantel
urine, pancreatitis
c. Thiabendazole
→ (+) disulfram reaction with alcohol d. Albendazole

Seconidazole 9. These drugs are not effective for luminal infection

• Longer acting a. Dichloroacetamides
→ Single 2 mg dose b. Systemic amebicides
c. Halogenated hydroquinolines
d. Oral bismuth salt
REVIEW QUESTIONS
1. It must be used with Oxantel to be effective against Trichuris 10. Routine deworming at __________
a. Pyrantel Pamoate a. 1 year of age and below at least every 6 months
b. 1 year of age and above at least every 6 months
b. Diethylcarbamazine Citrate
c. 6 years of age and below at least every 1 month
c. Ivermectin d. 6 years of age and above at least every 1 month
d. Piperazine Citrate

2. Characteristics of an Ideal Antiparasitic Agent, except:

a. Effective as an inducer of drug resistance A, A, A, A, B, A, C, B, B
b. Easily given preferably by oral route in single or divided
doses on the same day
c. Chemically stable for long periods under climatic REFERENCES
conditions of use 1. Katzung, BG. Basic & Clinical Pharmacology. 14th ed. Chapter
d. Inexpensive 53: Clinical Pharmacology of the Antihelminthic Drugs.
2. WVSU-MED 2021. Antihelminthics.
3. Associated with the Mazotti reaction
a. Diethylcarbamazine Citrate
b. Mebendazole
c. Albendazole
d. Pyrantel Pamoate

4. Mechanism of action is Toxic paralysis by release and binding

of GABA
a. Ivermectin
b. Praziquantel
c. ALlbendazole
d. Niclosamide

5. If you have extra-luminal amoebiasis you have a low chance

of also having luminal amoebiasis
a. True
b. False
c. Slightly True
d. Maybe False

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