Chapter 53 Benzimidazoles - act against nematodes by

inhibiting microtubule synthesis

Clinical Pharmacology of the Antihelminthic
Drugs Albendazole also has larvicidal effects in:

a. hydatid disease
b. cysticercosis
CHEMOTHERAPY OF HELMINTHIC INFECTIONS
c. ascariasis
Helminths (worms) - are multicellular organisms d. hookworm infection
that infect very large numbers of humans and
Albendazole also has larvicidal effects in:
cause a broad range of diseases
a. ascariasis
Note: complete elimination of parasites is the
b. ancylostomiasis
goal of therapy
c. trichuriasis

ALBENDAZOLE
Clinical Uses
Albendazole - a broad-spectrum oral
Note: Albendazole is administered on an empty
antihelminthic
stomach when used against intraluminal
 drug of choice and is approved in the parasites but with a fatty meal when used
USA for treatment of hydatid disease against tissue parasites
and cysticercosis

Albendazole is also used for the treatment of: 1. Ascariasis, trichuriasis, and hookworm
and pinworm infections - For adults and
a. pinworm and hookworm infections children older than 2 years with
b. ascariasis ascariasis and pinworm infections;
c. trichuriasis single dose of 400 mg orally
d. strongyloidiasis  For hookworm infections and
trichuriasis; albendazole at 400 mg
orally once daily for 3 days
Basic Pharmacology

Note: Albendazole is a benzimidazole 2. Hydatid disease - Albendazole is the

carbamate treatment of choice for medical therapy
and is a useful adjunct to surgical
Process of Albendazole: removal or aspiration of cysts
 more active against Echinococcus
→ erratically absorbed
oral administration granulosus than against Echinococcus
→ first-pass metabolism in the liver → multilocularis
 Dosing is 400 mg twice daily with meals
active metabolite albendazole sulfoxide
for 1 month or longer
sulfoxide - mostly protein-bound, distributes
well to tissues, and enters bile, cerebrospinal 3. Neurocysticercosis – therapy is
fluid, and hydatid cysts probably most appropriate for
 symptomatic parenchymal or Note: The drug should not be given to
intraventricular cysts patients with known hypersensitivity to
 Albendazole is given in a dosage of 400 other benzimidazole drugs or to those with
mg twice daily for up to 21 days cirrhosis

 The safety of albendazole in

4. Other infections—
pregnancy and in children younger
Albendazole is the drug of choice in the
than 2 years has not been
treatment of:
established
 cutaneous larva migrans (400 mg daily
for 3 days) BITHIONOL
 visceral larva migrans (400 mg twice
Bithionol - an alternative to triclabendazole for
daily for 5 days)
the treatment of fascioliasis (sheep liver fluke)
 intestinal capillariasis (400 mg daily for
and an alternative to praziquantel for the
10 days)
treatment of paragonimiasis
 microsporidial infections (400 mg twice
daily for 2 weeks or longer) Basic Pharmacology & Clinical Uses
 gnathostomiasis (400 mg twice daily for
3 weeks) - For treatment of paragonimiasis and
fascioliasis, the dosage of bithionol is
 taeniasis (400 mg daily for 3 days)
30–50 mg/kg in two or three divided
 trichinosis (400 mg twice daily for 1–2
doses, given orally after meals on
weeks)
alternate days for 10–15 doses
 clonorchiasis (400 mg twice daily for 1
- pulmonary paragonimiasis, cure rates
week)
are over 90%
Note: Albendazole has been recommended as
Adverse Reactions, Contraindications, &
empiric therapy to treat those who return from
Cautions
the tropics with persistent unexplained
eosinophilia Note: Bithionol should be used with caution in
children younger than 8 years because there
has been limited experience in this age group.
Adverse Reactions, Contraindications, &
Adverse effects (occurs in 40% of patients,
Cautions
generally mild and transient):
Note: When used for 1–3 days, albendazole is
a. diarrhea
nearly free of significant adverse effects
b. abdominal cramps
Possible adverse effects of Albendazole: c. anorexia
d. nausea
a. Mild and transient epigastric distress
e. vomiting
b. Diarrhea
f. dizziness
c. Headache
g. headache
d. Nausea
h. Skin rashes
e. Dizziness
f. Lassitude Skin rashes - a reaction to antigens released
g. Insomnia from dying worms
DIETHYLCARBAMAZINE CITRATE  Lymphatic filariasis is treated with 2
mg/kg three times a day for 12 days
Diethylcarbamazine - a drug of choice in the
treatment of filariasis, loiasis, and tropical Note: Antihistamines may be given for the first
eosinophilia few days of therapy to limit allergic reactions,
and corticosteroids should be started and doses
Note: It has been replaced by ivermectin for the
of diethylcarbamazine lowered or interrupted if
treatment of onchocerciasis
severe reactions occur
Basic Pharmacology
Apheresis - to remove microfilariae before
Diethylcarbamazine - a synthetic piperazine treatment with diethycarbamazine
derivative
therapy with albendazole - slower acting and
 plasma half-life is 2–3 hours in the better tolerated, followed by therapy with
presence of acidic urine but about diethylcarbamazine or ivermectin
10 hours if the urine is alkaline
2. Other uses –
(Henderson-Hasselbalch trapping
 tropical eosinophilia,
effect)
diethylcarbamazine is given orally at a
 immobilizes microfilariae and alters
dosage of 2 mg/kg three times daily for
their surface structure
2–3 weeks
Henderson-Hasselbalch trapping effect -  Mansonella streptocerca infections
developed independently by the American  reduce the prevalence of W bancrofti
biological chemist L. J. Henderson and the infection
Swedish physiologist K. A. Hasselbalch, for
relating the pH to the bicarbonate buffer
system of the blood Adverse Reactions, Contraindications, &
Note: The mode of action against adult worms Cautions
is unknown Note: Adverse effects also occur as a result of
Clinical Uses the release of proteins from dying microfilariae
or adult worms
Note: The drug should be taken after meals
Reactions to diethylcarbamazine (which are
1. Wuchereria bancrofti, Brugia malayi, generally mild and transient):
Brugia timori, and Loa loa -
Diethylcarbamazine is the drug of a. headache
choice for treatment of infections with b. malaise
these parasites because of its efficacy c. anorexia
and lack of serious toxicity d. weakness
 Microfilariae of all species are e. nausea
rapidly killed f. vomiting
 adult parasites are killed more g. dizziness
slowly Note: Patients with attacks of lymphangitis due
 effective against adult L loa to W bancrofti or B malayi should be treated
 W bancrofti and B malayi adults are during a quiescent period between attacks.
killed
  Caution is advised when using
diethylcarbamazine in patients with
hypertension or renal disease

DOXYCYCLINE

Doxycycline – a tetracycline antibiotic

 shown to have significant

macrofilaricidal activity against W
bancrofti, suggesting better activity
than any other available drug against
adult worms
 may prove to be an important drug for
filariasis, both for treatment of active
disease and in mass chemotherapy
campaigns

Wolbachia - an intracellular bacterial symbiont

of filarial parasites

IVERMECTIN

Ivermectin - the drug of choice in

strongyloidiasis and onchocerciasis, also an
alternative drug for a number of other
helminthic infections

Basic Pharmacology

Ivermectin - semisynthetic macrocyclic lactone

derived from the soil actinomycete
Streptomyces avermitilis, is a mixture of
avermectin B1a and B1b

Note: Ivermectin is available only for oral

administration in humans