Level 2
Semester 4
Module : Gastrointestinal system, liver, Nutrition& Metabolism(GLNM411)
Instructor information
▪ Contact: Rehab M. Elshahat
▪ Department: pharmacology
▪ Official email: rehab@azhar.edu.eg
▪ Mobile: 01006833432
74- Antiparasitic drugs I
(Antiprotozoal)
A-Therapeutic agents for amebiasis
I-Luminal: (e.g Iodoquinol, Diloxanide & Paromomycin)
act on the parasite in the lumen of the bowel
II-Systemic amebicides : (e.g Chloroquine & Emetine)
are effective against ameba in the intestinal
wall and liver
III-Mixed amebicides : (e.g Metronidazole, Tinidazole &Ornidazole)
are effective against both the luminal and the systemic forms of the
disease, although luminal concentrations are too low for single-drug
treatment
I-Luminal amebicides
1-Iodoquinol: is amebicidal against E. histolytica and is effective against the luminal
trophozoite and cyst forms.
Adverse effects:
1. GIT (should be taken with meals )
2. Dose-related peripheral neuropathy, including a rare optic neuritis.
3. They cause green stools and pruritis
It should be used with caution in patients with optic neuropathy, renal or
thyroid discase.
➢ Iodoquinol should be discontinued if it produces persistent diarrhea or
signs of iodine toxicity (dermatitis, urticaria, pruritus, fever).
➢ It is contraindicated in patients with intolerance to iodine.
2-Diloxanide
➢
Diloxanide is a luminal agent have a direct amoebicidal action,
affecting the parasites before encystment.
➢ Diloxanide, the drugs of choice for the asymptomatic intestinal
infected patient and are often given as a follow-up after the disease
has been reversed with metronidazole.
➢ Diloxanide furoate with metronidazole used in treating amoebic
hepatitis
➢ Diloxanide furoate is given orally and acts without being absorbed.
➢ Unwanted GI or other effects may be seen but it has an excellent
safety profile.
3-Paromomycin: an aminoglycoside antibiotic.
➢
➢
Paromomycin is only effective against the luminal forms of E.
histolytica, because it is not significantly absorbed from the
gastrointestinal tract.
Paromomycin is directly amoebicidal
➢ Adverse effects: gastrointestinal distress and diarrhea.
➢ Used with metronidazole for the treatment of amebic colitis and
amebic liver abscess.
II-Systemic amebicides
These drugs are useful for treating extraintestinal amebiasis, such as
liver abscesses, and for treating intestinal wall infections
Chloroquine:
Uses:
a. Treatment of amebic liver abscesses in combination with
metronidazole
b. In case of intolerance to nitroimidazoles
It eliminates trophozoites in liver abscesses.
Therapy should be followed with a luminal amebicide.
Chloroquine is also effective in the treatment of malaria
2. Emetine & Dehydroemetine: Emetine, an alkaloid derived from ipecac,
and dehydroemetine , a synthetic analog.
➢ Are effective against tissue trophozoites of E. histolytica, but
because of major toxicity concerns their use is limited to unusual
circumstances in which severe amebiasis requires effective therapy
and metronidazole cannot be used .
➢
Dehydroemetine is preferred because of its somewhat better toxicity
profile. The drugs should be used for the minimum period needed
to relieve severe symptoms (usually 3-5 days) administered SC
(preferred) or IM in a supervised setting.
Adverse effects: which are generally mild with use for 3-5 days, increase
over time and include:
1-Pain, tenderness , and sterile abscesses at the injection site.
2- GIT: diarrhea, nausea, and vomiting.
3-Muscle weakness and discomfort.
4-Minor electrocardiographic changes.
5-Serious toxicities include cardiac arrhythmias , heart failure,
and hypotension.
N.B The drugs should not be used in patients with cardiac or renal
disease, in young children, or in pregnancy unless necessary.
III-Mixed amebicides:
1-Metronidazole:
The drug of choice for treating amebic infections.
Pharmacokinetics:
Absorption: is completely and rapidly absorbed after oral administration.
Distributes well throughout body tissues and fluids.
Therapeutic levels can be found in vaginal and seminal fluids, saliva, breast milk,
and cerebrospinal fluid (CSF).
Metabolism by hepatic oxidation of so,
the drug accumulates in patients with severe hepatic disease
Excretion : the parent drug and its metabolites are excreted in the urine.
Pharmacodynamics:
Mechanism of action:
It targets DNA and by forming reduced
cytotoxic compounds that bind to DNA
and protein resulting in death of the
E. histolytica trophozoites.
Metronidazole is also used in the treatment of infections caused by:
Giardia lamblia, Trichomonas vaginalis, anaerobic cocci, anaerobic gramnegative bacilli and anaerobic gram-positive bacilli .
N.B: For the treatment of amebiasis, it is usually administered with a
luminal amebicide, such as iodoquinol or paromomycin. This
combination provides cure rates of greater than 90%.
Adverse effects:
The most common adverse effects are
1- GIT: Nausea, vomiting, epigastric distress,
and abdominal cramps
2- An unpleasant, metallic taste is due to the
excretion of metabolites in the saliva.
3- Other effects include oral moniliasis
4- Rarely, neurotoxicity (dizziness, vertigo, and
numbness or paresthesia), which may
necessitate discontinuation of the drug.
5- If taken with alcohol, a disulfiram-like reaction
may occur
2-Tinidazole: is a second-generation nitroimidazole that is have similar
activity, and better toxicity profile than metronidazole.
Can be administered as a single dose of 2 g in adults and at a dose of 30 to
50 mg/kg in children.
3-Ornidazole:
The spectrum and mechanism of ornidazole are like those of
metronidazole. And is reported to have longer t1/2 like tinidazole, therefore,
for chronic intestinal amoebiasis and asymptomatic cyst passers.
Ornidazole is used at a dose of 0.5 g twice daily for 5 to 7 days.
85- Antiparasitic drugs
Anti-helminthics
➢
Nematodes:
Mebendazole & Albendazole
Pyrantel pamoate
Ivermectin
Thiabendazole
➢
Cestodes: Niclosamide & Albendazole
➢
Trematodes: Praziquantel
1-Mebendazole &Albendazole
It is a first-line agent for the treatment of
infections caused by:
whipworms, Pinworms, Hookworms and Roundworms
Pharmacokinetics: minimal absorption,
➢ Less than 10% of orally administered drug is absorbed
➢ The absorbed drug is bound to pp and rapid converted to inactive
metabolites its t ½ 2-6 hs
➢ 75-90% is passed unabsorbed in the faeces,
Mechanism of action:
Act by inhibiting microtubule synthesis.
➢ Its bind with parasite β-tubulin and inhibiting microtubule
polymerization in the parasite.
➢ It blocks glucose uptake in parasite and depletes its glycogen stores
➢ Affected parasites are expelled in the feces.
Adverse effects
Abdominal pain, nausea ,vomiting , and diarrhea.
N.B: Mebendazole should not be used in pregnant women.
2-Pyrantel pamoate
is also effective in the treatment of infections caused by
roundworms, pinworms, and hookworms
Pharmacokinetics: is poorly absorbed after oral administration
and is only effective against intestinal infections.
Mechanism: It acts as a depolarizing, neuromuscular-blocking agent,
causing release of acetylcholine and inhibition of cholinesterase, leading
to paralysis of the worm and subsequent expulsion.
Adverse effects: are mild GIT disturbance
Nausea , vomiting, and diarrhea.
3-Ivermectin
is the drug of choice for the treatment of cutaneous larva migrans,
strongyloidiasis, and onchocerciasis
Mechanism of action:
➢ Ivermectin targets the glutamate-gated chloride channel receptors.
Chloride influx is enhanced, and hyperpolarization occurs , resulting in
paralysis and death of the worm.
➢ The drug is given orally and does not readily cross the blood–brain
barrier.
Adverse effects:
➢ Itching, dizziness, headache, hypotension , tachycardia, myalgia,
arthralgia, and facial and peripheral edema
Treatment : glucocorticoid therapy.
➢
The killing of the microfilaria in onchocerciasis can result in a
dangerous Mazzotti reaction (fever , headache, dizziness, somnolence,
and hypotension).
The severity of this reaction is related to parasite load.
Antihistaminic or steroids maybe given to ameliorate the symptoms
Treatment Of
Cestodes
Albendazole
Its primary therapeutic application, however, is in the treatment of cestode
infestations, such as cysticercosis and hydatid disease
Pharmacokinetics: Albendazole is irregularly absorbed after oral
administration, but absorption is enhanced by a high-fat meal.
It undergoes extensive first-pass metabolism in the liver, and its metabolites
are primarily excreted in the bile.
Mechanism of action:
-Albendazole, inhibits microtubule synthesis and glucose uptake in
nematodes. As mebendazole
Uses:
Drug of choice for neurocysticercosis
Drug of choice for nematodes (round worm)
Adverse effects
When used in short-course therapy (1 to 3 days) for nematodal
infestations are mild and transient and include:
➢ Headache and nausea.
➢ Treatment of hydatid disease (3 months) has a risk of hepatotoxicity
and, rarely, agranulocytosis or pancytopenia.
➢ Medical treatment of neurocysticercosis is associated with
inflammatory responses to dying parasites in the CNS, including
headache, vomiting, fever, and seizures.
Treatment Of
Trematodes
Praziquantel
It is an agent of choice for the treatment of all forms of
schistosomiasis, other trematode infections, and cestode infections such as
taeniasis.
Pharmacokinetic:
It is rapidly absorbed after oral administration and should be taken with food.
The drug is extensively metabolized, and the inactive metabolites are excreted
primarily in the urine.
Mechanism:
Praziquantel causes contracture and paralysis of parasites by increasing the
permeability of the cell membrane to calcium.
Adverse effects :
dizziness, malaise , and headache as well as gastrointestinal upset
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