Treatment of protozoal and helmenths

Treatment of Amoebiais and Giardiasis

 Treatment of Amebiasis

• Amebiasis (Amebic dysentery) is an infection of the intestinal

tract caused by Entamoeba histolytica.

• Classification of amebicidal drugs

• Mixed amebicides (metronidazole and tinidazole)
• Luminal amebicides (iodoquinol, paromomycin)
• Systemic amebicides
 Mixed amebicides
1. Metrinidazole:
 a nitroimidazole, kills the E. histolytica trophozoites.
 Mechanism of action:
 The nitro group of metronidazole is able to serve as an
electron acceptor, forming reduced cytotoxic compounds
that bind to proteins and DNA, resulting in cell death.

 completely and rapidly absorbed after oral administration

Use:
 amebiasis, giardiasis, trichomoniasis and
 Anaerobic bacteria which are typically sensitive are primarily Gram-
negative anaerobes belonging to the Bacteroides and Fusobacterium
spp.
 hence used to treat infections of the reproductive system, GIT, skin,

.
heart, bone, joint, lung, blood, nervous system, and other areas of the
body and sexually transmitted diseases (STDs).
 It is an option for a first episode of mild-to-moderate Clostridium difficile
colitis if vancomycin or fidaxomicin is unavailable

 ADE:
 Disulfiram-like rxn
 nausea, vomiting, epigastric distress,
 abdominal cramps.
 unpleasant, metallic taste

2. Tinidazole:
 a second-generation nitroimidazole that is similar to metronidazole in
spectrum of activity (It is used as an antiprotozoal &antibacterial agent)

 Tinidazole has the potential of being a more efficacious drug based on

 its longer half-life and its seemingly superior side effect profile as compared to oral
metronidazole.
 Luminal Amoebicides
1. Iodoquinol:
 Halogenated 8-hydroxy quinolone

 effective against the luminal trophozoite and cyst forms.

 Unknown M.O.A
 Side effects
 rash, diarrhea, and dose-related peripheral neuropathy,
including a rare optic neuritis.

 Long-term use of this drug should be avoided.

2. Paromomycin
:
An aminoglycoside antibiotic that causes protozoal cell
membraine leakage.
• Po. b/c Not significantly absorbed from GIT, exhibits luminal
effect.
– ADR. GI distress, diarrhea
3. Diloxanide furoate
• an effective luminal amebicide but is not active against tissue
trophozoites
• Oral route
• DOC for asymptomatic cysts form
Side Effects
• Flatuletnce ,Dry mouth, Pruritus,Uticaria
 Systemic amebicides
• These drugs are useful for treating liver abscesses or intestinal wall
infections caused by amebas.

a. Chloroquine:
• used in combination with metronidazole and diloxanide furoate to treat
and prevent amoebic liver abscesses.

b. Emetine and dehydroemetine

• an alkaloid derived from ipecac
• effective against tissue trophozoites of E. histolytica,
• but because of major toxicity concerns they have been almost
completely replaced by metronidazole.

• inhibit protein synthesis by blocking chain elongation

ADR
• pain at the site of injection, transient nausea, cardiotoxicity,
neuromuscular weakness, dizziness, and rashes.
 Giardiasis
• Giardia lamblia
– The treatment of choice is metronidazole for 5 days.

– One alternative agent is tinidazole, which is equally

effective as metronidazole in treatment of giardiasis but
with a much shorter course of treatment (2 g given once).

– Nitazoxanide, a nitrothiazole derivative structurally similar

to aspirin, was recently approved for treatment of
giardiasis.

– Nitazoxanide is also equally efficacious as metronidazole

and, in comparison, has a 2 day shorter course of therapy.
 Drugs for Trypanosomiasis
• Caused by Tryponosoma, vector tsetse fly
• Tryponosoma cruzi- American sleeping sickness
• T. brucei- African trypanosomiasis (sleeping sickness)
• Drugs:
– MELARSOPROL
– PENTAMIDINE
– SURAMIN
– NIFURTIMOX
 Melarsoprol

• a trivalent arsenical
• M.O.A- Inhibits sulfhydril groups in parasitic enzymes.
– IV or oral route
• DOC- for tt of African sleeping sickness with CNS involvement
• ADE:
• Encephalopathy
• GI distress
• Hypersensitivity reactions
• Hemolytic anemia
• C/I influenza
 Suramin
• Inhibits enzymes involved in energy metablolism.
– Iv
• Tt and prophylaxis of early stages of African
trypanosomiasis.
• DOC for Onchocerca volvulus
• ADE:
• Albuninuria
• Rash
• GI distress
• Uritcaria
• Neurological complications
• shock
 Leshmaniasis

• Caused by Leismania, vector : sandfly

Drugs :Sodium stibogluconate (pentostam)
 Through inhibition of glycolysis at the phosphofructokinase
reaction.
 Parenteral adminstration.
 Side effects
 Pain at site of injection, GI distress, Cardiac arrhythmias.
 Alternatives:
 Pentamidine- Visceral leshma.
 Metronidazole- cutaneous lesions
 Amphotericine B- mucocutaneous
Chemotherapy of Helminthes
 Classifications
• Nematodes (round Flat worms
worms) • Trematodes (flukes)
• Diethylcarbamaxine – praziqunatel
• Ivermectin
• Mebendazole
• Pyrental pamoate • Cestodes (tapeworms)
• Thiabendazole – Albendazole
– Niclosamide
 Mebndazole
• Is the drug of choice for
• Pinworm (enterobius vermicularis)
• Whipworm (trichuris trichiura)
• Hookworm (necator americanus0
• Roundworm (ascaris lumbricoides)
• Interferes with the synthesis of parasite microtubules
and decrease glucose uptake.
• Adminstration. Po
• C/I: Pregnancy
• ADE:
• GI distarbances (N,V)
• Intrahepatic cholestasis
 Pyrantel pamoate
 effective in the treatment of infections caused by
 roundworms, pinworms, and hookworms
 poorly absorbed orally and exerts its effects in the intestinal
tract.
 MOA. acts as a depolarizing, neuromuscular-blocking agent,
causing persistent activation of the parasite's nicotinic
receptors.
 The paralyzed worm is then expelled from the host's
intestinal tract

 Adverse effects are mild and include nausea, vomiting, and

diarrhea
 Praziquantel
• Trematode infections are generally treated with Praziquantel

• agent of choice for the treatment of

– all forms of schistosomiasis and other trematode
infections and
– for cestode infections like cysticercosis

• MOA. Permeability of the cell membrane to calcium is

increased, causing contracture and paralysis of the parasite.
• rapidly absorbed after oral administration

• Common adverse effects

– drowsiness, dizziness, malaise, and anorexia, as well as
gastrointestinal upsets
 Niclosamide
• Drug of choice for most cestode (tapeworm) infections
• MOA
– inhibition of the parasite's mitochondrial phosphorylation of
adenosine diphospate, which produces usable energy in the
form of adenosine triphospate.

• Alcohol should be avoided within 1 day of niclosamide

ADR: GI disturbance, headache and fever.

 Albendazole
Benzimidazole
• MOA. inhibits microtubule synthesis and glucose uptake
in nematodes
• treatment of cestodal infestations, such as
– cysticercosis (caused by Taenia solium larvae) and
– hydatid disease (caused by Echinococcus granulosis).
• Albendazole is erratically absorbed after oral
administration, but absorption is enhanced by a high-fat
meal.
• Side effect: Headache, nausea and dizziness.