ANTIPARASITICS Flashcards Preview

•Amebiasis (amebic dysentery) is an intestinal tract

infection caused by Entamoeba histolytica

• GI disease can be acute or chronic
• Infection can be symptomatic or latent

•Symptoms can range from mild diarrhea to fulminating dysentery

• E.Histolytica exists in two forms
(1) cysts (can survive outside body)
(2) trophozoites (do not survive outside body)

• Trophozoites are liberated from ingested cysts within the intestinal lumen

• Liberated trophozoites migrate to the large intestine where they multiply and invade the intestinal mucosa.

•Trophozoites can enter bloodstream to result in a systemic invasion

• Life cycle completes by trophozoites returning to the cyst

form in the rectum and being expelled in the feces

1) Eliminate invading trophozoites

&
2) Eradicate intestinal carriage of the organism

ANTIAMEBICS: 

• Luminal
Act on parasite in bowel lumen

• Systemic
Active both in intestinal wall and liver

• Mixed
Active against both luminal & systemic disease

METRONIDAZOLE

TINIDAZOLE

MOA:

• Once absorbed, metronidazole is non-enzymatically

reduced by reacting with reduced FERREDOXIN

• This reduction causes the production of cytotoxic compounds

• The cytotoxic compounds bind to proteins & DNA, resulting in unstable molecules and cell death

MIXED LUMINAL + SYSTEMIC AGENT

PK: 

• Oral

• Well distributed (inc. vaginal & seminal fluids, saliva, breast milk & CSF)

• Undergoes hepatic oxidation & glucuronidation (CYP P450’s)

AE: 

• GI distress
• ***Disulfiram-like reaction*** (avoid alcohol intake)

• Unpleasant metallic taste
• Oral moniliasis
• Dark coloration of urine
• Leukopenia, dizziness, ataxia.
• Safety in pregnancy NOT established*****

MIXED LUMINAL + SYSTEMIC AGENT

• 2nd generation nitroimidazole

• Similar to metronidazole but better tolerated and has shorter treatment course

Clinical Applications

• Amebiasis
• Amebic liver abscess

• Giardiasis
• Trichomoniasis

AE:

• Same as metronidazole but reports indicate shorter duration of effects with tinidazole

• 1) Diloxanide furoate

• 2) Iodoquinol

• 3) Paromomycin

• Used as sole agent for treatment of ASYMPTOMATIC AMEBIASIS 

• Converted in gut to active form

Adverse Effects

• Mild (GI distress)

Not currently available in US – however remains

luminal amebicide of choice

LUMINAL AGENT (ANTIAMEBIC)

• Orally active against luminal trophozoite and cyst forms of E.histolytica

• Used as an alternative to diloxanide furoate for mild- severe infections

Adverse Effects

• Rash, diarrhea, dose-related ***peripheral neuropathy**** (exam Q) 

• Long term use should be avoided (due to risk of optic neuritis)***

LUMINAL ANTIAMEBIC

• Aminoglycoside antibiotic
• Effective only against luminal forms of E.histolytica and tapeworm
•Sometimes used with tetracyclines for mild intestinal

disease
• Alternative agent for cryptosporidiosis in AIDS patient

MOE/AE: 

• AmebiCIDAL (causes cell membranes to leak)

• Interferes with bacterial protein synthesis (binds to 30S ribosomal subunits)

• Reduces intestinal flora population

Adverse Effects

• GI distress & diarrhea

• Systemic absorption may lead to headaches, dizziness, rashes and arthralgia

1) CHLOROQUINE

2) EMETINE

3) DEHYDROEMETINE

-useful for treating liver abscesses or intestinal wall infections 

SYSTEMIC ANTIAMEBIC

• Used in combination with

1. metronidazole & ("mixed" luminal and systemic agent)
2. diloxanide furoate (luminal agent) 

MOA

• Eliminates trophozoites in liver abscesses

SYSTEMIC ANTIAMEBIC

• BACKUP DRUGS for treatment of SEVERE intestinal or hepatic amebiasis

• Used in combination with a luminal agent

MOA

• Inhibit protein synthesis by blocking ribosomal movement along messenger RNA

PK: 

• IM or SC
• Concentrate in liver (persists for 1 month)

• Slowly metabolized & eliminated

• Pain at site of injection****** on exam!!! 
• Transient nausea
• Cardiotoxicity
• Neuromuscular weakness

• Dizziness

• Rash

DOC: 

1) DILOXANIDE FUROATE

ALTERNATIVE DRUG(S):

1) IODOQUINOL

2) PAROMOMYCIN

DOC: 

1) METRONIDAZOLE AND

2) DILOXANIDE FUROATE

ALTERNATIVE DRUGS:

1) Tinidazole OR

2) Tetracycline OR

3) Erythromycin + diloxanide furoate

DOC: 

1) METRONIDAZOLE OR TINIDAZOLE 

AND

2) DILOXANIDE FUROATE

ALTERNATIVE DRUGS: 

1) Tetracycline OR Emetine OR Dihydroemetine 

AND

2) DILOXANIDE FUROATE

DOC:

1) METRONIDAZOLE OR TINIDAZOLE

AND

2) DILOXANIDE FUROATE

Alterative drugs: 

1) Emetine OR Dihydroemetine 

AND

2) Chloroquine

AND

3) Diloxanide Furoate

Nematodes

• Elongated roundworms that possess a complete digestive system.

• Cause infections of intestine as well as blood & tissue.

Trematodes

• Leaf-shaped flatworms generally characterized by tissues they infect: liver, intestinal, blood flukes

Cestodes

• Flat, segmented body which attach to host’s intestine

• Lack mouth & digestive system throughout life cycle

• In most cases broad spectrum agents cure or control most human worm infections

• Some systemic infections only respond partially to

antihelminthic drugs (cysticercosis, echinococcosis,

filariasis, trichinosis)

Antihelminthic drugs can act either:

• locally (to expel worms from GI tract) or,

• systemically (to eradicate adult helminths or developmental forms)

ANTIHELMINTHICS

1) ALBENDAZOLE

2) MEBENDAZOLE

3) THIABENDAZOLE 

NOTE: ALL are CATEGORY C and CONTRINDICATED IN PREGNANCY!!!! 

BENZIMIDAZOLE - an ANTIHELMINTHIC DRUG

• Used in the treatment of CESTODE infestations, such as

1. cysticercosis (Taenia solium larvae) and
2. hydatid disease (Echinococcus granulosis)

MOA

• Inhibits microtubule synthesis & glucose uptake

• ATP production is decreased resulting in worm immobilization and death

PK: 

• Oral (erratically absorbed, enhanced by high-fat meal)

• Extensive first-pass metabolism, including rapid sulfoxidation to active metabolite

•Short course therapy (1-3 days) = mild & transient (headache, nausea)

• ****HYDATID treatment (3 months) = risk of hepatotoxicity, agranulocytosis or pancytopenia**************

• Treatment is associated with inflammatory responses to dying parasites in CNS******* (headache, vomiting, hyperthermia, convulsions, mental changes)

• Contraindicated in pregnancy & children < 2y (FDA Category C)

BENZIMIDAZOLE - ANTIHELMINTHIC DRUG

Drug of choice in the treatment of infections by:

• 1) Whipworm (Trichuris trichiura) (in tunnel) pig with spirals on his suit

• 2) Pin worm (Enterobius vermicularis) (in tunnel, "vermin lady" who's first character introduced, going into the hole)

• 3) Hookworms (Necator americanus & Ancylostoma duodenale) (in tunnel, is american dude swinging) 

• 4) Roundworm (Ascariasis lumbricoides) (in tunnel, huge lumbering tree man in back) 

BENZIMIDAZOLE (Antihelminthic drug)

• Inhibits formation of helminth microtubules

• Irreversibly blocks glucose uptake
• Affected parasites are expelled with feces

Pharmacokinetics

• Oral (chewable) – nearly insoluble in aqueous solution, take with high-fat meal

• Undergoes first-pass metabolism to inactive compounds

• Abdominal pain, diarrhea, headache, dizziness

• Contraindicated in pregnancy (FDA Category C)

• Use with caution in children < 2

• Use with caution in patients with cirrhosis