Antiparasites Flashcards
Antamebics
- Luminal: Act on parasite in bowel lumen
- Systemic: Active both in intestinal wall and liver
- Mixed: Active against both luminal & systemic disease
- metro & tinidazole
Metronidazole
- Amebicide of choice for treating invasive amebiasis
- Patients should receive a luminal amebicide in addition after treatment with metronidazole
Other Clinical Applications
- Giardia lamblia
- Trichomonas vaginalis
- Anaerobic cocci
- Anaerobic Gram-negative bacilli
- Combination regimens for H.pylori eradication
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
PK
- Oral
- Well distributed (inc. vaginal & seminal fluids, saliva, breast milk & CSF)
- Undergoes hepatic oxidation & glucuronidation (CYP P450’s)
Metro - Adverse
- 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
Tinidazole
- 2nd generation nitroimidazole
- Similar to metronidazole but better tolerated and has shorter treatment course
Clinical Applications
- Amebiasis
- Amebic liver abscess
- Giardiasis
- Trichomoniasis
Tinidazole - Adverse
Same as metronidazole but reports indicate shorter duration of effects with tinidazole
Luminal antiamebics
- Diloxanide furoate
- Iodoquinol
- Paromomycin
Diloaxanide furoate
- Used as sole agent for treatment of asymptomatic amebiasis
- Converted in gut to diloxanide freebase active form
- Adverse Effects: Mild (GI distress)
- Not currently available in US – however remains luminal amebicide of choice
Iodoquinol
- Orally active against luminal trophozoite and cyst forms of E.histolytica
- Used as an alternative to diloxanide furoate for mild- severe infections
Iodoquinol - Adverse
- Rash, diarrhea, dose-related peripheral neuropathy
- Long term use should be avoided (due to risk of optic neuritis)
Paromomycin including Adverse
- 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
- 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
Systemic antiamebics
- Chloroquine
- Emetine
- Dehydroemetine
- Useful for treating liver abscesses or intestinal wall infections
Chloroquine
- Used in combination with metronidazole & diloxanide furoate
- **Indication: **severe intestinal infection w E. Histolytica
- MOA: Eliminates trophozoites in liver abscesses
Emetine and Dihydroemetine
- 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
Emetine and Dihydroemetine - Adverse
- Pain at site of injection
- Transient nausea
- Cardiotoxicity
- Neuromuscular weakness
- Dizziness
- Rash
Amebiasis Rx
- Asymptomatic, intestinal infection: Diloxanide furoate
- Mild-moderate intestinal infection: Metronidazole + diloxanide furoate
- Severe intestinal infection: metro or tinidazole + diloxanide furoate
- Hepatic abscess & other extraintestinal disease: Metronidazole or tinidazole + diloxanide furoate
Antihelminthics durgs
- Nematode
- Trematode
- Cestode
- 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)
Benzimidazoles
- Albendazole
- Mebendazole
- Thiabendazole
Albendazole
Used in the treatment of cestodal infestations, such as cysticercosis (Taenia solium larvae) and 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
Albendazole - Adverse
- 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)
Mebendazole
Drug of choice in the treatment of infections by (will treat most infections):
- Whipworm (Trichuris trichiura)
- Pin worm (Enterobius vermicularis)
- Hookworms (Necator americanus & Ancylostoma duodenale)
- Roundworm (Ascariasis lumbricoides)
MOA
- 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
Mebendazole - Adverse
- Abdominal pain, diarrhea, headache, dizziness
- Contraindicated in pregnancy (FDA Category C)
- Use with caution in children < 2
- Use with caution in patients with cirrhosis
Thiabendazole
Effective in treatment of strongyloidiasis caused by Strongyloides stercoralis (threadworm), cutaneous larva migrans, and early stages of trichinosis
MOA: Affects microtubular aggregation
Pharmacokinetics
- Oral
- Nearly insoluble in H20
Thiabendazole - Adverse
- More toxic than other benzimidazoles
- Dizziness, anorexia, nausea, vomiting
- CNS disturbances (dizziness -> seizures)
- Cases of erythema multiforme & Stevens-Johnson reported
- Contraindicated in pregnancy (FDA Category C)
- Should not be used in presence of liver or kidney disease
Ivermectin
Drug of choice for the treatment of onchocerciasis (Onchocerca volvulus), cutaneous larva migrans & strongyloides
MOA
- GABA agonist
- Cl- influx increases leading to hyperpolarization of nerve /muscle cell. Death occurs due to paralysis of parasite
Pharmacokinetics: Oral (does not cross BBB)
Ivermectin - Adverse
- Mazotti-like reactions with onchoceriasis (fever, dizziness, somnolence, hypotension)
- Contraindicated in pregnancy (FDA Category C)
- Contraindicated in meningitis (may cross BBB)
- Best to avoid concomitant use of ivermectin & other drugs that enhance GABAergic activity (eg, barbiturates, benzodiazepines)
Piperazine
Alternative drug for treatment of pinworm & roundworm infections
MOA
- GABA agonist
- Expulsion of worm occurs by peristalsis
Contraindications: Patients with seizure disorders
Pyrantel Pamoate including Adverse
Effective in treatment of infections by roundworms, pinworms and hookworms
MOA: Acts as a depolarizing, neuromuscular-blocker (causes persistent activation of parasite’s nicotinic receptors by release of acetylcholine & inhibition of cholinesterase)
PK: Poorly absorbed orally (exerts effects in intestinal tract)
**Adverse: **Mild (nausea, vomiting, diarrhea)
Diethylcarbamazine
DOC for treatment of lymphatic filariasis, loiasis & tropical eosinophilia.
MOA: Immobilizes microfilariae & renders them susceptible to host defense mechanisms
**PK: **Oral (rapidly absorbed with meals)
Diethylcarbamazine - Adverse
- Most AE thought to be due to host responses following damage/death of parasite
- Fever, malaise, rash, myalgias, arthralgias, headache
- Leukocytosis (common)
- Antihistamines or steroids can be coadministered
Doxycycline - MOA
- Tetracycline antibiotic.
- Macrofilaricidal activity against Wuchereria bancrofti.
- Also active against onchocerciasis
- MOA: Acts indirectly by killing Wolbachia (intracellular bacterial symbiont of filarial parasites)
Praziquantal
DOC for all forms of schistosomiasis & most trematode & cestode infections
Cysticercosis – albendazole is drug of choice (praziquantel has similar efficacy)
MOA: Increases permeability of cell membrane to calcium, causing contracture & paralysis of worm musculature, resulting in detachment of suckers from blood vessel walls.
**PK: **
- Oral
- Extensive first-pass metabolism (CYPs)
- Inactive metabolites excreted via urine & bile
Praziquantal - Adverse
- Drowsiness, dizziness, malaise, anorexia & GI upsets
- Drug interactions (CYP P450)
- Contraindicated in pregnancy & nursing mothers (FDA Category B)
- Contraindicated for treatment of ocular cysticercosis (destruction of organism may damage eye)
Bithionol
- Drug of choice for fasciolosis (sheep liver fluke)
- Alternative drug for pulmonary paragonimiasis
- MOA: Inhibition of helminth’s electron transport chain (probably)
Niclosamide
- 2nd line drug for treatment of most cestode infections
- Use is uncommon due to excellent efficacy of praziquantel
- No longer available in US
MOA
- Inhibition of the parasite’s mitochondrial phosphorylation of ADP. Anaerobic metabolism may also be inhibited
- Drug is lethal for cestode’s scolex & segments of cestodes but not for the ova
PK
- Laxative is admin. prior to niclosamide (oral) to purge bowel of all dead segments in order to preclude digestions & liberation of ova (may lead to cysticercosis)
- Alcohol should be avoided within 1 day of dose
- Safety has not been established in pregnancy or children <2
