Antiparasitic Drugs Flashcards
Amebiasis (amebic dysentery) is an intestinal tract infection caused by what?
Entamoeba Histolytica
–symptoms range from mild diarrhea to fulminating dysentery
Entamoeba Histolytica exists in two forms:
- Cysts: can survive outside body
2. Trophozoites: do not survive outside body
What are the goals of therapy for Entamoeba Histolytica?
Eliminiate invading trophozoites
Eradicate intestinal carriage of the organism
What are the different classes of antiamebics?
Luminal (Acts on parasite in bowel lumen)
Systemic (active both in intestinal wall and liver)
Mixed
The first mixed antiamebic is metronidazole. What are some features?
Amebicide of choice for treating invasive amebiasis
–patients should receive a luminal amebicide in addition after treatments with metronidazole
What is the MOA of metronidazole?
Once absorbed, metronidazole is non enzymatically reduced by reacting with reduced ferredoxin
–this reduction causes the production of cytotoxic compounds
What are the pharmacokinetics for metronidazole?
Oral
Well absorbed in vaginal and seminal fluid, saliva, breast milk and CSF
Undergoes hepatic oxidation and glucuronidation
What are the adverse effects of metronidazole?
GI distress
Disulfiram like reaction (Avoid alcohol)
Do not use in pregos
The second mixed anti-amebic is Tinidazole. What are some features?
Similar to metro but better tolerated and has shorter treatment course but more expensive
-same AE has metro but shorter duration of effects
There are three luminal anti-amebics. The first is Diloxanide Furoate. What are some features?
Used as sole agent for tx of asymptomatic amebiasis
–converted in gut to diloxanide freebase active form.
Not available in the US
The second luminal anti-amebic is Iodoquinol. What are some features?
Orally active against luminal trophozoite and cyst forms of E. histolytica
–avoid long term used due to optic neuritis
The third luminal anti-amebic is Paromomycin. What are some features?
Aminoglycoside antibiotic
Effective only against luminal forms of E. histolytica and tapeworm
Alternative agent for cryptosporidiosis in AIDS patients
What is the MOA and AE for paromomycin?
Amebicidal (Causes cell membranes to leak)
Interferes with bacterial protein synthesis
Reduces intestinal flora production
GI distress and diarrhea
Moving on to the systemic anti-amebics, the first is Chloroquine. What are some features?
Used in combo with metro and diloxanide furoate
eliminates trophozoites in liver abscesses
The next two systemic anti-amebics are Emetine and Dihydroemetine. What are some features?
Backup drugs for tx of severe intestinal or hepatic amebiasis Used in combo with a luminal agent Given IM or SQ Concentrate in liver AE: pain at injection site
Moving on to the Helminths what does this include?
- Nematodes: elongated roundworms that possess a complete digestive system
- Trematodes: leaf-shaped flatworms generally characterized by tissues they infect: liver, intestinal, blood flukes
What are some features of anti-helminthic drugs?
In most cases broad spectrum agents cure or control most human worm infections
Drugs either act:
–locally (to expel worms from GI tract)
or
–systemically (to eradicate adult helminths or developmental forms)
First up for the anti-helminthic drugs are the Benzimidazoles. The first drug is Albendazole what are some features?
Used in tx of cestodal infestations (such as cysticercosis and hydatid disease)
MOA:
–inhibits microtubule synthesis and glucose uptake
–ATP production is decreased resulting in worm immobilization and death
What are the pharmacokinetics and AE for albendazole?
Oral (erractically absorbed and enhanced by high fat meal)
Extensive first pass metabolism, including rapid sulfoxidation to active metabolite
AE:
–short course therapy (1-3 days)
–Hydatid treatment (3 months)
–tx is associated with inflammatory responses to dying parasites in CNS (Convulsions and mental changes)
–contraindicated in pregnancy and children less than 2y.
The next anti-helminthic drug is Mebendazole. It is the drug of choice in the treatment of infections by?
Whipworm (Trichuris Trichiura)
Pin Worm (Enterobius vermicularis)
Hookworm (Necator americanus & Ancylostoma Duodenale)
Roundworm (Ascariasis Lumbricoides)
What is the MOA and Pharmacokinetics for Mebendazole?
Inhibits formation of helminth microtubules
Irreversibly blocks glucose uptake
Affected parasites are expelled with feces
PK (pharmacokinetics)
–oral (Chewable): take with high fat meal
–undergoes first pass metabolism
What are the adverse effects with mebendazole?
Contraindicated in pregos
Use with caution in kids less than 2
Use in caution in patients with cirrhosis
The next anti-helminthic drug is Thiabendazole. What are some features?
Effective in tx of strongyloidiasis caused by Strongyloides Stercoralis (threadworm), cutaneous larva migrans, and early stages of trichinosis PK: --oral and insoluble in H20 AE: --more toxic then other benzimidazoles --CNS disturbances --Contraindicated in pregos
The next set of drugs are anti-helminthic drugs but not Benzimidazoles. The first is ivermectin, what are some features?
Drug of choice for the tx of onchocerciasis, cutaneous larva migrans and strongyloides
MOA:
–GABA agonist
Does not cross BBB
AE:
–Mazotti-like reactions with onchoceriasis
Contraindicated in pregnancy
Contraindicated in meningitis
Dont use ivermectin with drugs that enhance GABAergic activity
Next anti-helminthic drug is Piperazine, what are some features?
Alternative drug for tx of pinworm and roundworm infections
GABA agonist
Dont give in patients with seizure disorder
Next anti-helminthic drug is Pyrantel Pamoate, what are some features?
Effective in tx of infections by roundworms, pinworms and hookworms
MOA:
–acts as a depolarizing, neuromuscular blocker
Next anti-helminthic drug is Diethylcarbamazine. What are some features?
Drug of choice for tx of lymphatic filariasis, loiasis and tropical eosinophilia
MOA:
–immobilizes microfilariae
AE:
–thought to be due to host responses following death/damage of parasite
Next anti-helminthic drug is Doxycycline. what are some features?
Tetracycline antibiotic
Macrofilaricidal activity against Wuchereria Bancrofti
Also active against onchocerciasis
Next Anti-helminthic drug is Praziquantel. What are some features?
Drug of choice for all forms of schistosomiasis and most trematode and cestode infections
MOA:
—increases permeability of cell membrane to calcium causing contracture and paralysis of worm
PK:
–extensive first pass metabolism
AE:
—drug interactions (CYP P450)
–contraindicated in pregos and nursing mothers
–contraindicated for tx of ocular cysticerosis
Next Anti-helminthic drug is Bithionol. What are some features?
Drug of choice for fasciolosis (sheep liver fluke)
The last anti-helminthic drug is Niclosamide. What are some features?
2nd line drug for tx of most cestode infections
Use is uncommon due to excellent efficacy of praziquantel
PK:
–laxative is administered prior to niclosamide (oral) to purse bowel of all dead segments in order to preclude digestion and liberation of ova
-no pregos or kids under 2
