Antiparasitic Drugs

Question 1

Amebiasis (amebic dysentery) is an intestinal tract infection caused by what?

Answer 1

Entamoeba Histolytica

–symptoms range from mild diarrhea to fulminating dysentery

Question 2

Entamoeba Histolytica exists in two forms:

Answer 2

1. Cysts: can survive outside body

2. Trophozoites: do not survive outside body

Question 3

What are the goals of therapy for Entamoeba Histolytica?

Answer 3

Eliminiate invading trophozoites

Eradicate intestinal carriage of the organism

Question 4

What are the different classes of antiamebics?

Answer 4

Luminal (Acts on parasite in bowel lumen)
Systemic (active both in intestinal wall and liver)
Mixed

Question 5

The first mixed antiamebic is metronidazole. What are some features?

Answer 5

Amebicide of choice for treating invasive amebiasis

–patients should receive a luminal amebicide in addition after treatments with metronidazole

Question 6

What is the MOA of metronidazole?

Answer 6

Once absorbed, metronidazole is non enzymatically reduced by reacting with reduced ferredoxin
–this reduction causes the production of cytotoxic compounds

Question 7

What are the pharmacokinetics for metronidazole?

Answer 7

Oral
Well absorbed in vaginal and seminal fluid, saliva, breast milk and CSF
Undergoes hepatic oxidation and glucuronidation

Question 8

What are the adverse effects of metronidazole?

Answer 8

GI distress
Disulfiram like reaction (Avoid alcohol)
Do not use in pregos

Question 9

The second mixed anti-amebic is Tinidazole. What are some features?

Answer 9

Similar to metro but better tolerated and has shorter treatment course but more expensive
-same AE has metro but shorter duration of effects

Question 10

There are three luminal anti-amebics. The first is Diloxanide Furoate. What are some features?

Answer 10

Used as sole agent for tx of asymptomatic amebiasis
–converted in gut to diloxanide freebase active form.
Not available in the US

Question 11

The second luminal anti-amebic is Iodoquinol. What are some features?

Answer 11

Orally active against luminal trophozoite and cyst forms of E. histolytica
–avoid long term used due to optic neuritis

Question 12

The third luminal anti-amebic is Paromomycin. What are some features?

Answer 12

Aminoglycoside antibiotic
Effective only against luminal forms of E. histolytica and tapeworm
Alternative agent for cryptosporidiosis in AIDS patients

Question 13

What is the MOA and AE for paromomycin?

Answer 13

Amebicidal (Causes cell membranes to leak)
Interferes with bacterial protein synthesis
Reduces intestinal flora production
GI distress and diarrhea

Question 14

Moving on to the systemic anti-amebics, the first is Chloroquine. What are some features?

Answer 14

Used in combo with metro and diloxanide furoate

eliminates trophozoites in liver abscesses

Question 15

The next two systemic anti-amebics are Emetine and Dihydroemetine. What are some features?

Answer 15

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

Question 16

Moving on to the Helminths what does this include?

Answer 16

1. Nematodes: elongated roundworms that possess a complete digestive system
2. Trematodes: leaf-shaped flatworms generally characterized by tissues they infect: liver, intestinal, blood flukes

Question 17

What are some features of anti-helminthic drugs?

Answer 17

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)

Question 18

First up for the anti-helminthic drugs are the Benzimidazoles. The first drug is Albendazole what are some features?

Answer 18

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

Question 19

What are the pharmacokinetics and AE for albendazole?

Answer 19

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.

Question 20

The next anti-helminthic drug is Mebendazole. It is the drug of choice in the treatment of infections by?

Answer 20

Whipworm (Trichuris Trichiura)
Pin Worm (Enterobius vermicularis)
Hookworm (Necator americanus & Ancylostoma Duodenale)
Roundworm (Ascariasis Lumbricoides)

Question 21

What is the MOA and Pharmacokinetics for Mebendazole?

Answer 21

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

Question 22

What are the adverse effects with mebendazole?

Answer 22

Contraindicated in pregos
Use with caution in kids less than 2
Use in caution in patients with cirrhosis

Question 23

The next anti-helminthic drug is Thiabendazole. What are some features?

Answer 23

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

Question 24

The next set of drugs are anti-helminthic drugs but not Benzimidazoles. The first is ivermectin, what are some features?

Answer 24

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

Question 25

Next anti-helminthic drug is Piperazine, what are some features?

Answer 25

Alternative drug for tx of pinworm and roundworm infections
GABA agonist
Dont give in patients with seizure disorder

Question 26

Next anti-helminthic drug is Pyrantel Pamoate, what are some features?

Answer 26

Effective in tx of infections by roundworms, pinworms and hookworms
MOA:
–acts as a depolarizing, neuromuscular blocker

Question 27

Next anti-helminthic drug is Diethylcarbamazine. What are some features?

Answer 27

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

Question 28

Next anti-helminthic drug is Doxycycline. what are some features?

Answer 28

Tetracycline antibiotic
Macrofilaricidal activity against Wuchereria Bancrofti
Also active against onchocerciasis

Question 29

Next Anti-helminthic drug is Praziquantel. What are some features?

Answer 29

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

Question 30

Next Anti-helminthic drug is Bithionol. What are some features?

Answer 30

Drug of choice for fasciolosis (sheep liver fluke)

Question 31

The last anti-helminthic drug is Niclosamide. What are some features?

Answer 31

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