Antiparasitics

Question 1

Two forms of E. histolytica?

Answer 1

1. cysts [survive outside body]

2. trophozoites [do not survive outside body]

Question 2

What is the difference b/t luminal, systemic and mixed antiamebics?

Answer 2

Luminal - act on parasite in bowel lumen [Diloxanide furoate, Iodoquinol, Paromomycin]

Systemic - active both in intestinal wall and liver [Chloroquine, Emetine, Dehydroemetine]

Mixed - active against both luminal and systemic disease [metronidazole, Tinidazole]

Question 3

Metronidazole?

Answer 3

Amebicide of choice for treating invasive amebiasis. [Giardia, trichomoniasis, anaerobic cocci, anaerobic gram negative bacilli, combination for H. pylori eradication]

MOA - once absorbed, metronidazole is non-enzymatically reduced by reacting with reduced ferredoxin leading to a production of CYTOTOXIC COMPOUNDS. These compounds bind to proteins and DNA resulting in unstable molecules and cell death.

Oral administration, well distributed, undergoes hepatic oxidation and glucuronidation (CYP450s).

AE - GI distress (very common esp if pt already had GI symptoms prior to drug administration), DILSULFIRAM-like reaction, unpleasant metallic taste, oral moniliasis, dark coloration of urine (nothing problematic), leukopenia, dizziness, ataxia

**safety in pregnancy is NOT establish

Question 4

Tinidazole?

Answer 4

2nd generation nitroimidazole used to treat amebiasis, amebic liver abscess, giardia and trichomoniasis. Metronidazole is 1st line!

AE - shorter duration, but similar effects compared to metronidazole [GI distress, DILSULFIRAM-like reaction, unpleasant metallic taste, oral moniliasis, dark coloration of urine, leukopenia, dizziness, ataxia]

Question 5

Diloxanide furoate?

Answer 5

Sole agent for treatment of asymptomatic amebiasis. Once ingested, it is converted in the gut to its active form, diloxanide freebase.

AE - mild GI distress [not significant]

**although this is not available in the US, you can receive the medication from the CDC and they can deliver the drug quickly if pt has amebiasis

Question 6

Iodoquinol?

Answer 6

Orally active against luminal trophozoite AND cyst forms of E. histolytica. It is used as an alternative to diloxanide furoate for mild to severe infections.

AE - rash, diarrhea, dose-related peripheral neuropathy, avoid long term use as it leads to increased risk of optic neuritis

**sometimes you can give iodoquinol to prevent infection

Question 7

Paromomycin?

Answer 7

Aminoglycoside antibiotic effective ONLY against LUMINAL FORM of E. histolytica and tapeworm. It is an alternative agent for cryptosporidiosis in AIDS pts. [best for luminal anti-parasitic, but also has effect as antimicrobial]

MOA - Paromomycin interferes with bacterial protein synthesis by binding to 30S ribosomal subunit. It is amebicidal as it causes cell membrane to leak. It also reduces intestinal flora population.

AE - GI distress, diarrhea, systemic absorption may lead to headaches, dizziness, rashes and arthralgia

Question 8

Chloroquine?

Answer 8

Used in combination with METRONIDAZOLE and DILOXANIDE FUROATE.

MOA - eliminates trophozoites in liver abscesses

[also an anti-malarial]

Question 9

Emetine and Dihydroemetine?

Answer 9

Back-up drugs for treatment of severe intestinal or hepatic amebiasis. It is used in combination with a luminal agent.

MOA - inhibit protein synthesis by blocking ribosomal movement along messenger RNA

Administered via IM or SC, then concentrates in liver for about a month prior to being slowly metabolized and eliminated.

AE- pain at the site of injection (as it is injectable), transient nausea, cardiotoxicity, neuromuscular weakness, dizziness, rash

Question 10

Tx asymptomatic intestinal infection from amebiasis?

Answer 10

DOC - Diloxanide furoate

Alternative - Iodoquinol, paromycin

Question 11

Tx for Mild-moderate intestinal infection from amebiasis?

Answer 11

DOC - Mitronidazole + diloxanide furoate

Alternative - Tinidazole or Tetracycline or Erythromycin + diloxanide furoate

Question 12

Tx for severe intestinal infection from amebiasis?

Answer 12

DOC - Metronidazole or Tinidazole + Diloxanide furoate

Alternative - Tetraocycline or Emetine or Dihydroemetine + diloxanide furoate

Question 13

Tx for hepatic abscess and extra-intestinal disease from amebiasis?

Answer 13

DOC - Metronidazole or Tinidazole + Diloxanide furoate

Alternative - Emetine or Dihydroemetine + Chloroquine + diloxanide furoate

Question 14

Types of Helminths?

Answer 14

Nematodes - elongated roundworms that possess complete digestive system

Trematodes – leaf-shaped flatworms

Cestodes - flat, segmented that attaches in hosts intestines, lack mouth and intestinal system during its entire life

Question 15

Benzimidazoles?

Answer 15

Albendazole
Mebendazole
Thiabendazole

Question 16

Albendazole

Answer 16

Used in tx of cestodal infestations - ex. taenia solium larvea or echinococcus granulosis

MOA - inhibits microtubule synthesis and glucose uptake. Decreased ATP production leading to immobilization and death of worm

Oral administration that has ERRATIC ABSORPTION that is enhanced with high-fat meal. There is also extensive first-pass metabolism, including rapid sulfoxidation to active metabolites.

AE - short course therapy (1-3 days presenting with headache and nausea), when taking for 3 months or longer (hydatid treatment) there is increased risk of hepatotoxicity, agranulocytosis and pancytopenia, inflammatory response to dying parents in CNS leading to headache, vomiting, hyperthermia, convulsions and mental changes

**contraindicated in pregnancy and children under age of 2 as we do not have much statistics on this

Question 17

Mebenedazole?

Answer 17

Drug of choice in the treatment of infections by:
• Whipworm (Trichuris trichiura)
• Pin worm (Enterobius vermicularis)
• Hookworms (Necator americanus & Ancylostoma duodenale)
• Roundworm (Ascariasis lumbricoides)

MOA - inhibits formation of helminth microtubules and irreversibly blocks glucose uptake causing affected parasite to be expelled in the feces

Oral (chewable) tablets are administered which are taken with a high-fat meal. It undergoes 1st pass metabolism to active compounds.

AE - abdominal pain, diarrhea, headache, dizziness, Contraindicated in pregnancy (category C), use with caution if pt is under 2 yo or if they have cirrhosis

Question 18

Thiabendazole?

Answer 18

Effective tx for strongyloidiasis caused by Strongyloides stercoralis (threadworm), cutaneous larva migrans and early stages of trichinosis.

MOA - affects microtubular aggregation

Oral administration that is nearly insoluble in water.

AE - less commonly used due to severe side effects that are more sever than other benzimidazoles, CNS disturbances are the biggest worry, stevens-johnsons

**contraindicated in pregnancy and children under age of 2 as we do not have much statistics on this

Question 19

Ivermectin?

Answer 19

DOC - onchocerciasis (onchocerca volvulus), cutaneous larva migrans and strongyloides

MOA - GABA agonist causing influx of chloride ions leading to hyperpolarization of nerves causing paralysis of parasites.

Oral admin - does not cross BBB

AE - Mazotti-like reactions with onchoceriasis (reaction due to dying parasite)

Contraindicated in pregnancy and meningitis

Question 20

Peperazine?

Answer 20

Alternative drug for tx of pinworm and roundworm infections

MOA - GABA agonist that causes expulsion of worm by peristalsis

Contraindicated in pts with seizure disorders

Question 21

Pyrantel Palmoate?

Answer 21

Effective in tx of infections by roundworms, pinworms and hookworms.

MOA - acts as a depolarizing, neuromuscular-blocker causing persistent activation of parasite’s nicotinic receptors by release of acetylcholine and inhibition of cholinesterase

Poor oral absorption

AE - mild (nausea, vomiting, diarrhea)

Question 22

Diethylcarbamazine?

Answer 22

DOC - tx of lymphatic filariasis loiasis and tropical eosinophilia

MOA - Immobilizes microfilariae and renders them susceptible to host defense mechanism

Oral administration that is rapidly absorbed with meals.

Used to dx onchoceriasis as the Mazotti reaction is so severe with this drug once worm dies.

AE - due to host response following damage/death of parasite, then fever, malaise, rash, myalgia, leukocytosis - usually administer with antihistamine or steroids

Question 23

Doxyclycline for parasites?

Answer 23

Tetracycline antibiotic that has macrofilaricidal activity against Wuchereria bancrofti. It is also active against onchocerciasis

MOA - acts indirectly by killing Wolbachia (intracellular bacterial symbiont of filarial parasites)

Question 24

Praziquantel?

Answer 24

DOC = schistosomiasis and most trematode and cestode infections

[cysticercosis - albendazole is DOC, but praziquantel has similar efficacy]

MOA - increased permeability of cell membrane to calcium, causing contracture and paralysis of worm musculature, resulting in detachment of suckers from blood vessel walls

Oral admin with extensive first-pass metabolism. Inactive metabolites are excreted via urine and bile.

AE - drowsiness, dizziness, malaise, anorexia, GI upset, drug interactions (CYP450)

Contraindicated in pregnancy and nursing mothers, and ocular cystercercosis b/c death of parasite within the eye leads to severe eye damage.

Question 25

Bithionol?

Answer 25

DOC - fasciolosis (sheep liver fluke)

Alternative drug for pulmonary paragonimiasis

MOA - inhibition of helminth’s electron transport chain

Question 26

Niclosamide?

Answer 26

2nd line drug for tx of most cestode infections but use is uncommon due to excellent efficacy of praziquantal. It is no longer available in the US.

MOA - inhibition of parasite’s mitochondrial phosphorylation of ADP as well as anaerobic metabolism. Drug is lethal for cestode’s scolex and segments of cestodes by not for the ova.

A laxative is administered prior to niclosamide (oral) to purge bowel of all dead segments in order to preclude digestions and liberation of ova (may lead to cysticercosis). Alcohol should be avoided within 1 day of dose.