Anti-Protozoal & Anti-Helminthic Drugs

Question 1

Treatment for Naegleria fowleri (brain-eating amoeba)

Answer 1

Miltefosine (trade names Impavido and Miltex)

Question 2

Mechanism of Miltefosine

Answer 2

A PL drug originally developed as an antineoplastic for topical use.
As an antiprotozoal drug, it can be oral or topical
Acts as an Akt inhibitor, thereby inhibiting the parasite or viruses from entering cells and spreading.
Also under investigation as a potential therapy against HIV infection.

Question 3

Treatment for amebiasis (amebic colitis and amebic liver abscess) (Entamoeba histolytica) and Giardia

Answer 3

Nitroimidazole antibiotics (metronidazole) + iodoquinol

Question 4

Mechanism of nitroimidazole ABx (i.e., metronidazole)

Answer 4

Taken up by diffusion and reduced to nitrose intermediates, which either deactivate cysteine-containing enzymes or intercalate within bacterial DNA to form unstable molecules.

Question 5

Mechanism of iodoquinol

Answer 5

chelates ferrous ions essential for metabolism of single-celled organisms

Question 6

Treatment for cyclospora, isospora

Answer 6

Bactrim (TMP-SMX)

Question 7

Mechanism of bactrim

Answer 7

Inhibits the folate synthesis pathway

Question 8

Treatment for cryptosporidium

Answer 8

Nitazoxanide

Question 9

Mechanism of nitazoxanide

Answer 9

Interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction which is essential to anaerobic energy metabolism
Following oral admin, it is rapidly hydrolyzed to its active metabolite, tizonoxanide

Question 10

Presents with 2-5 semi-formed stools (steatorrhea)/day and moderate gas/bloating. Can be associated with malabsorption syndrome and FTT

Answer 10

Giardia

Question 11

Presents with alternating (bloody) diarrhea and formed stools every 1-2 days and moderate fatigue and weight loss

Answer 11

Entamoeba histolytica

Question 12

Presents with sudden watery diarrhea followed by UGI sxs, severe gas/bloating, anorexia, fatigue and weight loss

Answer 12

cyclospora

Question 13

Presents with acute watery diarrhea of short duration (5-10 d) and mild to moderate weight loss

Answer 13

Cryptosporidium

Question 14

Treatment of giardiasis

Answer 14

Tinidazole, metronidazole, and nitazoxanide

Question 15

SIgns and symptoms of isosporosis

Answer 15

Chronic diarrhea (mos-yrs)
Abdominal pain, weakness, weight loss
Anorexia
EOSINOPHILIA (rare in protozoan infections)

Question 16

Intestinal flukes

Answer 16

Fasciolopsis buski
Metagonimus yokogawai
Heterophyes heterophyes

Question 17

Treatment for intestinal flukes

Answer 17

Praziquantel

Question 18

Liver flukes

Answer 18

Fasciola hepatica (sheep liver fluke)
Clonorchis senensis (Chinese liver fluke)
Dicrocoelium dendriticum

Question 19

Treatment for liver flukes

Answer 19

Triclabendazole
Nitazoxanide
Praziquantel (except for F. hepatica)
Albendazole

Question 20

Lung fluke

Answer 20

Paragonimus westermani

Question 21

Treatment for lung fluke

Answer 21

Praziquantel

Triclabendazole

Question 22

Blood flukes

Answer 22

Schistosomas: S. japonicum, S. mansoni

Question 23

Treatment for blood flukes

Answer 23

Praziquantel. But infections often resolve without treatment

Question 24

Mechanism of praziquantel

Answer 24

Increases Ca permeability of the schistosome and causes paralysis of the fluke, allowing phagocytosis. May interfere with adenosine uptake.
Absorbed very well in the GI tract
Metabolized through the cyto P450 pathway (CYP3A4)

Question 25

Mechanism of mebendazole

Answer 25

Inhibits the formation of worms' microtubules and causes the worms' glucose depletion

Question 26

Mechanism of albendazole

Answer 26

Inhibits tubulin polymerization, resulting in the loss of cytoplasmic microtubules (many drug interactions)

Question 27

Mechanism of Ivermectin

Answer 27

A macrocyclic lactone which kills by interfering with nerve and muscular fx, in particular by enhancing inhibitory neurotransmission. Causes bowel obstruction with heavy worm load.

Question 28

Mechanism of pyrantel pamoate

Answer 28

Acts as a depolarizing neuromuscular blocking agent, thereby causing sudden contraction, followed by paralysis, of the helminths. Worm "loses its grip" on the intestinal wall and may be passed out of the system then. Causes bowel obstruction with heavy worm load Popular heart worm medication for pets

Question 29

Mechanism of niclosamide

Answer 29

Used specifically to treat tapeworms by uncoupling oxphos; not effective against other worms

Question 30

Treatment for Enterobius vermicularis (pinworm)

Answer 30

Mebendazole Pyrantel pamoate Albendazole

Question 31

Prevalence of ascariasis

Answer 31

3-4 million US cases/year

Question 32

Treatment for ascarosis

Answer 32

Mebendazole Albendazole Ivermectin

Question 33

Treatment for trichuris trichiura

Answer 33

Mebendazole Albendazole Ivermectin Iron for microcytic anemia