Mebendazole is a highly effective, broad-spectrum antihelmintic indicated for the treatment of nematode infestations, including roundworm, hookworm, whipworm, threadworm (pinworm), and the intestinal form of trichinosis prior to its spread into the tissues beyond the digestive tract. Other drugs are used to treat worm infections outside the digestive tract, as mebendazole is poorly absorbed into the bloodstream.[11] Mebendazole is used alone in those with mild to moderate infestations. It kills parasites relatively slowly, and in those with very heavy infestations, it can cause some parasites to migrate out of the digestive system, leading to appendicitis, bile duct problems, or intestinal perforation. To avoid this, heavily infested patients may be treated with piperazine, either before or instead of mebendazole. Piperazine paralyses the parasites, causing them to pass in the feces.[12] It is also used rarely in the treatment of cystic echinococcosis, also known as hydatid disease. Evidence for effectiveness for this disease, however, is poor.[13]
Mebendazole and other benzimidazole antithelmetics are active against both larval and adult stages of nematodes, and in the cases of roundworm and whipworm, kill the eggs, as well. Paralysis and death of the parasites occurs slowly, and elimination in the feces may require several days.[11]
Special populations
Mebendazole has been shown to cause ill effects in pregnancy in animal models, and no adequate studies of its effects in human pregnancy have been conducted.[2] Whether it can be passed by breastfeeding is unknown.[14][2]
Adverse effects
Mebendazole sometimes causes diarrhea, abdominal pain, and elevated liver enzymes. In rare cases, it has been associated with a dangerously low white blood cell count, low platelet count, and hair loss,[14][15] with a risk of agranulocytosis in rare cases.
Drug interactions
Carbamazepine and phenytoin lower serum levels of mebendazole. Cimetidine does not appreciably raise serum mebendazole (in contrast to the similar drug albendazole), consistent with its poor systemic absorption.[16][17]
Mebendazole works by effectively inhibiting the formation of microtubules[19] via binding to the colchicine binding site of β-tubulin, thereby blocking polymerization of tubulin dimers in intestinal cells of parasites.[20] Administration of mebendazole results in the gradual immobilization and eventual death of the helminths.[11] The primary mechanism of action appears to be the disruption of cytoplasmic microtubules.[11][21] Effects of benzimidazoles like mebendazole on helminths include disruption of acetylcholinesterase secretion, inhibition of fumarate reductase and active glucose transport, uncoupling of oxidative phosphorylation and other metabolic perturbations.[21]:911–915
Poor absorption in the digestive tract makes mebendazole an efficient drug for treating intestinal parasitic infections with limited adverse effects. However, mebendazole has an impact on mammalian cells, mostly by inhibiting polymerization of tubulin dimers, thereby disrupting essential microtubule structures such as mitotic spindle.[22] Disassembly of the mitotic spindle then leads to apoptosis mediated via dephosphorylation of Bcl-2 which allows pro-apoptotic protein Bax to dimerize and initiate programmed cell death.[23]
Mebendazole has also been shown to have an effect on many different cancer cell lines. Since it can inhibit tubulin polymerization, it has a lethal effect on cancer cells. There have been studies in vitro and in vivo (mouse models) that show Mebendazole targets various important cell processes that are crucial to cancer survival and proliferation. When these pathways are inhibited it can lead to apoptosis in these cancer cells. [24]
12345678ASHP (3 June 2024). "Mebendazole". The American Society of Health-System Pharmacists. Archived from the original on 7 September 2015. Retrieved 12 December 2024.
↑ASHP. "Mebendazole". The American Society of Health-System Pharmacists. Archived from the original on 7 September 2015.
↑World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
↑Martin AR in Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry, 8th edition, Doerge RF, ed. J.B. Lippincott, 1982, Chapter 4
↑"Mebendazole". drugs.com. Archived from the original on 22 February 2015. Retrieved 25 January 2015.
12Finberg R, Fingeroth J in Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo, Ed. Harrison's Principles of Internal Medicine, 18th ed., McGraw-Hill, 2012, Chapter 217.
↑Luder PJ, Siffert B, Witassek F, Meister F, Bircher J (1986). "Treatment of hydatid disease with high oral doses of mebendazole. Long-term follow-up of plasma mebendazole levels and drug interactions". European Journal of Clinical Pharmacology. 31 (4): 443–8. doi:10.1007/bf00613522. PMID3816925. S2CID41447486.
12Lacey E (1988). "The role of the cytoskeletal protein, tubulin, in the mode of action and mechanism of drug resistance to benzimidazoles". International Journal for Parasitology. 18 (7): 885–936. doi:10.1016/0020-7519(88)90175-0. PMID3066771.
↑Islam N, Chowdhury NA (March 1976). "Mebendazole and pyrantel pamoate as broad-spectrum anthelmintics". The Southeast Asian Journal of Tropical Medicine and Public Health (1): 81–84. PMID1027113.
