- Ivermectin
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Ivermectin 
Systematic (IUPAC) name Ivermectin (22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b) Clinical data Trade names Stromectol AHFS/Drugs.com monograph MedlinePlus a607069 Pregnancy cat. B3(AU) C(US) Legal status ? Routes Oral Pharmacokinetic data Protein binding 93% Metabolism liver; CYP450 Half-life 18 hours Excretion feces; <1% urine Identifiers CAS number 70288-86-7 
71827-03-7ATC code P02CF01 QP54AA01 QS02QA03 PubChem CID 9812710 DrugBank APRD01058 ChemSpider 7988461 UNII 8883YP2R6D KEGG D00804 ChEMBL CHEMBL341047 
Chemical data Formula C48H74O14 (22,23-dihydroavermectin B1a)
C47H72O14 (22,23-dihydroavermectin B1b)Mol. mass 875.10 g/mol - InChI=1S/C48H74O14.C47H72O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-38;1-24(2)41-27(5)16-17-46(61-41)22-33-19-32(60-46)15-14-26(4)42(25(3)12-11-13-31-23-54-44-39(48)28(6)18-34(45(50)57-33)47(31,44)51)58-38-21-36(53-10)43(30(8)56-38)59-37-20-35(52-9)40(49)29(7)55-37/h12-15,19,25-26,28,30-31,33-45,49-50,52H,11,16-18,20-24H2,1-10H3;11-14,18,24-25,27,29-30,32-44,48-49,51H,15-17,19-23H2,1-10H3/b13-12+,27-15+,32-14+;12-11+,26-14+,31-13+/t25-,26-,28-,30-,31-,33+,34-,35-,36-,37-,38-,39-,40+,41-,42-,43+,44-,45+,47+,48+;25-,27-,29-,30-,32+,33-,34-,35-,36-,37-,38-,39+,40-,41+,42-,43-,44+,46+,47+/m00/s1
Key:SPBDXSGPUHCETR-JFUDTMANSA-N
(what is this?) (verify)Ivermectin (22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b) is a broad-spectrum antiparasitic avermectin medicine.
It is sold under brand names Stromectol in the United States, Ivomec in Europe by Merial Animal Health, Mectizan in Canada by Merck and Ivexterm in Mexico by Valeant Pharmaceuticals International. While in development, it was assigned the code MK-933 by Merck.[1]
Contents
Uses
Ivermectin is a broad-spectrum antiparasitic agent.
Helminth
It is traditionally used against worms.
It is mainly used in humans in the treatment of onchocerciasis, but is also effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis, filariasis, enterobiasis and some epidermal parasitic skin diseases (EPSDs) including scabies.
Ivermectin, under the brand name Mectizan, is currently being used to help eliminate river blindness (onchocerciasis) in the Americas, and to stop transmission of lymphatic filariasis and onchocerciasis around the world.[2][3][4] Currently, large amounts of ivermectin are donated by Merck to fight river blindness in countries unable to afford the drug.[5] The disease is endemic in 30 African countries, six Latin American countries, and Yemen, according to studies conducted by the World Health Organization.[6] The drug rapidly kills microfilariae, but not the adult worms. A single oral dose of ivermectin, taken annually for the 10-15 year life span of the adult worms, is all that is needed to protect the individual from onchocerciasis.[7]
Arthropod
More recent evidence supports its off-label use against arthropods:
- Mites such as scabies.[8][9][10] It is usually limited to cases that prove resistant to topical treatments and/or which present in an advanced state (such as Norwegian scabies).[10]
Veterinary use
Ivermectin is also used in veterinary medicine. It is sometimes administered in combination with other medications to treat a broad spectrum of animal parasites. Some dog breeds (especially the Rough Collie, the Smooth Collie, the Shetland Sheepdog and the Australian Shepherd), though, have a high incidence of a certain mutation within the MDR1 gene; affected animals are particularly sensitive to the toxic effects of ivermectin. Kittens are also very sensitive.[citation needed]. A 0.01% ivermectin topical preparation for treating ear mites in cats (Acarexx) is available.
Ivermectin is sometimes used as an acaricide in reptiles, both by injection and as a diluted spray. While this works well in some cases, care must be taken, as several species of reptile are very sensitive to ivermectin. Use in turtles is particularly contraindicated.
Pharmacodynamics
Ivermectin and other avermectins (insecticides most frequently used in home-use ant baits) are macrocyclic lactones derived from the bacterium Streptomyces avermitilis. Ivermectin kills by interfering with nervous system and muscle function, in particular by enhancing inhibitory neurotransmission.
The drug binds and activates glutamate-gated chloride channels (GluCls).[13] GluCls are invertebrate-specific members of the Cys-loop family of ligand-gated ion channels present in neurons and myocytes.
Pharmacokinetics
Ivermectin can be given either by mouth or injection. It does not readily cross the blood-brain barrier of mammals,[citation needed] although crossing may still become significant if ivermectin is given at high doses (in which case, brain levels peak 2–5 hours after administration). In contrast to mammals, ivermectin can cross the blood-brain barrier in tortoises, often with fatal consequences.
Toxicity
The main concern is neurotoxicity, which in most mammalian species may manifest as central nervous system depression, and consequent ataxia, as might be expected from potentiation of inhibitory GABA-ergic synapses. Dogs with defects in the P-glycoprotein gene can be severely poisoned by ivermectin.
Ecotoxicity
Field studies have demonstrated that the dung of animals treated with ivermectin supports a significantly reduced diversity of invertebrates, and that the dung persists for longer.[14]
See also
- Onchocerciasis
- The Carter Center
- Lymphatic filariasis
- Neglected diseases
- United Front Against Riverblindness
References
- ^ Pampiglione S, Majori G, Petrangeli G, Romi R (1985). "Avermectins, MK-933 and MK-936, for mosquito control". Trans R Soc Trop Med Hyg 79 (6): 797–9. PMID 3832491.
- ^ The Carter Center. "River Blindness (Onchocerciasis) Program". http://www.cartercenter.org/health/river_blindness/index.html. Retrieved 2008-07-17.
- ^ The Carter Center. "Lymphatic Filariasis Elimination Program". http://www.cartercenter.org/health/lf/index.html. Retrieved 2008-07-17.
- ^ WHO. accessdate=2009-11-12 "African Programme for Onchocerciasis Control". http://www.who.int/blindness/partnerships/APOC/en/ accessdate=2009-11-12.
- ^ http://www.mectizan.org/about.asp.
- ^ United Front Against Riverblindness. "Riverblindness". http://www.riverblindness.org/index.php?menu=tn2&page=aboutRiverblindness.
- ^ United Front Against Riverblindness. "Riverblindness". http://www.riverblindness.org/index.php?menu=tn3&page=Treatment.
- ^ Brooks PA, Grace RF (August 2002). "Ivermectin is better than benzyl benzoate for childhood scabies in developing countries". J Paediatr Child Health 38 (4): 401–4. doi:10.1046/j.1440-1754.2002.00015.x. PMID 12174005. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1034-4810&date=2002&volume=38&issue=4&spage=401.
- ^ Victoria J, Trujillo R (2001). "Topical ivermectin: a new successful treatment for scabies". Pediatr Dermatol 18 (1): 63–5. doi:10.1046/j.1525-1470.2001.018001063.x. PMID 11207977. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0736-8046&date=2001&volume=18&issue=1&spage=63.
- ^ a b Strong M, Johnstone PW (2007). Strong, Mark. ed. "Interventions for treating scabies". Cochrane Database of Systematic Reviews (Online) (3): CD000320. doi:10.1002/14651858.CD000320.pub2. PMID 17636630.
- ^ Dourmishev AL, Dourmishev LA, Schwartz RA (December 2005). "Ivermectin: pharmacology and application in dermatology". International Journal of Dermatology 44 (12): 981–8. doi:10.1111/j.1365-4632.2004.02253.x. PMID 16409259.
- ^ Strycharz JP, Yoon KS, Clark JM (January 2008). "A new ivermectin formulation topically kills permethrin-resistant human head lice (Anoplura: Pediculidae)". Journal of Medical Entomology 45 (1): 75–81. doi:10.1603/0022-2585(2008)45[75:ANIFTK]2.0.CO;2. ISSN 0022-2585. PMID 18283945.
- ^ Yates DM, Wolstenholme AJ (August 2004). "An ivermectin-sensitive glutamate-gated chloride channel subunit from Dirofilaria immitis". Int. J. Parasitol. 34 (9): 1075–81. doi:10.1016/j.ijpara.2004.04.010. PMID 15313134. http://linkinghub.elsevier.com/retrieve/pii/S0020751904000979.
- ^ Iglesias LE, Saumell CA, Fernández AS, et al. (December 2006). "Environmental impact of ivermectin excreted by cattle treated in autumn on dung fauna and degradation of faeces on pasture". Parasitology Research 100 (1): 93–102. doi:10.1007/s00436-006-0240-x. PMID 16821034.
External links
- Stromectol
- The Carter Center River Blindness (Onchocerciasis) Control Program
- Mectizan Donation Program
- American NGDO Treating River Blindness
- Ivermectin in generic and brand name forms for treatment of heartworm in dogs
Antiparasitics – Anthelmintics (P02) Antiplatyhelmintic agents Antitrematodals
(schistosomicides)Binds tubulinOther/unknownquinoline (Praziquantel#, Oxamniquine#) • phenol (Bithionol) • thiazole (Niridazole) • arylsulfonate (Stibophen)Anticestodals
(taeniacides)Binds tubulinOther/unknownsalicylanilide (Niclosamide)# • aminoacridine (Quinacrine) • butyrophenone (Desaspidin) • chlorophenol (Dichlorophen)Antinematodal agents
(including
macrofilaricides)Binds tubulinbenzimidazole (Mebendazole#, Albendazole#, Thiabendazole, Fenbendazole, Ciclobendazole, Flubendazole)macrolide (Ivermectin#)Other/unknownpiperazine (Piperazine • Diethylcarbamazine#) • thiazole (Levamisole#) • quinolinium (Pyrvinium) • benzylammonium (Bephenium) • naphthalenesulfonate (Suramin#) • TribendimidineM: IFT
helm,arth (acar)
helm, arth (lice), zoon
helm, arth
Ectoparasiticides / arthropod (P03A) Insecticide/pediculicide Chlorine-containing productsIvermectinAcaricide/miticide/scabicide PyrethrinesIvermectinSulfur-containing productsChlorine-containing productsOther/ungroupedM: IFT
helm,arth (acar)
helm, arth (lice), zoon
helm, arth
Categories:- Antiparasitic agents
- Merck
- World Health Organization essential medicines
- Macrolides
- Veterinary drugs
- Acaricides
- InChI=1S/C48H74O14.C47H72O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-38;1-24(2)41-27(5)16-17-46(61-41)22-33-19-32(60-46)15-14-26(4)42(25(3)12-11-13-31-23-54-44-39(48)28(6)18-34(45(50)57-33)47(31,44)51)58-38-21-36(53-10)43(30(8)56-38)59-37-20-35(52-9)40(49)29(7)55-37/h12-15,19,25-26,28,30-31,33-45,49-50,52H,11,16-18,20-24H2,1-10H3;11-14,18,24-25,27,29-30,32-44,48-49,51H,15-17,19-23H2,1-10H3/b13-12+,27-15+,32-14+;12-11+,26-14+,31-13+/t25-,26-,28-,30-,31-,33+,34-,35-,36-,37-,38-,39-,40+,41-,42-,43+,44-,45+,47+,48+;25-,27-,29-,30-,32+,33-,34-,35-,36-,37-,38-,39+,40-,41+,42-,43-,44+,46+,47+/m00/s1
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