Ivermectin

Ivermectin

File:Ivermectin skeletal.svg
Systematic (IUPAC) name
Ivermectin (22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b)
Clinical data
Pregnancy category	AU: B3 US: C (Risk not ruled out)
Routes of administration	Oral
Pharmacokinetic data
Protein binding	93%
Metabolism	liver; CYP450
Biological half-life	18 hours
Excretion	feces; <1% urine
Identifiers
CAS Number	70288-86-7 71827-03-7
ATC code	P02CF01 (WHO) QP54AA01 QS02QA03
PubChem	CID 6474909
DrugBank	APRD01058
Chemical data
Formula	C48H74O14 (22,23-dihydroavermectin B1a) C47H72O14 (22,23-dihydroavermectin B1b)
Molar mass	875.10 g/mol

Ivermectin (22,23-dihydroavermectin B_1a + 22,23-dihydroavermectin B_1b) is a broad-spectrum antiparasitic medication.

It is sold under brand names Stromectol in the United States, Mectizan in Canada by Merck and Ivexterm in Mexico by Valeant Pharmaceuticals International.

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 and enterobiasis).

Ivermectin, under the brand name Mectizan, is currently being used to help eliminate river blindness (onchocerciasis) in the Americas and stop transmission of lymphatic filariasis and onchocerciasis around the world. Currently, large amounts of ivermectin are donated by Merck to fight river blindness in countries that are unable to afford the drug . The disease is endemic in 30 African countries, 6 Latin American countries and Yemen, according to studies conducted by the World Health Organization. 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.

Arthropod

More recent evidence supports its off-label use against arthropods:

• mites such as scabies. It is usually limited to cases that prove resistant to topical treatments and/or who present in advanced state (such as Norwegian scabies).

• lice

Veterinary use

Ivermectin is also used in veterinary medicine, particularly for horses, dogs and cats. It is sometimes mixed with other medications to reach a wide spectrum of animal parasites. Some breeds (especially the Rough Collie, the Smooth Collie and the Australian Shepherd) are affected by a genetic defect, a mutation within the MDR1 gene. Affected dogs are very sensitive to some drugs, such as ivermectin, as well as to some antibiotics, opioids and steroids – over 100 drugs in total. Kittens are also very sensitive and ivermectin should never be used on kittens less than 10-12 weeks of age, nor should it be used on any weak, dehydrated or debilitated animal except in dire situations. Ivermectin is sometimes used as an acaricide in reptiles, both by injection and as a diluted spray. While this works really well in some cases, care must be taken as several species of reptile are very sensitive to ivermectin. Use in Chelonians is particularly contra-indicated, because it is nearly often fatal.

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). 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, 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, with often fatal consequences.

Toxicity

The main concern is neurotoxicity, which in most mammalian species may manifest as CNS 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.

See also

• Onchocerciasis
• The Carter Center
• Lymphatic filariasis
• Neglected diseases
• United Front Against Riverblindness

External links

• Stromectol
• The Carter Center River Blindness (Onchocerciasis) Control Program
• Mectizan Donation Program
• American NGDO Treating River Blindness

cs:Ivermektin it:Ivermectina