Ivermectin

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.

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]).

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. Currently, large amounts of ivermectin are donated by Merck to fight river blindness in countries unable to afford the drug. The disease is endemic in 30 African countries, six 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 which present in an advanced state (such as Norwegian scabies).


 * Lice

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.

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). 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, 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.