Ivermectin
Encyclopedia
Ivermectin 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.
s.
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. 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.
, 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. . 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.
s (insecticide
s 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 channel
s present in neuron
s and myocyte
s.
of mammal
s, 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.
, 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.
Avermectin
The avermectins are a series 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring compounds are generated as fermentation products by Streptomyces avermitilis, a soil actinomycete...
medicine.
It is sold under brand names Stromectol in the United States, Ivomec in Europe by Merial Animal Health, Mectizan in Canada by Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
and Ivexterm in Mexico by Valeant Pharmaceuticals International
Valeant Pharmaceuticals International
Valeant Pharmaceuticals International, Inc. is a pharmaceutical company with activities spanning the drug discovery pipeline from target identification through clinical trials and commercialization. The focus of the company is on neurology, dermatology and infectious disease with several drugs in...
. While in development, it was assigned the code MK-933 by Merck.
Helminth
It is traditionally used against wormWorm
The term worm refers to an obsolete taxon used by Carolus Linnaeus and Jean-Baptiste Lamarck for all non-arthropod invertebrate animals, and stems from the Old English word wyrm. Currently it is used to describe many different distantly-related animals that typically have a long cylindrical...
s.
It is mainly used in humans in the treatment of onchocerciasis
Onchocerciasis
Onchocerciasis , also known as river blindness and Robles' disease, is a parasitic disease caused by infection by Onchocerca volvulus, a nematode . Onchocerciasis is the world's second-leading infectious cause of blindness. It is not the nematode, but its endosymbiont, Wolbachia pipientis, that...
, but is also effective against other worm infestations (such as strongyloidiasis
Strongyloidiasis
Strongyloidiasis is a human parasitic disease caused by the nematode Strongyloides stercoralis, or sometimes S. fülleborni. It can cause a number of symptoms in people, principally skin symptoms, abdominal pain, diarrhea and weight loss...
, ascariasis
Ascariasis
Ascariasis is a human disease caused by the parasitic roundworm Ascaris lumbricoides. Perhaps as many as one quarter of the world's people are infected, with rates of 45% in Latin America and 95% in parts of Africa. Ascariasis is particularly prevalent in tropical regions and in areas of poor...
, trichuriasis
Trichuriasis
Trichuriasis is a parasitic infection primarily in the tissue of the cecum, appendix, colon and rectum that is caused by Trichuris trichiura , an intestinal parasitic nematode .-Agent :...
, filariasis
Filariasis
Filariasis is a parasitic disease and is considered an infectious tropical disease, that is caused by thread-like nematodes belonging to the superfamily Filarioidea, also known as "filariae"....
, enterobiasis
Enterobiasis
A pinworm infection or enterobiasis is a human parasitic disease and one of the most common childhood parasitic worm infections in the developed world. It is caused by infestation with the parasitic roundworm Enterobius vermicularis, commonly called the human pinworm...
and some epidermal parasitic skin diseases (EPSDs) including scabies
Scabies
Scabies , known colloquially as the seven-year itch, is a contagious skin infection that occurs among humans and other animals. It is caused by a tiny and usually not directly visible parasite, the mite Sarcoptes scabiei, which burrows under the host's skin, causing intense allergic itching...
.
Ivermectin, under the brand name Mectizan, is currently being used to help eliminate river blindness (onchocerciasis
Onchocerciasis
Onchocerciasis , also known as river blindness and Robles' disease, is a parasitic disease caused by infection by Onchocerca volvulus, a nematode . Onchocerciasis is the world's second-leading infectious cause of blindness. It is not the nematode, but its endosymbiont, Wolbachia pipientis, that...
) in the Americas
Americas
The Americas, or America , are lands in the Western hemisphere, also known as the New World. In English, the plural form the Americas is often used to refer to the landmasses of North America and South America with their associated islands and regions, while the singular form America is primarily...
, and to stop transmission
Transmission (medicine)
In medicine and biology, transmission is the passing of a communicable disease from an infected host individual or group to a conspecific individual or group, regardless of whether the other individual was previously infected...
of lymphatic filariasis and onchocerciasis around the world. Currently, large amounts of ivermectin are donated by Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
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:- MitesMITESMITES, or Minority Introduction to Engineering and Science, is a highly selective six-week summer program for rising high school seniors held at the Massachusetts Institute of Technology. Its purpose is to expose students from minority, or otherwise disadvantaged backgrounds, to the fields of...
such as scabiesScabiesScabies , known colloquially as the seven-year itch, is a contagious skin infection that occurs among humans and other animals. It is caused by a tiny and usually not directly visible parasite, the mite Sarcoptes scabiei, which burrows under the host's skin, causing intense allergic itching...
. It is usually limited to cases that prove resistant to topical treatments and/or which present in an advanced state (such as Norwegian scabies).
- LiceLouseLice is the common name for over 3,000 species of wingless insects of the order Phthiraptera; three of which are classified as human disease agents...
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 CollieRough Collie
The Rough Collie is a long coated breed of medium to large size dog that in its original form was a type of collie used and bred for herding in Scotland. Originating in the 1800's, it is now well known through the works of author Albert Payson Terhune, and through the Lassie novel, movies, and...
, the Smooth Collie
Smooth Collie
The Smooth Collie is a breed of dog developed originally for herding. It is a short-coated version of the Rough Collie of Lassie fame. Some breed organisations consider the smooth-coat and rough-coat dogs to be variations of the same breed.-History:...
, the Shetland Sheepdog
Shetland Sheepdog
The Shetland Sheepdog, often known as the Sheltie, is a breed of herding dog.They are small to medium dogs, and come in a variety of colors, such as sable/white, tri-color, and blue merle. They are vocal, excitable, energetic dogs who are always willing to please and work hard...
and the Australian Shepherd
Australian Shepherd
The Australian shepherd is a breed of herding dog that was developed on ranches in the Western United States. Despite its name, the breed, commonly known as an Aussie, did not originate in Australia They acquired their name because some of the Australian sheepdogs arrived in the United States with...
), 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. . 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 avermectinAvermectin
The avermectins are a series 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring compounds are generated as fermentation products by Streptomyces avermitilis, a soil actinomycete...
s (insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
s most frequently used in home-use ant
Ant
Ants are social insects of the family Formicidae and, along with the related wasps and bees, belong to the order Hymenoptera. Ants evolved from wasp-like ancestors in the mid-Cretaceous period between 110 and 130 million years ago and diversified after the rise of flowering plants. More than...
baits) are macrocyclic
Cyclic compound
In chemistry, a cyclic compound is a compound in which a series of atoms is connected to form a loop or ring.While the vast majority of cyclic compounds are organic, a few inorganic substances form cyclic compounds as well, including sulfur, silanes, phosphanes, phosphoric acid, and triboric acid. ...
lactones derived from the bacterium Streptomyces
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
avermitilis. Ivermectin kills by interfering with nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
and muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
function, in particular by enhancing inhibitory neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
.
The drug binds and activates glutamate-gated chloride channels (GluCls). GluCls are invertebrate-specific members of the Cys-loop family of ligand-gated ion channel
Ligand-gated ion channel
Ligand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger , such as a neurotransmitter.The binding site of endogenous ligands on LGICs...
s present in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s and myocyte
Myocyte
A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell....
s.
Pharmacokinetics
Ivermectin can be given either by mouth or injection. It does not readily cross the blood-brain barrierBlood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
of mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s, 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 ataxiaAtaxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, 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
- OnchocerciasisOnchocerciasisOnchocerciasis , also known as river blindness and Robles' disease, is a parasitic disease caused by infection by Onchocerca volvulus, a nematode . Onchocerciasis is the world's second-leading infectious cause of blindness. It is not the nematode, but its endosymbiont, Wolbachia pipientis, that...
- The Carter CenterCarter CenterThe Carter Center is a nongovernmental, not-for-profit organization founded in 1982 by former U.S. President Jimmy Carter and his wife Rosalynn Carter. In partnership with Emory University, The Carter Center works to advance human rights and alleviate human suffering...
- Lymphatic filariasis
- Neglected diseasesNeglected DiseasesThe neglected diseases are a group of tropical infections which are especially endemic in low-income populations in developing regions of Africa, Asia, and the Americas. Different organizations define the set of diseases differently...
- United Front Against RiverblindnessUnited Front Against RiverblindnessUnited Front Against Riverblindness is a Non-Governmental Development Organization that provides technical, managerial and financial support for the elimination of riverblindness, or onchocerciasis, in the Kasongo region of Maniema province in the east-southern region of the Democratic Republic...