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Ivermectin is a medication that is effective against many types of parasites. It is used to treat head lice, scabies, river blindness, strongyloidiasis, and lymphatic filariasis, among others. It can be either applied to the skin or taken by mouth. The eyes should be avoided.

Common side effects include red eyes, dry skin, and burning skin. It is unclear if it is safe for use during pregnancy, but is likely acceptable for use during breastfeeding. It is in the avermectin family of medications and works by causing an increase in permeability of cell membrane resulting in paralysis and death of the parasite.

Ivermectin was discovered in 1975 and came into medical use in 1981. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$0.12 for a course of treatment. In the United States it costs $25-50. In other animals it is used to prevent and treat heartworm among other diseases.


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Medical uses

Ivermectin is a broad-spectrum antiparasitic agent, traditionally against parasitic worms and other multicellular parasites. It is mainly used in humans in the treatment of onchocerciasis (river blindness), but is also effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis, filariasis and enterobiasis), and some epidermal parasitic skin diseases, including scabies.

Ivermectin 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 in programs sponsored by the Carter Center using ivermectin donated by Merck. The disease is common in 30 African countries, six Latin American countries, and Yemen. The drug rapidly kills microfilariae, but not the adult worms. A single oral dose of ivermectin, taken annually for the 10-15-year lifespan of the adult worms, is all that is needed to protect the individual from onchocerciasis.

Arthropod

More recent evidence supports its use against parasitic arthropods and insects:

  • Mites such as scabies: It is usually limited to cases that prove to be resistant to topical treatments or that present in an advanced state (such as Norwegian scabies).
  • Lice: Ivermectin lotion (0.5%) is FDA-approved for patients six months of age and older. After a single, 10-minute application of this formulation on dry hair, 78% of subjects were found to be free of lice after two weeks. This level of effectiveness is equivalent to other pediculicide treatments requiring two applications.
  • Bed bugs: Early research shows that the drug kills bed bugs when taken by humans at normal doses. The drug enters the human bloodstream and if the bedbugs bite during that time, they will die in a few days.

Rosacea

An ivermectin cream has been approved by the FDA, as well as in Europe, for the treatment of inflammatory lesions of rosacea. The treatment is based upon the hypothesis that parasitic mites of the genus Demodex play a role in rosacea. In a clinical study, ivermectin reduced lesions by 83% over 4 months, as compared to 74% under a metronidazole standard therapy.


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Contraindications

Ivermectin is contraindicated in children under the age of five, or those who weigh less than 15 kilograms (33 pounds) and those who are breastfeeding, and have a hepatic or renal disease.


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Side effects

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 (MDR1), often collie-like herding dogs, can be severely poisoned by ivermectin.

Since drugs that inhibit CYP3A4 enzymes often also inhibit P-glycoprotein transport, the risk of increased absorption past the blood-brain barrier exists when ivermectin is administered along with other CYP3A4 inhibitors. These drugs include statins, HIV protease inhibitors, many calcium channel blockers, and glucocorticoids such as dexamethasone, lidocaine, and the benzodiazepines.

For dogs, the insecticide spinosad may have the effect of increasing the potency of ivermectin.


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Pharmacology

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 to glutamate-gated chloride channels (GluCls) in the membranes of invertebrate nerve and muscle cells, causing increased permeability to chloride ions, resulting in cellular hyper-polarization, followed by paralysis and death. 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 due to the presence of P-glycoprotein, (the MDR1 gene mutation affects function of this protein). Crossing may still become significant if ivermectin is given at high doses (in which case, brain levels peak 2-5 hr after administration). In contrast to mammals, ivermectin can cross the blood-brain barrier in tortoises, often with fatal consequences.

Ecotoxicity

Field studies have demonstrated the dung of animals treated with ivermectin supports a significantly reduced diversity of invertebrates, and the dung persists longer.


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History

The discovery of the avermectin family of compounds, from which ivermectin is chemically derived, was made by Satoshi ?mura of Kitasato University, Tokyo and William C. Campbell of the Merck Institute for Therapeutic research. ?mura identified avermectin from the bacterium Streptomyces avermitilis. Campbell purified avermectin from cultures obtained from ?mura and led efforts leading to the discovery of ivermectin, a derivative of greater potency and lower toxicity. Ivermectin was introduced in 1981. Half of the 2015 Nobel Prize in Physiology or Medicine was awarded jointly to Campbell and ?mura for discovering avermectin, "the derivatives of which have radically lowered the incidence of river blindness and lymphatic filariasis, as well as showing efficacy against an expanding number of other parasitic diseases".


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Brand names

It is sold under brand names Heartgard, Sklice and Stromectol in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, Iver-DT in Nepal by Alive Pharmaceutical and Ivexterm in Mexico by Valeant Pharmaceuticals International. In Southeast Asian countries, it is marketed by Delta Pharma Ltd. under the trade name Scabo 6. While in development, it was assigned the code MK-933 by Merck.


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Veterinary use

In veterinary medicine ivermectin is used against many intestinal worms (but not tapeworms), most mites, and some lice. Despite this, it is not effective for eliminating ticks, flies, flukes, or fleas. Eggs and larvae mature and come back to the host. It is effective against larval heartworms, but not against adult heartworms, though it may shorten their lives. The dose of the medicine must be very accurately measured as it is very toxic in over-dosage. 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 (coding for P-glycoprotein); affected animals are particularly sensitive to the toxic effects of ivermectin. Clinical evidence suggests kittens are susceptible to ivermectin toxicity. 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 reptiles are very sensitive to ivermectin. Use in turtles is particularly contraindicated.


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Research

Ivermectin is also being studied as a potential antiviral agent against the viruses chikungunya and yellow fever.

A 2012 Cochrane review found weak evidence suggesting that ivermectin could result in the reduction of chorioretinal lesions and prevent loss of vision in people with onchocerciasis.

In 2013, this antiparasitic drug was demonstrated as a novel ligand of farnesoid X receptor (FXR), a therapeutic target for Nonalcoholic Fatty Liver Disease.

Source of the article : Wikipedia



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