Artemether is a medication used for the treatment of

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

. The injectable form is specifically used for severe malaria rather than

quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to ''Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg ...

. In adults, it may not be as effective as

artesunate Artesunate (AS) is a medication used to treat malaria. The intravenous form is preferred to quinine for severe malaria. Often it is used as part of combination therapy, such as artesunate plus mefloquine. It is not used for the prevention of ...

. It is given by injection in a muscle. It is also available by mouth in combination with lumefantrine, known as

artemether/lumefantrine Artemether/lumefantrine, sold under the trade name Coartem among others, is a combination of the two medications artemether and lumefantrine. It is used to treat malaria caused by ''Plasmodium falciparum'' that is not treatable with chloroquine ...

. Artemether causes relatively few side effects. An

irregular heartbeat Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beats ...

may rarely occur. While there is evidence that use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

may be harmful in animals, there is no evidence of concern in humans. The

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

(WHO) therefore recommends its use during pregnancy. It is in the

artemisinin Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to ''Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for he ...

class of medication. Artemether has been studied since at least 1981, and has been in medical use since 1987. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Medical uses

Artemether is an antimalarial drug for uncomplicated malaria caused by '' P. falciparum'' (and chloroquine-resistant '' P. falciparum'') or chloroquine-resistant '' P. vivax'' parasites. Artemether can also be used to treat severe malaria. The

(WHO) recommends the treatment of uncomplicated '' P. falciparum'' with artemisinin-based combination therapy. Given in combination with lumefantrine, it may be followed by a 14-day regimen of primaquine to prevent relapse of ''P. vivax'' or ''P. ovale'' malarial parasites and provide a complete cure. Artemether can also be used in treating and preventing trematode infections of

schistosomiasis Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever is a neglected tropical helminthiasis, disease caused by parasitism, parasitic Schistosoma, flatworms called schistosomes. It affects both humans and animals. It affects ...

when used in combination with

praziquantel Praziquantel, sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections in mammals, birds, amphibians, reptiles, and fish. In humans specifically, it is used to treat schist ...

. Artemether is rated category C by the FDA based on animal studies where artemisinin derivatives have shown an association with fetal loss and deformity. Some studies, however, do not show evidence of harm.

Side effects

Possible side effects include cardiac effects such as bradycardia and

QT interval The QT interval is a measurement made on an Electrocardiography, electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the QRS complex, Q wave to the end of the T wave, an ...

prolongation. Also, possible central nervous system toxicity has been shown in animal studies.

Drug interactions

Plasma artemether level was found to be lower when the combination product was used with lopinavir/ritonavir. There is also decreased drug exposure associated with concurrent use with efavirenz or nevirapine. Artemether/lumefantrine should not be used with drugs that inhibit

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

. Hormonal contraceptives may not be as efficacious when used with artemether/lumefantrine.

Pharmacology

Mechanism of action

A possible mechanism of action is that artemisinin drugs exert their cidal action by inhibiting PfATP6. Since PfATP6 is an enzyme regulating cellular calcium concentration, its malfunctioning will lead to intracellular calcium accumulation, which in turns causes cell death.

Pharmacokinetics

Absorption of artemether is improved 2- to 3-fold with food. It is highly bound to protein (95.4%). Peak concentrations of artemether are seen 2 hours after administration. Artemether is metabolized in the human body to the active metabolite, dihydroartemisinin, primarily by hepatic enzymes CYP3A4/5. Both the parent drug and active metabolite are eliminated with a half-life of about 2 hours.

Chemistry

Artemether is a

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

ether In organic chemistry, ethers are a class of compounds that contain an ether group, a single oxygen atom bonded to two separate carbon atoms, each part of an organyl group (e.g., alkyl or aryl). They have the general formula , where R and R� ...

derivative of

, which is a peroxide-containing

lactone Lactones are cyclic carboxylic esters. They are derived from the corresponding hydroxycarboxylic acids by esterification. They can be saturated or unsaturated. Lactones are formed by lactonization, the intramolecular esterification of the corresp ...

isolated from the antimalarial plant '' Artemisia annua''. It is also known as dihydroartemisinin methyl ether, but its correct chemical nomenclature is (+)-(3-alpha,5a-beta,6-beta,8a-beta, 9-alpha,12-beta,12aR)-decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin. It is a relatively lipophilic and unstable drug, which acts by creating reactive free radicals in addition to affecting the membrane transport system of the plasmodium organism.

References

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