Ethambutol (EMB, E) is a medication primarily used to treat

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

. It is usually given in combination with other tuberculosis medications, such as

isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis, it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. F ...

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...

and

pyrazinamide Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. It i ...

. It may also be used to treat ''Mycobacterium avium'' complex, and ''

Mycobacterium kansasii ''Mycobacterium kansasii'' is a Bacteria, bacterium in the ''Mycobacterium'' genus. It is an environmental bacteria that causes opportunistic infections in humans, and is one of the leading mycobacterial causes of human disease after tuberculosi ...

''. It is taken by mouth. Common side effects include problems with vision, joint pain, nausea, headaches, and feeling tired. Other side effects include

liver problems Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...

and

allergic reactions Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...

. It is not recommended in people with

optic neuritis Optic neuritis (ON) is a debilitating condition that is defined as inflammation of cranial nerve II which results in disruption of the neurologic pathways that allow visual sensory information received by the retina to be able to be transmitted to ...

, significant

kidney problems Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...

, or under the age of five. 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 ...

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

has not been found to cause harm. In the United States the FDA has raised concerns about eye issues in the baby if used during pregnancy. Ethambutol is believed to work by interfering with the bacteria's

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

. Ethambutol was discovered in 1961. It is on 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 ...

's List of Essential Medicines and is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

Chirality and biological activity

(''S'',''S'')-(+)-Ethambutol is powerful and selective antitubercular drug. It is a typical example of an old drug that was introduced for clinical use in its unichiral form. Ethambutol contains two constitutionally symmetrical

chiral center In stereochemistry, a stereocenter of a molecule is an atom (center), axis or plane that is the focus of stereoisomerism; that is, when having at least three different groups bound to the stereocenter, interchanging any two different groups cr ...

s in its structure and exists in three stereoisomeric forms, the enantiomeric pair (+)-(''S'',''S'')- and (−)-(''R'',''R'')-ethambutol, along with the achiral stereoisomer called ''meso''-form. The (+)-(''S'',''S'')-enantiomer harbors the antitubercular activity. This enantiomer is 500 and 12 fold more potent than (−)-(''R'',''R'')-ethambutol and the ''meso-''form respectively. On the other hand, all the three isomers are equipotent in terms of the major side-effect of the drug, optic neuritis. Toxicity is associated to both dose and duration of treatment. Hence the use of (''S'',''S'')-enantiomer greatly improved the risk/benefit balance.

Medical uses

Ethambutol is used along with other medications to treat a number of infections including:

, ''Mycobacterium avium'' complex, and ''

''.

Adverse effects

Optic neuritis Optic neuritis (ON) is a debilitating condition that is defined as inflammation of cranial nerve II which results in disruption of the neurologic pathways that allow visual sensory information received by the retina to be able to be transmitted to ...

(hence contraindicated in children below six years of age) *

Red–green color blindness Color blindness, color vision deficiency (CVD) or color deficiency is the decreased ability to see color or differences in color. The severity of color blindness ranges from mostly unnoticeable to full absence of color perception. Color bl ...

People taking ethambutol should be monitored for changes in visual acuity and color discrimination. *

Arthralgia Arthralgia () literally means ' joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceuti ...

* Hyperuricaemia * Vertical

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) Eye movement (sensory), eye movement. People can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in visual impairment, re ...

* Skin rash

Mechanism of action

Ethambutol is

bacteriostatic A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfec ...

against actively growing TB bacilli. It works by obstructing the formation of

cell wall A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...

Mycolic acid Mycolic acids are long fatty acids found in the cell walls of Mycobacteriales taxon, a group of bacteria that includes ''Mycobacterium tuberculosis'', the causative agent of the disease tuberculosis. They form the major component of the cell wall ...

s attach to the 5'-hydroxyl groups of D-arabinose residues of

arabinogalactan Arabinogalactan, also known as galactoarabinan, larch arabinogalactan, and larch gum, is a biopolymer consisting of arabinose and galactose monosaccharides. Two classes of arabinogalactans are found in nature: plant arabinogalactan and microbial ...

and form mycolyl-arabinogalactan-peptidoglycan complex in the cell wall. It disrupts arabinogalactan synthesis by inhibiting the enzyme arabinosyl transferase. Disruption of the arabinogalactan synthesis inhibits the formation of this complex and leads to increased permeability of the cell wall.

Pharmacokinetics

It is well absorbed from the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

and well distributed in body tissues and fluids. 50% is excreted unchanged in urine.

References

{{Portal bar , Medicine Anti-tuberculosis drugs Diamines Diols Secondary amines World Health Organization essential medicines Wikipedia medicine articles ready to translate Substances discovered in the 1960s