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

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

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

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

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

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

''. 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 and allergic reactions. It is not recommended in people with optic neuritis, significant kidney problems, or under the age of five. Use during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

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 el, μεταβολή ''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 cell ...

. Ethambutol was discovered in 1961. It is on the

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'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 centers in its structure and exists in three stereoisomeric forms. An enantiomeric pair (S,S)- and (R,R)-ethmabutol, 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 the (R,R)-ethmabutol 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 (hence contraindicated in children below six years of age) *

Red-green color blindness Color blindness or color vision deficiency (CVD) is the decreased ability to see color or differences in color. It can impair tasks such as selecting ripe fruit, choosing clothing, and reading traffic lights. Color blindness may make some aca ...

People taking ethambutol should be monitored for changes in visual acuity and color discrimination. * Arthralgia * Hyperuricaemia * Vertical nystagmus * Milk skin reaction

Mechanism of action

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

cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...

. Mycolic acids attach to the 5'-hydroxyl groups of D-arabinose residues of arabinogalactan and form mycolyl-arabinogalactan-peptidoglycan complex in the cell wall. It disrupts arabinogalactan synthesis by inhibiting the enzyme

arabinosyl transferase An arabinosyltransferase is a transferase enzyme acting upon arabinose. This enzyme is involved in polymerisation of arabinogalactan (an essential component of the mycobacterial cell wall). Mycobacterially, the more precise term is arabinofuranos ...

. 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 digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...

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

References

External links

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