Ethambutol

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Structural formula
Structural formula of ethambutol
General
Non-proprietary name Ethambutol
other names

( S , S ) -2- [2- (1-Hydroxybutan-2-ylamino) ethylamino] butan-1-ol

Molecular formula C 10 H 24 N 2 O 2
External identifiers / databases
CAS number
EC number 200-810-6
ECHA InfoCard 100,000,737
PubChem 14052
DrugBank DB00330
Wikidata Q412318
Drug information
ATC code

J04 AK02

Drug class

antibiotic

properties
Molar mass 204.31 g mol −1
Melting point
  • Free base: 87.5-88.8 ° C
  • Dihydrochloride: 198.5-200.3 ° C
solubility

50 mg ml −1 (water)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
08 - Dangerous to health

danger

H and P phrases H: 360
P: 201-308 + 313
Toxicological data

240 mg kg −1 ( LD 50 ,  mouse ,  iv )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Ethambutol , abbreviated to EMB, is a drug from the group of antibiotics that is preferred for the treatment of tuberculosis , but also for other infections caused by mycobacteria . It may only be used in combination with other antimycobacterial agents. Due to the considerable side effect profile, its use must be closely monitored - especially by an ophthalmologist.

Mode of action

Ethambutol is quickly absorbed by mycobacteria. It hinders the normal structure of the cell walls, which, due to their special structure, causes mycobacteria to be extraordinarily resistant by preventing the biosynthesis of specific polysaccharides , so-called arabinogalactans , arabinomannans and peptidoglycans . The reason for this is an inhibiting effect on a path of carbohydrate metabolism , which leads from glucose to arabinose and mannose .

Depending on the concentration, it has a bacteriostatic to bactericidal effect only on multiplying (proliferating) pathogens. A primary resistance of the mycobacteria to ethambutol is very rare and acquired develop only slowly. There is no cross-resistance to other tuberculosis drugs.

Pharmacokinetics

After ingestion, ethambutol is rapidly and almost completely absorbed by the gastrointestinal tract (absorption ~ 80%). The highest concentration in the blood (peak level) is reached about 2–4 hours after ingestion. Excretion is largely unchanged via the kidneys . Only a small proportion is excreted unchanged via the bile or in a modified form with the urine . After 24 hours, the concentration in the blood drops less than a tenth of the peak level. Both red blood cells ( erythrocytes ) and tissue cells in the lungs (alveolar cells, macrophages) can accumulate ethambutol, so that the concentration in these cells is considerably higher than in the serum .

Side effects

Depending on the dose administered and the duration of the treatment, inflammation of the optic nerve ( optic neuritis ) can occur, which initially manifests itself as a disorder of color vision, later in visual field defects up to complete loss of vision. Damage to both the central and peripheral nervous systems ( neuropathy ) with dizziness, headaches, confusion, hallucinations, weakness and sensory disorders ( paresthesia ) have also been described. Common side effects include an increase in the uric acid concentration in the serum, which returns to normal after discontinuation. Loss of appetite, heartburn , vomiting, diarrhea or allergic reactions with fever or itchy rashes occur rarely . Changes in the blood count with a decrease in the number of white blood cells ( leukocytes ) or blood platelets ( thrombocytes ) as well as liver and kidney dysfunction can also be observed very rarely .

Stereoisomerism

2- [2- (1-Hydroxybutan-2-ylamino) ethylamino] butan-1-ol contains two stereocenters, which are each provided with the same substituents, consequently there are three stereoisomers of this substance, namely the ( S , S ) - Form, the mirror image ( enantiomeric ) ( R , R ) form and the meso form. The ( S , S ) form is used exclusively as a medicinal substance .

Trade names

Monopreparations

EMB-Fatol (D), Etibi (A), Myambutol (D, A, CH)

Combination preparations

Rimstar (CH)

Individual evidence

  1. ↑ a b The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , p. 638.
  2. ↑ a b c Data sheet Ethambutol dihydrochloride from Sigma-Aldrich , accessed on June 11, 2019 ( PDF ).
  3. ↑ Entry on ethambutol. In: Römpp Online . Georg Thieme Verlag, accessed on November 11, 2014.
  4. ↑ K. Takayama, JO Kilburn: Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis. In: Antimicrobial Agents and Chemotherapy . 33 (1989), pp. 1493-1499. PMID 2817850 , PMC 172689 (free full text).
  5. ↑ G. Silve, P. Valero-Guillen, A. Quemard, M.-A. Dupont, M. Daffé, G. Laneelle: Ethambutol inhibition of glucose metabolism in mycobacteria: a possible target of the drug. In: Antimicrobial Agents and Chemotherapy. 37: 1536-1538 (1993). PMID 8363387 , PMC 188008 (free full text).
  6. ↑ K. Mikusová, RA Slayden, GS Besra, PJ Brennan: Biogenesis of the mycobacterial cell wall and the site of action of ethambutol. In: Antimicrobial Agents and Chemotherapy. 39: 2484-2489 (1995). PMID 8585730 , PMC 162969 (free full text).
  7. ↑ AE Belanger, GS Besra, ME Ford et al: The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol . In: Proc. Natl. Acad. Sci. USA band 93 , no. October 21 , 1996, p. 11919-11924 , PMID 8876238 , PMC 38159 (free full text).
  8. ↑ Red List (08/2009).
  9. ↑ AM comp. d. Switzerland (08/2009).
  10. ↑ AGES-PharmMed (08/2009).