Bumetanide

from Wikipedia, the free encyclopedia
Structural formula
Structure of the bumetanide
General
Non-proprietary name Bumetanide
other names
  • Bumetanide
  • 3-butylamino-4-phenoxy-5-sulfamoylbenzoic acid
  • PF1593
Molecular formula C 17 H 20 N 2 O 5 S
Brief description

white crystalline powder

External identifiers / databases
CAS number 28395-03-1
EC number 249-004-6
ECHA InfoCard 100.044.534
PubChem 2471
ChemSpider 2377
DrugBank DB00887
Wikidata Q275926
Drug information
ATC code

C03 CA02

Drug class

Diuretic

properties
Molar mass 364.4 g mol −1
Physical state

firmly

Melting point

232-237 ° C

solubility
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Bumetanide is a drug from the group of loop diuretics . The short-acting saludiuretic has been approved in Switzerland since 1974.

synthesis

In a first step, the sulfonyl chloride is converted into the corresponding sulfonamide with ammonia . The reaction with sodium phenolate gives the biphenyl ether in a nucleophilic substitution. The aniline is obtained by catalytic hydrogenation, which is then reacted with butanol to form the secondary amine.

Synthesis of bumetanide

pharmacology

Pharmacodynamics

Bumetanide is an inhibitor ; it inhibits the action of the sodium, potassium and chloride symporters (Na + -2Cl - -K + -Cotransporters), which are located in the nephrons in the thick ascending limb (TAL) at the interface between Henle's loop with the kidney tubules (tubules).

Pharmacokinetics

The bioavailability of bumetanide when taken orally is about 90%. Thirty minutes to two hours after administration, a maximum plasma concentration of 30 µg / l is measured at a dose of 1 mg. The metabolism takes place through the oxidation of the N- butyl side chain with the formation of alcoholic metabolites. These are mainly excreted as glucuronides in the urine and bile and are inactive.

Bumetanide has a plasma half-life of 60 to 90 minutes and around 80% of the ingested amount is excreted in the urine within 48 hours, around 50% of which is not metabolized. The remaining 10–20% is excreted in the bile with the faeces .

Clinical information

Application areas (indications)

Bumetanide can be used to treat or prevent edema in cirrhosis of the liver ( ascites ), kidney diseases including nephrotic syndrome, and heart failure.

Contraindications (contraindications)

Bumetanide should not be used or should not continue to be used if there is a marked increase in the creatinine or urea level in the blood during therapy and in oliguria or anuria . In the case of renal insufficiency due to poisoning with nephrotoxic and hepatotoxic substances and coma hepaticum and in the presence of hypokalaemia or hyponatremia , bumetanide must also not be used. Other contraindications are pregnancy and breastfeeding and hypersensitivity to bumetanide.

Drug interactions

Bumetanide can increase the effect of antihypertensive drugs , tricyclic antidepressants and the toxic effect of nephrotoxic agents (for example non-steroidal anti-inflammatory drugs, aminoglycosides, cephalosporins). Taking phenytoin or non-steroidal anti-inflammatory drugs at the same time weakens the effect of the bumetanide. Bumetanide reduces the serum clearance of lithium and thus leads to increased lithium play in the blood. The effect of simultaneous administration of digoxin , however, is indirect; Bumetanide can cause hypokalaemia which increases the toxic effects of the digitalis. Probenecid inhibits the secretion of bumetanide.

Use during pregnancy and breastfeeding

Bumetanide may only be used during pregnancy if there is an urgent need to use the lowest effective dose, as it can cross the placental barrier and damage the unborn child. Its use is contraindicated during breastfeeding; if it is vital, breastfeeding must be stopped .

Adverse effects (side effects)

The following side effects can occur: exanthema , calf cramps, muscle tension, head pressure, dizziness, weakness, visual and hearing impairments, dry mouth, gastrointestinal disorders, pancreatitis , electrolyte losses (sodium, potassium, magnesium, calcium), hypovolemia , hypovolemia-related tendency to thrombosis , dehydration , Hyperuricemia , gout attacks , increased cholesterol, triglycerides, worsening of a prediabetic or diabetic metabolic situation , worsening of metabolic alkalosis , undesired lowering of blood pressure, circulatory collapse, vasculitis , anemia , leukopenia , thrombopenia , increased agranulocytosis , increased urine flow, symptoms of urinary tract, increased urinary tract, and urinary symptoms acute interstitial nephritis , hypersensitivity reactions.

Trade names

Bumetanid is sold as Burinex (DE, CH), Bumex (USA), Edemex, Lixil, Burine, Segurex, Fontego, Bufenox, Lunetoron and Fordiuran, among others.

abuse

Bumetanide can mask the intake of other drugs such as steroids in the urine and is therefore on the doping list .

Individual evidence

  1. ↑ a b c Entry on bumetanide in Pharmawiki , accessed on January 28, 2017.
  2. ↑ a b c Bumetanide. (PDF; 4.9 MB) In: The Japanese Pharmacopoeia (JP17). MHLW , March 2016, p. 531 , accessed on June 13, 2017 (English).
  3. ↑ Bumetanide at Scibo.de
  4. ↑ a b Bumetanide data sheet from Sigma-Aldrich , accessed on June 13, 2017 ( PDF ).
  5. ↑ a b c d Entry on bumetanide in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  6. ↑ a b c Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 7, p. 614, 1976.
  7. ^ Drugs in Japan. Vol. 6, p. 683, 1982.
  8. ^ A b Franz von Bruchhausen: Hager's Handbook of Pharmaceutical Practice. Springer-Verlag, 1930, ISBN 978-3-540-52688-9 , p. 547 ( limited preview in Google book search).
  9. ↑ DailyMed entry .
  10. ↑ a b c d e Burinex in the Open Drug Database, accessed December 5, 2018.