Captopril

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Structural formula
Structural formula
General
Non-proprietary name Captopril
other names

( S ) -1 - [( S ) -2-methyl-3-sulfanylpropanoyl] pyrrolidine-2-carboxylic acid

Molecular formula C 9 H 15 NO 3 S
External identifiers / databases
CAS number 62571-86-2
EC number 263-607-1
ECHA InfoCard 100.057.806
PubChem 44093
ChemSpider 40130
DrugBank DB01197
Wikidata Q421119
Drug information
ATC code

C09 AA01

Drug class

ACE inhibitors

Mechanism of action

Inhibition of the angiotensin converting enzyme

properties
Molar mass 217.29 g mol −1
Physical state

firmly

Melting point

104-108 ° C

solubility

moderate in water (100 g l −1 at 20 ° C )

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

Caution

H and P phrases H: 317-361
P: 280
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Captopril is a drug in the group of ACE inhibitors that is used in particular to treat arterial hypertension (high blood pressure) and heart failure . Its operating principle is based on the inhibition of the angiotensin converting enzyme (ACE).

It was developed by Miguel Ondetti and David Cushman at Squibb in 1974 and approved in 1981.

chemistry

Captopril was modeled on the ACE-inhibiting peptides of the venom of the Jararaca lance viper ( Bothrops jararaca ), a Brazilian snake , and is the lead substance for the group of ACE inhibitors. The substance is formally a condensation product of the amino acid ( S ) - proline (synonym: L- proline ) and ( S ) -3-mercapto-2-methylpropionic acid and the only ACE inhibitor with an SH group.

Captopril synthesis starting from (S) -proline

The technical process for the production of captopril is based on the acylation of the natural amino acid ( S ) - proline with ( S ) -2-methyl-3-acetylsulfanylpropanoyl chloride and the subsequent cleavage of the acetyl group .

pharmacology

application areas

Captopril is used as monotherapy and in combination with diuretics for the treatment of arterial hypertension and heart failure, whereby the synergistic effects lead to an increased decrease in blood pressure. In severe chronic forms of heart failure, a combination with digitalis and beta blockers is possible and also indicated. Other areas of application are short-term treatment (4 weeks) after myocardial infarction and diabetic nephropathy with macroproteinuria in type I diabetes mellitus patients.

In kidney scintigraphy , captopril is often used to check kidney function under "stressful conditions".

Mechanism of action

Captopril leads as inhibitor of angiotensin converting enzyme in a decreased formation of angiotensin II from angiotensin I . This reduced formation of angiotensin II causes a decrease in the tone of the blood vessels and thus a decrease in blood pressure. The decrease in the angiotensin II level also leads to a reduction in the release of aldosterone from the adrenal cortex and thus to an influence on the water balance (see also renin-angiotensin-aldosterone system ). At the cellular level, a decrease in angiotensin-II-mediated mitogenic effects on cells of the heart, which lead to unfavorable changes (remodeling), especially after a myocardial infarction, can be observed.

Side effects

Most of the side effects of captopril are associated with slower breakdown and accumulation of bradykinin due to ACE inhibitors . These include skin reactions such as B. exanthema and hives , also angioedema . Serious allergic skin reactions, however, are only very rarely observed.

Respiratory side effects include dry cough , hoarseness, and sore throat. Asthma attacks and shortness of breath can also occur, albeit rarely.

An excessive decrease in blood pressure may occur as a result of the main action of captopril. As a result, dizziness , headache, and drowsiness may occasionally be observed. Serious cardiovascular events such as angina pectoris , myocardial infarction and syncope have only been reported in isolated cases.

Functional kidney dysfunctions can occasionally be observed through interference with the water and electrolyte balance. A proteinuria (excretion of protein in the urine ), however, was rarely observed.

Since captopril in pregnancy u. a. Can cause growth and bone formation disorders in the child, combined with increased mortality , captopril must not be taken during this time and should be replaced by other suitable therapeutic measures.

Interactions

Captopril increases the blood sugar lowering effect of insulin and oral antidiabetic drugs, as well as the blood count-altering effects of immunosuppressants.

By interfering with the water and electrolyte balance, the elimination of electrolytes can be slowed down, which should be taken into account in particular when treating with lithium and potassium-sparing diuretics.

When combined with other antihypertensive drugs, increased blood pressure lowering should be taken into account.

Trade names

Monopreparations

Captosol (CH), Cor tensobon (D), Debax (A), Lopirin aH (CH), Lopirin Cor (D), Tensobon (D), numerous generics (D, A)

Combination preparations
  • In combination with hydrochlorothiazide : Captosol comp. (CH), Capozide (A, CH), Tensobon comp. (D), generics (D, A, CH)
  • In combination with Verapamil : Veracapt (A)

Individual evidence

  1. a b c d data sheet captopril at Sigma-Aldrich , accessed on October 18, 2016 ( PDF ).Template: Sigma-Aldrich / name not given
  2. Mutschler, Geisslinger, Kroemer, Ruth, Schäfer-Korting, Mutschler: Medicinal Effects , 9th Edition, 2008, ISBN 3-8047-1952-X .
  3. ^ Axel Kleemann, Jürgen Engel, Bernd Kutscher and Dieter Reichert: Pharmaceutical Substances , 4th edition (2000) 2 volumes published by Thieme-Verlag Stuttgart, pp. 335–337, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.
  4. Captopril renography ( Memento of September 5, 2012 in the web archive archive.today ), www.medcyclopaedia.com, accessed on January 24, 2008.