Disopyramide

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Structural formula
Structure of (±) -disopyramide
1: 1 mixture of ( R ) -enantiomer (left) and ( S ) -enantiomer (right)
General
Non-proprietary name Disopyramide
other names
  • (±) -4-Dipropan-2-ylamino-2-phenyl-2-pyridin-2-yl-butanamide
  • ( RS ) -4-Dipropan-2-ylamino-2-phenyl-2-pyridin-2-yl-butanamide
  • rac -4-Dipropan-2-ylamino-2-phenyl-2-pyridin-2-yl-butanamide
Molecular formula C 21 H 29 N 3 O
Brief description

White dust

External identifiers / databases
CAS number 3737-09-5
EC number 223-110-2
ECHA InfoCard 100.021.010
PubChem 3114
DrugBank DB00280
Wikidata Q425120
Drug information
ATC code

C01 BA03

Drug class

Antiarrhythmic

Mechanism of action

Sodium channel blockers

properties
Molar mass 339.47 g mol −1
Physical state

firmly

Melting point

94.5-95 ° C ; 205 ° C (phosphate)

pK s value

8.34

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: 302-361
P: 281
Toxicological data

333 mg kg −1 ( LD 50 ,  rat ,  oral )

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

absorption 80-90%
Half-life 8–9 hours
Bioavailability > 80%
Plasma protein binding ~ 30-40%
Crosses the placenta Yes
usual dosage 4 x 100 to 200 mg / day
Dose range 400 to 1200 mg / day
elimination renal

Disopyramide is a drug from the group of antiarrhythmics IA according to Vaughan-Williams, for the treatment of ventricular cardiac arrhythmias and has similar pharmacological properties as quinidine and procainamide . It is only used clinically in oral form and is also available in a retarded dosage form. The phosphate (salt with phosphoric acid in a molar ratio of 1: 1) is used. Disopyramide is mainly excreted through the kidneys . Disopyramide was patented by Searle as an antiarrhythmic in 1962.

Stereochemistry

Disopyramide is used in practice as a racemate [1: 1 mixture of the enantiomeric ( S ) or ( R ) forms], although the importance of the enantiomeric purity of the synthetically produced active ingredients is increasingly being given attention, because the two enantiomers of a chiral drug almost always show different pharmacology and pharmacokinetics. In the past, this was often ignored due to a lack of knowledge of stereochemical relationships. The plasma concentrations of the enantiomeric ( S ) or ( R ) forms of disopyramide differ significantly after administration of the 1: 1 mixture.

Electrophysiological effects

Disopyramide primarily inhibits the sodium channels on the cell membrane of rhythm-generating cells in the heart muscle and thus extends the action potential. It has strong anti-parasympathetic, i.e. atropine- like, anticholinergic-vagolytic effects, and does not affect the alpha or beta adrenoceptors of the sympathetic nervous system. The refractory periods of the atria and ventricles are shortened by the drug.

Hemodynamic effects

Disopyramide noticeably reduces the force of contraction of the left ventricle and reduces cardiac output. It has a widening effect on the arterial blood vessels. This can lower your blood pressure. It is poorly tolerated by patients with impaired pumping function of the heart and should be discontinued.

Indications

In some patients, disopyramide is able to prevent ventricular extrasystoles (VES) and ventricular tachycardias (VT). Combination with other antiarrhythmic drugs such as mexiletine can be effective when one drug alone is not enough.

Disopyramide can prevent recurrence of atrial fibrillation after cardioversion and stop atrial flutter. It is important to check the ventricular rate before using it to prevent 1: 1 conduction.

The drug has been used to prevent neurogenic syncope and, due to its negative inotropic properties, also in hypertrophic cardiomyopathy with dynamic obstruction.

unwanted effects

There are three groups of side effects:

Contraindications and interactions

The substance should not be used in cases of decompensated heart failure , bradycardia and intoxication with cardiac glycosides . As with the class IC antiarrhythmics, according to the CAST study, if coronary artery disease is also present, there may be excess mortality, so that a cardiac catheter examination may be required before the use of disopyramide if there is a suspicion. Erythromycin extends the half-life and thus increases the effect of the substance, as do tricyclic antidepressants and neuroleptics .

Trade names

Monopreparations
Rytmodul, Diso-Duriles, Rythmodan

Web links

Individual evidence

  1. ↑ a b c d e entry on disopyramide. In: Römpp Online . Georg Thieme Verlag, accessed on June 30, 2019.
  2. ↑ a b Data sheet Disopyramide from Sigma-Aldrich , accessed on March 28, 2011 ( PDF ).
  3. ↑ Entry on disopyramide in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  4. ^ JM Miller, DP Zipes: Therapy for Cardiac Arrhythmias. In: DP Zipes, P. Libby, RO Bonow, E. Braunwald (Eds.): Braunwald's Heart Disease, A Textbook of Cardiovascular Medicine . Elsevier Saunders, Philadelphia 2005, ISBN 0-8089-2305-6 , p. 722.
  5. ↑ E. Mutschler, M. Schäfer-Korting: drug effects. Textbook of pharmacology and toxicology. 7th edition. Wissenschaftliche Verlagsgesellschaft, Stuttgart 1996, ISBN 3-8047-1377-7 , pp. 461-462.
  6. ^ EJ Ariëns: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. In: European Journal of Clinical Pharmacology . 26, 1984, pp. 663-668, doi: 10.1007 / BF00541922 .
  7. ↑ JJ Lima, GL Jungbluth, T. Devine, LW Robertson: Stereoselective binding of dispyramide to human plasma protein. In: Life Science. 35, 1984, p. 835.
  8. ↑ Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. 5th edition. Springer, Berlin / Heidelberg / New York et al. 1999, ISBN 3-540-65024-5 , p. 73.