DE2112648B2 - Orally administered drug for cardiac arrhythmias - Google Patents

Description

The invention relates to an orally administrable combination preparation for the treatment of cardiac arrhythmias, which is characterized in more detail in the claim.

It is already known that verapamil is very successful in the treatment of cardiac arrhythmias can achieve (see, for example, drug research 14, 461 [1964]). Quinidine can also be used for treatment use of such heart disorders. All means of treating cardiac arrhythmias - and that applies also for verapamil - are normally only applicable in those dose ranges in which side effects that are always present do not yet appear. There are, however, in clinical Practice cases in which, due to an exceptional situation, ■ excessive doses of cardiac medication must be administered to achieve success. Such treatment is always with one high risk involved.

The invention is based on the object of this

in reducing risk and improving healing results To achieve arrhythmias.

The invention relates to an orally administrable medicament against cardiac arrhythmias, thereby characterized that there is a) verapamil and b)

r. Quinidine in a weight ratio of la): 1b) to 1 a): 4b), preferably from 1 a): 2b) to 1 a): 3b).

This combination has the advantage, Jaß der

The safety margin between the therapeutically effective and cardiotoxic effects of verapamil is clear

jo is increased by adding Quantities of quinidine which, when administered alone, are below those used to combat cardiac arrhythmias needed gifts.

The table shows the superior effect of the new

_ · -> combination.

Tabel

Influence of various heart parameters on the dog's heart-lung preparation

Isoptin rj.g / 10 min Isoptin [jig / IO min

0 25 50 100 200 400 0 25 50 100

Quinidine rig / 10 min quinidine [ig / 10 min

0 250 250 250 250 250 -

200

400

preparation 7th 3 with preserved rhythm 29 57 85 0 6th 50 0 -4 2 9 24 heart 0 PQ duration: quiet Increase in% 0 7th 10 16 23 34 50 0 16 87 0 5 12th 15th 19th was standing 0 PP time: 5 12th 31 42 3 12th 13th 19th 46 0 Increase in% 0 13th Atrial pressure in mm H ₂ O 4th preparation 7th with an artificial pacemaker in the performance test 0 4th 0 -I I. 5 0 Refractory Chamber: Increase in% 0 6th 14th 37 114 191 0 Excitability chamber: Increase in stimulus voltage in%

Verapamil resp. Quinidine alone and in combination tested comparatively.

If the heart's own rhythm is preserved, the combination achieves an increased decrease in the beat frequency (Increase in PP-Zcit) as well as an increased duration of the transition time (increase in PQ duration), and to a greater extent than is possible with either of the two connections with a single application. The atrial pressure increases with load on the heart in the l.cistungstcst when using the combination in smaller dimensions than with single application, the same high crapamil levels, d. that is, the heart remains more efficient under the conditions of simultaneous use of quinidine and verapamil. this is also evidenced by the fact that verapamil is administered at a dose of 400 µg / kg / min together with quinidine without a standstill occurring.

If the sinus button is artificially switched off and if the pacemaker is artificial, the combination is prolonged the Kammerrefraklärzcit stronger than is possible with verapamil or quinidine alone. the Ventricular excitability, however, decreases with the simultaneous use of quinidine and verapamil to a lesser extent than with verapamil alone. All other measured Her / parameters (refractory period atrium. Excitability-atrium, conduction time,

Cardiac output and pressure in the right atrium with and without load on the heart) are determined by the Combination qualitatively and quantitatively as affected by verapamil alone That means that two for the treatment of cardiac arrhythmias is reinforced by the combination of very important criteria without the heart's efficiency dropping under stress

The new combination is intended to be administered orally. The daily dose is about 3 to 5 mg / kg / day Verapamil in combination with 5 to 12 mg / kg / day quinidine.

The known galenic preparation forms such as tablets, coated tablets, Capsules and juices.

example 1

Tablets of the following composition are pressed in the usual way on a tablet press:

80.00 mg verapamil (hydrochloride)
Quinidine 200.00 mg
80.00 mg corn starch

9.00 mg gelatin
30.00 mg milk sugar
15.00 mg talc

1.50 mg of flame-dispersed chemically pure
Silica in submicroscopic
fine distribution

4.50 mg potato starch (as a 6% solution)

Example 2

Will be in the usual way
Composition made:

Dragees following

50.00 mg verapamil (hydrochloride)
100.00 mg quinidine
85.00 mg core mass
80.00 mg saccharification massc

r> The core mass consists of 9 parts of corn starch, 3 Parts of milk sugar and I part of vinylpyrrolidone-vinyl acetate copolymer 60:40, see Pharm. Ind. 1% 2, 586. The saccharification mass consists of 5 parts Cane sugar, 2 parts corn starch, 2 parts calcium car-

> »Bonal and 1 part talc.

Example 3

A mixture of verapamil (hydrochloride) and quinidine in a ratio of 1: 4 is used in the usual way r> Capsules with a content of 350 mg are filled and the capsules are sealed.

Claims (2)

Patent claims: 1. Orally administered drug against Cardiac arrhythmias, characterized that it contains a) verapamil and b) quinidine in a weight ratio of la): Ib) to la): 4b). 2. Medicament according to claim 1, characterized characterized in that the ratio of a) to b) is 1 a): 2b) to 1 a): 3h).