Antispasmodic
A spasmolytic agent (also antispasmodic , Muskelrelaxantium or Tonolytikum ) is an anticonvulsant drug . It lowers the tension of the smooth muscles or relieves their cramping ( spasmolytic ).
These pharmaceuticals are used for spasms (cramps) of the smooth muscles of the gastrointestinal tract , the biliary and urinary tract, the bronchi and the blood vessels.
A distinction is made between neurotropic and myotropic spasmolytics.
Neurotropic antispasmodics
Neurotropic spasmolytics work by blocking the parasympathetic receptor ( parasympatholytic ) or by activating the receptor of the sympathetic ( sympathomimetic ).
Parasympatholytics
The effect of this group of substances is based on the competitive inhibition of the acetylcholine effect on muscarinic receptors. The substances themselves have no intrinsic effect, i. H. in organs with a low cholinergic tone their effect is also small. Therefore, unlike parasympathomimetics, they have no effect on the vessels.
The prototype of this group is atropine or hyoscyamine . The latter is an alkaloid that has been used as an intoxicant for thousands of years. Natural sources of hyoscyamine are thorn apple , mandrake , angel's trumpet , deadly nightshade and henbane . The natural alkaloids hyoscyamine and scopolamine as well as atropine, drofenine and the quaternary derivatives butylscopolamine (among other things gastrointestinal effects) and ipratropium are used medicinally.
Pharmacokinetics
The non-quaternary substances are well absorbed from the gastrointestinal tract and other mucous membranes and easily cross the blood-brain barrier . The opposite is true for the quaternary derivatives. Elimination half-lives:
| Active ingredient | Elimination
half-life |
|---|---|
| Atropine | 3h |
| Scopolamine | 2-3h |
| Butylscopolamine | 5h |
| Ipratropium | 2-4h |
application
- Bronchial asthma : elimination of the vagal component of spasm of the bronchial muscles. Ipratropium causes fewer side effects when inhaled because there is less receptor blockage in other organs. However, the effect is often too weak, so that it is usually combined with a β 2 agonist.
- Spasms in the gastrointestinal tract, the bile ducts and the urinary tract ("colic") : Quaternary derivatives are usually used.
Side effects
The side effects result from the anticholinergic effects caused by receptor blockade
- Heart: tachycardia , etc. U. Angina pectoris attacks
- Gastrointestinal tract: delayed bowel movement, intestinal atony
- Eye: disorders of accommodation , sensitivity to light
- Salivary glands: dry mouth, difficulty swallowing
- CNS: tiredness or restlessness, hallucinations (mainly in the case of an overdose)
Commercial preparations and dosage
| Active ingredient | Trade name | Single dose | |
|---|---|---|---|
| Hyoscyamine | Dysurgal 0.5 mg | 0.25-1 mg | |
| Scopolamine | Scopoderm TTS | transdermal patch to combat motion sickness | |
| Butylscopolamine | Buscopan | 10-20 mg | |
| Ipratropium | Atrovent N metering aerosol | 40-80 µg | for inhalation |
Sympathomimetics
Sympathomimetics activate adrenoreceptors and thus imitate a sympathetic effect. A distinction is made between two adrenergic receptors, α and β receptors (with a further subdivision into α 1 , α 2 , β 1 , β 2 , β 3 receptors). These receptors sometimes have opposite effects. The activation of α-receptors in the bronchial system leads to the contraction of the smooth muscles, while β-receptors cause relaxation. Only substances that have a selective effect on β (usually β 2 ) receptors are therefore suitable as spasmolytics . Salbutamol , fenoterol , terbutaline and clenbuterol are mostly used therapeutically .
Pharmacokinetics
Bronchospasmolytics can be inhaled to achieve a faster onset of action (a few minutes). 10–30% of the inhalation reaches the deep bronchi. The rest is gradually swallowed and absorbed through the gastrointestinal tract. Oral bioavailability varies between 10% and 100% depending on the preparation.
| Active ingredient | Half-life |
|---|---|
| Salbutamol | approx. 6 h |
| Fenoterol | approx. 3 h |
| Terbutaline | 3-4 h |
| Clenbuterol | biphasic
1h / 34h |
application
- Bronchial asthma: both as an aerosol for inhalation and in tablet form.
- Uterus: to prevent labor during childbirth (emergency tocolysis) and for premature labor during pregnancy
Side effects
- Muscles: fine-pitched tremor
- CNS: feeling restless
- Heart / circulation: tachycardia, increase or decrease in blood pressure
- Respiratory tract: paradoxical bronchospasm
Commercial preparations
| Active ingredient | Trade name | application | Administration |
|---|---|---|---|
| Salbutamol | Sultanol | Bronchospasmolysis | Inhalant |
| Paediamol | Bronchospasmolysis | Inhalant | |
| Volumac | Bronchospasmolysis | Tabl. | |
| Fenoterol | Berotec, Berodual (combination preparation) | Bronchospasmolysis | Inhalant |
| Partusists | Tocolysis | Infusion / tabl. | |
| Terbutaline | Acrodur | Bronchospasmolysis | Inhalant |
| Contimit | Bronchospasmolysis | Tabl. | |
| Clenbuterol | Spasmo-Mucosolvan | Bronchospasmolysis | Tabl./juice/drops |
Myotropic antispasmodics
This group of substances includes a number of other spasmolytic substances that do not work via neurotransmitter receptors.
Organic nitrates
The mechanism of action of these substances is due to the release of NO in the smooth muscles of the vessels (NO donors). There is a binding to the soluble isoform of guanylate cyclase, which GTP converts into the second messenger cGMP. Vascular relaxation then occurs with the mediation of the cGMP-dependent protein kinase (PKG). Nitrovasodilators are used in coronary artery disease. It is used for seizure docking or seizure prophylaxis in angina pectoris. Depending on the pharmacokinetics and the pharmaceutical preparation, the onset of action varies between 20 seconds and an hour, the duration of action from 30 minutes to 16 hours.
Glycerin trinitrate (nitroglycerin), isosorbide-2,5-dinitrate (ISDN) and isosorbide-endo-5-mononitrate (ISMN) are used therapeutically as NO donors. The high lipophilicity of nitroglycerin and ISDN allow sublingual administration, through which a quick onset of action occurs. Retard tablets and depot plasters are used to extend the duration of action.
Calcium channel blockers
These vasodilating substances act on the L-type calcium channels . These voltage-dependent ion channels are responsible for the Ca 2+ influx in the smooth vascular muscles and the heart muscle , which triggers the contraction. The calcium channel blockers belong to three different groups of substances:
- Dihydropyridine (prototype is nifedipine)
- Phenylalkylamines
- Benzothiazepines
The different substances have a different molecular point of attack on the calcium channels. The area of application is angina pectoris and arterial hypertension . While the dihydropyridines have hardly any direct effects on the heart cells, the vascular and cardiac effects of the phenylalkylamine and the benzothiazepines cannot be separated.
Potassium channel opener
This group of substances increases the probability of opening potassium channels . This leads to a lowering of the resting membrane potential ( hyperpolarization ) as a result of which the calcium influx is reduced. This effect is pronounced on the smooth muscles of arterial blood vessels, so that these substances are used as vasodilators.
Clinically, diazoxide, minoxidil and pinacidil are used as potassium channel openers. The area of application is the treatment of hypertension. Diazoxide is used to treat hypoglycemia because of its action on pancreatic beta cells . Pinacidil is not used in Germany.
Hydralazine and dihydralazine
The exact mechanism of action of the vasodilators is not yet known. The active ingredient is used as a combination partner of antihypertensive three-way combinations (hydralazine + β-blocker + diuretic ).
See also
literature
- Forth, Henschler (Ed.): General and special pharmacology and toxicology , spectrum, ISBN 3-8274-0088-0
- Lüllmann et al .: Pharmacology and Toxicology , Thieme, ISBN 3-13-368515-5
