ANTISPASMODICS: MEDICATIONS, MECHANISM OF ACTION, USES, EFFECTS - MEDICINE - 2024

The antispasmodic are drugs used to alleviate, prevent or reduce muscle spasms of smooth muscle, especially digestive and urinary tract, and thereby reduce colic pain that this causes spasm.

Antispasmodics are also called spasmolytics and from a pharmacological point of view they are parasympatholytic drugs, that is, they block the effect of the parasympathetic system, therefore, they block acetylcholine. The type drug in this group is atropine.

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They are drugs capable of blocking some of the muscarinic effects of acetylcholine in the parasympathetic endings of the smooth muscles, the glands, the heart and / or in the central nervous system.

Within this group of drugs we can mention those of natural origin, semi-synthetic and synthetic. The natural ones are natural alkaloids among which is atropine (DL-hyoscyamine), which is extracted from the bush called Atropa Belladonna.

Scopolamine (L-hyoscine) is extracted from Hyoscyamus niger and Jimson weed is extracted from Datura stramonium, which is a source of L-hyoscyamine.

Semisynthetics differ from the natural compounds from which they are synthesized by their way of distribution and body elimination, as well as the duration of their effects.

Among the antispasmodics of synthetic origin are tertiary amines, whose use is currently restricted to ophthalmological use as pupillary or cycloplegic dilators.

Finally, there are the quaternary antispasmodics, some of which have specific effects on certain subtypes of muscarinic receptors.

Medicines

Below is a list of parasympatholytic drugs of which natural ones and some quaternary amines are used as antispasmodics.

- Natural alkaloids

1. Atropine (DL-hyoscyamine): comes in tablets, injectable solution, ophthalmic ointment, ophthalmic solution, and belladonna extract and tincture.
2. Scopolamine (L-hyoscine): its presentation is in tablets, injectable and ophthalmic solution.

Structure of atropine (Source: Harbin / Public domain, via Wikimedia Commons)

- Tertiary amines

1. Homatropine hydrobromide (ophthalmic solution)
2. Eucatropin (ophthalmic solution)
3. Cyclopentolate (ophthalmic solution)
4. Tropicamide (ophthalmic solution)
5. Dicyclomide (tablets, capsules, syrup, solution for injection)
6. Flavoxate (tablets)
7. Metixen (tablets)
8. Oxyphencyclimine (tablets)
9. Piperidolate (tablets
10. Tifenamil (tablets)

- Quaternary amines

1. Benzotropin (tablets)
2. Homatropine methyl bromide (tablets and elixir)
3. Metescopolamine (tablets, syrup and solution for injection)
4. Glycopyrrolate (tablets and solution for injection)
5. Oxyphenonium (tablets)
6. Pentapiperium (tablets)
7. Pipenzolate (tablets)
8. Propanthelin (tablets, long-acting tablets, and solution for injection)
9. Pirenzepine (tablets)
10. Mepenzolate (tablets)
11. Dififmanil (tablets, long-acting tablets)
12. Hexocyclic (tablets, long-acting tablets)
13. Isopropamide (tablets)
14. Tridihexetil (tablets, capsules of sustained action and solution for injection)
15. Tiotropium (tablets)
16. Tolterodine (tablets)
17. Ipratropium (tablets)
18. Methylatropin (tablets)

Mechanism of action

The mechanism of action of antispasmodics is to compete with acetylcholine for muscarinic receptors. These receptors are located mainly in the smooth muscle of the gastrointestinal and genitourinary tract, in the glands, in the heart and in the central nervous system.

Since this antagonistic effect is competitive, it can be overcome if the concentration of acetylcholine in the vicinity of the receptor is high enough.

Applications

Antispasmodic medications are used to treat colic caused by spasmodic contraction of the gastrointestinal smooth muscles, the gallbladder, and the smooth muscles of the genitourinary tract.

Antispasmodic parasympatholytics inhibit the muscarinic cholinergic effect of acetylcholine, thereby inducing non-vascular smooth muscle relaxation or decreasing its activity.

They are used in a wide variety of symptoms related to gastrointestinal and gallbladder motor disorders. Among these we can name the pylorospasm, epigastric discomfort and colic that accompany diarrhea.

By relaxing the smooth muscle of the bladder wall, they are used to relieve the pain and tenesmus that accompany cystitis.

Although these drugs can experimentally inhibit the contraction of the ureter and bile ducts, biliary or ureteral colic requires narcotic analgesics and generally does not resolve with antispasmodics.

Due to the effect on glandular secretion, they are used in gastric and duodenal ulcers in combination with other specific medications.

Collateral damage

The most common side effects are pupil dilation and blurred vision, dry mouth, difficulty swallowing, urinary retention in older men, constipation, vertigo, and fatigue. In the cardiovascular system, tachycardia and a slight increase in blood pressure may occur.

These side effects are the reason that chronic use of these drugs is not well tolerated.

In the case of intoxications, the aforementioned effects are presented followed by behavioral changes ranging from sedation, delirium, hallucinations, seizures, coma and respiratory depression (large doses), dry and red skin and hyperthermia, especially in children.

The lethal dose of atropine for an adult is around 0.5g and scopolamine 0.2-0.3g.

Interactions

Pharmacological interactions refer to modifications of the effect of a drug in terms of duration and magnitude of its effects, due to the concomitant or previous use of another drug or ingested substance.

In this sense, antispasmodics that are parasympatholytic or anticholinergic have additive effects with the following drugs:

- amantadine

- antihistamines

- benzodiazepines

- tricyclic antidepressants

- disopyramide

- monoamine oxidase inhibitors

- meperidine

- methylphenidate

- procainamide

- thioxanthines

- quinidine

- nitrates and nitrites

- the primidona

- orphenadrine

- phenothiazines.

Antispasmodics or anticholinergics in general:

- Increase the depressant effect of alcohol on the central nervous system

- Increase the effect of atenolol and the gastrointestinal bioavailability of diuretics, nitrofurantoin and digoxin

- Increase the eye pressure generated by glucocorticoids

- They block the effect of metoclopramide

- Reduce the effect of phenothiazines and levodopa

Antacids reduce the absorption of anticholinergics by mouth. Guanethidine, histamine, and reserpine block the inhibition that anticholinergics produce on gastrointestinal secretions.

Contraindications

The contraindications for the use of parasympatholytics are glaucoma, urinary and gastric retention, and surgical abdomen pictures in the process of diagnosis. In cases of glaucoma, when the pupil needs to be dilated for some ophthalmological process, sympathomimetic drugs are used.

Other contraindications include hypersensitivity to the drug or its excipients, tachycardias, and myocardial ischemias.

References

1. Gilani, AUH, Shah, AJ, Ahmad, M., & Shaheen, F. (2006). Antispasmodic effect of Acorus calamus Linn. is mediated through calcium channel blockade. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 20 (12), 1080-1084.
2. Goodman and Gilman, A. (2001). The pharmacological basis of therapeutics. Tenth edition. McGraw-Hill
3. Hajhashemi, V., Sadraei, H., Ghannadi, AR, & Mohseni, M. (2000). Antispasmodic and anti-diarrhoeal effect of Satureja hortensis L. essential oil. Journal of ethnopharmacology, 71 (1-2), 187-192.
4. Hauser, S., Longo, DL, Jameson, JL, Kasper, DL, & Loscalzo, J. (Eds.). (2012). Harrison's principles of internal medicine. McGraw-Hill Companies, Incorporated.
5. Meyers, FH, Jawetz, E., Goldfien, A., & Schaubert, LV (1978). Review of medical pharmacology. Lange Medical Publications.