No-Shpa: contraindications, what they help with

No-Shpa is an antispasmodic drug that has been produced for over 60 years and has many positive reviews from consumers. It is very popular in the CIS countries, Eastern Europe and Asia. According to English-language sources, the main active component of this medicine, drotaverine, is mainly used intravenously to relieve pain during labor. Numerous studies have shown that drotaverine is effective in various situations and take No-Shpu with:

• menstruation;
• stomach cramps;
• headache.

The drug is also completely safe for children. Let's consider all the features of But Shpa : method of use, contraindications, how it affects the body and how it interacts with other medications.

Compound

The main active ingredient contained in the drug is drotaverine. This substance is a modified papaverine, a painkiller made from the opium poppy.

1 tablet of No-Shpa contains:

• drotaverine hydrochloride – 40 mg;
• magnesium stearate – 3 mg;
• talc – 4 mg;
• povidone – 6 mg;
• corn starch – 35 mg;
• lactose monohydrate – 52 mg.

The dosage form of the drug is convex yellow tablets with a greenish or orange tint and “spa” engraving on one side.

"No-Shpa": composition and other characteristics

The drug belongs to the category of antispasmodics. Available in the form of tablets (6, 10, 24 pieces in one package) or in the form of injections (25 ampoules of 2 ml each).

The active ingredient is drotavertin (represented as hydrochloride). Each tablet contains 40 mg, each ampoule solution contains 20 mg. In the No-Shpa Forte variety (dosage doubled - 80 mg).

The tablets may have a yellowish, greenish or orange color. The shape of the tablets is round, both surfaces are convex. On one side there is a fault line in the middle, on the other there is a monolithic surface with the inscription “NOSPA”. The solution in the ampoules is also colored in shades of yellow and green.

The shelf life depends on the form of release. Tablets can be stored for 5 years, and ampoules - 3 years from the date of release. The drug is protected from light and stored at room temperature in the range from 15 to 25 degrees.

Attention!

Tablets can be purchased without a doctor's prescription, but injections can only be purchased with a prescription.

Pharmacodynamics

The main component of the drug is drotaverine, which is an isoquinoline derivative. The substance has an antispasmodic effect, reduces the entry of Ca2 into smooth muscle cells, reduces intestinal motility and smooth muscle tone of internal organs, and dilates blood vessels. Does not affect the autonomic nervous system. Unlike papaverine, with which drotaverine is similar in chemical structure and pharmacological properties, it has a strong and long-lasting effect.

Drotaverine has a direct effect on smooth muscles, so it can be used in situations in which drugs from the M-anticholinergic group are contraindicated.

Composition and properties

The pharmacological properties of this drug contribute to the effective reduction of pain, which is of a different nature. At home or while waiting for a doctor, timely taking of tablets relieves spasms of smooth muscles, alleviating the person’s condition.

In addition to drotaverine hydrochloride (the active ingredient of the drug), the composition includes excipients in the form of:

• corn starch;
• magnesium stearate;
• talc;
• lactose monohydrate;
• polyvidone.

Thanks to the use of the drug, spasms in the digestive tract are relieved. The drug has a positive effect on smooth muscles and other body systems, such as:

• genitourinary system;
• cardiovascular;
• gall.

The drug does not depress the central nervous system and is approved for use when other antispasmodics are prohibited.

A positive property of the drug is its high absorption by the intestines, rapid action, which contributes to the rapid relief of pain and improvement of a person’s condition.

Indications and contraindications

You should use No-Shpu with arterial hypotension especially carefully. One tablet of No-Shpa contains 104 mg of lactose, so people with lactose intolerance should limit their intake of No-Shpa to avoid problems with the gastrointestinal tract. Those suffering from galactosemia, lactose deficiency or glucose/galactose malabsorption syndrome should avoid taking this medicine.

Contraindications for use

Contraindications to the use of the drug are the following diseases and features:

• low cardiac output;
• severe kidney and liver diseases (failure);
• hypersensitivity to the active substance (drotaverine) or to other components in the tablet;
• lactase deficiency (metabolism disorders of galactose and glucose).

During pregnancy (any period), the drug is taken with caution; similar recommendations are for children and people with low blood pressure. It is recommended to consult your doctor first.

Instructions for use

No spa tablets: instructions for use for adults: take 1-2 tablets at a time 2-3 times a day. The maximum dose of the drug is 6 tablets (240 mg of drotaverine) per day. You can take No-Shpa without a doctor’s prescription for 1-2 days; if it is used for auxiliary therapy, then 2-3 days.

Clinical studies of the active substance with the participation of children have not been conducted. If this drug is prescribed to children, it should be taken as follows:

• From 6 to 12 years – 1 tablet 1-2 times a day, maximum dose – 80 mg of drotaverine (2 tablets).
• 12 years and older - 1 tablet 1-4 times a day or 2 tablets 1-2 times a day, maximum dose of drotaverine - 160 mg (4 tablets).

The pain disappears a few hours after taking No-Shpa. If this does not happen, it is recommended to consult a doctor.

No-shpa - a classic of antispasmodic therapy

Introduction

Abdominal pain, or abdominal pain, usually reflects a pathological process in the abdominal cavity. In its duration it can be acute or chronic. Based on the mechanisms of occurrence, the following types of abdominal pain can be distinguished :

Abdominal pain, or abdominal pain, usually reflects a pathological process in the abdominal cavity. In its duration it can be acute or chronic. Based on the mechanisms of occurrence, the following can be distinguished:

• spastic
  (arising from spasms of the smooth muscles of the gastrointestinal tract),
• distensional
  (arising from stretching of the hollow organs of the abdominal cavity),
• peritoneal
  (associated with a pathological process in the peritoneum),
• vascular
  (associated with ischemia of the abdominal organs).

Thus, with diseases of the esophagus, stomach, and duodenum, pain is observed in the epigastric region. However, with myocardial infarction, lower lobe pneumonia, pleurisy, acute pyelonephritis, similar localization of pain may be observed.

In diseases of the biliary tract, gallbladder and liver, pain is most often noted in the right hypochondrium; with pancreatitis - often localized in the left hypochondrium (it should be remembered that pain in the right or left hypochondrium also accompanies lower lobe pleuropneumonia, renal colic, splenic infarction).

Pain in the umbilical area

are characteristic of diseases of the small intestine, and may also be associated with vascular damage, for example, an abdominal aortic aneurysm or a disorder of the mesenteric circulation.

Pain in the right iliac region

usually associated with disease of the cecum and appendix. Such pain can also accompany pathology of the ureter.

Pain in the left iliac region

, as a rule, are caused by pathology of the sigmoid colon, often by diverticulitis.

Pain in the suprapubic region

in most cases they are caused by pathological processes in the bladder, uterus and its appendages.

In addition to eliminating pain, relaxing the spasm is very important. Spasm

– pathological or physiological contraction of individual muscles or muscle groups (and sometimes many muscle groups) is an accompanying symptom of many diseases. It impairs the blood supply to the affected area, and in itself can be the beginning of the development of a pathological condition.

As is known, the state of the contractile apparatus of a muscle cell is directly dependent on the concentration of calcium ions in the cytoplasm. The latter, interacting with the cytoplasmic calcium-binding protein calmodulin, activate myosin light chain kinase. The kinase cleaves the phosphorus residue from the adenosine triphosphate molecule associated with the fibers of the myosin motor protein. Thanks to this, myosin acquires the ability to interact with another motor protein, actin. Active “molecular” bridges are established between actin and myosin, due to which actin and myosin “move” relative to each other, which leads to cell shortening.

Molecules of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) reduce the content of calcium ions in the cytoplasm and thereby contribute to a decrease in the contractile activity of the cell.

Cyclic forms of AMP and GMP are formed from inactive monophosphates. The enzyme phosphodiesterase catalyzes the breakdown of cyclic AMP and GMP to inactive forms. Thus, one of the necessary conditions for muscle fiber contraction is high phosphodiesterase activity; for relaxation, on the contrary, its low activity is needed.

What are the possibilities for therapeutic relief and prevention of attacks of abdominal pain?

Today, the following groups of drugs are used: nitrates, anticholinergics, calcium antagonists, b-agonists used in the treatment of bronchial asthma and myotropic antispasmodics - the most effective group for abdominal pain caused by spasm.

The main range of uses of antispasmodics

in everyday practice:

• Symptomatic treatment if spasm is a characteristic accompanying symptom of the disease, but does not play a role in pathogenesis.
• The antispasmodic is used as a means of etiotropic therapy if spasm underlies the pathological condition.
• Antispasmodics are used as premedication in preparing patients for various procedures, for example, ureteral catheterization, etc.

Mechanism of action of antispasmodics

Depending on the mechanisms of action, antispasmodics are divided into two groups: neurotropic and myotropic.

Neurotropic antispasmodics

act by disrupting the transmission of nerve impulses in the autonomic ganglia or nerve endings that stimulate smooth muscles.
Myotropic antispasmodics
reduce muscle tone due to a direct effect on biochemical intracellular processes.

The most important neurotropic antispasmodics are M-anticholinergic blockers.

M-anticholinergic agents (atropine-like drugs) have an antispasmodic effect in the upper gastrointestinal tract (GIT): they are 3–10 times more effective on the stomach than on the colon. Firstly, this is due to the unequal distribution density of M-cholinergic receptors in the gastrointestinal tract (the largest number of them is located in the stomach). Next in descending order are the colon, rectum, cecum, jejunum and duodenum. Secondly, the tone of the colon wall is regulated by the sacral parasympathetic nerve, which is resistant to the action of anticholinergic drugs. In addition, only 20–40% of contractions of the muscles of the colon are carried out through M-cholinergic receptors. Most contractions are activated by noncholinergic transmitters. This explains the limited effectiveness of anticholinergic drugs for spastic phenomena in the lower gastrointestinal tract.

Side effects of M-anticholinergics include a decrease in the secretion of various exocrine glands (salivary, mucous, sweat), HCl in the stomach, an increase in heart rate, mydriasis, paralysis of accommodation and an increase in intraocular pressure.

M-anticholinergic drugs according to their chemical structure are divided into tertiary, penetrating the blood-brain barrier and having a central effect (atropine, scopolamine, platyphylline), and quaternary ammonium compounds that do not penetrate the blood-brain barrier (methacin, chlorosyl).

The number of side effects and low antispasmodic activity make the use of atropine-like drugs very limited.

The first truly effective myotropic antispasmodic drugs were opium extracts. The further development of their use was driven by the knowledge that among opium alkaloids, papaverine is the drug that has the most pronounced antispasmodic effect on smooth muscles and the least effect on the central nervous system. Production of the drug in industrial quantities in the form of hydrochloric acid salt was carried out in 1930 at. In 1931, by replacing the methoxy groups of papaverine with ethoxy radicals, the drug perparin was developed with a stronger antispasmodic effect than papaverine, but less absorbable. Research continued with the goal of obtaining a more effective myotropic antispasmodic than papaverine, and, if possible, without side effects. Finally, in 1961, Meszaros, Szentmiklosi and Czibula developed hydrogenated derivatives of papaverine, namely drotaverine

, which received the trade name
“No-shpa”
. All pharmacological and clinical studies have proven the higher effectiveness of drotaverine in comparison with papaverine.

Myotropic antispasmodics exhibit a certain tropism for individual smooth muscle organs. Among them are bronchodilators, vasodilators, and gastrointestinal antispasmodics. They reduce the tone of smooth muscle cells by directly influencing biochemical intracellular processes, either leading to an increase in intracellular cAMP or a decrease in intracellular cGMP. cAMP activates the release of Ca2+ ions from the cell and its deposition, which leads to a decrease in cell contractility. cGMP, on the contrary, increases the contractility of smooth muscle cells due to stimulation of the release of Ca2+ ions from intracellular stores.

Antispasmodics with myotropic action also include calcium antagonists.

The muscle cell of the intestinal wall carries out its contractility with the help of Ca2+ ions. There are two possible ways for Ca2+ ions to enter the cell:

entry of Ca2+ from the extracellular space through slow voltage-dependent Ca2+ channels of membranes and release of Ca2+ from intracellular stores through receptor-dependent Ca2+ channels. There are two types of contractions of intestinal smooth muscles: tonic and phasic. Tonic contractions maintain the basal tone of the intestinal wall and sphincters during fasting; phasic contractions are rhythmic contractions of the intestinal wall that provide propulsive movement of food through the intestines. The mechanism of development of tonic and phasic contractions depends on different levels of Ca2+ ions entering the cells. The entry of Ca2+ ions into the cell through Ca2+ channels causes tonic contraction; mobilization of Ca2+ under the influence of neurotransmitters (acetylcholine, catecholamines) from dense Ca2+ stores, for example, the sarcoplasmic reticulum, leads to phasic contraction. The number of intracellular depots in the gastrointestinal tract varies: most of them are localized in the smooth muscles of the colon, least of all in the duodenum and small intestine.

The action of calcium antagonists is associated with blocking slow voltage-dependent Ca2+ channels in the smooth muscles of the gastrointestinal tract. These drugs have little effect on receptor-dependent Ca2+ channels and cannot block the release of Ca2+ from the depot, therefore they have an antispasmodic effect mainly in the upper gastrointestinal tract.

Mechanism of action of drotaverine

Phosphodiesterase inhibition

Phosphodiesterase inhibition

Adenosine 3'-5'-cyclomonophosphate (cAMP) and guanosine 3'-5'-cyclomonophosphate (cGMP) play an important role in the regulation of smooth muscle cell tone. An increase in the concentration of these substances is directly related to muscle relaxation.

The intracellular concentration of cyclic nucleotides is determined by the relative rate of their formation with the help of agonist-induced stimulation of adenylate cyclase (agonist - norepinephrine) and guanylate cyclase (agonist - acetylcholine), as well as the rate of their hydrolysis by cell phosphodiesterase enzymes (PDE).

cAMP and cGMP are synthesized from the corresponding nucleoside triphosphates using the membrane-bound enzymes adenylate cyclase and guanylate cyclase, respectively, cAMP and cGMP are inactivated by PDE to inactive non-cyclic ribose phosphates.

The adenylate cyclase system is universal, and cAMP and cGMP are the most important intracellular second messengers for smooth muscle cells of various organs (smooth muscles of the gastrointestinal tract, trachea, bronchi, uterus, ureters, blood vessels, myocardium), as well as for cells of other tissues (platelets, lymphocytes, secretory cells , CNS, etc.). The system provides various functions (muscle tone, secretion, aggregation, etc.). The wide range of functions of the adenylate cyclase system is ensured by the existence of numerous PDE isoenzymes in various types of tissues (tissue-specific and species-specific). PDE isoenzymes differ in physical and kinetic characteristics, substrate (cAMP or cGMP) specificity, sensitivity to endogenous activators and inhibitors, sensitivity to phosphorylation by protein kinases, tissue distribution and cellular localization. Thus, differences in the intracellular distribution of PDE isoenzymes are an important factor determining their individual regulatory role. According to a series of experimental studies, about 7 different families of PDEs have been established: Ca2+-calmodulin-dependent (PDE I), cGMP-stimulated (PDE II), c-GMP-inhibited (PDE III), cAMP-specific (PDE IV), cGMP- specific (PDE V), photospecific (PDE VI), high-affinity (resistant) (PDE VII).

Thus, PDE plays a major role in the regulation of smooth muscle tone

and represents a convenient cellular target for drug development.

PDE isolated from various tissues contain all isoenzymes, but in different quantities. Experimental studies have established the most significant types of PDE in different tissues and created selective PDE inhibitors. Thus, the selective PDE III inhibitor milrinone, the selective PDE IV inhibitor rolipram, and the selective PDE V inhibitor zaprinast are known. Milrinone is a non-catecholamine inotropic for cardiomyocytes and causes relaxation of vascular smooth muscle; Rolipram, according to initial data, was an inhibitor of brain PDE, and then its effect was shown on PDE IV of the respiratory tract muscles, liver cells, and lymphocytes. Research results have shown that the smooth muscle of the large intestine contains almost all isoforms of PDE, the main one of which is PDE IV.

In smooth muscle cells of the urinary tract, the existence of at least three different isoforms (I, II, IV) has been found, but PDE IV also predominates.

Myometrium during pregnancy contains large doses of PDE IV (50%) and PDE III (10%). PDE IV is found both in the initial period of pregnancy and in the last trimester. It is assumed that PDE IV at the end of pregnancy contributes (through changes in cAMP levels) to the preparation of the myometrium for childbirth. Studies in the isolated uterus have shown that selective PDE IV inhibitors can reduce the sensitivity of the organ to oxytocin and lead to rapid relaxation of the uterus after the application of maximum concentrations of oxytocin. This phenomenon can be used for premature birth.

Drotaverine and its main metabolites (CH 280895 and CH 281095) are strong and selective inhibitors of PDE IV smooth muscle cells. Thanks to the effects of drotaverine, not only an antispasmodic effect is provided, but also swelling and inflammation are reduced, in the pathogenesis of which PDE IV is also involved.

Action as a calcium antagonist

Smooth muscle contraction is a Ca2+-dependent process. The contractile process is initiated by any stimulus that causes an increase in the concentration of Ca2+ ions in the cytosol. Ca2+ ions required for contraction can come from an extracellular source through transmembrane Ca2+ channels, or intracellular cytoplasmic organelles (sarcoplasmic reticulum, mitochondria). Ca2+ channel antagonist drugs inhibit the penetration of Ca2+ ions from the extracellular space, which prevents spasm and promotes relaxation of smooth muscles. This is what determines the value of this class of drugs. This mechanism is especially useful in the treatment of cardiovascular diseases, including cardiac arrhythmia, angina pectoris, and hypertension.

Another class of Ca2+ antagonists are drugs that interact with calmodulin, a cytoplasmic Ca2+-modulating protein. Calmodulin functions as a necessary mediator of the action of Ca2+ ions in Ca2+-dependent intracellular processes: with an increase in the concentration of Ca2+ ions in a stimulated cell, calmodulin binds them, which leads to a conformational change in the calmodulin molecule, and it acquires the ability to bind to the actin-myosin contractile system.

Calmodulin antagonists prevent the formation of the active Ca2+–calmodulin complex and thus inactivate the enzyme. In addition, calmodulin antagonists are able to inhibit calmodulin-dependent PDEs, some of which affect the function of Ca2+ channels. Drotaverine and papaverine have virtually no effect on calmodulin-dependent type I PDEs. According to experimental studies, drotaverine has weak activity as a calmodulin antagonist and significant activity as a Ca2+ antagonist. Papaverine is 5 times stronger than drotaverine as a calmodulin antagonist, and does not exhibit the properties of a Ca2+ antagonist. Due to its special properties, drotaverine is classified, according to the classification of Ca2+ antagonists, in group III - calmodulin antagonists.

Sodium channel blocking effect

Sodium channels play a fundamental role in the generation and conduction of electrical stimuli and may be involved in the pathogenesis of many diseases. Binding sites for drugs have been identified on sodium channels. Na+ channel blockers are widely used as antiarrhythmics, antiepileptics and local anesthetics. Experimental studies have shown that drotaverine has an affinity for Na+ channels; its activity towards Na+ channels is 10 times higher than towards Ca2+ channels.

Drotaverine is an effective antispasmodic drug without cardiovascular effect

. PDE is an enzyme that hydrolyzes cAMP in cardiomyocytes and vascular smooth muscle cells, represented predominantly by type III PDE. cAMP is synthesized through stimulation of b1- and b2-adrenergic receptors, which activate membrane-bound adenylate cyclase. Elevated levels of intracellular cAMP in cardiomyocytes increase intracellular Ca2+ levels through activation of protein kinase, which phosphorylates proteins in the sarcolemma and sarcoplasmic reticulum. During the period of depolarization, Ca2+ channels open, through which Ca2+ enters the cell and activates contractile proteins. Intracellular cAMP is metabolized by PDE III, and inhibition of this enzyme increases the level of cAMP, which leads to an increase in intracellular Ca2+ concentration. An increase in intracellular Ca2+ concentration in myocardiocytes causes a positive inotropic effect. Elevated levels of intracellular cAMP and Ca2+ may also cause electrophysiological effects. Vascular smooth muscle cells also contain PDE III; inhibition of this enzyme and the resulting increase in cAMP levels causes relaxation of the smooth muscle cells of the vascular wall. This is achieved by depositing Ca2+ ions in the sarcoplasmic reticulum.

PDE III inhibitors may cause arrhythmias that occur due to an increase in intracellular cAMP levels and, consequently, an increase in Ca2+ levels in cardiomyocytes. Not only PDE III inhibitors, but also PDE V inhibitors have a pronounced cardiovascular effect.

Since drotaverine is a selective inhibitor of PDE IV and an antagonist of the action of Ca2+, its cardiovascular effect is weakly expressed.

Pharmacokinetics of drotaverine

Absorption

The peak concentration of drotaverine in plasma occurs between 45 and 60 minutes after administration, which characterizes it as a rapidly absorbed drug. After a single oral dose of 80 mg of drotaverine hydrochloride, the maximum plasma concentration of the parent compound (136–320 ng/ml) is achieved after 2 hours. The bioavailability of drotaverine when taken orally is 60%.

Drotaverine binds to plasma proteins (95–98%), especially albumin, b- and g-fractions of globulins and a-lipoproteins.

The drug penetrates well into various tissues: the central nervous system, adipose tissue, myocardium, lungs, kidneys, liver, walls of the urinary and gallbladder, intestines, vascular wall.

Removal

The half-life is 16 hours. About 60% of drotaverine when taken orally is excreted through the gastrointestinal tract and up to 25% in the urine.

Metabolism

The main metabolic pathway of drotaverine is oxidation. The drug is metabolized almost completely to monophenolic compounds. Its metabolites are rapidly conjugated with glucuronic acid.

Application of drotaverine

Many of the symptoms encountered by therapists and gastroenterologists are explained by a disorder of contraction of the smooth muscles of the gastrointestinal tract. Symptoms of spastic gastrointestinal dysfunction occur in almost 30% of healthy people. The majority of patients seeking consultation with a doctor suffer from various functional gastrointestinal disorders. First of all, these are non-ulcer dyspepsia and irritable bowel syndrome. Understanding the pathophysiology of visceral spasm may facilitate rational treatment approaches. Drotaverine is effective in the treatment of various gastrointestinal diseases characterized by spasm of smooth muscles.

Dosage forms of drotaverine (No-shpy)

1 ampoule of No-shpa (2 ml) contains 40 mg of drotaverine

1 tablet of No-shpa contains 40 mg of drotaverine

1 tablet of No-shpa forte contains 80 mg of drotaverine

Esophageal smooth muscle spasm

The main symptoms associated with spastic esophageal dysfunction are dysphagia and chest pain

.

Dysphagia is a feeling of slowness or obstruction in the movement of food through the pharynx and esophagus into the stomach.

Functional dysphagia develops due to impaired swallowing and decreased peristaltic activity of the esophagus due to pathology of its striated and smooth muscles. The most significant diseases of this group are achalasia, diffuse esophageal spasm and gastroesophageal reflux.

Chest pain in gastrointestinal diseases is spastic in nature, highly intense, localized in the middle third of the sternum and often radiates to the anterior surface of the chest. Such pain occurs with hypermotor dyskinesia of the thoracic esophagus (esophagospasm) and is a consequence of a violation of the peristaltic function of the smooth muscles of its wall. Pain can appear during eating or at any other time.

To treat dysphagia and pain associated with spastic dysfunction of the esophagus, nitrates, anticholinergic drugs, antispasmodics from the group of phosphodiesterase inhibitors and calcium antagonists (drotaverine) are used. They lead to a decrease in pressure in the esophagus. However, no drug alone provides complete effectiveness in the treatment of spastic disorders of the esophagus.

Non-ulcer dyspepsia

The term “non-ulcer dyspepsia” refers to a symptom complex that includes complaints of pain in the epigastric region, a feeling of heaviness and fullness in the epigastrium after eating, early satiety, nausea and vomiting, belching of air, heartburn, regurgitation, etc. Synonyms of this term are functional, idiopathic, inorganic dyspepsia. During a thorough examination, it is not possible to identify any organic disease (peptic ulcer, reflux esophagitis, stomach cancer, etc.). The prevalence of dyspeptic complaints among the population is very high - from 19 to 41% according to different authors, while from a third to half of all cases of dyspeptic disorders account for functional dyspepsia.

Depending on the main clinical symptoms, there are four types of non-ulcer dyspepsia:

ulcer-like, reflux-like, dyskinetic and nonspecific.

The leading place in the pathogenesis of non-ulcer dyspepsia is given to motility disorders of the upper gastrointestinal tract.

Treatment of patients includes a healthy lifestyle, prevention of infection with Helicobacter pyloricus, the use of antacids and antispasmodics for ulcer-like variants (especially when pylorospasm and hypermotor dyskinesia of the duodenum are detected). For reflux-like and dyskinetic variants, prokinetics are used.

Sphincter of Oddi dysfunction

Many other terms have been used to describe this functional biliary disorder: biliary dyskinesia, hypertensive sphincter of Oddi dyskinesia, spasm of the sphincter of Oddi, papillary dysfunction.

Disorders and the mechanism of development of pain with dysfunction of the sphincter of Oddi is the development of spasm of sphincter muscle fibers and increased pressure in the bile and/or pancreatic duct system.

The fact that dysfunction of the sphincter of Oddi most often manifests itself in patients with a removed gallbladder serves as indirect confirmation that the gallbladder serves as a reservoir that “quenches” excessive pressure surges throughout the biliary tract. After removal of the gallbladder, even a moderate contraction of the sphincter of Oddi can lead to a significant increase in pressure in the entire biliary tract and, as a result, pain may appear, as confirmed in experiments with the administration of morphine, which increases pressure in the biliary tract.

The factors that cause prolonged spasms of the sphincter of Oddi are unknown.

For therapeutic purposes, myotropic antispasmodics are most often used in practice, having a targeted effect on smooth myocytes of the gastrointestinal tract.

The main representatives of this group of drugs are drotaverine (No-shpa, No-shpa forte), otilonium bromide, etc. These drugs are used short-term (from a single dose to two to three weeks) to relieve spasm, and therefore pain.

In a double-blind, placebo-controlled clinical trial, the effectiveness of No-shpa was studied in patients with sphincter of Oddi stenosis as an adjuvant, including in patients with surgical interventions. The use of No-shpa showed a significant significant reduction in pain in 60% of patients and a small effect in another 23%

, while placebo in 55% of cases did not affect the intensity of pain. In this study, No-shpa was 2 times more effective than analgesics.

In addition, in a pilot study it was found that the use of No-shpa reduces AST activity by 15–60% in patients with diseases of the biliary system

.

The results of these studies showed that No-shpa is the drug of choice for spasms of the smooth muscles of the biliary system. No-shpa can be used both in monotherapy and in combination with antibiotics and surgical treatment methods.

Irritable bowel syndrome

Symptoms of hypertensive lower gastrointestinal motility disorder include constipation, with or without lower abdominal pain. Most often, patients with such symptoms are diagnosed with irritable bowel syndrome and chronic constipation.

Irritable bowel syndrome (IBS) is a common clinical problem encountered by emergency physicians and gastroenterologists. IBS is one of the manifestations of functional disorders of the gastrointestinal tract, in which the colon is predominantly involved in the pathological process. IBS is characterized mainly by disturbances in the motor and secretory function of the colon without morphological changes in the mucous membrane.

Epidemiological studies indicate a high incidence of the disease in the general population: 14–24% of women and 5–19% of men. IBS is a biopsychosocial disorder in which abnormalities in psychoemotional order, motor skills and sensitivity lead to abdominal pain and defecation disorders. To evaluate symptoms, a unified set of criteria, the Rome Diagnostic Criteria, is used.

Principles of IBS treatment

include normalization of the diet and nature of nutrition, normalization of the psycho-emotional sphere, correction of movement disorders of the colon. In case of IBS, which occurs predominantly with pain, the optimal prescription should be considered drugs that have an antispasmodic effect (drotaverine, pinaverium bromide, butylscopolamine).

Several clinical studies have been conducted to evaluate the effectiveness and tolerability of No-shpa in patients with irritable bowel syndrome and other intestinal disorders.

A double-blind, randomized, placebo-controlled study included 62 patients (age 50.8±14.2 years) with IBS and constipation. Patients recorded their complaints daily for 2 weeks before the start of treatment and during 8 weeks of treatment with No-shpa 80 mg 3 times a day or 2 placebo tablets 3 times a day. Active treatment significantly reduced abdominal pain by 47%, while in the placebo group pain increased by 3% (p < 0.05). While taking No-shpa, other symptoms, including flatulence, also decreased.

In another randomized, double-blind study, the effectiveness of No-shpa was studied in 70 patients aged 18–60 years diagnosed with IBS according to their own criteria. Patients received No-shpa 80 mg 3 times a day for 4 weeks, and then were observed for another 4 weeks. The results showed that No-shpa significantly reduces the incidence of pain compared to placebo – by 47% (p<0.001) (Fig. 1), flatulence by 21% (Fig. 2) and dyspepsia – by 20% (p<0.001) (Fig. 3). At the same time, normalization of stool frequency occurred in 40% of patients receiving No-shpa and placebo, but an improvement in passage time in the colon was noted significantly more often with the use of No-shpa (Fig. 4 and 5).

Rice. 1. Frequency of abdominal pain syndrome while taking No-shpa and placebo

Rice. 2. Frequency of flatulence while taking No-shpa and placebo

Rice. 3. Frequency of dyspepsia while taking No-shpa and placebo

Rice. 4. Frequency of constipation while taking No-shpa and placebo

Rice.
5. Change in passage time in the colon while taking No-shpa and placebo Chronic constipation
Constipation is a very common complaint. Constipation can be caused by a variety of factors affecting smooth or striated muscle, impairing the function of autonomic or somatic nerves, or factors associated with changes in colorectal anatomy or intestinal contents.

Constipation is a very common complaint. Constipation can be caused by a variety of factors affecting smooth or striated muscle, impairing the function of autonomic or somatic nerves, or factors associated with changes in colorectal anatomy or intestinal contents.

Among the diseases that cause secondary constipation are systemic endocrine and metabolic diseases, disorders and diseases of the central nervous system (damage to the spinal cord, peripheral nerves), as well as myopathy and muscular dystrophy. Constipation can be caused by a number of drugs belonging to different groups, including drugs that interact with neurons of the central nervous system (eg, opiates), drugs that directly affect smooth muscle (calcium antagonists), and drugs that alter the contents of the intestines (cholestyramine). Habitual consumption of low-fiber foods can lead to infrequent bowel movements and complaints of constipation.

In the treatment of constipation, a diet with a high content of fiber and cellulose, various laxatives and medications that improve the neuromuscular regulation of motor function of the colon (prokinetics) or antispasmodics are used. Drugs that activate intestinal motility, in combination with antispasmodics, help avoid the use of toxic laxatives.

Conclusion

Pain is a universal symptom for a wide variety of lesions of the gastrointestinal tract; its occurrence is often based on spasm of the smooth muscles of the abdominal organs. Of the entire group of antispasmodic drugs, the most popular today is drotaverine (No-shpa)

.
A review of the results of clinical studies shows that No-shpa is an effective drug for the rapid relief of spasms and pain. For a quick onset of effect, the first administration of No-shpa should be intravenous or intramuscular; for long-term treatment, it should be administered orally. Literature:
1. Belousov Yu. B. Antispasmodics. Pharm. Bulletin, 36 (235, 2001).

2. Belousov Yu. B., Leonova M. V. Clinical pharmacology of no-shpa. Methodological manual for doctors. M., 2002.

3. “Gastroenterology” Directory. P/r V. T. Ivashkin and S. I. Rappoport. M., Russian doctor, 1998, pp. 84–90

4. Grigoriev P. Ya., Yakovenko E. P., Pryanishnikova A. S. et al. The place of the drug No-shpa forte in the management of patients with abdominal pain syndrome. Practitioner, 16 (3, 1999), pp.39–40

5. Ivashkin V. T., Shulpekova Yu. O., Drapkina O. M. Abdominal pain syndrome. Submitted for publication in the Russian Journal of Gastroenterology, Hepatology and Coloproctology.

6. Leonova M.V., Shishkina T.I., Belousov Yu.B. New dosage form No-shpa forte in clinical practice.

7. Akos Pap MD The management of smooth muscle spasm. Budapest, 1998, 266 p.

8. Blasko G. Pharmacology, mechanism of action and clinical significance of a convenient antispasmodic agent: drotaverine. JAMA India – The physician's update, 1998, v.1, N 6, p.63–70.

9. Kapui Z., Bence J., Boronkay E. et al. Behavioral effects of selective PDE4 inhibitors in relation to inhibition of catalytic activity and competition for [3H]rolipram binding. Neurobiology, 1999, v.7, N 1, p.71–73.

Side effects

The body may react adversely to the components of the drug. Possible symptoms include:

• Nervous system: headache, dizziness, sleep disorder, vertigo.
• Cardiovascular system: decreased blood pressure, palpitations.
• Digestive system: nausea, constipation.
• Immune system: allergic reactions (rash, itching, urticaria).

All side effects of the drug are rarely detected: approximately 1 case in 10,000.

An overdose of No-Spa causes cardiac rhythm and conduction problems, which can lead to drug failure and death. In case of an overdose of the drug, you should immediately consult a doctor and subsequently receive symptomatic treatment under his supervision.

Contraindications

Despite the relative safety of use, and the fact that nasal spray helps relieve spasms, there are some contraindications to its use. The main ones are intolerance to drug components and low blood pressure.

It is also not recommended to take the drug in:

• atherosclerosis;
• Acute failure of the cardiovascular system;
• Glaucoma, high intraocular pressure;
• prostate prostate;
• Severe chronic or acute kidney and liver diseases.

In addition, it is not recommended to take pills to reduce pain in neighbors by the kidneys before the ambulance arrives, because due to their effective work, the clinical picture of the disease can distort the disease, which will interfere with the correct diagnosis. Refusal

No-SHPA is not recommended by many doctors for children under 6 years of age, and is also contraindicated for women while breastfeeding.

Pregnancy and lactation

Clinical studies have shown that drotaverine does not have a teratogenic or embryotoxic effect, therefore its use during pregnancy is allowed . It is important to be careful and take drotaverine only after weighing the benefits for the mother and the potential risk for the child. There are no preclinical and clinical data on the use of the drug during lactation, therefore, taking No Shpu while breastfeeding is not recommended .

During menstruation

The peculiarity of drotaverine, which is part of No Shpa, is that it relaxes the smooth muscles of various organs, including the uterus. It relieves spasms and improves blood flow, which helps get rid of painful sensations. The drug is taken 1-2 pills 2-3 times a day for 1-2 days or until the pain disappears. The maximum dosage of no spa is 2 tablets at a time. Note! But Shpu should be taken during menstruation only if you are sure that this is pain during a natural process.

What do No-Spa tablets help with?

The drug is taken in tablets, as well as in the form of injections (both intramuscularly and intravenously) to quickly relieve spasms of smooth muscles. This is necessary to relieve pain that manifests itself against the background of such diseases:

• pyelitis;
• cystitis;
• cholecystitis;
• papillitis;
• pnephrolithiasis;
• cholecystolithiasis;
• Urolithiasis

“No-Shpu” is also used to relieve spasms associated with pathologies of the stomach and intestines. Such symptoms may occur due to constipation, ulcers, colitis, IBS and other disorders. Another indication for use is headache and dysmenorrhea. However, in this case, the drug will only work if the pain is associated with vasospasm (felt like tension in the head).

In ordinary cases, the “No-Shpa” form is used. An increased concentration in the composition of the drug “No-Shpa Forte” is used if necessary to ensure a lasting long-term effect (for days, weeks in advance). Forte is also taken if it is necessary to reduce the frequency, for example, to 1 time per day.

Interaction with other drugs

PDE inhibitors like papaverine, which includes drotaverine, which is part of No-Shpa, weaken the antiparkinsonian effect of the substance levodopa (dihydroxyphenylalanine). Therefore, the combination of No Shpa and drugs containing levodopa can lead to increased tremor and rigidity. In combination with other antispasmodic drugs, No Shpa enhances its analgesic effect. Before combining this drug with other medications, you should consult your doctor.

Features of application

The drug can be used in combination with other drugs, but it is recommended to first consult with your doctor. To get rid of migraines before taking the drug, it is recommended to measure your blood pressure, since this condition is possible with both high and low pressure.

For hypertension

No-aspa as an antispasmodic against the background of high blood pressure is permissible if necessary:

• relieves spasms in the intestines caused by poisoning, uncontrolled medication, but not associated with organ pathology;
• Reducing pain in the lower abdomen and lower back due to cystitis;
• Soothes spasms of the bronchi and lungs during severe coughing.

If the fever is accompanied by cramps, the medicine helps relieve them and is used in combination with antipyretics.

The tablets will have a pronounced antispasmodic effect for spasms of various locations (in the liver, kidneys, intestines) caused by the abuse of alcoholic beverages, spicy and fatty foods. They quickly relieve pain, but do not eliminate the cause of its occurrence.

For hypotension

No-SHPA for low blood pressure is used for the same purposes as for high blood pressure, but must be more careful with respect to the dosage.

If it is exceeded, the drug in people with reduced vascular tension can cause:

• dizziness;
• increased fatigue, drowsiness;
• and poor concentration.

Excessive amounts of the drug cause fainting and confusion.

These side effects most often occur in patients whose blood pressure is below 100/60. This is due to the deterioration of oxygen delivery to the bleeding brain.

Precautionary measures

No-Shpa contains disulfite, a substance that can cause allergic reactions, including anaphylactic symptoms and bronchospasm in people with hypersensitivity, especially in patients with asthma or allergic diseases. If you are sensitive to parenteral disulfite, you should not take the drug. When administering drotaverine intravenously, patients with low blood pressure should be in a horizontal position to minimize the risk of collapse.

Side effects from taking No-Shpa tablets

In most cases, no side effects are observed. But with long-term use, as well as due to the individual characteristics of the body and human condition, the following consequences may appear:

• increased heart rate;
• sleep disorders;
• headaches;
• dizziness;
• decreased blood pressure;
• nausea;
• bowel dysfunction (constipation);
• allergic reactions.

If an injection is administered, a local reaction (redness, foreign sensations) may additionally be observed.

Effect on driving

When taken orally in small doses, No-Shpa has no effect on people driving or operating other equipment. However, during treatment with the drug when driving a vehicle or other activities that require increased concentration, you should be careful. If dizziness occurs after taking No-Shpa, then these types of activities should be abandoned. The question of whether it is possible to drive a car and operate machinery if there are side effects from using No-Shpa is decided by the attending physician.

Package

No-Shpa is available in the form of pills and solution for intravenous administration. Tablets of 40 or 80 mg are packaged in plastic blisters of 20 pieces. Each such tablet of medicine, along with instructions, is placed in a cardboard box. The packaging varies depending on the number of tablets inside:

• No. 12: 12 tablets per plate. 1 record per package.
• No. 24: 24 tablets per strip, 1 strip per package.
• No. 60: 60 tablets in a dosing container with protective tape, 1 container per box.
• No. 100: 100 ballet shoes per bottle, 1 bottle per package with a tamper-evident sticker.

The solution for injection is a clear, colorless liquid, which is collected in dark-colored ampoules of 2 ml, which are packed in 5 pieces in a plastic contour package.

Side effects

Like any drug, uncontrolled administration of the nasal finger can provoke adverse reactions:

• Rapid heartbeat, which is especially dangerous for people with cardiovascular disorders;
• Dizziness, excessive sweating.

When administered intravenously, arrhythmias and respiratory inhibition are possible. Hypotensives are at risk because sometimes the rapid effect of the drug slowly lowers blood pressure, interfering with blood circulation and oxygen supply to the brain.

Reviews

I was diagnosed with a stomach ulcer quite a long time ago, because of which I often have to suffer from pain in the stomach area. In such cases, I almost always use No-shpa - it is inexpensive and helps quickly - almost always everything goes away in 30 minutes. I did not find any side effects during use. I usually take 2 tablets after meals; if there are any special circumstances, I call my doctor, he will advise me on how to calculate the dosage.

Andrey, 37 years old

Excellent medicine, I have been using it for many years, I always have it on hand. When I take a severe headache along with analgin, they get along well, there are no side effects, and all the symptoms go away. In general, all relatives, when any pain or spasms appear, take noshpa, even my grandmother drinks for high blood pressure.

Irina, 29 years old

I most often take it for headaches, although it also helps with stomach and back pain. A doctor prescribed No-shpa to a friend for prostatitis, and my sister takes it for vegetative-vascular dystonia. It starts to work in about half an hour, not always the effect that we would like, but in terms of price/quality ratio it’s simply top!

Oleg, 26 years old

Question answer

Unlike analgesics, No-shpa eliminates the spasm that causes pain. The medicine has a high safety profile and is well tolerated by various groups of people.

The manufacturer does not indicate the time of taking the drug, so it is most often taken after meals. In order to relieve acute pain, No-shpa can be drunk outside, regardless of meals.

the manufacturer of the original drug has registered the official trademark NO-SHPA, therefore any analogues produced as domestic analogues are fakes. The original packaging of No-shpa contains a holographic image confirming its originality. Another one is to purchase medications from large, reputable chain pharmacies.

Alcohol in large quantities can cause side effects of the drug: headache, dizziness, nausea, heart palpitations, etc. During the course of treatment, you must stop drinking alcohol. It is strictly forbidden to treat hangover syndrome with No-shpa.

During pregnancy

There are no particular contraindications for nasal administration during pregnancy, which runs without complications.

The main activity of the drug is to reduce the contraction, which is not faster, but with a smooth transition to normal. For expectant mothers, it is important that the medicine is not only effective, but also safe for the child. In addition, it works selectively, directly on the muscles of the uterus and other organs.

Often the drug is prescribed before birth to prepare for the normal arrival of the baby and to relieve the mother by optimizing uterine tension.

Despite the safety of the medicine for the expectant mother and child, taking it even for medical reasons (colic, headache) should only occur after consultation with a visiting doctor. The use of NO-SHPA in the first trimester of pregnancy is extremely undesirable as it can reduce the tension of the uterus and cause miscarriage.

If a pregnant woman has low blood pressure, it is recommended to take a horizontal position from the injection to avoid rupees.