No-Shpa: contraindications, what they help with

The drug "No-Shpa" refers to antispasmodic medications. It relieves pain from smooth muscle spasms. The drug is taken to relieve pain in diseases of the stomach, intestines, liver, kidneys and other internal organs. The product rarely causes side effects and is effective.

"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.

Treatment of headaches in children

What are the causes of headaches in children? What drugs are used to treat headaches? What non-drug treatments for headaches are used today?

Headache (cephalgia) in children is observed quite often and can serve as the main, or even the only symptom of more than 50 different diseases. Cephalgia is any unpleasant sensation that occurs in the area from the eyebrows to the back of the head (the term is derived from the Greek words cephal - brain and algos - pain).

It is known that 80% of European adults suffer from headaches. It can be assumed that the prevalence of cephalgia among children is approximately similar. Before 7 years of age, 75% of patients experience migraine-type headaches; however, the most common type of cephalgia is tension-type headache [1, 2].

The classification of the International Headache Society includes the following cephalgia: migraine; GB voltage; cluster (beam) headache and chronic paroxysmal hemicrania; headache not associated with structural brain damage; headache due to head injury; headache due to vascular diseases; headache due to intracranial non-vascular diseases; headache due to taking certain substances or their withdrawal; headache due to extracerebral infections; headache due to metabolic disorders; headache or facial pain due to pathology of the skull, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cranial structures; cranial neuralgia, pain due to pathology of nerve trunks and deafferentation pain; unclassifiable headache [3]. All of these types of cephalgia can occur in children, although in practice migraines, tension headaches, and cluster headaches are more common.

In general, in the etiopathogenesis of cephalalgia, areas of the dura mater can serve as sources of pain; arteries of the base of the brain and intracranial arteries; tissues covering the skull; nerves (including cranial nerves - trigeminal, glossopharyngeal, vagus, as well as the first and second cervical spinal roots) [1]. The morpho-functional basis of the peripheral part of the system responsible for pain sensitivity is the trigeminal nerve and the nucleus of its spinal tract. The dura mater and large blood vessels, as well as the sensory endings of the fibers of the second cervical root of the spinal cord, have pain receptors. The described systems form various types of headaches [4].

Headache can be caused by intracranial lesions, such as subdural and intracerebral hematomas, subarachnoid hemorrhages, thrombosis, arteriovenous malformations, brain abscess, meningitis, encephalitis, vasculitis, obstructive hydrocephalus, condition after lumbar puncture, ischemic cerebrovascular accident, stretching or inflammation of large intracranial vessels , damage to the dura mater of the base of the brain and sensory cranial nerves. Extracranial causes of headache include sinusitis, cervical spine injuries, temporomandibular joint syndrome, giant cell arteritis, glaucoma, optic neuropathy, and dental diseases. There are also “common” causes of headaches: fever, viremia, hypoxia, hypercapnia, arterial hypertension, allergies, anemia, as well as the action of vasodilators (nitrites, carbon monoxide, etc.) [5].

The pathophysiological features of the three main types of headaches in pediatric patients are discussed below, since these features determine different approaches to treatment.

Migraine. Classic migraine is characterized by two attack phases: in the first phase, vascular spasm occurs, causing cerebral ischemia and various focal symptoms that trigger the attack; in the second phase (transcranial and extracranial vasodilation), pulsating headache begins, which is distributed in the area of ​​​​innervation of the trigeminal nerve and the upper cervical roots [6]. In migraine with aura, the mechanism of headache development involves paroxysmal depolarization of neurons in the cerebral cortex. In the first phase of the attack, cortical depression spreading at a speed of 2 mm per minute is observed in the region of the occipital pole of the brain. In the area of ​​wave propagation, profound changes in the ion distribution occur, leading to a decrease in the level of cerebral blood flow. Cerebral ischemia results from arteriolar constriction. The most characteristic feature of classical migraine is general hypovolemia in the posterior part of the brain [7]. HD is caused by the effect of spreading depression on the trigeminal nerve fibers on the meninges, which releases vasoactive intestinal peptide, substance P and some other peptides [8]. The factors that trigger the mechanism of spreading cortical depression are very numerous. These include any disturbances in potassium homeostasis, genetic predisposition, stress, nutritional factors, as well as the release of vasoactive peptides from the trigeminovascular system.

With simple migraine (without aura), there are no significant changes in cerebral blood flow, and the mechanisms of its development themselves are difficult to explain [9]. In addition to vascular changes (characteristic of classic migraine), with simple migraine there are disturbances in metabolism and the concentration of neurotransmitters (serotonin and its metabolites).

The cause of migraine may be prostaglandin E1, tyramine or phenylethylamine (the latter two amines are found in chocolate and cheese) [10].

Tension headache. Previously it was believed that this type of headache is a direct consequence of repeated contractions of the muscles of the neck and temples, leading to local ischemia of these structures. In recent years, a number of other links in pathogenesis have been considered, including the involvement of “trigger” points of certain muscles (trapezius, sternocleidomastoid, suboccipital, temporal, etc.), compression of blood vessels by a spasmodic muscle with venous stagnation, spread of pain to the temporal, parotid and occipital areas due to dysfunction of the temporomandibular joint, impaired closure of the teeth of the upper and lower jaws, etc.

Cluster headache. The pathogenesis of the disease has so far been poorly studied and is not entirely clear, although it is known that with this type of headache in the external jugular vein there is an increase in the content of some pain peptides (calcitonin gene-related and intestinal peptide). As a result, a neurogenic origin of cluster headache with activation of sensory fibers of the trigeminal nerve is assumed. A defect in the chemoreceptors of the carotid bodies on the pain side, as well as disturbances in the secretion of certain humoral factors (melatonin, cortisol, testosterone, β-endorphin, β-lipoprotein, prolactin) may play a certain role.

Symptoms of headache. In each specific case, the symptoms of headache are determined by the type of cephalgia present. Below are the characteristics of various types of chronic and recurrent headaches according to a number of indicators (nature, location, duration of attack, frequency, associated symptoms). Simple migraine: headache character is pulsating; localization - one- or two-sided; duration of attack - 6-48 hours; frequency - sporadic attacks (up to several times a month); accompanying symptoms are nausea, vomiting, malaise, photophobia. Classic migraine: headache character is pulsating; localization - one-sided; duration of attack - 3-12 hours; frequency - sporadic attacks (up to several times a month); accompanying symptoms are visual aura, nausea, vomiting, malaise, photophobia. Facial migraine: the nature of headache is dull or pulsating; localization - unilateral, in the lower half of the face; duration of attack - 6-48 hours; frequency - sporadic attacks; accompanying symptoms are nausea, vomiting. Cluster headache (Horton's histamine cephalgia): the nature of the headache is sharp, boring; localization - unilateral (mainly in the orbital area); attack duration - 15-20 minutes; frequency - periods of daily attacks alternate with long-term remissions; associated symptoms - on the side of pain, lacrimation, facial flushing, nasal congestion and Horner's sign may be noted. Psychogenic headache: the nature of the headache is dull, compressive; localization - diffuse bilateral; the duration of the attack is often constant; frequency - often constant; accompanying symptoms are depression, anxiety. Trigeminal neuralgia: the nature of the pain is shooting; localization - in the zone of innervation of the trigeminal nerve; the duration of the attack is short-term (15-60 seconds); frequency - many times a day; accompanying symptoms—trigger zones are identified. Atypical facial pain: the nature of headache is dull, localization is unilateral or bilateral, the duration of the attack is often constant; frequency - often constant; accompanying symptoms are depression, sometimes psychosis. Headache due to sinusitis: headache type - dull or acute; localization - one- or two-sided, in the paranasal sinus area; the duration of the attack varies; frequency - sporadic or constant; associated symptoms are nasal discharge [11].

Diagnostics. A specific diagnosis in children is established primarily on the basis of clinical signs and the above-mentioned criteria for cephalgic syndromes. So-called headache diaries, some laboratory and instrumental studies (x-ray of the skull, computed tomography and magnetic resonance imaging of the brain, EEG, transcranial Doppler examination of cerebral vessels) can help in diagnosis. An important diagnostic measure is consultation with an ophthalmologist, and if a patient is suspected of having depression, consultation with a child psychiatrist is required.

The diagnosis of migraine is usually made on the basis of a collected medical history, and no significant changes can be detected with a thorough physical, neurological and ophthalmological examination. Diagnosis of most other cephalgic syndromes is carried out using a similar algorithm.

Approaches to headache treatment

Not all drugs used in the treatment of hypertension in adults can be used in pediatric practice due to age restrictions. A classic example is analgin (metamizole sodium), which in world practice is not prescribed to children under 14 years of age (in the Russian Federation - up to 6 years). Another drug that should be used with caution in patients under 16 years of age is the non-narcotic analgesic naproxen (nalixan).

Below we list modern approaches to the treatment of three main cephalgic syndromes - migraine, cluster headache and tension headache.

Migraine treatment. Preventive treatment is carried out only for recurrent cephalgia that is resistant to the emergency treatment used [5]. Migraine attacks should be treated only when we are talking about frequently recurring severe attacks that interfere with the child’s active life [12]. In some cases, one has to count on only a partial effect, although the administration of vasoconstrictors such as ergotamine and/or caffeine at the first symptoms of an attack can help stop it (in the Russian Federation, the drug caffeamine, which combines both of these components, is widely used). It is prescribed to children over 10 years of age twice, with an interval of 30 minutes, 1 tablet per dose (each tablet contains 0.1 g of caffeine and 0.001 g of ergotamine tartrate). The prescription of simple (non-narcotic) analgesics (paracetamol, etc.) is often no less effective.

In case of an acute attack of migraine, the regime must be combined with the use of analgesics: resting the child in bed (in a dark room) and taking paracetamol or acetylsalicylic acid. The latter is used with caution in pediatrics (in children under 2 years of age - only for health reasons) to avoid the development of Reye's syndrome [13]. It is paracetamol (at a dose of 15 mg/kg/day) that is the most effective and safe remedy prescribed for migraine attacks of moderate and severe severity. Acetylsalicylic acid is effective only for mild attacks [14]. Other drugs to treat severe attacks include naproxen, ibuprofen, phenacetin, or caffeine (alone or in combination with other drugs).

For children over 10 years of age, ergotamine is considered the drug of choice. It is prescribed orally at the very beginning of the attack (the dose depends on the dosage form used, the duration of treatment should not exceed 7 days). The drug is contraindicated in children who have hemianopia or hemiparesis during the constrictor phase of the attack.

Phenacetin, like paracetamol, is a non-narcotic analgesic. It is used 2-3 times a day in combination with drugs such as analgin (taking into account age), caffeine, etc. Its use is limited due to the presence of side effects (allergic reactions, “phenacetin” nephritis, methemoglobinemia, anemia, etc. .) [15]. Phenacetin is prescribed at the rate (single dose) of 0.15 g for 3-4 year old patients, 0.2 g for children 5-6 years old, 0.25 g for 7-9 year olds and 0.25-0 .3 g - for 10-14 year old children (for patients up to 1 year - 0.025-0.05 g, up to 2 years - 0.1 g per dose). In the Russian Federation, phenacetin is produced mainly in tablets containing 0.25 g of phenacetin itself and acetylsalicylic acid, 0.05 g of caffeine). Phenacetin is part of combination products (asphen, coficil, novomygrofen, pircofen, sedalgin, citramon, etc.).

Ibuprofen (Brufen) is a non-steroidal anti-inflammatory drug (NSAID). Children are prescribed at a rate of 20-40 mg/kg/day (3-4 times a day, per os or rectally) [13].

Naproxen is another NSAID prescribed to children under 5 years of age at a dose of 2.5-5 mg/kg/day in 1-3 doses (duration of treatment course - up to 14 days), and to patients over 5 years of age - at a dose 10 mg/kg/day [16].

Caffeine is a psychomotor stimulant, used in combination with other medications (analgesics, etc.). For children over 2 years of age (before this age the drug is not prescribed), caffeine is dosed at 0.03-0.075 g per dose (2-3 times a day). Caffeine is part of combination tablets (caffetamine, askofen, novomygrofen, cofitil, pyramein, citramon, etc.).

Sumatriptan (a selective 5-HT1 receptor agonist) is effective in the treatment of migraine attacks in adults. However, in the treatment of children with migraine, sumatriptan does not have any advantages compared to ibuprofen [17].

Preventive treatment. Propranolol for children is prescribed orally at an initial dose of 0.5-1.0 mg/kg/day 2 times a day, a maintenance dose of 2-4 mg/kg/day. In the presence of heart failure or bronchospasm, the drug is not used [13, 16].

Flunarizine is a calcium channel blocker. Children weighing up to 40 kg are prescribed a dose of 5 mg once a day. For other categories of children, flunarizine is prescribed in the same way as adults (20 mg 1 time in the first 2 weeks of preventive treatment, then 5-10 mg/day in 1-2 doses) [13].

Anticonvulsants of the phenobarbital or valproic acid class can in some cases prevent an attack, but are prescribed only for frequently recurring attacks. Dosages for both anticonvulsants are selected individually (under the supervision of a physician).

Tricyclic antidepressants (amitriptyline, etc.) are rarely used to prevent migraines (more often these drugs are used for tension headaches).

Symptomatic remedies. For nausea and vomiting, metoclopramide (cerucal, raglan) is used at a dose of 0.5 mg/kg (intravenously, intramuscularly or orally). In this case, chlorpromazine (an antipsychotic from the group of phenothiazine derivatives) and prochlorperazine are also used [5].

Chlorpromazine. To achieve a quick effect, you can use up to 3 age-specific doses of the drug (intravenously) every 15 minutes. When administered parenterally in children over one year of age, a single dose is 250-500 mcg/kg (the maximum dose in children under 5 years of age or weighing up to 23 kg reaches 49 mg/kg/day, and at the age of 5-12 years or with body weight 23-46 kg - 75 mg/kg/day). When administered orally to patients aged 1-5 years, the drug is prescribed in a daily dose of 500 mcg/kg (every 4-6 hours), children over 5 years old - from 1/3 to 1/2 the adult dose (a single dose for adults is 10- 100 mg, daily - 25-600 mg). The maximum dose for children under 5 years of age when taken orally is 40 mg per day, for patients over 5 years of age - 75 mg per day [16].

Non-drug treatments for migraines

Diet therapy. Since food allergies often play the role of a trigger factor for migraines in children, it is recommended to exclude a number of foods from the diet of a child suffering from migraines (milk, cheese, eggs, chocolate, oranges, products made from wheat and rye flour, tomatoes, etc.) [ 18]. Products with food additives such as monosodium glutamate and nitrites should be avoided [19].

Other non-drug approaches to the preventive treatment of migraine include wushu, karate, yoga, a biofeedback training system, and acupuncture.

Treatment of cluster headaches. Sumatriptan is widely used in the treatment of acute attacks of the disease. NSAIDs and ergotamine derivatives are considered less effective. Inhalation of pure oxygen is also included in the number of therapeutic measures for the development of attacks of cluster headaches (inhalation of 100% oxygen).

Preventive treatment of cluster headache involves the administration of β-blockers (propranolol, etc.), carbamazepine, lithium preparations, as well as prednisolone (a course lasting no more than 5 days) and calcium channel blockers (verapamil) [20]. The dosage of propranolol is given above.

Carbamazepine (Tegretol, Finlepsin) is an anticonvulsant (iminostilbene derivative). The average daily dose of the drug (orally) is 20 mg/kg/day (on average in children under one year - 0.1-0.2 g, 1-5 years - 0.2-0.4 g, 5-10 years - 0.4-0.6 g, 10-15 years - 0.6-1.0 g/day) [15].

Of the lithium preparations, lithium carbonate (contemnol, sedalite) is most often used. This mood stabilizer is taken during meals with water or milk. At the same time, the lithium content in the blood is controlled, maintaining its concentration at 0.5-1.0 mmol/l. At a dose of lithium carbonate of 1.0 g/day, normalization of lithium concentration should be expected after 10-14 days. The course of preventive monotherapy with lithium carbonate preparations should be at least 6 months [13].

Prednisolone. If necessary, in the first days of treatment, this corticosteroid hormone is prescribed (per os) at the rate of 1-1.5 mg/kg body weight/day, then the dose is reduced and the drug is discontinued [16].

Verapamil (isoptin, phenoptin) is a calcium channel blocker. Taken orally during or immediately after meals (in 2-3 doses). The drug is taken with a sufficient amount of liquid. For children aged 1-15 years, the dosage is 0.1-0.3 mcg/kg/day (single dose no more than 2-5 mg) [13, 16].

Treatment of tension headaches. In this disease, the leading role belongs to the treatment of NSAIDs. In addition, a combination of NSAIDs with diazepam (Seduxen, Relanium) can be used. The latter is prescribed (when taken orally) in the following single dosage: 1-3 years - 0.001 g, 3-7 years - 0.002 g, 7 years and more - 0.003-0.005 g [13].

Tizanidine (sirdalud) is a centrally acting muscle relaxant widely used in the treatment of tension-type hypertension in adults. Experience with its use in children is limited [16].

Tricyclic antidepressants (amitriptyline, imipramine). Regardless of age and route of administration (orally, intramuscularly, intravenously), amitriptyline is prescribed from 0.05-0.075 g/day, gradually increasing the dose by 0.025-0.05 g until the effect is achieved [15]. Imipramine (melipramine, imizin) is prescribed to children starting from 0.01 g 1 time per day, gradually (over 10 days) the dose is increased to 0.02 g for children 1-7 years old, to 0.02-0.05 g for children 8-14 years of age (patients over 14 years old - up to 0.05 g or more per day).

Literature

1. Yakhno N. N., Parfenov V. A., Alekseev V. V. Headache: A reference guide for doctors “R-Doctor”. Series "Nosologies". M., 2000. 150 p.
2. Chu ML, Shinnar S. Headaches in children younger than 7 years of age // Arch. Neurol. 1992. vol. 49. P. 79-82.
3. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain // Cephalalgia. 1988. V. 8. Suppl. 7.96 p.
4. Goadsby JP Update of the anatomy and physiology of headache // Abstr. of 2-d Congress Eur. Fed. Chapt. of IASP. Barcelona. 1997. P. 79.
5. Therapeutic reference book of the University of Washington / Ed. M. Woodley, A. Whelan; lane from English M.: Practice. 1995. 832 p.
6. Dalessio DJ Wolff's headache and other head pain. Oxford University Press. New York. 1980.
7. Oleson J., Edvindsson L. Migraine: a research field matured for the basic neurosciences // Trends Neurosci. 1991. Vol. 14. P. 3-5.
8. Lauritzen M. Pathophysiology of the migraine aura. The spreading depression therapy //Brain. 1994. Vol. 117. P. 199-210.
9. Ferrari MD Cerebral blood flow during migraine attacks without aura and effect of sumatriptan // Arch. Neurol. 1995. Vol. 52. P. 135-139.
10. Congden PJ, Forsythe WI Migraine in childhood: a study of 300 children // Dev. Med. Child Neurol. 1979. Vol. 21. P. 209-216.
11. Neurology/Ed. M. Samuels; Per. from English M.: Practice. 1997. 640 p.
12. Child Neurology (Menkes JH, Sarnat HB, eds.).-16th ed. Lippincott Williams and Wilkins. Philadelphia-Baltimore. 2000. 1280 p.
13. Vidal Directory. Medicines in Russia: Directory. 8th ed., revised. and additional M.: AstraPharmService. 2002. 1488 p.
14. Hamalainen ML Ibuprofen or acetaminophen for the acute treatment of migraine in children. A double-blind, randomized, placebo-controlled, crossover study // Neurology. 1997. Vol. 48. P. 103-107.
15. Mashkovsky M.D. Medicines. In 2 hours. 12th ed., revised. and additional M.: Medicine. 1993.
16. Register of Medicines of Russia “Encyclopedia of Medicines”/ Ch. ed. G. L. Vyshkovsky. 9th ed., revised. and additional M., RLS-2002. 2002. 1504 p.
17. Hamalainen M.L., Koppu K., Santavuori P. Sumatriptan for migraine attacks in children: a randomized, placebo-controlled study // Neurology. 1997. Vol. 48. P. 1100-1103.
18. Egger J. Is migraine a food allergy? // Lancet. 1983. Vol. 2. P. 865-869.
19. Wilkinson M. Migraines and headaches / Transl. from English K.: “Sofia.” 1997. 112 p.
20. Clinical recommendations based on evidence-based medicine / Trans. from English edited by I. N. Denisova, V. I. Kulakova, R. M. Khaitova. M.: GEOTAR-MED, 2001. 1248 p.

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.

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.

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.

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.

Instructions for use "No-Shpa"

Dosage and rules of administration depend on the form of the drug and the age of the person:

1. The daily dosage of the active substance for an adult is in the range of 120-240 mg, which corresponds to 3-6 tablets of the regular drug and 2-3 tablets of the “Forte” variety. In this case, it is allowed to consume no more than 40 mg at a time, i.e. maximum 2 tablets.
2. For children under 11 years of age inclusive, the optimal dose is 80 mg - this amount is taken 2 times a day.
3. For older children, a dose of 160 mg is indicated, divided into 2-4 times.

The general course of therapy (with self-treatment) is no more than 2 days. If during this time your health does not improve, you need to contact a specialist for a possible replacement of the drug and diagnostics. If No-Shpa is used as an additional medication as part of complex therapy, then the course without consulting a specialist can last up to 3 days.

List of effective headache pills

There are no universal painkillers that can be used in any situation. Even the strongest pills will not bring the desired effect if their action is not aimed at eliminating the cause of the pain syndrome. Despite this, you can find ratings for 2021 on the Internet with lists of the best headache medications. You cannot rely on this information, since the selection of medications should be carried out by the attending physician.

Below is a list of inexpensive medications that are in demand and can be purchased without a prescription as a one-time headache relief.

Aspirin

Tablets based on acetylsalicylic acid are almost certainly in every home medicine cabinet. The medicine can be used for migraines, cerebrovascular accidents, inflammatory diseases, and alcohol dependence syndrome. Aspirin is a good blood thinner and can prevent the formation of blood clots. Due to this quality, the drug is recognized by experts as one of the most effective in the treatment of vascular diseases. However, acetylsalicylic acid is not recommended for people with diagnoses such as gastric and intestinal ulcers, blood clotting disorders, etc.

Aspirin, according to the instructions, can be taken 1 tablet 3 times a day after meals. The duration of treatment is determined by the doctor and is usually no more than 2 weeks.

Paracetamol

The active ingredient of this drug is in most cases well absorbed by the body and helps with headaches of various etiologies. Paracetamol is one of the affordable, but at the same time effective and gentle antipyretic drugs. Other medications in this group are also made on its basis, for example, Panadol for children.

The drug, in accordance with the instructions, can be taken once or up to 4 times a day, but no more than 5 days in a row, otherwise unwanted complications associated with an overdose of the active substance may develop.

Citramon

This drug is one of the most common and accessible analgesics. You can take Citramon, according to the instructions, for mild headaches that may occur against the background of an increase in temperature or certain inflammatory processes. The therapeutic effect is achieved by increasing vascular tone and improving blood circulation. The active ingredients of most forms of Citramon are aspirin, paracetamol, caffeine, that is, the drug can have a combined effect.

Doctors recommend not to overuse these headache pills due to the likelihood of side effects. The duration of taking the medicine can be no more than 3 days. The daily dose can be no more than 8 tablets.

Tempalgin

A combined action drug that eliminates headaches and has a sedative effect. This means that taking Tempalgin is not recommended if after this a person has to do work that requires concentration. At the same time, the active ingredient of this drug shows good effectiveness for pain of various types and severity.

In accordance with the instructions, Tempalgin can be taken up to 3 times a day. As a rule, in this case we are talking about persistent pain syndrome. The duration of treatment for headaches with this drug should be no more than 5 days.

Pentalgin

This is another popular combination drug. The use of Pentalgin, in accordance with the instructions, has an antispasmodic, anti-inflammatory and antipyretic effect. Its action is aimed at slowing down the production of hormones that provoke pain. In most cases, the desired result is achieved after taking one tablet.

It is recommended to take the drug no more than 3 times a day. The permissible duration of treatment for headaches is up to 5 days.

Ibuprofen

A fast-acting drug indicated for migraines, as well as headaches that can be caused by inflammatory processes and nervous tension. Ibuprofen has antipyretic and blood thinning properties similar to Aspirin. The first effect after taking the medicine is usually observed after 10 minutes, but the drug shows its peak effect on average after 2 hours.

It is allowed to take no more than 4 tablets per day; other cases should be discussed with your doctor. The duration of treatment depends on the characteristics of the disease.

Spazgan

The product relieves spasm of the walls of blood vessels, eliminates the inflammatory process and relieves pain. “Spazgan” quickly brings relief and maintains its therapeutic effect for 4-8 hours. Despite the fact that the drug is available without a prescription and is indicated for a wide range of conditions, it is advisable to coordinate its use with your doctor.

“Spazgan” is a single-use drug, so the duration of taking the drug, in accordance with the instructions, should be no more than 3 days. If this rule is violated, there may be a risk of side effects.

No-Shpa

The drug is prescribed primarily for headaches that occur after stress, physical or emotional stress. As a rule, such pain syndrome is characterized by moderation and absence of pulsation. “No-Spa” has an antispasmodic effect, relaxing the walls of blood vessels and normalizing blood circulation. The therapeutic effect occurs approximately 15 minutes after taking the medicine.

At a time, according to the instructions, it is recommended to take no more than two tablets. The daily dose of the drug should not exceed 8 tablets. It is prohibited to take No-Shpu for more than two days without consulting a doctor.

Nurofen

A combined action drug that has an analgesic, antipyretic and anti-inflammatory effect. Nurofen has pronounced analgesic properties. If the patient does not know what to do with a severe headache that accompanies a migraine attack, then some experts recommend taking this drug once. Further treatment in this case should be prescribed by a doctor.

In accordance with the instructions, Nurofen can be used one tablet no more than 4 times a day. The breaks between doses of the drug should be about 4 hours. It is not recommended to use tablets for longer than 3 days, as there is a risk of side effects.

Papaverine

An affordable antispasmodic, which, like No-Shpa, has a relaxing effect on the muscles of blood vessels, helps to expand their lumen and normalize blood circulation. Additionally, “Papaverine” has a sedative effect, so some doctors recommend taking it for frequent stress and insomnia.

According to the instructions, this remedy for headaches should be used no more than 4 times a day. You can take no more than 2 tablets at a time.

Buscopan

An antispasmodic drug that can be used for severe headaches. Buscopan is also recommended by doctors as a remedy for seasickness or air sickness. In some cases, the drug is prescribed to children. Buscopan has a pronounced therapeutic effect after a single use, but it can also be used as part of a complex treatment.

In accordance with the instructions, adults can take this drug 1-2 tablets up to 3 times a day. If the pain does not go away, consult a doctor. The dosage for children is selected individually.

Drotaverine

An antispasmodic drug, which in composition and properties is close to Papaverine, but surpasses it in effectiveness and duration of action. "Drotaverine" relieves pain by eliminating vascular spasms and restoring tissue nutrition.

Since the drug can cause a number of side effects, its use must be discussed with your doctor. If it is necessary to eliminate pain at home, it is important for the patient to follow the instructions.

special instructions

No-Shpa contains lactose, so patients with impaired absorption of glucose and galactose should take the tablets with caution and only after the doctor’s approval.

If the solution is administered intravenously, the patient should lie down for several minutes at rest. If you have high blood pressure, use is allowed only in consultation with your doctor.

The injection solution contains sodium metabisulfite, which can cause an allergic reaction. In rare cases (especially in the presence of bronchial asthma, chronic allergies), bronchospasm and the onset of individual signs of anaphylactic shock are possible.