Pharmacological properties of the drug No-shpa
Pharmacodynamics. Drotaverine is an isoquinoline derivative that has an antispasmodic effect on smooth muscles by inhibiting the action of the PDE IV enzyme, causing an increase in the concentration of cAMP and, due to the inactivation of myosin light chain kinase (MLCK), leads to relaxation of smooth muscles. In vitro, drotaverine inhibits the action of the PDE IV enzyme and does not affect the action of the PDE III and PDE V isoenzymes. PDE IV is of great functional importance for reducing the contractile activity of smooth muscles, therefore selective inhibitors of this enzyme may be useful for the treatment of diseases that are accompanied by motor hyperfunction, as well as various diseases during which gastrointestinal spasms occur. In the smooth muscle cells of the myocardium and blood vessels, cAMP is hydrolyzed to a greater extent by the PDE III isoenzyme, therefore drotaverine is an effective antispasmodic agent that does not have significant side effects on the cardiovascular system and a strong therapeutic effect on this system. Drotaverine is effective for smooth muscle spasms of both nervous and muscular origin. Drotaverine acts on the smooth muscles of the gastrointestinal, biliary, genitourinary and cardiovascular systems, regardless of the type of innervation. Increases blood circulation in tissues due to its ability to dilate blood vessels. The action of drotaverine is more effective than that of papaverine, absorption is faster and more complete, it binds less to blood plasma proteins. The advantage of drotaverine, in contrast to papaverine, is that after its parenteral administration there is no such side effect as stimulation of respiration. Pharmacokinetics. Drotaverine is quickly and completely absorbed after parenteral and oral administration. It binds to a high degree (95-98%) with blood plasma proteins, especially with albumin, gamma and beta globulins. After primary metabolism, 65% of the administered dose enters the blood circulation unchanged. Metabolized in the liver. The half-life is 8–10 hours. Within 72 hours, drotaverine is almost completely eliminated from the body, more than 50% is excreted in the urine and approximately 30% in feces. Drotaverine is mainly excreted in the form of metabolites and is not found in unchanged form in the urine.
Instructions for use NO-SPALGIN
Paracetamol
has analgesic and antipyretic effects, mainly due to the suppression of the synthesis of prostaglandins in the tissues of the central nervous system and, to a lesser extent, due to the suppression of the synthesis of prostaglandins and other substances that stimulate pain receptors in the periphery.
Drotaverine
is an isoquinolone derivative that has an antispasmodic effect directly on smooth muscles. The decisive mechanism of action is the selective blockade of the enzyme phosphodiesterase IV with a subsequent increase in the level of cAMP, which, by inactivating myosin light chain kinase (MLCK), leads to relaxation of smooth muscles. Its action does not depend on the influence of the autonomic nervous system.
Codeine
is an analgesic of central action, acting on μ and κ receptors involved in the transmission of pain signals in the central nervous system.
Study of the interactions of the active ingredients of the combination
Based on clinical results
One pilot, open-label, randomized, parallel-group phase I clinical trial in healthy male volunteers found that active ingredients used in combination (8 mg codeine, 40 mg drotaverine, and 500 mg paracetamol) and alone were safe and well tolerated . No severe adverse reactions were recorded; We observed 5 cases of non-severe reactions, but only 2 of them were possibly related to taking the drug or taking blood for testing (1 case of a temporarily positive complicated Romberg test and 1 case of superficial phlebitis of the forearm).
During pharmacokinetic measurements, it was shown that when taking the combination, the saturation stage is reached within 6 days with a single daily dose, and within 3 days with a double dose.
The combination of codeine + drotaverine + paracetamol increased the AUC and Cmax of drotaverine,
those. the use of the combination improved the relative bioavailability of drotaverine. According to the results of the study, Cmax values were in the range of 132÷171 ng/ml, and AUC0-24 values were 463.4÷830.2 ng*h/ml.
These data meant more effective
analgesic effect and a slight increase in duration of action.
Similar results were obtained in the case of paracetamol:
the combination increased AUC and significantly decreased clearance at both doses.
According to the results of the study, Cmax values were in the range of 5495÷6752 ng/ml, AUC0-24 values were 21760.8÷26524.7 ng*h/ml, and clearance values were 356-418 ml/min. Previous trials and kinetic studies have shown that codeine
does not interact with either paracetamol or drotaverine.
To compare the effectiveness of the combination with that of paracetamol alone, one comparative, multicenter, randomized, double-blind, double-placebo-controlled, parallel-group phase III study was conducted.
Results of preclinical safety tests
Results of preclinical safety studies of each active substance separately
Paracetamol
Oral LD50 in mice was 295-1212 mg/kg body weight, in rats - > 4 g/kg. The approximate IV lethal dose of paracetamol is 826 mg/kg and the oral LD50 is 2404 mg/kg. Long-term use of very high doses (1-7 g/kg) caused damage to the liver and kidneys of laboratory animals.
Paracetamol had no effect on reproductive function and was neither mutagenic nor carcinogenic.
Drotaverine
There are no preclinical data that could influence the clinical use of the drug.
Codeine
There are no preclinical data that could influence the clinical use of the drug.
Indications for use of the drug No-shpa
Pills. For therapeutic purposes in adults and children over 1 year of age with:
- spasms of smooth muscles associated with diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;
- spasms of smooth muscles in diseases of the urinary tract: nephrolithiasis, urethorolithiasis, pyelitis, cystitis, bladder tenesmus.
As an auxiliary treatment for:
- spasms of smooth muscles of the gastrointestinal tract: gastric and duodenal ulcers, gastritis, cardio- and/or pylorospasm, enteritis, colitis, spastic colitis with constipation and irritable bowel syndrome accompanied by flatulence; tension headache;
- gynecological diseases (dysmenorrhea).
Solution for injections . Spasms of smooth muscles associated with diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis. Spasms of smooth muscles in diseases of the urinary tract: nephrolithiasis, urethorolithiasis, pyelitis, cystitis, bladder tenesmus. During uncomplicated labor at the dilatation stage: to reduce the cervical dilatation phase and the duration of labor. As an auxiliary treatment (when the use of the drug in tablet form is not possible): for spasms of smooth muscles of the gastrointestinal tract: stomach and duodenal ulcers, gastritis, cardio- and/or pylorospasm, enteritis, colitis; for gynecological diseases: dysmenorrhea, severe labor pains.
Buy No-spa solution intravenously and intramuscularly 40mg/2ml 2ml No. 25 in pharmacies
Instructions for use No-spa solution IV and IM 40mg/2ml 2ml No. 25 Dosage forms solution for injection 20mg/ml 2ml
Synonyms Droverin Nosh-bra Spazmol Spazmonet Group Antispasmodics - isoquinoline derivatives International nonproprietary name Drotaverine Composition Active substance - Drotaverine. Manufacturers Hinoin (Hungary), Hinoin Pharmaceutical and Chemical Products Plant A.O. (Hungary), Hinoin Pharmaceutical and Chemical Products Plant CJSC (Hungary) Pharmacological action Antispasmodic, myotropic, vasodilator, hypotensive. Quickly and completely absorbed into the gastrointestinal tract. It is evenly distributed throughout the tissues and penetrates smooth muscle cells. Excreted by the kidneys. Pronouncedly and for a long time expands the smooth muscles of internal organs and blood vessels, reduces blood pressure, and increases cardiac output. It has virtually no effect on the autonomic nervous system and does not penetrate the central nervous system. Side effects: Feeling of heat, dizziness, arrhythmias, hypotension, palpitations, sweating (more often with parenteral administration), allergic dermatitis. Indications for use Spasm of smooth muscles of internal organs (cardio- and pylorospasm), chronic gastroduodenitis, peptic ulcer of the stomach and duodenum, cholelithiasis (hepatic colic), chronic cholecystitis, postcholecystectomy syndrome, hypermotor dyskinesia of the biliary tract, spastic intestinal dyskinesia, intestinal colic due to gas retention after surgery, colitis, proctitis, tenesmus, flatulence, urolithiasis (renal colic), pyelitis, spasm of cerebral vessels, coronary and peripheral arteries, the need to weaken uterine contractions and relieve cervical spasm during childbirth, smooth muscle spasm during childbirth time of instrumental interventions Contraindications Hypersensitivity, glaucoma. Overdose AV blockade, cardiac arrest, paralysis of the respiratory center. Interaction Enhances (especially with intravenous administration) the effect of other antispasmodics (including m-anticholinergics), hypotension caused by tricyclic antidepressants, quinidine, novocainamide. Phenobarbital increases the reliability of eliminating spasms. Reduces the spasmogenic activity of morphine and the antiparkinsonian properties of levodopa. Special instructions Restrictions on use. Prostate adenoma, severe atherosclerosis of the coronary arteries. Storage conditions List B. In a place protected from light at room temperature.
Use of the drug No-shpa
Pills . Adults : The usual average dose is 120–240 mg per day in 2–3 divided doses. Children aged 1–6 years : the usual average dose is 40–120 mg per day in 2–3 divided doses. Children over 6 years of age : the usual average dose is 80–200 mg per day in 2–5 divided doses. Solution for injection : the usual average daily dose for adults is 40–240 mg (in 1–3 separate administrations) IM. For attacks of renal or hepatic colic - 40–80 mg IV slowly. To reduce the dilatation phase of the cervix during uncomplicated labor at the beginning of the dilatation stage - 40 mg IM. If this dose is ineffective, another 40 mg of No-Shpa is administered at intervals of 2 hours.
Side effects of the drug No-shpa
Side effects observed in clinical studies and caused by taking drotaverine are classified by organs and systems, as well as by frequency of occurrence: very often (≥1/10), often (≥1/100, but ≤1/10), infrequently (≥ 1/1000, but ≤1/100), rare (≥1/10,000, but ≤1/1000), very rare (≤1/10,000), including isolated cases. Gastrointestinal disorders: rarely - nausea, constipation. From the nervous system: rarely - headache, dizziness, insomnia. From the cardiovascular system: rarely - tachycardia, arterial hypotension. From the immune system: isolated: allergic reactions, especially in patients with hypersensitivity to metabisulfite.
Pharmacokinetics
Paracetamol is quickly absorbed from the gastrointestinal tract and distributed to most organs and tissues. Absorption is high, the time to reach maximum concentration is reached after 0.5-2 hours; maximum concentration - 5-20 μg/ml. Communication with plasma proteins - 15%. Penetrates the blood-brain barrier. Less than 1% of the dose of paracetamol taken by a nursing mother passes into breast milk. Metabolized in the liver (90-95%): 80% enters into conjugation reactions with glucuronic acid and sulfates to form inactive metabolites. With a lack of glutathione, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. The CYP2E1 isoenzyme is also involved in the metabolism of the drug. The half-life is 1-4 hours. It is excreted by the kidneys in the form of metabolites, mainly conjugates, only 3% unchanged. In elderly patients, the clearance of the drug decreases and the half-life increases.
Drotaverine, when taken orally, is quickly and almost completely absorbed, absorption is high, the half-absorption period is 12 minutes. Bioavailability - 100%. Evenly distributed in tissues, penetrates smooth muscle cells. The time to reach maximum concentration is 2 hours. Communication with plasma proteins is 95-98%. The half-life is 1-4 hours. It is mainly excreted by the kidneys, to a lesser extent - with bile. Does not penetrate the blood-brain barrier.
Special instructions for the use of the drug No-shpa
Each tablet of No-Shpa contains 52 mg of lactose. When used according to recommended doses, up to 156 mg of lactose can enter the body at one time, which can cause gastrointestinal complaints in patients with lactose intolerance. Do not use for the treatment of patients with congenital lactase deficiency, galactosemia or glucose-galactose malabsorption syndrome. Use with caution to treat children, since no studies have been conducted on the effect of drotaverine on children. Use with caution in case of hypotension. Due to the risk of collapse during intravenous administration of the drug No-Shpa, the patient should be in a supine position. The drug contains metabisulfite, which may cause allergic-type reactions, including symptoms of anaphylactic shock and bronchospasm, especially in patients with a history of asthma or allergies. In case of hypersensitivity to sodium metabisulfite, parenteral administration of the drug should be avoided. You need to be careful when administering the drug parenterally to women during pregnancy. Use during pregnancy and lactation. As shown by the results of retrospective clinical studies, oral administration of the drug did not have a teratogenic or embryotoxic effect. However, caution should be exercised when prescribing the drug to women during pregnancy. Due to the lack of relevant research data, administration of the drug during breastfeeding is not recommended. Impact on the ability to drive a car and perform work that requires increased attention. If patients experience dizziness after using the drug, they should avoid potentially hazardous activities. It is necessary to warn patients that after parenteral, especially intravenous administration of the drug, it is recommended to refrain from driving and performing work that requires increased attention.
