Pharmacological properties
Pharmacodynamics
Drotaverine is an isoquinoline derivative that exhibits a powerful antispasmodic effect on smooth muscle due to inhibition of the enzyme phosphodiesterase type IV (PDE IV).
Inhibition of the PDE IV enzyme leads to an increase in cAMP concentration, inactivation of myosin light chain kinase, which subsequently causes relaxation of smooth muscles. The effect of drotaverine in reducing the cytosolic concentration of Ca2+ ions through cAMP explains its antagonistic effect towards Ca2+ ions.
In vitro, drotaverine inhibits the PDE IV enzyme without inhibiting the PDE III and PDE V enzymes. Therefore, the effectiveness of drotaverine depends on the concentrations of PDE IV in different tissues. PDE IV is most important for suppressing the contractile activity of smooth muscles, and therefore selective inhibition of PDE IV may be useful for the treatment of hyperkinetic dyskinesias and various diseases accompanied by a spastic state of the gastrointestinal tract.
The hydrolysis of cAMP in the myocardium and vascular smooth muscle occurs mainly with the help of the enzyme PDE III, which explains the fact that with high antispasmodic activity, drotaverine has no serious side effects on the heart and blood vessels and no pronounced effects on the cardiovascular system.
Drotaverine is effective against smooth muscle spasms of both neurogenic and muscular origin. Regardless of the type of autonomic innervation, drotaverine relaxes the smooth muscles of the gastrointestinal tract, biliary tract, genitourinary system, and blood vessels.
Due to its vasodilating effect, drotaverine improves blood supply to tissues.
Thus, the mechanisms of action of drotaverine described above eliminate spasm of smooth muscles, which leads to a decrease in pain.
No-spa forte for abdominal pain tablets 80 mg No. 24
A country
Hungary
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Compound
1 tablet contains: active ingredient: drotaverine hydrochloride – 80 mg; excipients: magnesium stearate, talc, povidone, corn starch, lactose monohydrate. Description Oblong biconvex tablets, yellow with a greenish or orange tint, engraved “NOSPA” on one side and a break line on the other side. Release form Tablets 80 mg. 10 tablets in a blister made of aluminum foil/aluminum foil laminated with a polymer. 10 tablets per blister made of PVC/aluminum foil. 1 or 2 blisters along with instructions for use in a cardboard box. 24 tablets per blister made of PVC/aluminum foil. 1 blister along with instructions for use in a cardboard box.
Pharmacological properties
Pharmacodynamics Drotaverine is an isoquinoline derivative, similar in chemical structure and pharmacological properties to papaverine, but with a stronger and longer-lasting effect. Drotaverine has a powerful antispasmodic effect on smooth muscle due to inhibition of the enzyme phosphodiesterase (PDE). The enzyme phosphodiesterase is necessary for the hydrolysis of cAMP (cyclic adenosine-3´, 5´-monophosphate) to AMP (adenosine-5´-monophosphate). Inhibition of the phosphodiesterase enzyme leads to an increase in cAMP concentration, which triggers the following cascade reaction: high concentrations of cAMP activate cAMP-dependent phosphorylation of myosin light chain kinase (MLCK). Phosphorylation of MLCK leads to a decrease in its affinity for the Ca2+-calmodulin complex, resulting in an inactivated form of MLCK supporting muscle relaxation. cAMP, in addition, affects the cytosolic concentration of Ca2+ ion by stimulating the transport of Ca2+ into the extracellular space and the sarcoplasmic reticulum. This effect of drotaverine in lowering the cytosolic concentration of Ca2+ ion through cAMP explains its antagonistic effect towards Ca2+. In vitro, drotaverine inhibits the PDE IV isoenzyme without inhibiting the PDE III and PDE V isoenzymes. Therefore, the effectiveness of drotaverine depends on the concentrations of PDE IV in tissues, the content of which varies in different tissues. PDE IV is most important for suppressing the contractile activity of smooth muscles, and therefore selective inhibition of PDE IV may be useful for the treatment of hyperkinetic dyskinesias and various diseases accompanied by a spastic state of the gastrointestinal tract. The hydrolysis of cAMP in the myocardium and vascular smooth muscle occurs mainly with the help of the PDE III isoenzyme, which explains the fact that with high antispasmodic activity, drotaverine has no serious side effects on the heart and blood vessels and no pronounced effects on the cardiovascular system. Drotaverine is effective against smooth muscle spasms of both neurogenic and muscular origin. Regardless of the type of autonomic innervation, drotaverine relaxes the smooth muscles of the gastrointestinal tract, biliary tract, genitourinary system, and blood vessels. Due to its vasodilating effect, drotaverine improves blood supply to tissues. Pharmacokinetics: Compared with papaverine, drotaverine, when taken orally, is absorbed faster and more completely from the gastrointestinal tract. Absorption is 100%. However, after metabolism during the “first pass through the liver,” 65% of the dose taken enters the systemic circulation. Maximum plasma concentration (Cmax) is achieved after 45-60 minutes. In vitro, drotaverine is highly bound to plasma proteins (95-97%), especially with albumin, γ and β-globulins. Drotaverine is evenly distributed throughout the tissues and penetrates smooth muscle cells. Does not penetrate the blood-brain barrier. Drotaverine and/or its metabolites may slightly penetrate the placental barrier. In humans, drotaverine is almost completely metabolized in the liver by Odesethylation. Its metabolites quickly conjugate with glucuronic acid. The main metabolite is 4'-desethyldrotaverine, in addition to which 6-desethyldrotaverine and 4'-desethyldrotaveraldine have been identified. The half-life of drotaverine is 8-10 hours. Within 72 hours, drotaverine is almost completely eliminated from the body, more than 50% of the drug is excreted by the kidneys (mainly in the form of metabolites) and about 30% through the gastrointestinal tract (excretion into bile). Unchanged drotaverine is not detected in urine.
Indications for use
— Smooth muscle spasms in diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, inflammation of the duodenal papilla. — Spasms of smooth muscles in diseases of the urinary tract: nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder spasms. As an auxiliary therapy: - for spasms of smooth muscles of the gastrointestinal tract: peptic ulcer of the stomach and duodenum, gastritis, spasms of the cardia and pylorus, enteritis, colitis, spastic colitis with constipation and irritable bowel syndrome with flatulence; - for tensor headaches (tension headaches); - with algodismenorrhea.
Contraindications
— Hypersensitivity to drotaverine and/or excipients included in the drug. - Severe liver or kidney failure. - Severe heart failure (decreased cardiac output). — Breastfeeding period (see section “Pregnancy and lactation”). — Children's age (clinical studies have not been conducted in children). — Hereditary lactose intolerance, lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome (due to the presence of lactose in the drug) (see “Special Instructions”). With caution - For arterial hypotension. — In pregnant women (see section “Pregnancy and lactation”). Pregnancy and lactation According to the limited amount of retrospective data on the use of the drug in humans and data from studies in animals when taking drotaverine orally, there is no evidence of its teratogenic or embryotoxic effect, or adverse effects on the course of pregnancy. Despite this, when using the drug in pregnant women, caution should be exercised and the drug should be prescribed only after carefully weighing the balance of benefits and risks for the mother and the risk for the child. Studies on the excretion of drotaverine into human milk in animals have not been conducted. Due to the lack of such studies in animals and clinical data, prescribing drotaverine during lactation is not recommended.
Mode of application
The drug is taken orally. Typically, the average daily dose is 120-240 mg (the daily dose is divided into 2-3 doses).
Side effect
The following side effects, which in clinical studies were regarded as at least possibly associated with drotaverine, are given in accordance with the following gradations of their frequency of occurrence: very often (1/10), often (≥1/100, 1/ 10); rarely (≥1/1000, 1/100); sometimes (≥1/10000, 1/1000); very rare (including isolated reports) ( 1/10000); unknown frequency (it is impossible to determine the frequency of occurrence from the available data) and are grouped by organ system. From the nervous system - Sometimes: headache, dizziness, insomnia. From the cardiovascular system - Sometimes: rapid heartbeat, decreased blood pressure. From the gastrointestinal tract - Sometimes: nausea, constipation. From the immune system - Sometimes - allergic reactions (angioedema, urticaria, rash, itching) (see section "Contraindications").
Overdose
Drotaverine overdose has been associated with cardiac rhythm and conduction disturbances, including complete bundle branch block and cardiac arrest, which can be fatal. In case of overdose, patients should be under medical supervision and, if necessary, they should receive symptomatic treatment aimed at maintaining basic body functions.
Interaction
With levodopa When used simultaneously, drotaverine can weaken the antiparkinsonian effect of levodopa, that is, increase rigidity and tremor. With papaverine, bendazole and other antispasmodics (including antispasmodics) Strengthening the antispasmodic effect. With morphine Reducing the spasmogenic activity of morphine. With phenobarbital Strengthening the antispasmodic effect of drotaverine.
special instructions
The use of the drug for arterial hypotension requires increased caution. Each tablet of No-shpa® forte contains 104 mg of lactose. When taken according to the recommended dosage regimen, up to 156 mg of lactose (1.5 tablets of No-shpa® forte) can be delivered with each dose, which can cause gastrointestinal disorders in patients suffering from lactose intolerance. This form of the drug is unacceptable for patients suffering from lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome. Effect on the ability to drive a car and other mechanisms When taken orally in therapeutic doses, drotaverine does not affect the ability to drive vehicles and perform work that requires increased attention. If any side effects occur, the question of driving or engaging in other potentially hazardous activities requires individual consideration. If dizziness occurs, you should avoid engaging in potentially hazardous activities, such as driving vehicles and operating machinery.
Pharmacokinetics
Absorption
Compared with papaverine, drotaverine, when taken orally, is absorbed faster and more completely from the gastrointestinal tract. However, after first-pass metabolism, 65% of the administered dose of drotaverine enters the systemic circulation. The maximum concentration (Cmax) of drotaverine in blood plasma is reached after 45-60 minutes.
Distribution
In vitro, drotaverine has a high binding to plasma proteins (95-97%), especially with albumin, γ- and β-globulins.
Drotaverine is evenly distributed in tissues and penetrates smooth muscle cells. Does not penetrate the blood-brain barrier. Drotaverine and/or its metabolites may slightly penetrate the placental barrier.
Metabolism
Drotaverine is almost completely metabolized in the liver.
About the drug
No-Shpa is a synthetic myotropic antispasmodic.
No-shpa forte belongs to the group of synthetic myotropic antispasmodics and is available in tablets.
The main active ingredient is drotaverine hydrochloride, 80 mg of it is contained in each tablet. They are oblong in shape, yellow in color, and may have an orange or greenish tint.
On one side the tablet bears the marking “nospa”, on the other there is a line with which you can split the tablet in half. Additional substances, fillers:
- magnesium stearate,
- talc,
- corn starch,
- polyvidone,
- lactose.
No-shpa forte is supplied to the pharmacy chain in blisters of 10 pieces, placed in cardboard packaging.
Interaction with other drugs
Phenobarbital can be taken together with the drug No-Shpa.
When taken simultaneously with other drugs, the peculiarities of their interaction should be taken into account.
- Levodopa – when taken together with No-shpa forte, its ability to relieve the effect of parkinsonism is weakened, that is, the tremor of the limbs and the rigidity of the patient increases;
- Morphine – its activity as an antispasmodic decreases;
- Phenobarbital – when taken simultaneously, the activity of No-shpa forte increases;
- Anticholinergics and antispasmodics - their resistance to spasms is enhanced.
Manufacturer
Manufacturer and packer (primary packaging):
Hinoin Pharmaceutical and Chemical Products Plant CJSC, st. Levai 5, 2112 Veresegyház, Hungary.
Packer (secondary (consumer) packaging) and releasing quality control:
1. Hinoin Pharmaceutical and Chemical Products Plant CJSC, st. Levai 5, 2112 Veresegyház, Hungary.
2. JSC "ORTAT", Russia 157092, Kostroma region, Susaninsky district, village. Severnoye, Kharitonovo microdistrict.
Consumer complaints should be sent to the address in Russia: 125009, Moscow, st. Tverskaya, 22.
Tel.; Fax.
Directions for use and doses
Adults: The usual average dose is 120-240 mg per day in 2-3 divided doses.
Children over 12 years of age: if necessary, as prescribed by a doctor, the maximum daily dose is 160 mg (1/2 tablet 2-4 times a day).
The duration of treatment is determined by the doctor individually.
The NO-SPA Ò forte tablet can be divided in half.
Children
The use of the drug in the treatment of children under 12 years of age is contraindicated.
Use during pregnancy or breastfeeding
Pregnancy. The results of retrospective clinical studies showed that oral administration of the drug did not cause any evidence of any direct or indirect effect on pregnancy. However, caution should be exercised when prescribing the drug to pregnant women.
Lactation. Due to the lack of data, use of the drug during breastfeeding is not recommended.
Use during pregnancy and breastfeeding
The studies conducted did not reveal the teratogenic and embryotoxic effects of drotaverine, as well as any adverse effects on the course of pregnancy. However, if it is necessary to use the drug No-shpa® forte during pregnancy, caution should be exercised and the drug should be prescribed only after assessing the ratio of the potential benefit to the mother and the possible risk to the fetus.
Due to the lack of animal studies and clinical data, it is not recommended to prescribe drotaverine during breastfeeding.
Advantages
Antispasmodics affect smooth muscles and relieve pain caused by spasms. The antispasmodic drug drotaverine is used in gastroenterology, therapy, urology and gynecology in many countries around the world.
- Gastroenterology. In this area, the drug is prescribed for spastic pain accompanying pathology of the biliary tract - cholelithiasis, acute or chronic cholecystitis, cholangitis, etc.
- Urology. Inflammatory processes in the urinary organs (cystitis, pyelitis) can also lead to spasms, so the use of drotaverine for these diseases is completely justified.
- Tension headaches. Drotaverine
The favorable safety profile has been confirmed by numerous clinical studies.
Contraindications
hypersensitivity to the active substance or to any of the excipients of the drug;
severe liver or kidney failure;
severe heart failure (low cardiac output syndrome);
hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome (due to the presence of lactose monohydrate in the composition of the drug - see “Special Instructions”);
period of breastfeeding (see “Use during pregnancy and lactation”);
childhood.
Carefully:
arterial hypotension; pregnancy (see “Use during pregnancy and lactation”).
Side effects and special instructions
Headache is a side effect after taking the drug.
A side effect from the use of this drug was recorded in only 3% of cases of use. In this case, the following deviations from the normal state may be observed:
- tachycardia, rarely hypotension – from the cardiovascular system;
- headache, sleep disturbances, dizziness - from the cardiovascular system;
- nausea, constipation - from the gastrointestinal tract.
Special instructions - No-shpa forte does not affect the ability to interact with complex mechanisms, drive a vehicle, make responsible decisions and perform work that requires concentration.
Indications of the drug No-shpa® forte
spasms of smooth muscles in diseases of the biliary tract (cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis);
spasms of smooth muscles of the urinary tract (nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder spasms).
As an adjuvant therapy for the following diseases and conditions:
spasms of smooth muscles of the gastrointestinal tract (peptic ulcer of the stomach and duodenum, gastritis, spasms of the cardia and pylorus, enteritis, colitis, spastic colitis with constipation, irritable bowel syndrome with flatulence);
tension headaches;
dysmenorrhea (menstrual pain).
