Dot (Drotaverine)

smooth muscle spasms in diseases of the biliary tract (cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis),

spasms of the smooth muscles of the urinary tract (nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder spasms),

spasms of the smooth muscles of the gastrointestinal tract (gastric ulcer and duodenal ulcer, gastritis, spasms of the cardia and pylorus, enteritis, colitis, spastic colitis with constipation, irritable bowel syndrome with flatulence) - as an adjunct therapy,

tension headache — as an adjunct therapy,

dysmenorrhea (menstrual pain) - as an adjunct therapy.

smooth muscle spasms associated with diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis,

spasms of the smooth muscles of the urinary tract: nephrolithiasis, urethrolithiasis, pyelitis, cystitis, tenesmus of the bladder,

As an adjunct therapy (if oral therapy is not possible):

spasms of the smooth muscles of the gastrointestinal tract: peptic ulcer of the stomach and duodenum, gastritis, spasms of the cardia and pylorus, enteritis, colitis,

gynecological diseases: dysmenorrhea.

Inside.

Adults — 40-80 mg (1-2 tablets) 2-3 times a day. The maximum daily dose is 240 mg.

Children aged 3-6 years — in a single dose of 20 mg, the maximum daily dose-120 mg (in 2-3 doses), 6-12 years — a single dose of 40 mg, the maximum daily dose-200 mg, the frequency of use-2-5 times a day.

Inside, adults: 40-80 mg 3 times a day. For children: up to 6 years — 10-20 mg 1-2 times a day, 6-12 years - 20 mg 1-2 times a day.

Inside.

Adults. 1-2 tablets per 1 dose 2-3 times a day, the maximum daily dose is 6 tablets (240 mg).

Children. Clinical studies on the use of drotaverine in children have not been conducted. If drotaverine is prescribed to children from 6 to 12 years of age — 1 tablet per 1 dose 1-2 times a day, the maximum daily dose is 2 tablets (80 mg), over 12 years of age-1 tablet per 1 dose 1-4 times a day or 2 tablets per 1 dose 1-2 times a day, the maximum daily dose is 4 tablets (160 mg).

When taking the drug without consulting a doctor, the recommended duration of taking the drug is usually 1-2 days. In cases where drotaverine is used as an auxiliary therapy, the duration of treatment without consulting a doctor may be longer (2-3 days). If the pain persists, the patient should consult a doctor.

V / m, v / V.

Adults: the average daily dose is 40-240 mg, divided into 1-3 I / m administration.

In acute renal and cholelithiasis-40-80 mg / day, slowly (the duration of administration is about 30 seconds).

hypersensitivity to the active substance or any of the auxiliary components of the drug,

severe renal or hepatic insufficiency,

severe heart failure (low cardiac output syndrome),

hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome (the drug contains lactose monohydrate),

breastfeeding period (no clinical data available),

children under 6 years of age.

With caution: arterial hypotension, children (lack of clinical experience of use), pregnancy (see "Use during pregnancy and lactation").

Solution for intravenous and intravenous administration

hypersensitivity to the active substance or any of the excipients of the drug,

hypersensitivity to sodium disulfite (see " Special instructions»),

severe liver or kidney failure,

severe chronic heart failure,

children's age (the use of drotaverine in children in clinical studies has not been studied),

breast-feeding period (no clinical studies available).

With caution: hypotension (risk of collapse, see "Special instructions"), pregnancy (see "Use during pregnancy and lactation").

Below are the adverse reactions observed in clinical trials, divided by organ system, indicating the frequency of their occurrence in accordance with the following gradations recommended by WHO: very common (≥10%), common (≥1%, <10%), infrequently (≥0,1%, <1%), rarely (≥0,01%, <0,1%), very rarely, including individual messages (<0.01 %), the frequency is unknown (according to available data, the frequency cannot be determined).

From the nervous system: rarely-headache, dizziness, insomnia.

From the CCC side: rarely-a feeling of palpitation, a decrease in blood pressure.

From the gastrointestinal tract: rarely-nausea, constipation.

On the part of the immune system: allergic reactions (angioedema, urticaria, rash, itching) (see "Contraindications").

Below are the adverse reactions observed in clinical trials, divided by organ system, indicating the frequency of their occurrence according to the following gradation: very common (≥10%), common (≥1, <10%), infrequent (≥0.1, <1%), rare (≥0.01, <0.1%), very rare, including individual reports (<0.01%), unknown frequency (according to available data, the frequency cannot be determined).

From the CCC side: rarely-rapid heartbeat, decreased blood pressure.

From the central nervous system: rarely-headache, dizziness, insomnia.

From the gastrointestinal tract: rarely-nausea, constipation.

On the part of the immune system: rarely-allergic reactions (angioedema, urticaria, rash, itching) (see "Contraindications"), unknown frequency-when using the drug, the development of anaphylactic shock with a fatal outcome and without a fatal outcome has been reported.

Local reactions: rarely-reactions at the injection site.

Symptoms: cardiac rhythm and conduction disorders, including complete blockage of the Gis beam and cardiac arrest, which can be fatal.

Treatment: patients should be under medical supervision, and if necessary, they should be treated symptomatically and aimed at maintaining the basic functions of the body, including artificial induction of vomiting or gastric lavage.

Symptoms: drotaverine overdose has been associated with cardiac arrhythmias and conduction disorders, including complete blockage of the legs of the Gis bundle and cardiac arrest, which can be fatal.

Treatment: In the event of an overdose, patients should be under close medical supervision and should be treated with symptomatic therapy and treatment aimed at maintaining the basic functions of the body.

Drotaverine is an isoquinoline derivative that exhibits a powerful antispasmodic effect on smooth muscle by inhibiting the PDE-4 enzyme. Inhibition of the PDE-4 enzyme leads to an increase in the concentration of cAMP, inactivation of the myosin light chain kinase, which further causes relaxation of smooth muscles.

Reducing the concentration of Ca ions² the effect of drotaverine via cAMP explains the antagonistic effect of drotaverine with respect to Ca ions² . In vitro drotaverine inhibits the PDE-4 enzyme without inhibiting the PDE-3 and PDE-5 enzymes. Therefore, the effectiveness of drotaverine depends on the concentrations of PDE-4 in different tissues. PDE-4 is most important for suppressing the contractile activity of smooth muscles, and therefore selective inhibition of PDE-4 can be useful for the treatment of hyperkinetic dyskinesia and various diseases accompanied by a spastic state of the gastrointestinal tract. Hydrolysis of cAMP in the myocardium and vascular smooth muscle occurs mainly with the help of the enzyme PDE-3, which explains the fact that with high antispasmodic activity, drotaverine has no serious side effects from the heart and blood vessels and pronounced effects on CCC

Drotaverine is effective for smooth muscle spasms of both neurogenic and muscular origin. Regardless of the type of vegetative innervation, drotaverine relaxes the smooth muscles of the gastrointestinal tract, biliary tract, and genitourinary system.

Due to its vasodilating effect, drotaverine improves blood supply to tissues.

Thus, the above mechanisms of action of drotaverine eliminate smooth muscle spasm, which leads to a reduction in pain.

Drotaverine is an isoquinoline derivative that exhibits a powerful antispasmodic effect on smooth muscle by inhibiting the PDE enzyme. The PDE enzyme is required for the hydrolysis of cAMP to AMP. Inhibition of the PDE enzyme leads to an increase in cAMP concentration, which triggers the following cascade reaction: high cAMP concentrations activate cAMP-dependent phosphorylation of myosin light chain kinase( CLCM), phosphorylation of CLCM leads to a decrease in its affinity for Ca² - calmodulin complex, resulting in the inactivated form of CLCM supports muscle relaxation. cAMP also affects the cytosolic concentration of the Ca ion² thanks to the promotion of transport Ca² into the extracellular space and the sarcoplasmic reticulum. This lowers the concentration of the Ca ion² the effect of drotaverine via cAMP explains the antagonistic effect of drotaverine with respect to Ca² .

In vitro drotaverine inhibits the PDE-4 enzyme without inhibiting the PDE-3 and PDE-5 isoenzymes. Therefore, the effectiveness of drotaverine depends on the concentrations of PDE-4 in the tissues, which differ in different tissues. PDE-4 is most important for suppressing the contractile activity of smooth muscles, and therefore selective inhibition of PDE-4 can be useful for the treatment of hyperkinetic dyskinesia and various diseases accompanied by a spastic state of the gastrointestinal tract.

Hydrolysis of cAMP in the myocardium and vascular smooth muscle occurs mainly with the help of the PDE-3 isoenzyme, which explains the fact that with high antispasmodic activity, drotaverine has no serious side effects from the heart and blood vessels and pronounced effects on CCC.

Drotaverine is effective for smooth muscle spasms of both neurogenic and muscular origin. Regardless of the type of vegetative innervation, drotaverine relaxes the smooth muscles of the gastrointestinal tract, biliary tract, and genitourinary system.

Absorption. Compared with papaverine, drotaverine is absorbed more quickly and more completely from the gastrointestinal tract when taken orally. After presystemic metabolism, 65% of the received dose of drotaverine enters the systemic bloodstream. C_max drotaverine in the blood plasma is reached after 45-60 minutes.

Distribution. In vitro drotaverine has a high binding to plasma proteins (95-98%), especially to albumin, γ-and β-globulins. Drotaverine is evenly distributed in the tissues, penetrates into smooth muscle cells. It does not penetrate through the BBB. Drotaverine and / or its metabolites may only slightly cross the placental barrier.

Metabolism. Drotaverine is almost completely metabolized in the liver.

Output. T_1/2 drotaverine is 8-10 hours. Within 72 hours, drotaverine is almost completely eliminated from the body. About 50% of drotaverine is excreted by the kidneys and about 30% - through the gastrointestinal tract. Drotaverine is mainly excreted as metabolites, the unchanged form of drotaverine is not detected in the urine.

Drotaverine and / or its metabolites may only slightly cross the placental barrier.

In vitro drotaverine has a high association with plasma proteins (95-97%), especially with albumin, gamma - and β-globulins, as well as with alpha-HDL.

In humans, drotaverine is almost completely metabolized in the liver by O-desethylation. Its metabolites rapidly conjugate with glucuronic acid. The main metabolite is 4' - desethyldrotaverine, in addition to which 6-desethyldrotaverine and 4'-desethyldrotaveraldine have been identified.

In humans, a two-chamber mathematical model was used to evaluate the pharmacokinetics of drotaverine. Final T_1/2 plasma radioactivity was 16 hours.

T_1/2 it is 8-10 hours. Within 72 hours, drotaverine is almost completely eliminated from the body, more than 50% of drotaverine is excreted by the kidneys (mainly in the form of metabolites) and about 30% — through the intestine. Unchanged drotaverine is not detected in the urine.

Levodopa. PDE inhibitors like papaverine reduce the antiparkinsonian effect of levodopa. When prescribing drotaverine simultaneously with levodopa, it is possible to increase rigidity and tremor.

Other antispasmodics, including m-holinoblokatoryami. Mutual strengthening of the antispasmodic effect.

Levodopa. PDE inhibitors like papaverine weaken the antiparkinsonian effect of levodopa. When prescribing drotaverine simultaneously with levodopa, it is possible to increase rigidity and tremor.

Papaverine, bendazole and other antispasmodics (including m-cholinolytics). Drotaverine enhances the antispasmodic effect of papaverine, bendazole, and other antispasmodics, including m-holinoblockers.

Tricyclic antidepressants, quinidine and procainamide. Increases hypotension caused by tricyclic antidepressants, quinidine and procainamide.

Morphine. Reduces the spasmogenic activity of morphine.

Phenobarbital. Increased antispasmodic effect of drotaverine.