NO-SPA FORTE PILLS 80MG

Mechanism of action

An antispasmodic agent, an isoquinoline derivative, is similar in chemical structure and pharmacological properties to papaverine, but has a stronger and more lasting effect. It has a powerful antispasmodic effect on smooth muscles due to inhibition of the PDE enzyme. The PDE enzyme is necessary for the hydrolysis of cAMP to AMP. Inhibition of PDE leads to an increase in the concentration of cAMP, which triggers the following cascade reaction: high concentrations of cAMP activate cAMP-dependent phosphorylation of myosin light chain kinase (MLCC). Phosphorylation of MLCC leads to a decrease in its affinity for Ca2+-calodulin complex, as a result of this inactivated form of MLCK supports muscle relaxation. In addition, cAMP affects the cytosolic concentration of Ca ion.2+ thanks to the stimulation of sa transport2+ into extracellular space and sarcoplasmic reticulum. This decreasing Ca ion concentration2+ effect of Drotaverine through cAMP explains the antagonistic effect of drotaverine in relation to Ca2+.

In vitro, Drotaverine inhibits PDE4 isoenzyme without inhibiting PDE3 and PDE5 isoenzymes. Therefore, the effectiveness of drotaverine depends on the concentration of PDE4 in the tissues (the content of PDE4 in different tissues varies).PDE4 is most important for suppressing the contractile activity of smooth muscles, and therefore selective inhibition of PDE4 may be useful for the treatment of hyperkinetic dyskinesias and various diseases involving the spastic state of the gastrointestinal tract.

Hydrolysis of cAMP in the myocardium and vascular smooth muscle occurs mainly with the aid of the PDE3 isoenzyme, which explains the fact that with high spasmolytic activity in Drotaverine there are no serious side effects from the heart and vessels and pronounced effects on the cardiovascular system.

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, the biliary tract, and the urogenital system.

Due to its vasodilating action, Drotaverine improves blood circulation in tissues.

Pharmacokinetics

Suction

Compared with papaverine, drotaverine when administered orally is faster and more completely absorbed from the gastrointestinal tract. Absorption is 100%. After metabolism, during the "first passage" through the liver, 65% of the dose of drotaverine is fed into the systemic circulation. WITHmaxin blood plasma is reached in 45-60 minutes.

Distribution

In vitro - Drotaverine is highly bound to plasma proteins (95-98%), especially albumin, β- and γ-globulins.

Drotaverine is evenly distributed in the tissues, penetrates into the smooth muscle cells.

Does not penetrate the BBB. Drotaverine and / or its metabolites are able to slightly penetrate the placental barrier.

Metabolism

In humans, drotaverine is almost completely metabolized in the liver by O-dezetilirovaniya. Its metabolites are rapidly conjugated with glucuronic acid. The main metabolite is 4'-deethyldrotaverine, in addition to which 6-deethyldrotaverin and 4'-deethyldrotaveraldine were identified.

Removal

T1/2 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 and about 30% through the intestines (excretion into the bile). Drotaverine is mainly excreted as metabolites, unchanged drotaverine is not detected in the urine.

Indications

- spasms of smooth muscles in diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;

- spasms of smooth muscles of the urinary system: nephrolithiasis, urethrolithiasis, pyelitis, cystitis, spasms of the bladder.

As an adjuvant therapy:

- with spasms of smooth muscles of the gastrointestinal tract: gastric ulcer and duodenal ulcer, gastritis, cardia and pylorus spasms, enteritis, colitis, spastic colitis with constipation and irritable bowel syndrome with flatulence;

- tension headaches;

- Algomenorrhea.

Dosage and administration

The drug is administered orally in a daily dose of 120-240 mg in 2-3 doses.

Side effect

The following side effects, which were considered in clinical studies to be at least possibly related to drotaverine, are given according to the following frequency of occurrence: very often (≥ 1/10), often (≥1 / 100, <1/10); rarely (≥ 1/1000, <1/100); sometimes (≥ 1/10 000, <1/1000); very rarely, including individual messages (<1/10 000); frequency is unknown (according to the available data, the frequency of occurrence cannot be determined).

Nervous system: sometimes - headache, dizziness, insomnia.

Cardiovascular: sometimes - rapid heartbeat, lower blood pressure.

Gastrointestinal: sometimes nausea, constipation.

Allergic reactions: rarely - itching, rash, urticaria, angioedema.

Contraindications

- severe renal failure;

- severe liver failure;

- severe heart failure (decrease in cardiac output);

- children's age (clinical studies in children were not conducted);

- breastfeeding period;

- hereditary lactose intolerance, lactase deficiency, galactosemia, glucose-galactose malabsorption syndrome (due to the presence of lactose in the composition of the tablets);

- hypersensitivity to the drug.

with caution use the drug for arterial hypotension during pregnancy.

Use during pregnancy and lactation

According to a limited number of retrospective data on the use of the drug in humans and research data in animals, the use of drotaverine during pregnancy did not have any teratogenic,neither embryotoxic action, as well as adverse effects on the course of pregnancy.

In pregnancy, the drug should be used with caution and only in cases where the potential benefit of therapy for the mother outweighs the possible risk to the fetus.

Studies on the allocation of drotaverine with breast milk in animals have not been conducted, clinical data are also missing, so the drug is contraindicated during lactation (breastfeeding).

Application for violations of the liver

Contraindicated for use in severe liver failure.

Application for violations of kidney function

Contraindicated for use in severe renal failure.

Use in children

Clinical studies in children has not been conducted.

Special notes

When using the drug in patients with arterial hypotension requires increased caution.

Each pill No-spa® Forte contains 104 mg of lactose. When taken in accordance with the recommended dosing regimen, each dose can receive up to 156 mg of lactose (1.5 pills of No-spa® forte), which can cause in patients suffering from lactose intolerance, disorders of the gastrointestinal tract. This form of the drug is unacceptable for patients with lactase deficiency, galactosemia, or glucose / galactose malabsorption syndrome.

Influence on ability to drive motor transport and control mechanisms

When ingested in therapeutic doses, Drotaverine does not affect the ability to drive vehicles and perform work that requires high concentration of attention.

When any adverse reactions are manifested, the question of driving a vehicle and working with mechanisms requires an individual consideration. In the event of dizziness after taking the drug, the patient should avoid practicing potentially hazardous activities, such as driving and working with mechanisms.

Overdosage

Drotaverine overdose was associated with impaired heart rate and conduction, including complete blockade of the bundle of the His bundle and cardiac arrest, which can be fatal.

Treatment: in case of overdose, patients should be under medical supervision. If necessary, symptomatic treatment aimed at maintaining the basic functions of the body should be carried out.

Drug interaction

With simultaneous use of No-spa® Forte may decrease the anti-Parkinsonian effect of levodopa, i.e. increased rigidity and tremor.

With simultaneous use of No-spa® Forte enhances the antispasmodic action of papaverine, bendazole and other antispasmodics (including m-anticholinergics).

With simultaneous use of No-spa® Forte reduces spasmogenic activity of morphine.

With simultaneous use of phenobarbital increases the severity of the antispasmodic action of drotaverine.

Terms and conditions of storage

The drug should be stored out of reach of children at a temperature not exceeding 25 ° C.Shelf life for pills in blisters of aluminum foil / aluminum foil, polymer-laminated - 5 years; for pills in blisters made of PVC / aluminum foil - 3 years.

Pharmacy sales terms

The drug is approved for use as a means of OTC.