No-spa pills 40mg №6

Mechanism of action

Myotropic antispasmodic, isoquinoline derivative. 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 in spasms of smooth muscles 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.

Pharmacokinetics

In humans, a two-chamber mathematical model was used to assess the pharmacokinetics of drotaverine.

Suction

After oral administration, drotaverine is rapidly and completely absorbed. After the presystemic metabolism, 65% of the dose of drotaverine injected into the systemic circulation. WITH_max in 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

T_1/2 makes 8-10 h. Final T_1/2 plasma radioactivity was 16 h.

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 for use of the drug

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

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

As an adjuvant therapy:

- with spasms of the 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 meteorism after exclusion of diseases manifested by acute stomach syndrome (appendicitis, peritonitis, ulcer perforation, acute pancreatitis);

- tension headaches (for oral administration);

- Algomenorrhea.

When used as an adjuvant, the drug is administered parenterally when it is impossible to use tablets.

Dosage and administration

when administered, the recommended daily dose is 120-240 mg (in 2-3 doses). The maximum single dose is 80 mg. The maximum daily dose is 240 mg.

The average daily dose for intramuscular administration in adults is 40-240 mg (divided into 1-3 injections / day). At acute colic (renal or biliary) the drug is introduced into / in slowly at a dose of 40-80 mg (the duration of administration is approximately 30 seconds).

Clinical studies with the use of drotaverine with the participation children was not conducted.

In the case of the appointment of the drug No-spa maximum daily intake dose for children in age from 6 to 12 years makes 80 mg in 2 doses, at over 12 years old - 160 mg in 2-4 doses.

Duration of treatment without consulting a doctor

When taking the drug without consulting the doctor, the recommended duration of the drug is usually 1-2 days. If during this period the pain syndrome does not decrease, the patient should consult a doctor to clarify the diagnosis and, if necessary, change therapy. In cases where drotaverine is used as an adjuvant therapy, the duration of treatment without consulting a doctor may be longer (2-3 days).

Evaluation Method

If the patient can easily self-diagnose the symptoms of his illness, because they are well known to him, then the effectiveness of the treatment, namely the disappearance of pain, is also easily measurable by the patient.If within a few hours after taking the drug in the maximum single dose there is a moderate decrease in pain or no decrease in pain, or if the pain does not significantly decrease after taking the maximum daily dose, it is recommended to consult a doctor.

Side effect

Determination of the frequency of adverse reactions: very often (≥10%), often (≥1%, <10); infrequently (≥ 0.1%, <1%); rarely (≥ 0.01%, <0.1%), very rarely, including individual messages (<0.01%), frequency unknown (according to the available data, the frequency cannot be determined.

Cardiovascular: rarely - rapid heartbeat, lower blood pressure.

Nervous system: rarely - headache, dizziness, insomnia.

Gastrointestinal: rarely nausea, constipation.

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

Local reactions: rarely, reactions at the site of administration.

Contraindications to the use of the drug

- renal failure severe;

- severe liver failure;

- severe heart failure (low cardiac output syndrome);

- children's age up to 6 years (for tablets);

- children's age (for parenteral administration, since no clinical studies have been conducted in children);

- breastfeeding period (no clinical data);

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

- hypersensitivity to the drug;

- Hypersensitivity to sodium disulfite (for solution for intravenous and intramuscular injection).

WITH caution use the drug for arterial hypotension (due to the danger of collapse), during pregnancy; in children (for tablets).

Use of the drug during pregnancy and lactation

As shown by animal reproductive studies and retrospective data on the clinical use of drotaverine, the use of drotaverine during pregnancy did not have any teratogenic or embryotoxic effects.

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.

Due to the lack of necessary clinical data, the drug is contraindicated during lactation (breastfeeding).

Application for violations of the liver

Contraindicated use in severe liver failure.

Application for violations of kidney function

Contraindicated use in severe renal failure.

special instructions

The composition of the tablets includes 52 mg of lactose, as a result, complaints from the digestive system in patients suffering from latex intolerance are possible. Therefore, the drug in the form of tablets is not prescribed to patients with lactase deficiency, galactosemia or impaired glucose / galactose absorption syndrome.

The composition of the solution for in / in and / m injection includes sodium bisulfite, which can cause allergic reactions, including anaphylactic and bronchospasm, in sensitive individuals (especially in individuals with bronchial asthma or a history of allergic reactions). In case of hypersensitivity to sodium metabisulfite, parenteral administration of the drug should be avoided.

When a / in the introduction of the drug to patients with low blood pressure, the patient must be in a horizontal position due to the risk of developing collapse.

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 individual consideration. In the case of dizziness after taking the drug, you should avoid engaging in potentially hazardous activities, such as driving and working with mechanisms.

After parenteral administration of the drug, it is recommended to refrain from driving vehicles and engaging in other potentially hazardous activities that require high concentration of attention and quickness of psychomotor reactions.

Overdose

Data on drug overdose No-spa^® are missing.

Treatment: in case of overdose, patients should be under medical supervision.If the drug has recently been ingested, you can artificially induce vomiting or flush the stomach. If necessary, symptomatic treatment aimed at maintaining the basic functions of the body should be carried out.

Drug interaction

PDE inhibitors, like papaverine, weaken the anti-Parkinsonian effect of levodopa. When prescribing the drug No-spa^® simultaneously with levodopa, stiffness and tremor may be increased.

With simultaneous use with drotaverine, the antispasmodic action of papaverine, bendazole and other antispasmodics, including m-anticholinergic blockers, is mutually enhanced.

No-shpa^® increases arterial hypotension caused by tricyclic antidepressants, quinidine and procainamide.

No-shpa^® reduces spasmogenic activity of morphine.

Phenobarbital enhances the spasmolytic effect of drotaverine.

Drotaverine is largely bound to plasma proteins, predominantly albumin, β-and γ-globulins. Data on the interaction of drotaverine with drugs significantly binding to plasma proteins are not available. However, it can be assumed that they can interact with drotaverine at the level of plasma protein binding — displacing one of the drugs from the binding sites to others and increasing the concentration of the free fraction in the blood of a drug with weaker protein binding. This hypothetically may increase the risk of pharmacodynamic and / or toxic side effects of this drug.

Terms and conditions of storage

Tablets in blister packs aluminum / aluminum should be stored at a temperature not exceeding 30 ° C.

Tablets in PVC / aluminum blisters should be stored at a temperature not exceeding 25 ° C.

Tablets in bottles and solution for in / in and in / m the introduction should be stored in a dark place at a temperature of 15 ° to 25 ° C.

The drug should be kept out of the reach of children.