No-shpa, 20 mg/ml 2 ml 25 pcs

No-shpa is an antispasmodic agent.

Pharmacodynamics

Drotaverine is an isoquinoline derivative. It has a powerful antispasmodic effect on smooth muscle by inhibiting the enzyme phosphodiesterase (PDE). PDE enzyme is necessary for hydrolysis of cAMP to AMP.

PDE inhibition 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 (CLSM); phosphorylation of CLSM leads to a decrease in its affinity for the Ca2+-calmodulin complex, resulting in the inactivated form of CLSM maintaining muscle relaxation. In addition, cAMP affects cytosolic Ca2+ ion concentration by stimulating Ca2+ transport into the extracellular space and the sarcoplasmic reticulum. This downregulation of Ca2+ ion concentration by drotaverine via cAMP explains the antagonistic effect of drotaverine with respect to Ca2+.

In vitro, drotaverine inhibits the FDE4 isoenzyme without inhibiting the FDE3 and FDE5 isoenzymes. Therefore, the efficacy of drotaverine depends on the concentrations of FDE4 in tissues, which vary from tissue to tissue. FDE4 is most important for suppression of contractile activity of smooth muscles, therefore selective inhibition of FDE4 may be useful for treatment of hyperkinetic dyskinesias and various diseases accompanied by spastic state of the GIT.

The hydrolysis of CAMP in the myocardium and vascular smooth muscle occurs mainly by isoenzyme FDE3, which explains the fact that with high antispasmodic activity, drotaverine has no serious side effects on the heart and vessels and pronounced effects on the CSS.

Drotaverine is effective for 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, and urogenital system.

Due to its vasodilator effect, drotaverine improves blood flow to tissues.

Pharmacokinetics

Drotaverine when taken orally is quickly and completely absorbed from the gastrointestinal tract. Absorption is 100%. However, after metabolism during the first passage through the liver, 65% of the administered dose enters the systemic bloodstream. Cmax in plasma is reached after 45-60 min.

In vitro drotaverine has high binding to plasma proteins (95-97%), especially to albumin, γ- and β-globulins.

Drotaverine is evenly distributed in tissues, penetrates smooth muscle cells. It does not penetrate through the HEB. Drotaverine and/or its metabolites may slightly penetrate through the placental barrier.

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

The T1/2 of drotaverine is 8-10 h. Within 72 h, drotaverine is almost completely eliminated from the body. More than 50% of the drug is eliminated by the kidneys (mainly as metabolites) and about 30% is eliminated through the gastrointestinal tract (excretion into the bile). Unchanged drotaverine is not detected in the urine.

Indications

spasms of the stomach and intestines
renal colic
painful menstruation
increased excitability of the uterus during pregnancy
biliary dyskinesia, biliary colic, cholecystitis.

Pharmacological effect

No-spa is an antispasmodic agent.

Pharmacodynamics

Drotaverine is an isoquinoline derivative. Shows a powerful antispasmodic effect on smooth muscles due to inhibition of the phosphodiesterase enzyme (PDE). The enzyme PDE is necessary for the hydrolysis of cAMP to AMP.

Inhibition of PDE 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, as a result of which the inactivated form of MLCK maintains muscle relaxation. cAMP also affects the cytosolic concentration of the Ca2+ ion by stimulating the transport of Ca2+ into the extracellular space and the sarcoplasmic reticulum. This Ca2+-lowering effect of drotaverine via cAMP explains the antagonistic effect of drotaverine on Ca2+.

In vitro, drotaverine inhibits the PDE4 isoenzyme without inhibiting the PDE3 and PDE5 isoenzymes. Therefore, the effectiveness of drotaverine depends on tissue concentrations of PDE4, which vary from tissue to tissue. 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 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 PDE3 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, and genitourinary system.

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

Pharmacokinetics

Drotaverine, when taken orally, is quickly and completely absorbed from the gastrointestinal tract. Absorption is 100%. However, after metabolism during the first passage through the liver, 65% of the dose taken enters the systemic circulation. Cmax in plasma is reached 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 BBB. Drotaverine and/or its metabolites may slightly penetrate the placental barrier.

In humans, drotaverine is almost completely metabolized in the liver by O-desethylation. 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.

T1/2 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.

Special instructions

Contains sodium disulfite, which may cause allergic-type reactions, including anaphylactic symptoms and bronchospasm in sensitive individuals, especially those with a history of asthma or allergic diseases.

In case of hypersensitivity to sodium disulfite, parenteral use of the drug should be avoided (see “Contraindications”).

When administering drotaverine intravenously in patients with low blood pressure, the patient should be in a horizontal position due to the risk of collapse.

Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions.

During the treatment period, it is necessary to refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Drotaverine

Composition

Active ingredient:

drotaverine hydrochloride;

Excipients:

sodium disulfite (sodium metabisulfite) – 2 mg;

ethanol 96% – 132 mg;

water for injection – up to 2 ml.

Pregnancy

During pregnancy and lactation it can be used according to indications.

Contraindicated in children under 6 years of age.

Contraindications

hypersensitivity to drotaverine and/or excipients included in the drug;
severe liver or kidney failure;
severe heart failure (decreased cardiac output);
hereditary lactose intolerance, lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome (due to the presence of lactose in the drug).

With caution: arterial hypotension.

Side Effects

From the cardiovascular system: rarely – rapid heartbeat, decreased blood pressure.

From the side of the central nervous system: rarely – headache, dizziness, insomnia.

From the gastrointestinal tract: rarely – nausea, constipation.

From the immune system: rarely – allergic reactions (angioedema, urticaria, rash, itching); unknown frequency – fatal and non-fatal anaphylactic shock has been reported with the use of the drug.

Interaction

Levodopa. With simultaneous use, drotaverine can weaken the antiparkinsonian effect of levodopa, i.e. increase rigidity and tremors.

Papaverine, bendazole and other antispasmodics (including m-anticholinergics). Strengthening the antispasmodic effect.

Morphine. Reducing the spasmogenic activity of morphine.

Phenobarbital. Strengthening the antispasmodic effect of drotaverine.

Overdose

Symptoms: Heart rhythm and conduction abnormalities, including complete bundle branch block and cardiac arrest, which can be fatal.

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

Storage conditions

At a temperature not exceeding 25 °C.

Shelf life

5 years

Manufacturer

Hinoine Pharmaceutical and Chemical Plant, Hungary