No-shpa, 20 mg/ml 2 ml 5 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 primarily through the isoenzyme FDE3, which explains the fact that with high antispasmodic activity, drotaverine has no serious cardiovascular side effects and no pronounced effects on the CPS.

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

Active ingredient

Composition

Active substance:

drotaverine hydrochloride;

Supplementary substances:

sodium disulfite (sodium metabisulfite) – 2 mg;

Ethanol 96% – 132 mg;

Injection water – up to 2 ml;

How to take, the dosage

Intramuscularly, intravenously.

Adults: average daily dose is 40-240 mg divided into 1-3 intravenous injections.

In acute renal and biliary colic, 40-80 mg w/v, slowly (duration of injection about 30 seconds).

Interaction

Levodopa. When used concomitantly, drotaverine may weaken the anti-Parkinsonian effect of levodopa, i.e., increase stiffness and tremor.

Papaverine, bendazole and other antispasmodics (including m-cholinolytics). Increased antispasmodic action.

Morphine. Reduction of the spasmogenic activity of morphine.

Phenobarbital. Enhancement of the antispasmodic action of drotaverine.

Special Instructions

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

In cases of hypersensitivity to sodium disulfite, parenteral administration of the drug should be avoided (see Contraindications).

In IV administration of Drotaverine 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 or perform work requiring increased speed of physical and mental reactions.

During treatment, it is necessary to refrain from driving and engaging in other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

With caution: arterial hypotension.

Side effects

Systemic system disorders: rarely – palpitations, decreased blood pressure.

CNS disorders: rarely – headache, dizziness, insomnia.

Gastrointestinal disorders: rarely – nausea, constipation.

The immune system: rare – allergic reactions (angioedema, urticaria, rash, itching); unknown frequency – when using the drug it was reported the development of anaphylactic shock with fatal and non-fatal outcome.

Overdose

Symptoms: cardiac rhythm and conduction disorders, including complete Gis bundle leg block and cardiac arrest, which can be fatal.

Treatment: In cases of overdose, patients should be under medical supervision and, if necessary, they should be given symptomatic and supportive treatment for basic body functions, including induction of vomiting or gastric lavage.

Pregnancy use

During pregnancy and lactation can be used when indicated.

It is contraindicated in children under 6 years of age.

Similarities