Drotaverine is a myotropic antispasmodic. Isoquinoline derivative with chemical structure and pharmacological properties similar to papaverine but with stronger and more prolonged action.
Drotaverine has a powerful antispasmodic effect on smooth muscles by inhibiting the enzyme phosphodiesterase 4 (PDE-4). The enzyme FDE-4 is required for hydrolysis of cAMP to AMP. Inhibition of the enzyme FDE-4 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 (MLCK or MLCK). 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 the cytosolic concentration of Ca2+ ion by stimulating Ca2+ transport into the extracellular space and the sarcoplasmic reticulum. This effect of drotaverine on lowering the cytosolic concentration of Ca2+ ion through cAMP explains its antagonistic effect toward Ca2+.
In vivorotaverine inhibits the FDE-4 isoenzyme without inhibiting the FDE-3 and FDE-5 isoenzymes. Therefore, the effectiveness of drotaverine depends on the concentrations of FDE-4 in tissues, the content of which varies in different tissues. FDE-4 is most important for inhibition of contractile activity of smooth muscles and therefore selective inhibition of FDE-4 may be useful for treatment of hyperkinetic dyskinesia and various diseases accompanied by spastic state of the gastrointestinal tract (GIT).
The hydrolysis of CAMP in the myocardium and vascular smooth muscle occurs mainly via the FDE-3 isoenzyme, which explains the fact that with high spasmolytic activity drotaverine has no serious cardiovascular side effects and pronounced effects on the cardiovascular system.
Drotaverine effectively relieves smooth muscle spasms of nervous and muscular etiology. Regardless of the type of autonomic innervation, drotaverine relaxes the smooth muscles of the gastrointestinal tract biliary vasculature.
Because of its vasodilator effect, drotaverine improves blood supply to tissues. It does not affect the autonomic nervous system does not penetrate into the central nervous system (CNS). Its direct effect on the smooth muscles allows drotaverine to be used as an antispasmodic when drugs from the group of m-cholinoblockers are contraindicated (closed-angle glaucoma, prostate hypertrophy).
In comparison with papaverine, drotaverine when taken orally is faster and more completely absorbed from the gastrointestinal tract. Bioavailability is about 100%. The half-absorption period is 12 minutes.
But after metabolism during “first passage through the liver” 65% of the dose taken enters the systemic bloodstream. The maximum plasma concentration (Cmax) is reached within 45-60 minutes.
In vitro drotaverine has high binding to plasma proteins (95-97%) especially to γ- and β-globulin albumin.
Drotaverine is evenly distributed in tissues penetrates smooth muscle cells. It does not penetrate the blood-brain barrier. Drotaverine and/or its metabolites may slightly penetrate through the placental barrier.
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 half-life (T1/2) of drotaverine is 8-10 hours.
In 72 hours drotaverine is almost completely eliminated from the body more than 50% of the drug is eliminated by the kidneys (mostly as metabolites) and about 30% through the gastrointestinal tract (excretion into the bile). Unchanged drotaverine is not detected in the urine.
– Smooth muscle spasms in diseases of the biliary tract: cholecystolithiasis cholangiolithiasis cholecystitis pericholecystitis cholangitis inflammation of duodenal papilla (papillitis);
– smooth muscle spasms in diseases of the urinary tract: nephrolithiasis urethrolithiasis pyelitis cystitis bladder spasms.
As adjuvant therapy:
– in spasms of the smooth muscles of the gastrointestinal tract: gastric and duodenal ulcer gastritis spasms of cardia and pylorus enteritis colitis spastic colitis accompanied by constipation and irritable bowel syndrome with flatulence;
– in strain headaches (tension headaches);
– in algodysmenorrhea.
In one tablet:
The active ingredient: drotaverine hydrochloride – 80.0 mg.
Auxiliary substances: povidone (polyvinylpyrrolidone low molecular weight medical 12600 ± 2700, plasdon K-17), lactose monohydrate (milk sugar), calcium stearate, potato starch, talc.
How to take, the dosage
1-2 tablets (40-80 mg) 2-3 times a day. The maximum daily dose is 6 tablets (240 mg).
There have been no clinical studies on the use of drotaverine in children.
For children aged 12 years and older: 1 tablet (40 mg) 1-4 times daily or 2 tablets (80 mg) 1-2 times daily. The maximum daily dose is 4 tablets (160 mg).
For children aged 6 to 12 years:1 tablet (40 mg) 1 to 2 times a day. The maximum daily dose is 2 tablets (80 mg).
The recommended duration of treatment without medical advice is 1-2 days. In cases where drotaverine is used as adjunctive therapy, the duration of treatment without medical consultation may be longer (2-3 days). If the pain persists, the patient should consult a physician.
If the patient can self-diagnose symptoms of his illness because they are well known to him, the efficacy of the treatment, namely, the disappearance of pain, is also easily assessed by the patient.
If there is moderate or no pain relief within a few hours, or if there is no significant decrease in pain after the maximum daily dose, it is recommended that a physician be seen.
With levodopa: when used concomitantly, drotaverine may weaken the antiparkinsonian effect of levodopa, i.e., increase stiffness and tremor.
With papaverine bendazole and other antispasmodics (including m-cholinoblockers): increased antispasmodic effects.
With morphine: reduction of the antispasmodic activity of morphine.
With phenobarbital: enhancement of the antispasmodic effect of drotaverine.
The use of the drug in patients with arterial hypotension requires increased caution.
Each tablet contains 6645 mg of lactose monohydrate which may cause gastrointestinal disorders in patients with lactose intolerance. This form of the drug is not acceptable for patients with lactase deficiency galactosemia or glucose-galactose malabsorption syndrome (see section “Contraindications”).
Influence on ability to drive vehicles and machines:
When taken orally in therapeutic doses, drotaverine has no effect on the ability to drive vehicles and perform work requiring increased concentration and quick psychomotor reactions.
If any side effects occur, the question of driving or engaging in other potentially hazardous activities requires individual consideration.
In case of dizziness, potentially dangerous activities such as driving and operating machinery should be avoided.
– Hypersensitivity to drotaverine and/or excipients in the drug;
– severe hepatic or renal failure;
– severe heart failure (low cardiac output syndrome);
– breastfeeding period;
– children under 6 years of age;
– hereditary lactose intolerance galactosemia or glucose-galactose malabsorption syndrome (due to the presence of lactose monohydrate in the drug).
– In arterial hypotension;
– In children (insufficient clinical experience of use);
– In pregnant women (see.
– concomitant use with levodopa (see section “Interaction with other medicinal products”).
The incidence of adverse reactions is given in accordance with the classification of the World Health Organization (WHO): very common – more than 1/10 common – more than 1 /100 and less than 1/10 infrequent – more than 1 /1000 and less than 1/100 rare – more than 1/10000 and less than 1/1000 very rare – less than 1/10000 including some reports frequency is unknown (it is impossible to determine the incidence based on available data).
Nervous system disorders: rare – headache dizziness insomnia.
Cardiovascular system: rare – feeling of palpitations decrease in blood pressure.
Gastrointestinal tract: rare – nausea constipation.
The immune system: rare – angioedema urticaria rash itching; very rare – anaphylactic shock (see section “Contraindications”).
The symptoms of drotaverine overdose may include cardiac rhythm and conduction disorders (including complete Gis bundle leg block) and cardiac arrest up to and including death.
Treatment: gastric lavage symptomatic therapy.
Drotaverine has no teratogenic and embryotoxic effects and no adverse effects on pregnancy. Nevertheless, caution should be exercised when using the drug in pregnant women and the drug should be prescribed only after assessing the ratio of the expected benefit to the mother and the possible risk to the fetus.
In the absence of clinical data the drug is not recommended for use during breast feeding.
No-shpa, Drotaverine, Spasmonet, Drotaverine-Teva
3 years. Do not use after the expiration date.
|Conditions of storage|
In the dark place at a temperature not exceeding 25 ° C. Store out of the reach of children.
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