No-shpa is an antispasmodic agent.
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. 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 (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 decreasing Ca2+ ion concentration effect of drotaverine via cAMP explains the antagonistic effect of drotaverine toward 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.
Drotaverine when taken orally is quickly and completely absorbed from the gastrointestinal tract. Absorption is 100%. However, after metabolism on 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 excreted by the kidneys (mainly as metabolites) and about 30% through the gastrointestinal tract (excretion into the bile). Unchanged drotaverine is not detected in the urine.
- stomach and intestinal spasms
- renal colic
- painful menstruation
- biliary tract dyskinesia, biliary colic, cholecystitis.
How to take, the dosage
The average daily dose is usually 120-240 mg (the daily dose is divided into 2-3 doses).
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.
The use of the drug in case of arterial hypotension requires increased caution.
Each tablet contains 104 mg of lactose.
Lactose can take up to 156 mg (1.5 tablets) when taken, which can cause GI disorders in patients who are lactose intolerant.
The tablets are not appropriate for patients with lactose deficiency, galactosemia, or impaired glucose/galactose absorption syndrome (see Contraindications).
Impact on the ability to drive a car or perform work requiring increased speed of physical and mental reactions.
When taken orally in therapeutic doses, drotaverine has no effect on the ability to drive and perform work requiring increased attention.
If any side effects occur, driving and operating machinery require individual consideration.
In case of dizziness, potentially hazardous activities such as driving and operating machinery should be avoided.
- high sensitivity to drotaverine and/or excipients in the drug;
- explicit hepatic or renal impairment;
- Heart insufficiency (reduced cardiac output).
- Healthy heart failure (decreased cardiac output)
- Hereditary lactose intolerance, lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome (due to the presence of lactose in the preparation).
With caution: arterial hypotension.
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 of anaphylactic shock with and without fatal outcome has been reported with the use of the drug.
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, should receive symptomatic and supportive treatment for basic body functions, including induction of vomiting or gastric lavage.
During pregnancy and lactation can be used when indicated.
It is contraindicated in children under 6 years of age.
No-shpa, Drotaverine, Spasmonet, Drotaverine-Teva
|Conditions of storage|
In a light-protected place at 15-25 °C
Hinoin Pharmaceutical and Chemical Works, Hungary
Hinoin Pharmaceutical and Chemical Works
Buy No-shpa tablets 40 mg, 60 pcs. with dispenser with delivery to USA, UK, Europe and over 120 other countries.