pharmachologic effect
Drotaverine is an isoquinoline derivative; its chemical structure and pharmacological properties are similar to papaverine, but its effect is more pronounced and lasting.
Drotaverine has a pronounced antispasmodic effect on smooth muscles due to inhibition of the enzyme phosphodiesterase-4 (PDE-4). The PDE-4 enzyme is necessary for the hydrolysis of cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP). Inhibition of the PDE-4 enzyme 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 calcium ions - the calmodulin complex, resulting in an inactivated form of MLCK supporting muscle relaxation. In addition, cAMP affects the cytosolic concentration of calcium ions by stimulating the transport of calcium ions into the extracellular space and the sarcoplasmic reticulum. This calcium ion-lowering effect of drotaverine through cAMP explains the antagonistic effect of drotaverine towards calcium ions.
In vitro, drotaverine inhibits the PDE-4 isoenzyme without inhibiting the PDE-3 and PDE-5 isoenzymes, therefore the effectiveness of drotaverine depends on the concentrations of PDE-4 in tissues, the content of which varies in different tissues. High levels are observed in the bile and urinary tracts, uterus, and gastrointestinal tract. PDE-4 is most important for suppressing the contractile activity of smooth muscles, and therefore selective inhibition of PDE-4 may be useful for the treatment of hyperkinetic dyskinesias and various diseases accompanied by a spastic state of the gastrointestinal tract (GIT). The hydrolysis of cAMP in the myocardium and smooth muscles of blood vessels occurs mainly with the help of PDE-3, 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.
Pharmacological properties
Pharmacodynamics.
drotaverine, an isoquinoline derivative, has an antispasmodic effect on smooth muscles by inhibiting the action of the PDE IV enzyme, which leads to an increase in the concentration of camp and, due to the inactivation of myosin light chain kinase (mlck), leads to relaxation of smooth muscles. In vitro, drotaverine inhibits the action of the PDE IV enzyme and inhibits PDE III and V isoenzymes. PDE IV is of great functional importance for reducing the contractile activity of smooth muscles, therefore selective inhibitors of this enzyme may be useful for the treatment of patients with diseases that are accompanied by hypermobility, as well as various diseases that cause gastrointestinal spasms.
In the smooth muscle cells of the myocardium and blood vessels, cAMP is hydrolyzed mainly by the PDE III isoenzyme, therefore drotaverine is an effective antispasmodic agent, does not cause significant side effects on the cardiovascular system and does not have a pronounced therapeutic effect on this system.
Drotaverine is effective against smooth muscle spasms of both nervous and muscular origin. Drotaverine acts on the smooth muscles of the digestive, biliary, genitourinary and vascular systems, regardless of the type of their autonomous innervation. The product increases blood circulation in tissues due to its ability to dilate blood vessels.
The effect of drotaverine is stronger than that of papaverine, absorption is faster and more complete, it binds less to blood plasma proteins. The advantage of drotaverine is also that, unlike papaverine, after its parenteral administration there is no such side effect as stimulation of respiration.
Pharmacokinetics. Drotaverine is quickly and completely absorbed after oral administration. In many ways (95–98%) binds to blood plasma proteins, especially albumin, gamma and beta globulins. Cmax in the blood after oral administration is achieved within 45–60 minutes. After primary metabolism, 65% of the dose taken enters the bloodstream unchanged. Metabolized in the liver. T½ is 8–10 hours. Within 72 hours, drotaverine is almost completely eliminated from the body, more than 50% is excreted in the urine, 30% in feces. Drotaverine is mainly excreted in the form of metabolites and is not detected unchanged in the urine.
Pharmacokinetics
Bioavailability 100%. Drotaverine and its metabolites can penetrate the placental barrier. Does not penetrate the blood-brain barrier. Bonding with plasma proteins is 95-97%. Within 72 hours it is almost completely eliminated from the body.
When administered parenterally, the effect of the drug appears after 2-4 minutes. The maximum effect occurs after 30 minutes. It is released from the connection with blood plasma proteins gradually, providing a long-lasting effect. The half-life is 2-4 hours.
Metabolism occurs in the liver, the main part of the metabolites is excreted by the kidneys. Drotaverine is almost completely metabolized 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.
Application
Pills. apply the drug internally.
Adults: the average daily dose is 120–240 mg (3–6 tablets), divided into 2–3 doses.
Children aged 6–12 years: the maximum daily dose is 80 mg, divided into 2 doses.
Children over 12 years of age: the maximum daily dose is 160 mg, divided into 2–4 doses.
The duration of treatment is determined individually.
R-r. The drug is used for adults intramuscularly at a dose of 40–240 mg in 1–3 administrations.
For acute colic, the drug should be administered to adults intravenously slowly at a dose of 40–80 mg.
Indications for use
- spasms of smooth muscles in diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;
- spasms of smooth muscles of the urinary tract: urolithiasis (including nephrolithiasis, ureterolithiasis), pyelitis, cystitis, bladder tenesmus;
As an adjuvant therapy (when the tablet dosage form cannot be used):
- for spasms of smooth muscles of the gastrointestinal tract: peptic ulcer of the stomach and duodenum, gastritis, spasm of the cardia and pylorus, enteritis, colitis, irritable bowel syndrome;
- for gynecological diseases: dysmenorrhea; — when conducting certain instrumental studies, including cholecystography.
Drotaverine hydrochloride 40 mg No. 50 tab.
Instructions for medical use of the drug Drotaverine Trade name Drotaverine International nonproprietary name Drotaverine Dosage form Tablets 0.04 g Composition One tablet contains the active substance - drotaverine hydrochloride (in terms of 100% substance) - 0.04 g, excipients: lactose monohydrate ( milk sugar), potato starch, povidone (low molecular weight medical polyvinylpyrrolidone), magnesium stearate, talc. Description Tablets of yellow color with a greenish tint, flat-cylindrical with a chamfer. Pharmacotherapeutic group Drugs for the treatment of functional intestinal disorders. Papaverine and its derivatives. Drotaverine. ATC code A03AD02 Pharmacological action Pharmacokinetics When taken orally, absorption is high, half-absorption period is 12 minutes. Bioavailability - 100%. Evenly distributed in tissues, penetrates smooth muscle cells. Time to reach maximum concentration (TCmax) - 2 hours. Communication with blood plasma proteins - 95-98%. The half-life is 2.4 hours. It is mainly excreted by the kidneys, to a lesser extent - with bile. Does not penetrate the blood-brain barrier (BBB). Pharmacodynamics An antispasmodic agent from the group of isoquinoline derivatives, has a pronounced relaxing effect on the smooth muscles of internal organs and blood vessels. The mechanism of action is associated with inhibition of the enzyme phosphodiesterase type IV (PDE IV). Inhibition of PDE IV leads to the cessation of the destruction of cAMP and its accumulation inside the smooth muscle cell. In terms of chemical structure and pharmacological properties, it is close to papaverine, but has a stronger and longer-lasting effect. Reduces the tone and motor activity of the smooth muscles of internal organs, dilates blood vessels. In the smooth muscle cells of the myocardium and blood vessels, cAMP hydrolysis occurs mainly with the participation of the PDE III isoenzyme, which explains the high selectivity of the action of drotaverine as an antispasmodic in the absence of a pronounced therapeutic effect on the cardiovascular system and the development of serious cardiovascular adverse events. Indications for use - spasms of smooth muscles in diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis - spasms of smooth muscles of the urinary tract: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, bladder tenesmus As an adjuvant therapy: - for spasms of smooth muscles muscles of the gastrointestinal tract: peptic ulcer of the stomach and duodenum, gastritis, spasms of the cardia and pylorus, enteritis, colitis, spastic colitis with constipation and flatulence with irritable bowel syndrome - with tension headaches - with gynecological diseases: dysmenorrhea (painful menstruation) Method Applications and doses Adults are prescribed 0.04-0.08 g (1-2 tablets) orally 2-3 times a day. For children over 12 years of age, the drug is prescribed 0.04 g (1 tablet) 1-3 times a day. Side effects Possible - dizziness, headache, insomnia - palpitations, arterial hypotension - feeling of heat, sweating - nausea, constipation - allergic reactions: infrequently angioedema, urticaria, rash, itching Contraindications - hypersensitivity to drotaverine or to any excipient of the drug - severe renal or liver failure - severe heart failure (low cardiac output syndrome), AV block II-III degree - lactation period - lactose deficiency - galactosemia - impaired glucose/galactose absorption syndrome - children under 12 years of age Drug interactions With simultaneous use, drotaverine may weaken the antiparkinsonian effect of levodopa. When used simultaneously, it enhances the effect of papaverine, bendazole and other antispasmodics (including m-anticholinergics). When tricyclic antidepressants, quinidine and procainamide are used simultaneously with drotaverine, their hypotensive effect is enhanced. Special instructions Prescribe the drug with caution to patients with severe atherosclerosis of the coronary arteries, prostate adenoma, and glaucoma. Caution should be exercised when prescribing to patients with coronary vascular pathology and benign prostatic hyperplasia. Pregnancy Drotaverine does not have teratogenic or embryotoxic effects. However, the use of the drug is recommended only after carefully weighing the benefit-risk ratio in the mother and fetus. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms Considering the side effects, care should be taken when driving vehicles and potentially dangerous mechanisms. Overdose Symptoms: in large doses, it disrupts atrioventricular conduction, reduces the excitability of the heart muscle, and can cause cardiac arrest and paralysis of the respiratory center. Treatment: drug withdrawal, symptomatic therapy aimed at eliminating the resulting disorders. There is no specific antidote. Release form and packaging 10 tablets in a blister pack made of polyvinyl chloride film and printed varnished aluminum foil. 2 or 5 blister packs with instructions for medical use in the state and Russian languages are placed in a cardboard pack. Storage conditions Store in a dry place, protected from light, at a temperature not exceeding 25 ºС. Keep out of the reach of children! Shelf life: 4 years Do not use after expiration date. Conditions for dispensing from pharmacies Without a prescription 623856, Sverdlovsk region, Irbit, st. Kirova, 172 Tel/fax (34355) 3-60-90 Name and country of the owner of the registration certificate OJSC “Irbitsky Chemical-Pharmaceutical Plant”, Russia Address of the organization receiving complaints from consumers regarding the quality of products (products) OJSC “Irbitsky Chemical and Pharmaceutical Plant” 623856, Sverdlovsk region, Irbit, st. Kirova, 172 Tel/fax (34355) 3-60-90 Email address
Contraindications
- hypersensitivity to the active substance or any of the excipients of the drug;
- hypersensitivity to sodium disulfite (see “Special Instructions”);
- severe liver or kidney failure;
- severe chronic heart failure;
— AV blockade II-III degree;
- childhood (the use of drotaverine in children has not been studied in clinical studies);
- period of childbirth;
- period of breastfeeding.
Carefully
- with arterial hypotension (danger of collapse, see “Special Instructions”);
- with severe atherosclerosis of the coronary arteries;
- with prostate adenoma;
- for glaucoma;
— during pregnancy (see “Use during pregnancy and breastfeeding”).
Use during pregnancy and breastfeeding
The use of drotaverine during pregnancy does not have a teratogenic or embryotoxic effect. In pregnant women, the drug is prescribed only in cases where the potential benefit to the mother outweighs the potential risk to the fetus. If it is necessary to use the drug during breastfeeding, it is necessary to decide on stopping breastfeeding.
Note!
Description of the drug Drotaverin-Darnitsa solution d/in. 20mg/ml amp. 2ml No. 5 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
special instructions
This medicine contains sodium disulfite (sodium metabisulfite), 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 to patients with low blood pressure, the patient should be in a horizontal position due to the risk of collapse.
Effect of the drug on the ability to drive vehicles and machinery
During the treatment period, it is necessary to refrain from driving vehicles, machinery and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Side effect
From the immune system: allergic reactions (angioedema, urticaria, rash, itching, anaphylactic shock) (see “Contraindications”).
From the nervous system: headache, dizziness, insomnia.
From the heart and blood vessels: tachycardia, decreased blood pressure, arrhythmia, collapse (with intravenous administration).
From the gastrointestinal tract: nausea, vomiting, constipation.
General disorders and disorders at the injection site: reactions at the injection site, feeling hot, sweating.
Overdose
In case of overdose, dose-dependent side effects may increase.
Symptoms: atrioventricular block, cardiac arrest, paralysis of the respiratory center.
Treatment: In case of overdose, patients should be under close medical supervision and should receive symptomatic therapy and treatment aimed at maintaining basic body functions.
Interaction with other drugs
With levodopa
Phosphodiesterase inhibitors like papaverine reduce the antiparkinsonian effect of levodopa. When prescribing drotaverine simultaneously with levodopa, increased rigidity and tremor may occur.
With papaverine, bendazole and other antispasmodics (including m-anticholinergics)
Drotaverine enhances the antispasmodic effect of papaverine, bendazole and other antispasmodics, including m-anticholinergics.
With tricyclic antidepressants, quinidine and procainamide
Increases hypotension caused by tricyclic antidepressants, quinidine and procainamide.
With morphine
Reduces the spasmogenic activity of morphine.
With phenobarbital
Phenobarbital enhances the antispasmodic effect of drotaverine.
