pharmachologic effect
Papaverine hydrochloride is a myotropic antispasmodic agent. Reduces the tone and reduces the contractile activity of smooth muscles and therefore has a vasodilator and antispasmodic effect. Causes dilation of arteries, increases blood flow, incl. cerebral. When used in average therapeutic doses, papaverine hydrochloride has virtually no effect on the central nervous system. In large doses, it reduces the excitability of the heart muscle and slows down intracardiac conduction. It is an inhibitor of the phosphodiesterase enzyme and causes intracellular accumulation of cyclic 3,5-adenosine monophosphate, which leads to impaired contractility of smooth muscles and their relaxation during spastic conditions.
Pharmacological properties
Pharmacodynamics.
Papaverine is an alkaloid found in opium. Papaverine is a myotropic antispasmodic agent. It reduces tone, reduces the contractile activity of smooth muscles and therefore causes a vasodilator and antispasmodic effect. Papaverine is an inhibitor of the phosphodiesterase enzyme, which leads to the intracellular accumulation of cyclic 3′,5′-adenosine monophosphate (cAMP). The accumulation of cAMP leads to impaired contractility of smooth muscles and their relaxation during spastic conditions. The effect of the drug on the central nervous system is weak; only in higher doses does it exhibit some sedative effect.
Pharmacokinetics.
When administered parenterally, the drug quickly forms stable complexes with serum albumin. Easily penetrates histohematic barriers. Metabolized in the liver. About 60% is excreted in the form of compounds, mainly phenolics, with glucuronic acid and only in small quantities unchanged. The half-life (T1/2) is 0.5–2 hours.
Clinical characteristics.
Contraindications
Hypersensitivity, coma, respiratory depression, atrioventricular conduction disorder, glaucoma, liver dysfunction, old age (risk of hyperthermia), children's age (up to 1 year).
Carefully
The drug should be prescribed with caution and in small doses to elderly and debilitated patients, as well as patients with traumatic brain injury, impaired renal function, hypothyroidism, adrenal insufficiency, prostatic hypertrophy, as well as patients with supraventricular tachycardia and those in a state of shock.
Application Features
The drug should be prescribed with caution and in doses lower than the average therapeutic value:
- elderly and weakened patients;
- patients with traumatic brain injury;
- patients with chronic renal failure;
- patients with supraventricular tachycardia, severe heart failure with symptoms of decompensation;
- with adrenal insufficiency, hypothyroidism, prostatic hyperplasia, shock conditions.
The drug should be administered intravenously very slowly and under the control of blood pressure, heart rate, and electrocardiogram.
Intravenous injections of the drug should be prescribed with caution for stenosing coronary sclerosis.
In elderly people, hyperthermia may occur.
Smoking impairs the effectiveness of the drug.
During the period of use of the drug, it is necessary to avoid drinking alcohol.
Important information about excipients.
This medicinal product contains less than 1 mmol/dose sodium, which means it is almost sodium-free.
Use during pregnancy or breastfeeding.
The safety and effectiveness of the drug during pregnancy and lactation have not been established. Breastfeeding should be stopped during treatment.
The ability to influence the reaction rate when driving vehicles or other mechanisms.
During treatment with the drug, you should refrain from driving vehicles or other complex mechanisms.
Directions for use and doses
The drug is administered subcutaneously, intramuscularly and intravenously. 1-2 ml of solution is injected subcutaneously and intramuscularly 2-4 times a day. Intravenously - 1 - 2 ml of a 2% solution with preliminary dilution in 10-20 ml of isotonic sodium chloride solution. It should be administered very slowly and carefully, given that the drug can cause the development of atrioventricular block, ventricular extrasystoles and ventricular fibrillation.
A single dose for adults is 0.02-0.04 g (1-2 ml of 2% solution); the interval between administrations is at least 4 hours. For elderly patients, the initial single dose should not exceed 0.01 g. For children from 1 year to 12 years, the maximum single dose is 0.3 mg/kg body weight.
How to use papaverine injections?
First of all, you should check the quality of the medicine. In addition to the date of manufacture and expiration date, it is necessary to pay attention to the physicochemical properties of a particular dosage form. Papaverine hydrochloride is a white crystalline powder that is odorless and slightly bitter in taste. More necessary data is contained in the pharmacopoeia. Usually sold in the form of tablets, rectal suppositories or ampoules in dissolved form.
For intravenous injections, it must be diluted in 10-20 ml of physiological solution. It is administered intramuscularly in its original form. The exact dosage is usually prescribed by a doctor, it depends on the patient’s condition and the specific disease.
The average single dose for adults contains about 0.1 g; no more than 0.3 g can be injected per day. No more than 2 injections are allowed during the day to avoid overdose. To relieve a hypertensive crisis, 1-2 ml of a 2% solution is administered intramuscularly. More often, to treat this condition, Papaverine is combined with Dibazol.
In pharmacies, Papaverine is available only with a prescription.
Side effect
Allergic reactions, nausea, drowsiness, decreased blood pressure, constipation, increased transaminase levels in the blood, eosinophilia, and increased sweating are possible. With rapid intravenous administration, as well as with high doses, atrioventricular block and heart rhythm disturbances may develop.
Overdose
Symptoms: blurred vision (double vision), weakness, drowsiness, hypotension. Treatment: gastric lavage (milk, activated carbon), maintaining blood pressure.
Are there any possible side effects?
Instructions for the use of Papaverine hydrochloride injections contain instructions for the following side effects:
- general weakness, drowsiness.
- development of arrhythmias: atrioventricular block, tachycardia, ventricular extrasystole;
- arterial hypotension, very rarely - collapse;
- dyspeptic symptoms (nausea, bloating, constipation);
- increased levels of liver transaminases (ALT, LDH);
- allergic hypersensitivity reactions (itching, urticaria);
- eosinophilia.
In case of an overdose of the drug, the following symptoms are possible:
- diplopia (double vision);
- severe weakness;
- drop in blood pressure, collapse;
- drowsiness.
In this case, it is necessary to stop taking it, prescribe detoxification therapy and use medications that increase blood pressure.
Overdose
Symptoms:
blurred vision, diplopia, weakness, dry mouth, constipation, redness of the skin of the upper body, hyperventilation, nystagmus, ataxia, tachycardia, arterial hypotension, asystole, ventricular flutter, collapse. When using high doses of the drug and quickly injecting it into a vein, arrhythmias or complete atrioventricular block may develop. Papaverine in very high doses has a moderate sedative effect.
Treatment:
stop using the drug. Treatment is symptomatic. It is completely removed from the blood by hemodialysis. There is no specific antidote.
Side effects
From the organs of vision:
visual impairment, diplopia.
From the respiratory system, chest and mediastinal organs:
apnea.
From the gastrointestinal tract:
anorexia, nausea, constipation, dry mouth, diarrhea.
From the liver and biliary tract:
jaundice, impaired liver function, increased activity of liver transaminases.
From the nervous system:
drowsiness, increased sweating, weakness, headache, dizziness.
From the cardiovascular system:
arrhythmias, tachycardia, arterial hypotension, partial or complete atrioventricular block, asystole, ventricular extrasystole, ventricular fibrillation, ventricular flutter, collapse.
From the blood and lymphatic system:
eosinophilia.
From the immune system:
hypersensitivity reactions, including respiratory reactions, anaphylactic shock, urticaria.
From the skin and subcutaneous tissue:
itching, skin rashes, hyperemia of the skin of the upper body, face and hands.
General disorders and reactions at the injection site:
increased body temperature, reactions at the injection site, including thrombosis at the injection site.
Reports of suspected adverse reactions.
Reporting suspected adverse reactions after drug registration is an important procedure. This allows continued monitoring of the benefit/risk profile for the respective medicinal product. Healthcare professionals should report any suspected adverse reactions through the national reporting system.
Papaverine
A person who is more or less familiar with the intricacies of Latin terminology knows that “papaver somniferum” means nothing more than poppy somniferum. Therefore, the guess that papaverine is an alkaloid obtained from the opium poppy would be absolutely correct. It would be naive to believe that efficient pharmacologists will ignore the opportunity to use the antispasmodic properties of this substance for the benefit of humanity. Thus, the drug papaverine was obtained, which reduces smooth muscle tone and has antispasmodic, vasodilating and hypotensive effects. The pharmacological effect of papaverine is based on its ability to suppress the enzyme phosphodiesterase and potentiate the accumulation of 3,5-adenosine monophosphate in cells while simultaneously reducing the level of calcium ions. All this affects the smooth muscles of internal organs (digestive and genitourinary tract, respiratory system) and blood vessels better than any psychotherapist: they relax, their excess tone decreases during spastic conditions. In high concentrations, papaverine can reduce myocardial excitability and slow down atrioventricular conduction. The drug has a weak effect on the central nervous system, providing only a barely noticeable sedative effect.
Possessing the property of easily passing through histohematic barriers, the drug is quickly and completely absorbed from the injection site and distributed in the body.
The drug under the name “papaverine” is produced by purely domestic pharmaceutical companies in three dosage forms: tablets, solution for injection and rectal suppositories. For tablets, the recommended daily dose is 40-60 mg (adults) and 20 mg (children aged 10 to 14 years). The maximum doses for the tablet form are: 200 mg (highest single) and 600 mg (daily). Papaverine solution can be administered intravenously, intramuscularly or subcutaneously. The time interval between administrations of the drug should be at least 4 hours; adults are given 1-2 ml of a 2% solution (0.02-0.04 g) at a time, and for elderly patients the initial single dose is 0.5 ml. For children from 1 to 12 years old, the highest single dose is 0.2-0.3 g per 1 kg of weight. Suppositories are found in 1-2 pieces. (equivalent to 0.02-0.04 g) 2-3 times a day.
While taking papaverine, you should completely avoid alcohol.
