Rauwolfia snake roots -RadicesRauwolfiaeserpentinae

Rauwolfiaserpentine- Rauwolfia serpentina Benth.

Semactionkutrovye - Apocynaceae

In addition to snake rauwolfia, which has been grown since ancient times in India, Burma, and the Indonesian islands, currently, as a result of the work carried out, gray rauwolfia - Rauwolfia canescens L. from India and emetic rauwolfia - Rauwolfia vomitoria Af. from Africa. The study of other species is ongoing. Under the conditions of culture, rauwolfia gray has proven itself well.

Botanical characteristic. Rauwolfia serpentine is an evergreen perennial shrub up to 1-1.5 m high with milky juice. It has a small rhizome and a long taproot curved root with large lateral roots. The leaves are arranged in whorls of 3-4, oval, slightly pointed, dense, glabrous. The flowers are pink, red or white in dense umbellate inflorescences. The fruits are red, consist of 2 juicy drupes. A botanical description of the plant was made in the 16th century. German doctor Leonhard Rauwolf.

Spreading. India, Indonesia, Burma, Sri Lanka. In India introduced into the culture. Culture is mastered in Georgia.

Habitat. On the edges of subtropical forests.

blank. Harvest roots and very small rhizomes. The roots are dug up in autumn. Cut into pieces. On plantations in India, the roots are dug up in the 3-4th year. Washed.

Drying. In natural dryers, in a draft.

External signs. The roots are cylindrical or cut longitudinally, longitudinally striated, covered with brown cork on the outside. The wood is yellow and brittle. The smell is characteristic, unpleasant. The taste is bitter.

Chemical composition. The plant has been studied since the 1950s. In a short time, Europeans isolated more than 25 alkaloids from rauwolfia.

Roots and rhizomes contain about 20 indole alkaloids, making up about 1-2%. The most famous of them are: reserpine (serpazil), mined in Switzerland (1952) in its pure form, aymaline, papaverine, etc. Among domestic scientists, professor D. G. Kolesnikov was engaged in the study of the chemical composition of rauwolfia.

Storage."Reserpine" in powder is stored according to list A. All drugs in tablets - according to list B.

pharmacological properties. Rauwolfia alkaloids have valuable pharmacological properties. Some of them, especially reserpine and, to a lesser extent, rescinamine, have a sedative and hypotensive effect, others (aymalin, rauwolfine, serpagin, yohimbine) have an adrenolytic effect. Aymalin has an antiarrhythmic effect.

The main pharmacological property of reserpine is its sympatholytic effect, due to the fact that under its influence catecholamines are rapidly released (released) from the granular depot of presynaptic nerve endings. The released catecholamines are subjected to the inactivating action of monoamine oxidase, which leads to a decrease in the release of catecholamines into the synaptic cleft and a weakening of adrenergic effects on the effector systems of peripheral organs, including adrenoreceptors of blood vessels.

The action of reserpine also extends to the central nervous system. Under its influence, the content of neurotransmitters in the brain tissues - norepinephrine, dopamine, serotonin, decreases, which is due to its ability to disrupt the transport of these substances from the cellular plasma (where their biosynthesis occurs) to the granules, where they are deposited. In plasma, they are exposed to the action of the monoamine oxidase contained in it and are converted into inactive (deaminated) metabolites.

Reserpine has a complex effect on the body. Its antihypertensive effect is largely associated with the effect on the peripheral nervous system, and its antipsychotic effect is largely associated with the effect on the central neurochemical processes.

Under the influence of reserpine, systolic and diastolic pressure gradually decreases in various forms and stages of hypertension. The best effect is observed in the early stages of hypertension, in the absence of pronounced organic changes in the cardiovascular system. The hypotensive effect persists for a relatively long time after discontinuation of reserpine.

Along with a decrease in blood pressure, kidney function improves: renal blood flow increases, glomerular filtration increases. There is evidence of a positive effect of reserpine on lipid and protein metabolism in patients with hypertension and coronary atherosclerosis.

Reserpine has the ability to enhance the secretion of prolactin. Under experimental conditions on linear rats of a certain strain, it can stimulate the development of breast cancer. Careful clinical and experimental studies at the All-Union Cancer Research Center of the Academy of Medical Sciences (since 1992 - Cancer Research Center of the Russian Academy of Medical Sciences) have confirmed, however, the inconsistency of the idea that human breast cancer can occur under the influence of reserpine.

Medicines."Reserpine" (tablets) and its preparations: "Adelfan", "Adelfan-ezidreks", "Tirezide", "Brinerdin"; "Aimalin" (tablets, ampoules). "Raunatin" (tablets) contains the amount of alkaloids of rauwolfia roots.

Application. Drugs are used to lower blood pressure in hypertension, as well as in mental disorders (reserpine). "Raunatin" acts softer than reserpine - as a hypotensive and antiarrhythmic agent "Aymalin" is an effective tool for stopping attacks of atrial fibrillation.

Reserpine (Reserpinum). Initially, before the advent of modern antipsychotics, reserpine was used to treat mental illness. Currently, reserpine is rarely used as an antipsychotic agent, it is mainly used as an antihypertensive agent for the treatment of arterial hypertension. Assign more often in combination with other antihypertensive agents (diuretics, etc.). Assign reserpine inside in the form of tablets (after eating). Doses and duration of treatment are selected individually.

With arterial hypertension in the early stages, reserpine is usually prescribed at a dose of 0.05-0.1 mg 2-3 times a day. In some cases, it is enough to continue using the drug at these doses, in others, the dose is gradually increased. Usually, in order to avoid depression, they are limited to a daily dose of 0.5 mg, but with good tolerance, it is increased to 1 mg. If within 10-14 days the hypotensive effect does not occur, the drug is canceled.

Upon reaching the effect, the dose is gradually reduced to 0.5-0.2-0.1 mg per day. Treatment with small (maintenance) doses is carried out for a long time (courses of 2-3 months, if necessary 3-4 times a year) under medical supervision.

Reserpine is also used for mild forms of heart failure with tachycardia (together with cardiac glycosides), hypersympathicotonia, late toxicosis of pregnant women. In thyrotoxicosis, reserpine is prescribed together with thyreostatic substances. Reserpine itself does not have a thyreostatic effect, but it reduces neurovegetative disorders and causes a slowing of the pulse. The use of reserpine allows you to reduce the dose of antithyroid drugs.

In psychiatric and neurological practice, reserpine is prescribed mainly for neuropsychiatric disorders, which are based on high blood pressure, as well as for persistent insomnia and other diseases. In the treatment of schizophrenia, reserpine is sometimes used in combination with other antipsychotics. Reserpine is also recommended for the treatment of alcoholic psychoses.

Higher doses for adults inside: single 0.002 g (2 mg), daily 0.01 g (10 mg). In mental illness, reserpine is taken orally on the first day from 0.25 to 2 mg, then the dose is increased to 10-15 mg per day. With neurosis, it is prescribed in small doses, starting from 0.25 mg 2-3 times a day to 0.5 mg 3-4 times a day. For children, reserpine is prescribed at a dose of 0.1 to 0.4 mg per day (in 2-4 doses), depending on age.

In small doses, reserpine usually does not cause side effects. At high doses and hypersensitivity, hyperemia of the mucous membranes of the eyes, skin rash, stomach pain, diarrhea, bradycardia, weakness, dizziness, shortness of breath, nausea, vomiting, nightmares can be observed. With prolonged use, the phenomena of parkinsonism are possible. During the course of treatment in patients with mental illness, a feeling of anxiety, anxiety, persistent insomnia, and a state of depression may develop. In patients with bronchial obstruction, reserpine can cause an acute attack of bronchospasm. Bronchospasm is relieved with atropine.

Contraindications: severe organic cardiovascular disease with symptoms of decompensation and severe bradycardia, nephrosclerosis, cerebral sclerosis, peptic ulcer of the stomach and duodenum.

Reserpine is part of a number of combined drugs used in hypertension.

Adelfan (Adelphan) - tablets containing reserpine 0.0001 g (0.1 mg) and dihydralazine 0.01 g (10 mg). Dihydralazine, similar in structure and action to apressin, is a peripheral vasodilator. Apply with hypertension 1-2 tablets 3 times a day (after meals).

Adelphan-esidrex (Adelphan-Esidrex) contains reserpine 0.1 mg, dihydralazine 10 mg and dichlothiazide 10 mg, and adelfan-esidrex-K (Adelphan-Esidrex K) contains reserpine 0.1 mg, dihydralizine 10 mg, hydrochlorothiazide 10 mg and potassium chloride 0.6 g and one dragee. The addition of potassium chloride is designed to prevent possible hypokalemia from the use of hydrochlorothiazide. Assign 1/2-1 tablet 1-2-3 times a day.

Brinerdin (Brinerdin) - dragees containing reserpine 0.0001 g (0.1 mg), dihydroergocristine 0.0005 g (0.5 mg), clopamide (brinaldix) 0.005 g (5 mg). Dihydroergocristine is a peripheral and central adrenergic blocking agent; clopamide is a saluretic. Used for hypertension and symptomatic hypertension. Take orally 1 tablet 1 to 3 times a day (depending on the nature of the disease and the patient's condition). The course of treatment - from 10 days to several months.

Kristepin (Crusterin) - dragees containing 0.1 mg of reserpine, 0.5 mg of dihydroergocristine and 5 mg of the diuretic clopamid. Used in various forms of arterial hypertension. Accepted, starting with 1 tablet per day, then, as necessary, increasing the dose to 2-3 tablets per day in 2-3 doses. Maintenance dose - 1 tablet per day or every other day.

Triresid (Tiresid) - tablets of the composition: reserpine 0.1 mg, dihydralazine sulfate (see Apressin) 10 mg and hydrochlorothiazide 10 mg. Trirezide is also available with an additional content of 0.35 g of potassium chloride in each tablet. Indications for the use of trirezide are the same as for kristepin, etc.

When taking all these tablets (except those containing potassium chloride), patients should be advised to eat foods rich in potassium. It is necessary to monitor potassium.

Raunatin (Raunatinum) - a preparation containing the amount of alkaloids from the roots of rauwolfia snake or other types of rauwolfia. The main indication for the use of raunatin is hypertension, especially in stages I and II. In psychiatric practice, raunatin is not widely used due to an insufficiently pronounced neuroleptic effect, but it can be used in neurotic conditions.

Assign inside in tablets. Usually start with taking 1 tablet containing 0.002 g (2 mg) of total alkaloids at night; on the 2nd day, take 1 tablet 2 times a day, on the 3rd day - 3 tablets and bring the total dose to 4-5-6 tablets per day; take the drug after a meal. After the onset of a therapeutic effect (usually after 10-14 days), the dose is gradually reduced to 1-2 tablets per day. The course of treatment usually lasts 3-4 weeks, but sometimes the drug is taken for a long time in a maintenance dose (1 tablet per day). Treatment should be carried out under medical supervision. Simultaneously with raunatin (or sequentially), other antihypertensive drugs, ganglion blocking drugs, apressin, dichlothiazide, etc. can be prescribed.

Raunatin usually does not cause side effects. Some patients tolerate it better than reserpine. In some cases, swelling of the nasal mucosa, sweating, general weakness are observed; in patients with angina pectoris, pain in the region of the heart sometimes increases. Side effects disappear when the dose is reduced or after a short (1-3 day) break in taking the drug.

Aimalin (Ajmalinum) (unlike reserpine, also contained in rauwolfia) does not have antipsychotic activity, moderately lowers blood pressure, slightly increases coronary blood flow, has a negative ionotropic effect and a moderate adrenolytic effect.

A characteristic feature of Aymaline is its antiarrhythmic properties. It lowers myocardial excitability, lengthens the refractory period, inhibits atrioventricular and intraventricular conduction, somewhat inhibits the automatism of the sinus node, and suppresses impulse formation in ectopic foci of automatism. Refers to antiarrhythmic drugs of group I.

Aymalin is able to stop attacks of atrial fibrillation and paroxysmal tachycardia. It is also effective in rhythm disturbances associated with digitalis intoxication.

Assign intravenously, intramuscularly and inside; more effective when administered parenterally.

To stop acute attacks of atrial fibrillation and paroxysmal tachycardia, 0.05 g (2 ml of a 2.5% solution) is administered intravenously in 10 ml of isotonic sodium chloride solution or 5% glucose solution. Enter slowly - within 7-10 minutes. If necessary, another 0.05 g can be re-introduced during the day. The drug can be administered drip: 2-4 ml of a 2.5% solution in 100-200 ml of isotonic sodium chloride solution.

Intramuscularly administered at 0.05 g (2 ml of a 2.5% solution) every 8 hours to 0.15 g per day (that is, up to 3 times). If necessary, the drug is administered for several days in a row.

When a therapeutic effect is achieved from parenteral administration, they switch to taking the drug orally, 1-2 tablets (0.05-0.1 g) 3-4 times a day (for 1-3 weeks).

Aymalin is usually well tolerated. Some patients have hypotension, general weakness, nausea, vomiting; when administered intravenously - a feeling of heat.

Contraindications (especially for intravenous administration): severe damage to the conduction system of the heart, pronounced sclerotic and inflammatory changes in the myocardium, circulatory failure III degree, severe hypotension. Caution is necessary when administering Aymalin to patients with recent myocardial infarction: a decrease in blood pressure and conduction disturbances are possible.

Rauwolfia snake (Rauwolila serpentina Benth.)

perennial evergreen shrub with Kurdish families(Arosupaseae) with a vertical rhizome and numerous root, with ascending stems that are covered with whitish bark, up to 1 m tall. They are first opposite, and then collected 4-5 elliptical or broadly lanceolate leaves. Flowers with a dark red calyx with a pale or pink corolla. The fruits consist of two red drupes that have grown to the middle. The plant is very poisonous.

Spreading. Grows wildly in the Himalayas, northern India, Burma, the Indonesian islands. Introduced into culture in India. Measures are being taken to grow in the CIS.

blank. The bark and roots are collected and dried.

Chemical composition. The raw material contains up to 25 indole alkaloids (1-2%), including reserpine, rescinamine, aymaline, aimapicin, isoaymalin, aymalinine, rauhimbine, isorauhimbine, rauwolfinine, reserpilin, reserpinine, sarppagin, serpentine, serpentinine, serpin, 3-epi -a-yohimbine, aloyohimbine, β-yohimbine, serpenine, thebaine, papaverine, deserpidin.

Reserpine, raunatin and aymalin are obtained from raw materials.

Application. Reserpine has antihypertensive properties and a calming effect on the central nervous system, enhances and deepens physiological sleep, potentiates the action of hypnotic drugs, causes a number of parasympathomimetic effects: slows down cardiac activity with lengthening of diastole, increases gastrointestinal motility, increases the formation of hydrochloric acid in the stomach, miosis , causes hypothermia, to some extent reduces metabolism. It enhances the release of catecholamines and reduces their content, as well as serotonin in the central nervous system. It is used to gradually reduce systolic and diastolic blood pressure in various forms and stages of hypertension. The hypotensive effect develops gradually and persists for a relatively long time. Take 0.1-0.3 mg per day after meals. If necessary, the dose is gradually increased to 0.5-1 mg, and in the absence of effect - up to 1.5-2 mg per day. If within 10-14 days the effect has not come, then the reception is stopped. It is also prescribed for mild forms of heart failure with tachycardia, together with cardiac glycosides, hypersympathicotonia, toxicosis of pregnant women, with thyrotoxicosis, together with thyreostatic drugs. It is also used for neuropsychiatric disorders associated with increased blood pressure, with prolonged insomnia, psychomotor agitation in patients with schizophrenia, manic arousal in the context of circular psychosis, circular form of schizophrenia, depressive-agitated state in patients with presenile psychosis. In schizophrenia, reserpine with neuroleptics is selectively used. It is prescribed for mental illness on the first day of 0.25 mg, and then the dose is gradually increased to 10-15 mg per day, and for neurosis, 0.25 mg 2-3 times a day, and then the dose is increased to 0.5 mg 3 4 times a day. Take for 3-6 months, and then give maintenance doses of 0.5-1 mg 1-3 times a day. Large doses can cause redness of the eyes, skin rash, stomach pain, diarrhea, bradycardia, nausea, vomiting, weakness, suffocation, dizziness, nightmares, and with prolonged use - parkinsonism, anxiety, depression, insomnia. In such cases, reduce the dose of the drug and prescribe appropriate treatment. Contraindicated in severe organic diseases of the cardiovascular system with symptoms of decompensation and severe bradycardia, nephrosclerosis, cerebrosclerosis, gastric ulcer and duodenal ulcer. Released in tablets of 0.1 and 0.25 mg. List B.

Raunatin - sum of alkaloids of rauwolfia roots. It has a hypotensive and antiarrhythmic effect, has a calming effect on the central nervous system. It is prescribed for hypertension stage I and II, neurotic conditions, 2 mg after meals on the 1st day 1 time, on the 2nd day - 2 times, on the 3rd day - 3 times and adjusted 4-6 times a day . After achieving the effect (10-14 days), the dose of the drug is reduced to 2 mg 1-2 times a day. It is taken for 3-4 weeks, but sometimes a maintenance dose of 2 mg is taken for a long time. In some cases, in patients it can cause swelling of the nasal mucosa, sweating, general weakness, and in patients with angina pectoris, increased pain in the region of the heart. These phenomena disappear with a decrease in the dose of the drug or after a short break (1-3 days). Produced in tablets of 2 mg. List B.

Aymalin- has antiarrhythmic properties, reduces myocardial excitability, lengthens the refractory period, inhibits atrioventricular and intraventricular conduction, to a certain extent suppresses the automatism of the sinus node and the formation of impulses in ectopic foci of automatism. It is prescribed for atrial and ventricular extrasystole, paroxysmal supraventricular and ventricular tachycardia, paroxysmal atrial fibrillation, with a lesser effect with a stable form of flashing arrhythmias, atrial flutter, sinus tachycardia, 0.05-0.1 g 3-4 times a day, in total day 0.15-0.3 g, and parenterally - up to 0.15 g per day. In attacks of paroxysmal tachycardia and atrial fibrillation, 2 ml of a 2.5% solution in 10 ml of isotonic sodium chloride solution or 5% glucose solution is injected into a vein for 3-5 minutes. May cause hypotension, weakness, nausea, vomiting. Contraindicated in severe lesions of the conduction system of the heart, severe sclerotic and inflammatory changes in the myocardium, circulatory failure III degree, hypotension. Produced in tablets of 0.05 g and in ampoules of 2 mg of a 2.5% solution. List B.

Homeopathic remedy Rauvolfia serpentina It is used in states of depression and to lower blood pressure. This remedy is used in low dilutions to lower blood pressure, in high dilutions - to treat nervous diseases and psychoses.

Other plant names:

serpentina, sarpagandha.

Brief Description of Rauwolfia Snake:

Rauwolfia snake (serpentina) is a shrub up to 1–1.5 m high, of the kutrov family (Apocynaceae).

Rauwolfia snake (serpentina) grows in tropical countries.

Rauwolfia roots and rhizomes are harvested, from which the medical industry produces reserpine, raunatin, aymalin.

The chemical composition of rauwolfia snake:

Rauwolfia rhizomes and roots contain about 20 indole alkaloids, which, in terms of dry raw materials of the plant, make up 1–2%. The most famous of them are reserpine, reserpinine, raupin, serpentine, rescinamine, aymalicin, aymalin, aymalinin, serpin, yohimbine, thebaine, papaverine, etc.

All these active substances form the basis of the chemical composition of serpentine rauwolfia (serpentines).

Pharmacological properties of rauwolfia snake:

The pharmacological properties of rauwolfia are determined by its chemical composition.

The pharmacological properties of plant alkaloids are diverse. Basically, they affect the central nervous system, have a hypotensive and adrenolytic effect, which is due mainly to the specific properties of reserpine and the amount of alkaloids close to it in structure. In connection with the widespread use in medical practice of reserpine and total alkaloid preparations from rauwolfia, the pharmacological properties of reserpine and raunatin are presented below.

Reserpine:

Reserpine is a white crystalline powder, poorly soluble in water and well - in organic solvents. It has mainly hypotensive and sedative (tranquilizing) effect.

The hypotensive effect of reserpine develops slowly and persists for a long time. The hypotensive effect is associated with a decrease in cardiac output, with a decrease in total peripheral vascular resistance, as well as with the presence of an inhibitory effect of the drug on pressor centers. The direct effect of rauwolfia alkaloid on vasomotor centers has not yet been proven, since reserpine in an animal experiment does not affect efferent impulses in the preganglionic fibers of sympathetic innervation. Under the action of reserpine, however, bradycardia, increased motor activity and secretion of the gastrointestinal tract, as well as miosis are observed, which indicates the suppression of adrenergic mechanisms by the drug and the predominance of cholinergic effects.

The effect of reserpine on the central nervous system is manifested in the deepening and strengthening of physiological sleep, in the potentiation of the action of barbiturates and other hypnotic drugs and drugs, in the inhibition of interoreceptive reflexes, in a decrease in body temperature. All this allows us to attribute reserpine to the category of neuroleptics. However, at present, reserpine is rarely used as an antipsychotic in practical medicine.

The mechanism of action of reserpine is associated with its effect on biogenic amines, although it does not apply to monoamine oxidase inhibitors. In an animal experiment, the administration of rauwolfia alkaloid in large doses markedly decreases the content of biogenic amines in the central nervous system and other organs and tissues. For example, the content of catecholamines in the central nervous system of norepinephrine decreases - in the heart muscle, blood vessels, and the adrenal medulla.

Raunatin:

In contrast to the individual alkaloid of the plant, the total drug from rauwolfia serpentine - raunatin - has a milder hypotensive and sedative effect, however, due to other plant alkaloids, it also has antiarrhythmic and antispasmodic properties. Despite the fact that raunatin is inferior to reserpine in terms of the strength of the hypotensive effect, the mechanism for reducing the level of blood pressure of raunatin consists of two components - the central reserpine-like and peripheral adrenolytic effect.

The use of rauwolfia in medicine, treatment with rauwolfia. Dosage forms, method of administration and doses of rauwolfia serpentine preparations:

From the rhizomes and roots of rauwolfia, effective drugs and forms are made that are used in the treatment of many diseases. Let's consider the main ones.

Reserpine drug:

Reserpine (Reserpinum) is used mainly for hypertension. Under the influence of the drug, there is a gradual decrease in the maximum and minimum blood pressure in various forms of hypertension (including hyperthyroidism). The greatest effect is observed in the early stages of the disease in the absence of organic changes in the cardiovascular system. The therapeutic effect of reserpine usually appears 3-6 days after the start of the drug. The hypotensive effect persists for a relatively long time after discontinuation of reserpine. Assign it usually inside in the form of tablets; sometimes administered intramuscularly or intravenously, however, parenteral administration has no significant advantages over oral administration.

Doses of the drug and the duration of its use should be individualized. With hypertension, they usually begin with the appointment of reserpine at a dose of 0.1-0.3 mg / day (0.0001-0.0003 g / day); take the drug reserpine after meals. In some cases, it is enough to continue using the drug at these doses, in other cases, the dose is gradually increased to 0.5-1 mg / day; in the absence of effect, the dose can be increased to 1.5–2 mg / day. If within 10-14 days the hypotensive effect does not occur, further administration of the drug is canceled. If there is an effect, the dose is gradually reduced to 0.5-0.2-0.1 mg / day. Treatment with small (maintenance) doses is carried out for a long time for several months under medical supervision.

If necessary, you can prescribe reserpine in conjunction with other antihypertensive drugs, especially with apressin, as well as hexonium, pentamine and other ganglion blocking drugs.

The drug reserpine is also used for mild forms of heart failure with tachycardia (together with cardiac glycosides), for hypersympathicotonia, thyrotoxicosis (together with thyreostatic substances), and for late pregnancy toxicosis.

The highest doses of reserpine for adults inside: single 0.001 g (1 mg), daily 0.01 g (10 mg). When prescribing the drug in higher doses, an appropriate indication in the prescription should be made.

For children, reserpine is prescribed at the age of up to 1 year no more than 0.1 mg 1-2 times a day, up to 5 years - 0.1 mg 2 times a day and from 6 to 12 years - 0.1 mg 2-3 times a day .

In small doses, reserpine usually does not cause side effects. At high doses and hypersensitivity, hyperemia of the mucous membranes of the eyes, skin rash, stomach pain, diarrhea, bradycardia, weakness, dizziness, shortness of breath, nausea, vomiting, nightmares can be observed. With prolonged use, the phenomena of parkinsonism are possible.

During the course of treatment in patients with mental illness, a feeling of anxiety, anxiety, persistent insomnia, and a state of depression may develop.

In case of side effects, the dose of reserpine should be reduced or it should be temporarily canceled. For pain in the stomach and diarrhea, anticholinergics are prescribed, for parkinsonism - atropine, tropacin, amizil or similar drugs. With severe depression, CNS stimulants are used. When prescribing the drug on an outpatient basis, the possibility of developing drowsiness and general weakness should be taken into account.

Reserpine contraindications: reserpine is contraindicated in severe organic cardiovascular diseases with circulatory failure and severe bradycardia, with coronary sclerosis and sclerosis of cerebral vessels, nephrosclerosis, gastric ulcer and duodenal ulcer.

Available in the form of powder and tablets of 0.0001 g (0.1 mg) and 0.00025 g (0.25 mg).

Reserpine in powder is kept under lock and key (list A); tablets - with caution (list B). Store reserpine in a tightly closed container in a dry, dark place.

The drug raunatin:

Raunatin (Raunatinum). The main indication for the use of raunatin is hypertension, especially in stages I and II. In psychiatric practice, raunatin is not widely used due to an insufficiently pronounced neuroleptic effect, but can, however, be used in neurotic conditions.

Assign the drug inside in tablets. Usually start with taking 1 tablet containing 0.002 g (2 mg) of total alkaloids at night; on the 2nd day take 1 tablet 2 times a day; on the 3rd day - 3 tablets and bring the total daily dose of the drug to 5-6 tablets per day; take raunatin after meals.

After the onset of a therapeutic effect (usually after 10-14 days), the dose is gradually reduced to 1-2 tablets per day. The course of treatment lasts 3-4 weeks. However, sometimes the drug is taken for quite a long time in a maintenance dose (1 tablet per day). Treatment with raunatin should be carried out under medical supervision. Simultaneously with raunatin (or sequentially), other antihypertensive drugs, ganglionic blocking drugs, apressin, dichlothiazide, etc. can be used.

Raunatin usually does not cause side effects. Some patients tolerate it better than reserpine. However, in some cases, there is swelling of the mucous membranes of the nose, sweating, general weakness; in patients with angina pectoris, pain in the region of the heart sometimes increases. Side effects disappear when the dose is reduced or after a short break (1-3 days) in taking the drug.

Raunatin is produced in coated tablets containing 0.002 g (2 mg) of the drug. Storage: list B. Keep the drug raunatin in well-closed jars or dark glass bottles.

Aymalin preparation:

Ajmalin (Ajmalinum) chemically belongs to the group of indole derivatives and is a white or white with a slightly yellowish tint crystalline powder. Very slightly soluble in water, difficult - in alcohol. Aymaline hydrochloride and acetate are readily soluble in water.

Aimalin, unlike reserpine, does not have antipsychotic activity, moderately lowers blood pressure, slightly increases coronary blood flow, has a negative inotropic effect and a moderate adrenolytic effect.

A characteristic feature of Aymaline is its antiarrhythmic properties. It lowers myocardial excitability, lengthens the refractory period, inhibits atrioventricular and intraventricular conduction, somewhat inhibits the automatism of the sinus node, and suppresses impulse formation in ectopic foci of automatism.

Aymalin is an effective remedy for stopping attacks of atrial fibrillation and paroxysmal tachycardia. It is also effective in rhythm disturbances associated with digitalis intoxication.

The drug is prescribed intravenously, intramuscularly and orally; it is especially effective when administered parenterally.

To stop acute attacks of atrial fibrillation and paroxysmal tachycardia, 0.05 g (2 ml of a 2.5% solution) is administered intravenously in 10 ml of isotonic sodium chloride solution or 5% glucose solution. Enter slowly - within 3-5 minutes. If necessary, you can re-introduce another 0.05 g during the day. You can administer the drug drip: 2-4 ml of a 2.5% solution in 100-200 ml of isotonic sodium chloride solution. Intramuscular injection of 0.05 g (2 ml of a 2.5% solution) every 8 hours up to 0.15 g / day (i.e. up to 3 times). If necessary, the drug is administered for several days in a row.

When a therapeutic effect is achieved from parenteral administration, they switch to taking the drug orally, 1-2 tablets (0.05-0.1 g) 3-4 times a day (for 1-3 weeks). Aymalin is usually well tolerated. Some patients have hypotension, general weakness, nausea, vomiting; when administered intravenously - a feeling of heat.

Aymalin contraindications (especially for intravenous administration): severe damage to the conduction system of the heart, pronounced sclerotic and inflammatory changes in the myocardium, stage III circulatory failure, severe hypotension. Caution is necessary in the case of the introduction of Aymaline to patients with recent myocardial infarction: a decrease in blood pressure and conduction disturbances are possible.

Aimalin is produced in tablets of 0.05 g, in ampoules of 2 ml of a 2.5% solution (25 mg in 1 ml). Store the drug according to list B in a place protected from light.

doctor of agricultural sciences, professor vegetable growing RGAU-MSHA named after K.A. Timiryazev

Genus rauwolfia (Rauwolfia) from the kutrovye family is quite extensive, including, according to various authors, from 45 to 100 species. These are tropical and subtropical woody shrubs or even herbaceous plants. The genus got its name after the botanist Leonard Rauwolf, who in 1582, after an expedition to Asia, in particular to India, described a plant that the locals used for snake bites. In memory of this, in 1703, the French botanist Charles Plumier named a whole genus of plants like this.

The most famous member of this genus is rauwolfia serpentine (Rauwolfiaserpentine Benth. syn. R.obverse,R.trifoliata) - an evergreen shrub up to 1 m high with a short rhizome and long, up to 3 m in length, roots. Leaves opposite or in whorls of 3 - 5 pieces, have oblong - ovoid, obovate or lanceolate and short petiole. Flowers with a white or dark pink corolla are collected in apical or axillary umbellate inflorescences. The fruit consists of two fused purple, sometimes almost black, drupes with rounded yellowish - brown seeds.

Her homeland is India, the tropical regions of the Himalayas, northern and central Bengal, as well as Burma, Ceylon, Thailand, the island of Java. In the wild, it is found along the edges of tropical forests, in the mountains it rises to a height of 1200 m. But the main raw material of this plant is obtained in culture.

The first mention of this plant is in ancient Indian manuscripts of 1 thousand years BC, where rauwolfia is called "sarpagandha". The roots of rauwolfia serpentine have been used in India since ancient times as a sedative and for snake bites, for which it received the name - serpentine. Peasants from areas infested with snakes planted 2-3 plant bushes near their dwellings, just in case. According to another, less common version, in the "viper" name, long, like snakes, roots are "to blame", which are used as medicinal raw materials.

In 1931, Indian chemists S. Sidiki and R. Sidiki isolated a number of alkaloids from the root of the plant, and in 1944, scientists G. Sen and C. Bose isolated a substance that lowers blood pressure. In 1952, this substance was named reserpine and found that it reduces the excitation of the central nervous system and, as a result, reduces pressure.

The plant turned out to be so in demand that in India there was even a threat of extermination of wild-growing resources. Therefore, there are plantations of this plant, primarily in India and Malaysia, and technologies for the production of raw materials in tissue culture have also been developed.

In addition to this species, others are admitted to medicine. grown in India for its roots. rauwolfia greyish (Rauwolfiacanescens L., syn. R.tetrapfylla, R.hirsuta). In the wild, it can be found not only in Asia, but also in Australia and even in Cuba.

In the forests of tropical Africa, primarily the Congo, grows rauwolfia emetic (Rauwolfia vomitoria Afz.). It is also grown in culture and exported raw materials around the world. Like the snake rauwolfia, it is a small tree or shrub. The local population used it for dysentery, leprosy, fever and other infectious diseases.

Rauwolfia kaffir (Rauwolfiacaffra Soud.), which also grows in Africa, is used entirely for the production of reserpine.

It is now known that rauwolfia roots contain up to 2% alkaloids derived from indole (reserpine, rescinamine, aymaline, aymalicine, isoaymaline, rauhimbine, isorauhimbine, rauwolfinine, serpentine, serpentinine, and even yohimbine, as well as some others). Interestingly, up to 90% of this wealth is concentrated in the bark, so if pieces of roots are left without bark, this is already considered a lack of raw materials, because the total content of active substances in it will be lower. In addition to alkaloids, calcium oxalate, sterol, resins, and starch were found in the roots.

At present, it is already known which substance and for which action is responsible. Reserpine and rescinamine have a sedative and hypotensive effect, aymalin has an antiarrhythmic effect.

The leaves and stems also contain alkaloids, as well as flavonoids and milky juice.

Rauwolfia has been used in India for more than one century. It is mentioned in Ayurveda. It has been used as a sedative, for anxiety, manic behavior, insanity, insomnia, and seizures (in the modern interpretation, probably epilepsy). The juice of the leaves has been used for cataracts. In Java, the roots were considered an anthelmintic, and in Vietnamese folk medicine it was prescribed for dermatoses and even malaria.

In modern scientific medicine, preparations are used that consist either of individual isolated alkaloids (reserpine) or of the sum (raunatin). Reserpine is used as an antiarrhythmic and hypotensive agent. It causes sleep close to physiological, reduces the content of noradrenaline, dopamine and serotonin in the brain, which dampens excitability and, accordingly, has a positive effect on hypertension. Raunatin is used for hypertension of 1 and 2 degrees. When taking raunatin, headache, dizziness, irritability decrease, sleep improves.

Rauwolfia is also of interest to homeopaths. In dilutions of 3x and 6x, it is effective in depression and hypertension.

MINISTRY OF EDUCATION AND SCIENCE OF RUSSIA

"Maikop State Technological University"

Faculty of Pharmacy

Department of Pharmacy

Coursework in pharmacognosy

Rauwolfia serpentine and periwinkle small - sources of antihypertensive drugs

Completed by: 3rd year student,

full-time education

group F-31

Maleeva V.E.

Checked:

department teacher

pharmacy

Artemyeva V.V.

Maikop, 2011

I Introduction

II. Literature review

2.1 General characteristics of hypertension

2 Classification of antihypertensive drugs

III. Characteristics of plants used to obtain antihypertensive drugs

1 Characteristics of rauwolfia snake

2.5 Characteristics of the small periwinkle

IV. Conclusion. List of used literature

I Introduction

The chosen topic is an interesting and relevant direction for course design.

Hypertension is one of the most common diseases of the cardiovascular system and is one of the most acute, unresolved problems.

Despite numerous medical studies in different countries, the synthesis of new drugs, the incidence of essential hypertension does not decrease. In the last 20-30 years, in some countries, the incidence of hypertension has increased dramatically and amounted to 40% of the working population, i.e. took on the character of an epidemic. Moreover, men are more likely to suffer from hypertension before the age of 40, and women after 40, by the age of 50, the ratio of ill women and men levels off.

In our age of information explosion, patients are well aware of the drugs used to treat a variety of diseases, including hypertension. Such knowledge will not hurt if a person meaningfully fulfills the doctor's prescriptions and does not seek, according to his own understanding, to get and take medicines that are recommended, for example, to a colleague. After all, even the most commonly used and widely known drugs are prescribed by a doctor to his patient in various dosages, replaced by other medicines depending on his condition and many other circumstances, which only a specialist can evaluate. In addition, patients react differently to antihypertensive drugs, so patience is required not only from the doctor, but also from the patient in order to choose the dose and the best combination of medications that provide the necessary reduction in blood pressure. This problem is also relevant for preparations obtained from the alkaloid-bearing plants Rauwolfia serpentine and Periwinkle, as their improper use leads to disruption of the normal functioning of internal organs, the appearance of Parkinson's disease and other undesirable effects associated with the misuse of drugs.

Modern treatment should be aimed not only at eliminating the symptoms of the disease, but also at preventing the progression of target organ damage and the occurrence of complications.

In modern medicine, preparations of rauwolfia serpentine and periwinkle as an effective remedy for hypertension have become known since 1953. In the 50s of the current century, alkaloids were isolated from them, among which substances with exceptionally high sedative and hypotensive activity were found; widely used in therapy and research. It was revealed that during the treatment with reserpine, tolerance to physical activity increases, well-being and mood improve, reactive anxiety, emotional lability and tension of patients decrease. These pharmacological properties are of great importance for the treatment of arterial hypertension, since chronic emotional stress and neuropsychic overload play an important role in the development and stabilization of this disease. Periwinkle preparations dilate the coronary vessels of the heart and the vessels of the brain.

An important goal of this course project is to deepen and expand knowledge on this topic. The study of the production of preparations from medicinal plant materials of rauwolfia serpentine and periwinkle small, its preparation, acceptance, processing is carried out by different specialists. They should be well versed in the regulatory and technical requirements for the quality of raw materials, know its external features, conditions and terms of storage of raw materials and the correct use of this group of drugs. This work summarizes the literature data and briefly highlights these issues. . Literature review

2.1 General characteristics of hypertension

Hypertension is a disease, the main symptom of which is an increase in blood pressure due to neuro-functional disorders of vascular tone. Men and women are equally affected by hypertension. Usually the disease begins after 40 years. This is a very common pathology. It is called the disease of the autumn of life, although in recent decades, hypertension has become much younger.

Hypertension is one of the causes of disability and mortality in patients with disorders of the cardiovascular system.

Causes of hypertension

One of the reasons is prolonged and frequent neuropsychic stress, prolonged stress. Very often, hypertension occurs in people whose work is associated with constant emotional stress. Often it affects people who have suffered a concussion.

The second reason is hereditary predisposition. Usually, patients with a survey can reveal the presence of relatives with the same disease.

One of the important causes of hypertension is hypodynamia. Age-related restructuring in the body (in particular, the central nervous system) also affects the appearance and development of the symptoms of this disease. The high frequency of hypertension among the elderly is due to changes in blood vessels due to the addition of atherosclerosis. There is a certain relationship between these diseases. Hypertension contributes to the increased development and progression of atherosclerosis. This combination is dangerous because with a strong vasospasm, the blood flow to the organs (to the brain, heart, kidneys) is insufficient. With excessive spasm and the presence of plaques on the walls of blood vessels, blood can stop circulating through the artery. In this case, a stroke or myocardial infarction occurs.

Also of some importance are the excessive consumption of table salt (namely, sodium, which is part of this salt), smoking, alcohol abuse, overweight, which increases the load on the cardiovascular system.

The main links in the occurrence of hypertension are:

Violation of the processes of excitation and inhibition in the central nervous system;

Overproduction of substances that increase blood pressure. One of them is the stress hormone adrenaline. In addition, renal factor is also isolated. The kidneys produce substances that can raise and lower blood pressure. Therefore, when signs of hypertension appear, the patient needs to check the functioning of the kidneys;

contraction and spasm of the arteries.

Blood pressure (systolic and diastolic)

Pressure should be measured at rest - physical and emotional. The upper (systolic) pressure corresponds to the moment of contraction of the heart muscle, and the lower (diastolic) - to the moment of relaxation of the heart (table 1.). In young healthy people, normal blood pressure is defined as 110/70 - 120/80 mm Hg. Art. But, given the dependence of blood pressure figures on age, individual characteristics, fitness, we can name the boundaries of 125/65 - 80 mm Hg. Art. in men and 110 - 120/60 - 75 mm Hg. Art. among women. With age, blood pressure increases, for middle-aged people, normal numbers are close to 140/90 mm Hg. Art. The main symptom is an increase in blood pressure to 140 - 160/90 mm Hg. Art.

Table 1. Blood pressure indicators in normal and with hypertension of varying severity.

Symptoms of hypertension

Headache is one of the most common manifestations of high blood pressure. This symptom is caused by spasm of cerebral vessels. This often causes tinnitus, flickering of "flies" before the eyes, blurred vision, weakness, decreased performance, insomnia, dizziness, heaviness in the head, palpitations. These complaints in the early stages of the development of the disease are neurotic in nature. When examining a patient, heart murmurs, rhythm disturbances, expansion of the borders of the heart to the left are detected. In the later stages, heart failure may occur due to overwork of the heart muscle due to increased pressure.

A hypertensive crisis is one of the formidable manifestations of hypertension. With a sharp increase in pressure, all of the above symptoms may be accompanied by nausea, vomiting, sweating, decreased vision. Crises can last from several minutes to several hours. In this case, patients are usually excited, tearful, complain of palpitations. Often red spots appear on the chest and cheeks. There is an increase in heart rate. An attack may result in profuse urination or loose stools. Such crises are typical for the early stages of hypertension, they are more often observed in women in menopause, after emotional stress, when the weather changes. They often occur at night or in the afternoon. There are other types of hypertensive crises. They have a more severe course, but develop gradually. Their duration can reach 4-5 hours. They occur at later stages against the background of high initial blood pressure. Often, crises are accompanied by brain symptoms: impaired speech, confusion, changes in sensitivity in the limbs. At the same time, patients complain of severe pain in the heart.

Diagnostics

To establish the correct diagnosis in identifying this disease, it is important to interview the patient in order to identify a hereditary predisposition. Information about the state of the cardiovascular system in close relatives - parents, siblings is very important. Another important link in the diagnosis is the patient's complaints about repeated rises in blood pressure. To make a correct diagnosis, it is necessary to regularly measure the pressure of the patient. In the conditions of the clinic, a number of studies are also carried out: electrocardiography (ECG), examination of the fundus by an oculist, general blood and urine tests. Those patients who do not have a sufficient effect of the prescribed treatment, as well as patients with suspected secondary hypertension, are sent to specialized hospitals to rule out diseases of the kidneys, thyroid gland, and tumors.

2 Classification of antihypertensive drugs

Antihypertensive drugs are drugs of various pharmacological groups that cause a decrease in blood pressure and are used mainly with a pathological increase in systemic pressure.
The main task of treating patients with hypertension is to normalize systolic and diastolic pressure in order to prevent a number of complications, such as stroke, myocardial infarction, heart and kidney failure.

Classification of antihypertensive drugs. Drugs affecting the adrenergic innervation of the heart.

Calming drugs.

· sedatives;

sleeping pills (in small doses);

tranquilizers.

2. Antihypertensive agents of central action.

clonidine

methyldopa

3. Ganglioblockers.

Hygronium

· pyrilene

benzohexonium

4. Sympatholytics.

octadin

reserpine

phentolamine

tropafen

prazosin

6. β-blockers.

labetalol

talinolol

metoprolol. myotropic agents.

1. Arterial vasodilators.

apressin

Mixed vasodilators.

sodium nitroprusside

3. Drugs with different mechanisms of action, with myotropic activity.

dibazol

Magnesium sulfate

papaverine

Eufillin. Potassium channel activators.

Minoxidil

diazoxide. Calcium channel blockers.

fenigidin

diltiazem. Diuretics.

furosemide

dichlorothiazide

spironolactone. Drugs affecting the renin-angiotensin-aldosterone system.

Angiotensin-converting enzyme (ACE) inhibitors.

captopril

enalapril

ramipril

Angiotensin receptor blockers.

losartan

Candepsortan

tazosartan

irbesartan

Despite the success of synthetic chemistry, plant preparations are still the main means for the treatment and prevention of cardiovascular diseases.

Characteristics of plants used to obtain antihypertensive drugs

1 Characteristics of rauwolfia snake

Plant. Rauwolfia serpentine (serpentina) - (Rauwolfia serpentina Benth.), Kutrovye family - Apocynaceae.

Semi-shrub 0.2-1 m tall, with milky juice. The rhizome is vertical, 20-40 cm long, with numerous roots. Rhizome and roots lignified, gray-rusty color. Stem ascending, usually unbranched, covered with whitish bark with a few lenticels. Leaves are short-petiolate, whorled, 3-5 per whorl, rarely opposite or alternate, oblong-elliptical, obovate or lanceolate, pointed at the apex, narrowed into a petiole at the base, thin, glabrous, shiny, light green above, paler below , 7.5-17.5 cm long. The flowers are white or pink, collected in apical, less often - axillary umbellate inflorescences with a diameter of 2.5-5 cm. The bracts are very small, the calyx remaining with the fruits is five-parted. Its lobes are almost free, sharp, from triangular to lanceolate, 1.3-3 mm long. The calyx and pedicels are bright red. Corolla tubular, with five-lobed limb, glabrous outside, hairy inside; its tube is 11-16 mm long, slightly swollen above the middle. The lobes are round-ovate, 1.5-3.5 mm long, slightly wavy along the edges. The stamens, 5 in number, are attached to the corolla tube at the place of swelling. The pistil consists of 2 free carpels connected by a filiform column 8 mm long, ending in a well-developed cylindrical stigma. The fruit consists of 2 drupes fused to the middle (Fig. 1.). The drupes are obovate or ovoid, slightly flattened, dirty purple. Seeds are round-ovoid, asymmetrical, 6 mm long, compressed at the base, yellowish or grayish, reticulate tuberculate.

In the wild state, rauwolfia snake is found in the tropical regions of the Himalayas, in Sikkim, North and Central Bengal, Peru, on the Deccan Plateau, in Sri Lanka and Java.

Medicinal plant material of serpentine rauwolfia - serpentine rauwolfia roots (Rauwolfiae serpentinae radices).

Usually harvest 3-4-year-old plants. Rauwolfia roots are harvested in the fruiting phase, both from wild and cultivated plants. They are dug up, cleared of the earth and cut into pieces up to 20 cm long (Fig. 2). Dry in a well-ventilated place. The roots are covered with brown cork with longitudinal grooves. The bark is not wide, it can peel off in the raw material.

The loss of bark leads to a decrease in the content of alkaloids, so pieces of roots without bark are a defect in the raw material. The wood is brittle, yellowish, the fracture is even (there are no fibers). The smell is unpleasant. The taste is bitter (according to modern ideas, the taste of potent raw materials is not determined during its analysis). Raw materials are stored as potent (List B).

Microscopy. Cork has a characteristic layering - alternating layers of smaller and larger cells. The phloem contains solitary secretory cells with brown resinous contents. In the cells of the parenchyma, starch grains are often found, less often - prismatic crystals of calcium oxalate. There are no mechanical elements in the bark (difference from the roots of other types of rauwolfia) (Fig. 3.)

Fig.3. Microscopy of Rauwolfia serpentine.

A - a fragment of a transverse section of the outer part of the root - periderm;

B - a fragment of a cross section of a root in the area of ​​wood: 1 - a vessel;

B - cells of the phloem parenchyma with starch grains and prismatic crystals of calcium oxalate.

Chemical composition. Roots and rhizomes contain up to 2% of indole alkaloids: reserpine, serpentinine, aimaline, aimalicin, rescinamine, isoaymalin, rauchimbine, isorauhimbine, rauwolfinine, reserpilin, reserpenine, sarpagin, serpentine, serpin, alloihimbine, thebaine, papaverine, chaindrin. The bark of the roots contains 90% of the total amount of alkaloids in the roots. The content of alkaloids depends on the geographical location of the plants and the time of year. Harvested in December in the state of Assam (India), Rauwolfia roots have the highest percentage (2.57) of alkaloids. The age of the plant does not affect the accumulation of alkaloids. In addition, calcium oxalate, sterol, resins, and starch were found in the roots.

Leaves and stems contain alkaloids, carotenoids, flavonoids, milky juice (rubber).

Qualitative and quantitative analysis of reserpine alkaloid.

Reserpine is sparingly soluble in water and petroleum ether, it dissolves in ethyl alcohol in a ratio of 1: 2000, in methyl alcohol 1: 400, in chloroform 1: 6. It dissolves in acetic acid. Melting point 261-265 (with decomposition). With mineral (HC1, HNO3, H2SO4, HClO4) and some organic (oxalic, picric) acids, reserpine gives easily hydrolyzed salts. Under the influence of light, air and oxidants easily decomposes.

Isolation is carried out with acidified water, it is recommended to use 10% acetic acid, and isolation is carried out for 24 hours in a place protected from light. Extraction is carried out with chloroform at pH 4.0 and 8.5 (reserpine and metabolites), and purification is carried out using electrophoresis on paper.

quality detection.

General alkaloid precipitation reagents give amorphous precipitates with reserpine. A particularly sensitive reagent is phosphomolybdic acid; reaction sensitivity 0.6 μg at a limiting dilution of 1:3200; I2/KY solutions; CdI2/KY; HgI2/KY and BiI3/KY have a sensitivity of 2.5 µg at a limiting dilution of 1:8000 and phosphotungstic acid - 5 µg at a dilution of 1:4000.

Staining reactions are uncharacteristic. The most characteristic violet coloration gives with reserpine a solution of vanillin in the presence of hydrochloric and sulfuric acids. The reaction can detect 0.6 µg of a substance in the analyzed object.

A characteristic property of reserpine is its ability to give a yellow-green fluorescence, which is observed in freshly prepared solutions at a dilution of 1: 1,000,000.

With solutions of ammonium thiocyanate, mercuric chloride in the presence of sodium chloride and ammonium tetrarhodanomercuriate, reserpine gives characteristic crystalline precipitates. The reactions are quite specific and allow the detection of reserpine at dilutions of 1:200,000 and 1:20,000, respectively (data refer to aqueous solutions of the alkaloid).

Quantitative determination of reserpine and its decay products is carried out by the fluorometric method after isolation and purification of the alkaloid using electrophoresis on paper.

Pharmacological properties and preparations. Rauwolfia alkaloids have valuable pharmacological properties. Reserpine and rescinamine have a sedative and hypotensive effect. Aymalicin, raufolvin, serpagin, yohimbine adrenolytic. Aymalin was found to have an antiarrhythmic effect.

Most rauwolfia preparations contain reserpine. Reserpine has a complex effect on the body. Influencing the peripheral nervous system, it has an antihypertensive effect, affecting the central neurochemical processes - neuroleptic. The hypotensive effect of reserpine develops slowly and lasts for several hours. It slows down the rhythm of heart contractions, without changing or increasing the minute volume of the heart, lowers the content of norepinephrine in tissues. Reserpine causes sleep close to physiological.

The sympatholytic effect of reserpine is due to the fact that under its influence catecholamines are rapidly released from the granular depot of presynaptic nerve endings. The released catecholamines are inactivated by monoamine oxidase, which leads to a decrease in the release of catecholamines into the synaptic cleft. Reserpine weakens the adrenergic effect on the effector systems of peripheral organs, including adrenoceptors of blood vessels. The action of reserpine extends to the central nervous system (CNS). It disrupts the transport of neurotransmitters from the cellular plasma, where they are synthesized, into granules for storage. Therefore, the content of norepinephrine, dopamine and serotonin in the brain tissues decreases, tk. they are inactivated by monoamine oxidase in cellular plasma.

Reserpine pharmacological action: sympatholytic agent, has hypotensive, antipsychotic and sedative effects. Penetrating into the presynaptic endings of postganglionic sympathetic fibers, it releases norepinephrine from vesicles with a simultaneous violation of its reverse neuronal uptake and an increase in the process of MAO inactivation. It causes depletion of neurotransmitter stores and a persistent decrease in blood pressure. It helps to reduce the concentration of dopamine in neurons (which explains possible extrapyramidal disorders), serotonin and other neurotransmitters, providing an antipsychotic effect. Weakens the influence of sympathetic innervation on the cardiovascular system, reduces heart rate and OPSS; maintains activity and even compensatory enhances the activity of the parasympathetic nervous system; deepens and enhances physiological sleep, inhibits interoreceptive reflexes. Increases peristalsis of the gastrointestinal tract, increases the production of HCl in the stomach; slows down metabolic processes in the body; reduces and deepens respiratory movements, causes miosis, hypothermia; reduces the metabolic rate. It has a positive effect on lipid and protein metabolism in patients with arterial hypertension and coronary atherosclerosis; increases renal blood flow, enhances glomerular filtration. The effect develops in a few days and reaches a maximum after 3-6 weeks; duration of action - 1-6 weeks.

Indications: arterial hypertension, thyrotoxicosis, neurosis, psychosis, late preeclampsia, psychomotor agitation in patients with schizophrenia, manic agitation in the framework of cycloid psychosis and circular form of schizophrenia, depressive - agitated state in patients with presenile psychosis - as part of combination therapy.

Contraindications: hypersensitivity, epilepsy, Parkinson's disease, depression, gastric and duodenal ulcer (in the acute phase), erosive gastritis, ulcerative colitis, bronchial asthma, pheochromocytoma, angle-closure glaucoma, bradycardia, AV blockade, electroconvulsive therapy; atherosclerosis of cerebral vessels, nephrosclerosis, concomitant treatment with MAO inhibitors; pregnancy, lactation.

Side effects: extrapyramidal disorders, headache, dizziness, weakness, drowsiness, insomnia, anxiety, fatigue, depression, hyporeflexia, decreased ability to concentrate; dyspepsia, nausea, vomiting, diarrhea, abdominal pain, gastrointestinal bleeding, loss of appetite; dry mouth, bradycardia, arrhythmias, thoracalgia; peripheral edema, swelling and dryness of the mucous membranes of the nose, urinary retention, increased urination; decreased potency and / or libido, herpes, pruritus, hyperemia of the mucous membrane of the eyes, weight gain, allergic reactions. Overdose. Symptoms: "nightmare" dreams, parkinsonism, angina pectoris; with prolonged use in high doses - impaired liver function.

Method of application and dose: inside: with arterial hypertension in the initial dose - 0.1 mg 2 times a day (morning and evening), if the desired hypotensive effect is not achieved within 5-7 days of treatment, the dose is increased to 0.25-0.5 mg / day in 2-3 doses. After stabilization of the hypotensive effect, the dose is gradually reduced to 0.2-0.1 mg / day. The course of treatment is 2-3 months. With neuroses, the initial dose is 0.25 mg 2-3 times a day, with a gradual increase to 0.5 mg 3-4 times a day. In mental illness, the initial dose is 0.25 mg, with a gradual increase to 10-15 mg / day; course of treatment - 3-6 months. The maximum single dose is 1 mg, the daily dose is 10 mg.

Interaction: increases the risk of developing bradycardia, arrhythmogenic effects of digitalis drugs; reduces the effectiveness of antiepileptic drugs and levodopa, anticholinergics, reduces the analgesic effect of morphine. Enhances the central effect of barbiturates, ethanol, drugs for inhalation anesthesia, antihistamine drugs, tricyclic antidepressants. Reserpine eliminates the effect of sympathomimetic drugs, depleting the depot of catecholamines; reserpine can prolong the action of direct-acting adrenomimetic drugs, preventing the capture of the mediator in the depot granules. A significant increase in blood pressure was registered when prescribing eye drops with phenylephrine during treatment with reserpine; with simultaneous use with fenfluramine, it is possible to increase the hypotensive effect of reserpine. Methyldopa increases the risk of developing depression; tricyclic antidepressants weaken the hypotensive effect; MAO inhibitors increase the risk of developing hyperreactivity, hypertensive crisis.

Reserpine is part of a number of combined drugs used in hypertension. Combined reserpine-containing drugs have advantages over taking reserpine alone, since the hypotensive effect occurs faster and with minimal doses of their components. Combination preparations usually include ingredients with different pharmacological effects, which offset each other's side effects and enhance the overall therapeutic effect.

Contraindicated in severe organic diseases of the cardiovascular system, peptic ulcer of the stomach and duodenum, kidney disease with impaired function.

Side effects hyperemia (redness) of the mucous membranes of the eyes, skin rashes, dyspepsia, bradycardia, weakness, dizziness, shortness of breath. Sometimes anxiety, depression, insomnia, parkinsonism phenomena.

Adelfan-esidrex (Adelphan-Esidrex) contains reserpine 0.1 mg, dihydralazine 10 mg and dichlothiazide 10 mg, and Adelfan-esidrex-K (Adelphan-Esidrex K) contains reserpine 0.1 mg, dihydralizine 10 mg, hydrochlorothiazide 10 mg and potassium chloride 0.6 g and one dragee.

Pharmachologic effect. Along with the properties of Adelfan, it has a diuretic effect, and also restores the electrolyte balance in the body. The components of the drug are absorbed in the stomach, and potassium chloride, thanks to a special manufacturing technology of the drug, is slowly and gradually absorbed in the small intestine, without irritating the stomach and duodenum. Hypothiazide promotes the excretion of sodium chloride from the body, enhancing the hypotensive effect of Adelfan.

Indications for use. All forms of hypertension, especially cases of essential and renal hypertension (persistent rise in blood pressure of unknown cause and persistent rise in blood pressure due to kidney disease). When taking the drug, a salt-free diet can not be followed.

Method of application and dose. Initially, 1 tablet of the drug is prescribed 3 times a day, then this dose is gradually increased to 2 tablets 3 times a day. For long-term treatment, 2 tablets per day are usually sufficient.

Side effect. Pain in the epigastric region (the region of the abdomen located directly under the convergence of the costal arches and the sternum), nasal congestion, bradycardia, drowsiness.

Contraindications. Severe renal failure. (See Appendix)

Brinerdin (Brinerdin) - dragees containing reserpine 0.0001, gdihydroergocristine 0.0005 g (0.5 mg), clopamide (brinaldix) 0.005 g. Dihydroergocristine is a peripheral and central adrenoblocking agent; clopamide is a saluretic. Used for hypertension and symptomatic hypertension (see appendices)

Kristepin (Crusterin) - dragees containing 0.1 mg of reserpine, 0.5 mg of dihydroergocristine and 5 mg of the diuretic clopamid. Used in various forms of arterial hypertension.

Pharmacological action blocks sympathetic impulses (transmitter release and its acceptance by the postsynaptic membrane), which leads to a decrease in the tone of vascular smooth muscles, a decrease in heart function; has diuretic activity.

Indications of the drug Arterial hypertension of mild to moderate severity.

Contraindications hypersensitivity hypokalemia, pronounced violations of the liver and kidneys, the state after a recent myocardial infarction, depression exacerbation of peptic ulcer; pregnancy, lactation.

Side effects of the drug feeling of fatigue, muscle weakness, headache, dyspepsia, orthostatic hypotension, electrolyte imbalance (especially hypokalemia).

Interaction: weakens the effect of indirect anticoagulants, oral hypoglycemic agents; enhances the action of cardiac glycosides.

Method of administration and doses: inside, at first, 1 tablet per day, if necessary, the dose can be increased to 2 tablets per day; maintenance dose is 1 tablet daily or every other day.

Precautions: with caution prescribed for diabetes, gout. During treatment, food containing potassium is recommended; should not engage in activities that require increased attention.

Storage conditions of the drug List B in a dry, dark place at a temperature of 10-25 ° C. (look at the application)

Triresid (Tiresid) - tablets of the composition: reserpine 0.1 mg, dihydralazine sulfate 10 mg and hydrochlorothiazide 10 mg. Trirezide is also available with an additional content of 0.35 g of potassium chloride in each tablet. When taking all these tablets (except those containing potassium chloride), patients should be advised to eat foods rich in potassium. It is necessary to monitor potassium.

The total preparations of rauwolfia in the mechanism of action, along with sympatholytic activity, exhibit peripheral adrenergic and antispasmodic properties. It has an antiarrhythmic effect, restoring the processes of excitation and conduction in the heart muscle. Aymalin alkaloid has antiarrhythmic activity, stabilizing the membranes of myocardial cells and lowering their excitability, lengthening the refractory phase of the heart and slowing down the conduction of impulses through the conduction system.

Raunatin (Raunatinum) - a preparation containing the amount of alkaloids from the roots of rauwolfia snake or other types of rauwolfia. The main indication for the use of raunatin is hypertension, especially in stages I and II. In psychiatric practice, raunatin is not widely used due to an insufficiently pronounced neuroleptic effect, but it can be used in neurotic conditions.

Raunatin usually does not cause side effects. Some patients tolerate it better than reserpine. In some cases, swelling of the nasal mucosa, sweating, general weakness are observed; in patients with angina pectoris, pain in the region of the heart sometimes increases. Side effects disappear when the dose is reduced or after a short (1-3 day) break in taking the drug (see Appendix).

Aimalin (Ajmalinum), unlike reserpine, does not have antipsychotic activity, moderately lowers blood pressure, slightly increases coronary blood flow, has a negative ionotropic effect and a moderate adrenolytic effect.

A characteristic feature of Aymaline is its antiarrhythmic properties. It lowers myocardial excitability, lengthens the refractory period, inhibits atrioventricular and intraventricular conduction, somewhat inhibits the automatism of the sinus node, and suppresses impulse formation in ectopic foci of automatism. Refers to antiarrhythmic drugs of group I.

Aymalin is able to stop attacks of atrial fibrillation and paroxysmal tachycardia. It is also effective in rhythm disturbances associated with digitalis intoxication.

Aymalin is usually well tolerated. Some patients have hypotension, general weakness, nausea, vomiting; when administered intravenously - a feeling of heat.

Contraindications (especially for intravenous administration): severe damage to the conduction system of the heart, pronounced sclerotic and inflammatory changes in the myocardium, circulatory failure III degree, severe hypotension. Caution is necessary when administering Aymaline to patients with recent myocardial infarction: a decrease in blood pressure and conduction disturbances are possible (see Appendix).

Extracts from the roots and leaves of the plant are traditionally used in Indian folk medicine as a remedy with well-defined sedative properties for anxiety, manic behavior, schizophrenia, insomnia and epilepsy. A decoction of the roots increases the contraction of the uterus, contributing to the expulsion of the fetus. Leaf juice is used for cataracts. The roots are used in complex preparations for dysentery, cholera, intestinal diseases, as an insecticidal agent, as well as for snake and scorpion bites. In Java - as an anthelmintic.

LS storage. Pure alkaloids (substances) are stored as toxic substances (List A). Finished medicines - tablets of reserpine, raunatin and aymaline are stored as potent substances (List B). Adelfan-ezidreks, brinerdine, kristepin, etc. are stored according to the general list.

2 Characteristics of periwinkle small

Plants: Small periwinkle - (Vinca minor), kutrovye family - Apocynaceae

Small evergreen shrub with opposite leaves, in the axils of which azure flowers develop. Stem recumbent, rooting, branched, up to 60cm. length. Flowering shoots are erect. The leaves are wintering, glabrous, shiny above, elliptical, pointed at the end, with a short petiole. Calyx glabrous, five-parted, several times shorter than corolla tube. Corolla funnel-shaped, with a long narrow tube, swollen in the middle, with a five-part limb; its lobes are widened upwards, bluntly cut. Stamens 5 anthers converge above the stigma and have a hairy appendage. There are two ovaries with one common column, bearing a membranous ring at the top, bent downwards, above which there is a stigma with a hairy crown. After flowering, the ovaries diverge to the sides, and two leaflets with seeds that open with one seam, without tufts, develop from them (Fig. 5.). Blooms in spring. Grows in shrubs, forest edges and steppe slopes.

Medicinal plant material of small periwinkle - herb small periwinkle (Herba vincae minoris). Raw materials are harvested in the phase of flowering - the beginning of fruiting, cutting off only vertical shoots at a height of 1-5 cm from the soil surface. Drying is possible in artificial dryers at a temperature of 40-50 ° C, under sheds, in attics with good ventilation, spreading a thin layer (3-5 cm). It is better to lay out the grass on a stretched mesh, gauze. In good weather, the raw material dries out in 5-7 days. According to existing requirements, the raw material should be represented by aerial stems with and without flowers, with leathery leaves, dark green above, shiny below, lighter, with slightly turned down edges. Stems are light green. There is no smell. Moisture should be no more than 14%, stems without leaves are allowed no more than 20% of the total mass of raw materials. The amount of crumbled leaves is not limited, mineral impurities are not more than 1%

Other types of periwinkle are not allowed, which have distinctive features: herbaceous periwinkle - leaves are round-ovate, thin, non-leather, purple corolla, fluffy periwinkle - leaves are sharp-ovate, heart-shaped at the base, azure flowers.

Microscopy. The cells of the upper and lower epidermis are sinuous-walled, partly clearly visible thickened. The stomata are paracytic, located only on the underside of the leaf. Along the main vein on the upper side of the leaf are unicellular thick-walled pointed hairs and small papillae along the edge of the leaf. The leaves have numerous straight, non-segmented lactifers with a greenish-yellow content. Numerous glands are visible on the petiole.

Fig.6. Microscopy of Periwinkle minor.

Epidermis of the upper (A) and lower (B) sides of the scaffold from the surface:

Epidermal cell, 2 - stomata, 3 - hairs, 4 - lactic,

Bead-like thickening of the cell wall; B - the edge of the leaf with succulent outgrowths; G - petiole epidermis; 1 - a piece of iron, 2 - a hair.

Chemical composition. The herb contains over 20 alkaloids of the indole group close in nature to reserpine, their total amount is 2% (vincamine, isovincamine, vincaminorine, minorine, vinine, pubescin, ervamine, etc.). The herb also contains triterpene saponins, vitamin C (993> mg%), rutin, carotene (8 mg%), tannins, organic acids (malic, succinic, ursolic), phytosterol, sugars and mineral salts, flavonoid glycoside - robinin.

hypertensive officinalis rauwolfia periwinkle

Standardization. The quality of raw materials is regulated by the requirements of VFS 42-1728-87

Pharmacological properties and preparations. The healing properties of periwinkle were known to Pliny and Dioscorides. In the Middle Ages, the periwinkle was considered a symbol of fidelity and constancy. Currently, the scope of the plant covers mainly therapeutic, obstetric-gynecological, dermatological diseases. The results of experimental studies of galenic preparations and individual alkaloids from various types of periwinkle made it possible to establish that most of them cause a decrease in blood pressure, expansion of the coronary vessels of the heart and brain vessels, relaxation of the muscles of the small intestine and stimulation of uterine contractions.

Vinkaton international name: Vincamine (Vincamine)

Group affiliation: vasodilator

Dosage form: coated tablets

Pharmacological action: herbal preparation, alkaloid vinca minor (Vinca minor L.), has hypotensive, antispasmodic and sedative effects. Improves cerebral and coronary circulation, oxygen supply to cells.

Increases mental performance, facilitates the process of memorization. Indications: arterial hypertension of the first and second type, condition after ischemic stroke, intracranial hypertension, neurogenic tachycardia; dizziness, decreased ability to concentrate, memory and intellectual abilities in elderly patients (cerebrovascular atherosclerosis, diabetic angiopathy, consequences of cerebrovascular accident, TBI); menopause in women; visual impairment, hearing impairment, vestibular and labyrinth disorders of vascular origin; absent-mindedness, speech impairment, impaired coordination of movements in mental illness (as part of combination therapy); migraine; slow development of intellectual abilities in children and adolescents.

Contraindications: hypersensitivity, arrhythmias, arterial hypotension, brain tumor, ischemic heart disease; pregnancy, lactation. Side effects: allergic reactions, skin rash, lowering blood pressure, tachycardia.

Dosage and administration: tablets inside, regardless of food intake, 20-40 mg 3 times a day for 10 days. The multiplicity can be increased up to 4 times a day, and the duration of treatment up to 30 days. A maintenance dose of 20 mg 1-2 times a day can be taken long-term. Syrup: adults 10-20 mg 3 times a day. Retard capsules: adults 30 mg 2 times a day. If necessary, intravenously drip or intramuscularly 15 mg 1-2 times a day. Children inside in the form of syrup, 5 mg 3 times a day; in / in drip or in / m - 7.5 mg 2 times a day.

Special instructions: care should be taken when prescribing to patients who have had a myocardial infarction, as well as to patients with arrhythmias.

Interaction: if necessary, can be used in combination with other antihypertensive drugs and antiplatelet agents (enhances the effect).

Vincapan. Foreign drug (Bulgaria), similar in composition and action to vinkanor. Contains a sum of vinca alkaloids (Vinca minor L.).

Used for spasms of cerebral vessels, neurogenic tachycardia, initial forms of hypertension.

Taken orally, starting with 0.005 g and then 0.01 g 2 to 3 times a day. After achieving a therapeutic effect, maintenance doses are individually selected. Children are prescribed starting from 0.0025 per day.

Release form: tablets of 0.01 g.

A similar foreign drug (Hungary) is produced under the name "Vinkaton" (Vincaton).

Cavinton. Cavinton is a semi-synthetic derivative of the alkaloid devincan contained in the periwinkle plant (Vinica minor L. and Vinca erecta Rgl. et Sschmalth); family kutrovye (Arosynaceae). Previously, it was found that extracts from periwinkle have a vasodilating and hypotensive effect, have some sedative effect. Vincamine alkaloid isolated from periwinkle (methyl ester of vincamic acid) was proposed for use (under the names "Devincan", "Minorin" - Devincan, Minorin) as a vasodilator. As a result of clinical studies, it was found that devincan is especially effective in cerebrovascular disorders, and later the drug Cavinton was created, which received the international name "Vinpocetine".

Cavinton dilates the vessels of the brain, increases blood flow, improves the supply of oxygen to the brain, and also promotes the utilization of glucose. By inhibiting phosphodiesterase, cavinton leads to accumulation of cAMP in tissues; reduces platelet aggregation. There is only a slight decrease in systemic arterial pressure. The vasodilating effect of Cavinton is associated with a direct relaxing effect on smooth muscles. Cavinton enhances the metabolism of norepinephrine and serotonin in the brain tissues, reduces pathologically increased blood viscosity, and contributes to the deformability of erythrocytes.

Cavinton is used for neurological and mental disorders associated with disorders of cerebral circulation (after a stroke , post-traumatic, atherosclerotic origin); with memory disorders, dizziness, aphasia, etc .; with hypertensive encephalopathy, vasovegetative symptoms in menopause, etc. In ophthalmic practice, Cavinton is prescribed for atherosclerotic and angiospastic changes in the retina and choroid, degenerative changes in the macula, secondary glaucoma associated with partial vascular thrombosis, etc. Cavinton is also effective in hearing loss of vascular or toxic (drug) origin and dizziness of labyrinthine origin.

Cavinton is taken orally in the form of tablets 1-2 tablets 3 times a day. Maintenance dose of Cavinton 1 tablet 3 times a day. Cavinton is used for a long time. Improvement is usually observed after 1 - 2 weeks; a course of treatment with Cavinton for about 2 months or more. Intravenous (only drip) Cavinton is used in neurological practice for acute focal ischemic disorders of cerebral circulation, in the absence of hemorrhage. Enter first 10 - 20 mg in 500 - 1000 ml of isotonic sodium chloride solution (drip infusion). If necessary, repeat (3 times a day) slow drip infusions are prescribed, then they switch to taking Cavinton inside. There is evidence of the use of Cavinton for the prevention of convulsive syndrome in children who have had a brain injury. Cavinton is administered intravenously at the rate of 8-10 mg/kg per day in a 5% glucose solution with the transition after 2-3 weeks to an oral dose of 0.5-1 mg/kg per day. Usually Cavinton is well tolerated. With intravenous administration of Cavinton, hypotension and tachycardia are possible.

Contraindications for the use of Cavinton: severe ischemic heart disease, severe arrhythmias; do not use during pregnancy. It is not recommended to prescribe Cavinton for labile blood pressure and low vascular tone. Caventon injection solution is incompatible with heparin. Do not inject Cavinton solution under the skin.

Cavinton release forms: tablets of 0.005 g in a package of 50 pieces; 0.5% solution in 2 ml ampoules.

Cavinton storage: list B. In a place protected from light (see attachments)

Some recipes. In case of hypertension, pour 1 cup of boiling water over 1 teaspoon of dry grass, keep in a steam bath for 15 minutes, cool the strain, half a cup a day. Pour 20 g of small periwinkle herb with flowers into 250 ml of vodka, heat in a water bath to a boil and immediately turn it off, leave for 10 minutes. Apply morning and evening 8-10 drops for 6 days, 1 day break and 6 more days. Such small courses must be completed at least 5.

For washing purulent wounds, ulcers and itchy dermatitis:
1 st. l dry grass brew in 1 cup boiling water, leave for half an hour, not boiling, cool, strain.

In homeopathy, an alcoholic tincture of the herb is used for headaches, nosebleeds, eczema, rashes on the face, as well as for coughs and mats (a skin disease on the head in which the hair sticks together in a tight lump).

Conclusion

Medicinal plants came to the twentieth century from ancient times and still occupy a significant place in the arsenal of medicinal products. Although chemical remedies continue to be an effective weapon of modern medicine and are now much more commonly used, they cannot completely replace herbal medicines. It is difficult, and more often almost impossible, to recreate the finest processes that take place in plants, different species of which, growing side by side, under the same conditions, create the most complex combinations of individual organic substances inherent only to them.

Attending physicians and pharmacists should pay special attention to the side effects caused by alkaloid-containing preparations of rauwolfia serpentine. Because the misuse of drugs containing the alkaloid reserpine and overdose have repeatedly caused poisoning, in some cases with a fatal outcome.

Turning off the sympathetic tone leads to the dominance of the parasympathetic system, hence the side effects:

) There may be disorders of the gastrointestinal tract, implemented by increased intestinal motility, intestinal spasms, hyperacid conditions, exacerbation of gastritis and peptic ulcer associated with the release of histamine.

) Due to the increased effects of histamine, patients experience swelling of the nasal mucosa and difficulty in nasal breathing.

) Taking reserpine may be accompanied by CNS depression, weakness, even the development of depressive states. Therefore, it is necessary to strictly clarify the anamnesis before prescribing the drug.

) Reducing the amount of catecholamines in the bronchi contributes to the development of bronchospasm in patients with bronchial asthma.

Vinca drugs are also effective, the main active principle of which is the alkaloid vincamine, which has a less pronounced hypotensive, but more significant sedative effect. They selectively improve the blood circulation of the brain, which improves the trophism and functional state of the centers, have a sedative effect and help slow down the pulse. Therefore, they are especially indicated in the initial stages of a disease that proceeds according to the cerebral variant; with tachycardia, they cannot be used to stop hypertensive crises, but they can be effectively used for prevention. And what is very important for patients, side effects are usually not observed.

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Kachalov A.A., Encyclopedic Dictionary of Medicinal, Essential Oil and Poisonous Plants. - M. - 1951.

Kuznetsova M.A., Medicinal plant raw materials and preparations, M.: Higher school. - 1987.

Mashkovsky M.D. Medicines. - 15th ed., revised, corrected. And extra. - M.: RIA New wave: Publisher Umerenkov, 2008. - 1206 p.

Muravieva D.A., Samylina I.A., Yakovlev G.P. - Pharmacognosy. M.: Medicine. - 2007. - 656s.

Pristupa A.A., Basic raw plants and their use. - L.: Science. - 1973.

Turishchev S.N., Phytotherapy, M.: Academy. - 2003. - 304 p.

Fedorov A.A., Kiryalov N.I., Resin-bearing plants of the USSR, p. Sat.: Plant raw materials of the USSR, T. 1. M. - L .: Academy of Sciences of the USSR. - 1950.

Shupinskaya M.D., Karpovich V.N., Pharmacognosy. State publishing house of medical literature. - 1963. - 368s.

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