The occurrence of orthostatic hypotension with the use of guanethidine is due. Octadin - a drug for the treatment of hypertension

Octadine is a synthetic medicine, which is used to treat the most common disease of the cardiovascular system - arterial hypertension.

Usually, the drug is prescribed to patients with severe forms of hypertension, so there are few reviews about it.

Before using the medicine, you should read the contraindications, side effects and the order of application. This information is presented in the instructions for the drug.

pharmachologic effect

It is a sympatholytic, has a hypotensive effect. It is able to accumulate in the granules of sympathetic nerve endings, reduce the amount of mediator entering the receptors, weaken or stop the transmission of nerve excitation. It has a short-term ganglion blocking, small beta2-adrenostimulating, and local anesthetic effect.

Reduces diastolic and systolic blood pressure, surpasses reserpine in the strength of the hypotensive effect, reduces myocardial contractility, heart rate and conductivity, has a cardiodepressive effect. At the beginning of therapy, a vasoconstrictor reaction (massive influx of norepinephrine into the nerve endings) may develop, which eventually gives way to persistent vasodilation.

When long-term use due to the gradual increase in IOC, the severity of the hypotensive effect may decrease. The ability of sympatholytics to cause water and sodium retention in the body partly reduces their hypotensive activity. During therapy, a decrease in glomerular filtration, renal, coronary and cerebral blood flow is possible.

The therapeutic effect develops 8 hours after a single dose, 1-3 weeks after multiple doses and continues for 1-3 weeks after drug withdrawal.

Indications for use

It is used as an antihypertensive (reducing blood pressure) facilities. It has a pronounced hypotensive effect.

With the correct selection of doses, it causes a decrease in blood pressure in patients with hypertension at different stages, incl. for severe forms with persistent and high pressure rise. Also used for glaucoma (increased intraocular pressure).

Mode of application

Hypertension is treated with oral pills. Doses are selected individually, based on the tolerance of the drug, general condition patient, stage of the disease, etc.

Therapy begins with a low dose of 10-12.5 mg per day. Over time, the dose is gradually increased (usually by 10-12.5 mg weekly).

As a rule, smaller doses are enough: up to 60 mg per day in severe cases and from 10 to 30 mg in lighter cases. Take a daily dose in the morning at one time. When it is possible to achieve therapeutic effect, proceed to the selection of a maintenance dose. The therapy is carried out for a long time.

It is recommended to start treatment with Octadin in a hospital (hospital). In outpatient settings, the drug is used carefully, with constant medical supervision. Individual fluctuations in the sensitivity of patients to Octadine are possible. For senile and elderly people, drugs are prescribed in smaller doses (from 6.25 mg per day with a gradual increase in the dose to 25-50 mg).

For patients with primary open-angle glaucoma, Octadin is instilled into the conjunctival sac, 1-2 drops of a 5% solution once or twice a day.

Release form, composition

The drug is available in the form of tablets or powder. The active ingredient is octadine.

Interaction with other drugs

Octadine is incompatible with MAO inhibitors (including selegiline, procarbazine, furazolidone): with the parallel use of guanethidine, hypertension can be observed - from moderate to severe - due to the release of catecholamines.

Ethanol, methotrimeprazine, alpha-blockers (labetalol, phentolamine, terazosin, doxazosin, tolazoline, phenoxybenzamine, prazosin), narcotic analgesics, barbiturates, rauwolfia alkaloids, drugs with alpha-adrenoceptor blocking drugs, dylotheroxidamine, dylotheroxidamine, dyrenoxydamines, eergotoxin , loxapine) and beta-blockers increase the risk of bradycardia and orthostatic hypotensive effects.

T ricyclic antidepressants, haloperidol, maprotiline, chlorpromazine, trimeprazine, amphetamines, anorexigenic drugs (except fenfluramine), loxapine, methylphenidate, thioxanthenes reduce the hypotensive effect.

Anticholinergic drugs (atropine, etc.) reduce the inhibitory effect on gastric acid production.

Doxepin, taken at a dose of up to 150 mg / day, does not affect the hypotensive effect.

NSAIDs (indomethacin, etc.) reduce the effect due to fluid and sodium retention in the body, suppression of Pg synthesis in the kidneys.

Enhances the effect of oral hypoglycemic agents and insulin (a change in the dosage regimen may be required).

Enhances the pressor effect of dobutamine, phenylephrine, epinephrine, norepinephrine, cocaine, dopamine and methoxamine, which can lead to the development of arrhythmias and arterial hypertension.

Estrogens can cause fluid retention in the body and reduce the hypotensive effect of the drug.

Minoxidil, fenfluramine and other antihypertensive drugs enhance (mutually) the effect.

Sympathomimetic drugs (dobutamine, ephedrine, methoxamine, norepinephrine, phenylpropanolamine, cocaine, dopamine, epinephrine, metaraminol, phenylephrine) reduce the effect.

Side effects

Treatment with Octadin can cause the following undesirable reactions: general weakness, dizziness, adynamia (decreased range of motion), vomiting, swelling of the nasal mucosa, nausea, pain in the parotid gland, tissue fluid retention, diarrhea (due to increased intestinal peristalsis).

Increase in daily fluctuations in blood pressure is possible.

Often the hypotensive effect of the drug is accompanied by the appearance of orthostatic hypotension (a decrease in blood pressure during the transition to vertical position from horizontal), in some cases orthostatic collapse occurs (a sharp drop in blood pressure when moving to a vertical position from a horizontal one).

This usually happens in the first weeks of therapy. To prevent collapse, the patient should be in a horizontal position for 30 minutes to 2 hours after taking the medicine. Changing the position of the body from horizontal to vertical should be very slow. Some cases require dose reduction.

Overdose

It is characterized by an excessive decrease in blood pressure. It is treated by gastric lavage, the appointment of activated charcoal, giving a person a horizontal position with raised legs, the appointment of vasoconstrictor and antiarrhythmic drugs, anti-shock measures.

For diarrhea, anticholinergic drugs are prescribed, symptomatic treatment, electrolyte balance and fluid volume are monitored.

Contraindications

Acute circulatory disorders of the brain, pronounced atherosclerosis, hypotension (low blood pressure), myocardial infarction, severe renal failure.

In adrenal tumor (pheochromocytoma), Octadin is contraindicated, because at the beginning of action, the drug can cause an increase in pressure. The drug should not be administered concurrently with ephedrine, aminazine, tricyclic antidepressants.

In people who received MAO inhibitors, a break of 2 weeks should be taken before taking Octadine. Patients subject to surgical intervention, you need to stop taking the medicine a few days before the operation.

Patients with glaucoma with a narrow and closed chamber angle are not prescribed the drug, since this is fraught with the onset of an increase in ophthalmotonus (pressure exerted on the outer shell eyeball its contents). When acute glaucoma Octadine is not used.

During pregnancy

Not prescribed.

Terms, storage conditions

Storage of Octadin requires a dry place, out of the reach of children and protected from light. In such conditions, the drug can be stored for up to five years.

Price

In Russian pharmacies Octadin has not been presented to date.

On the territory of Ukraine the drug is also not sold.

Analogs

On the advice of a doctor, the drug can be replaced by the following drugs: Guanethidine sulfate, Declidin, Ipoctal, Isobarine, Azetidine, Guanexil, Visutencil, Ophthalmotonil, Pressedin, Ismelin, Abapressin, Guanisol, Iporal, Antipres, Eutenzol, Ipoginanine, Octotensin, Sanotensin.

Gross formula

C 10 H 22 N 4

Pharmacological group of substance Guanethidine

CAS code

55-65-2

Application during pregnancy and lactation

Typical clinical and pharmacological article 1

Pharmaceutical action. Sympatholytic, has a hypotensive effect. It accumulates in the granules of sympathetic nerve endings, reduces the amount of mediator entering the receptors, as a result of which the transmission of nerve excitation is weakened or stopped. It has a short-term ganglion-blocking and small beta 2 -adrenostimulating and local anesthetic effect. It causes a decrease in systolic and diastolic blood pressure, in terms of the strength of the hypotensive effect it is superior to reserpine, it has a cardiodepressant effect, reduces myocardial contractility, conduction and heart rate (thus, a decrease in blood pressure is due to both a decrease in the systemic vascular resistance and IOC). At the beginning of treatment (sometimes up to several hours), a vasoconstrictor reaction may develop (massive inflow of norepinephrine into the nerve endings), which is then replaced by persistent vasodilation. With long-term use, it is possible to reduce the severity of the hypotensive effect due to the gradual increase in IOC. The ability of sympatholytics, as well as other vasodilators, to cause retention of Na + and water in the body partly reduces their hypotensive activity. During treatment, a decrease in coronary, cerebral and renal blood flow, and glomerular filtration is possible. The therapeutic effect after a single dose develops after 8 hours, after multiple doses - after 1-3 weeks and lasts 1-3 weeks after discontinuation of the drug.

Pharmacokinetics. Absorption with prolonged ingestion is 3-30%. Bioavailability varies dramatically due to the different severity of the "first pass" effect. It practically does not bind to plasma proteins, however, being fixed for a long time at the endings of the sympathetic nerves, it has a large T 1/2 (96-190 h), which can increase almost 2 times in chronic renal failure in the terminal stage. Poorly penetrates the BBB. It is found in small quantities in breast milk... Approximately half metabolized in the liver. Metabolites are pharmacologically practically inactive. It is excreted mainly by the kidneys (25-50% - unchanged).

Indications. Arterial hypertension of moderate and severe severity (including renal origin, including secondary hypertension with pyelonephritis, renal amyloidosis, renal artery stenosis).

Contraindications. Hypersensitivity, recent myocardial infarction, unstable angina, acute disturbance of cerebral circulation, pregnancy, lactation.

Carefully. Atherosclerosis of the coronary and cerebral arteries; Ischemic heart disease, exertional angina, sinus bradycardia, not associated with hypertension, CHF, renal failure, broncho-obstructive syndrome, bronchial asthma history, gastric ulcer and 12 duodenal ulcer in history, diarrhea, liver failure, hyperthermia, diabetes, pheochromocytoma, previous treatment with MAO inhibitors, advanced age.

Dosing. Inside.

Adults. Outpatients: the initial dose is 10-12.5 mg once a day, preferably in the morning. If the hypotensive effect is insufficient, the dose is gradually increased by 10-12.5 mg every 5-7 days until the desired therapeutic effect is obtained. The average recommended dose is 30-75 mg / day. With stabilization of blood pressure, the dose is gradually reduced to the minimum effective dose. The maintenance dose is 25-50 mg once a day.

Hospital patients: the initial dose is 25-50 mg once a day, to achieve the required therapeutic effect, the dose is increased by 25-50 mg daily or every other day under the control of blood pressure.

Children: 0.2 mg / kg (or 6 mg / m2) once a day; the dose is increased by 0.2 mg / kg (or 6 mg / m2) every 7-10 days under the control of blood pressure.

Side effect. From the CVS: orthostatic hypotension, stress collapse (decrease in blood pressure during exercise), bradycardia, angina pectoris.

From the side nervous system: excessive fatigue or weakness, headache, dizziness, fainting.

From the respiratory system: nasal congestion, pulmonary edema.

From the side digestive system: dryness of the oral mucosa, nausea, vomiting, diarrhea, increased intestinal motility. Others: peripheral edema, nocturia, blurred vision, hair loss, myalgia, tremor, skin rash, reversible ejaculation disorder (while maintaining potency).

Overdose. Symptoms: excessive decrease in blood pressure.

Treatment: gastric lavage, appointment activated carbon, giving the patient a supine position with raised legs, anti-shock measures, prescribing antiarrhythmic, vasoconstrictor drugs; with diarrhea - the appointment of anticholinergic drugs; symptomatic therapy, control of fluid volume and electrolyte balance.

Interaction. Incompatible with MAO inhibitors (including with furazolidone, procarbazine, selegiline): with simultaneous use with guanethidine hypertension may occur - from moderate to severe - due to the release of catecholamines (it is recommended to cancel MAO inhibitors for at least 1 week before starting guanethidine therapy ).

Ethanol, barbiturates, methotrimeprazine, narcotic analgesics, alpha-blockers (doxazosin, labetalol, phenoxybenzamine, phentolamine, prazosin, terazosin, tolazoline), drugs with alpha-adrenoceptor blocking activity (including dyloxidroxidamine, digidrgidine phenothiazines, thioxanthenes), beta-blockers, rauwolfia alkaloids increase the risk of orthostatic hypotensive effects and bradycardia.

Amphetamines, tricyclic antidepressants, anorexigenic drugs (with the exception of fenfluramine), haloperidol, loxapine, maprotiline, methylphenidate, chlorpromazine, thioxanthenes, trimeprazine reduce the hypotensive effect due to the displacement of guanethidine from adrenergic neuron uptake by these neurons and suppression of it.

Doxepin in doses up to 150 mg / day does not affect the hypotensive effect.

Anticholinergic drugs (atropine, etc.) reduce the inhibitory effect on gastric acid secretion.

Enhances the effect of insulin and oral hypoglycemic drugs due to their displacement from the sites of binding to serum proteins (dosage adjustment may be required).

NSAIDs (indomethacin, etc.) reduce the effect as a result of suppression of Pg synthesis in the kidneys and retention of Na + and fluid in the body.

Estrogens can cause fluid retention in the body, thereby reducing the hypotensive effect of guanethidine.

Fenfluramine, minoxidil and other antihypertensive drugs enhance (mutually) the effect (correction of the dosage regimen may be required).

Sympathomimetic drugs (cocaine, dobutamine, dopamine, ephedrine, epinephrine, methoxamine, metaraminol, norepinephrine, phenylephrine, phenylpropanolamine) reduce the effect.

Enhances the pressor effect of cocaine, dobutamine, dopamine, epinephrine, methoxamine, norepinephrine, phenylephrine due to the suppression of their capture by adrenergic neurons, which can lead to the development of arterial hypertension and arrhythmias.

Special instructions. During treatment, blood pressure should be constantly monitored at periodic intervals. The hypotensive effect of guanethidine is especially pronounced in the standing position. Measurement of blood pressure is recommended in the "supine" position after standing for 10 minutes and immediately after physical exercise... The dose should be increased only when the blood pressure in the "standing" position does not decrease in comparison with the previous values. The dose is reduced in case of excessive orthostatic hypotension, normal blood pressure in the supine position, and severe diarrhea.

Hospitalized patients can be discharged only after determining the effect of guanethidine on their blood pressure in the "standing" position.

With prolonged use, tolerance to the drug may develop due to fluid retention and an increase in plasma volume. In these cases, the simultaneous administration of diuretic drugs is recommended.

MAO inhibitors should be canceled at least 1 week before starting treatment.

Before surgery, the surgeon or anesthesiologist must be informed in advance that the patient is taking guanethidine. In emergency operations, atropine is prescribed to prevent excessive bradycardia.

To avoid orthostatic hypotension, caution should be exercised when moving abruptly to an upright position from a lying or sitting position, prolonged standing, exercising, and in hot weather.

If the body temperature rises, it is necessary to inform the doctor (the dosage regimen may need to be adjusted).

State Register of Medicines. Official edition: in 2 volumes - M .: Medical Council, 2009. - V.2, part 1 - 568 p .; Part 2 - 560 p.

Guanethidine
Chemical compound
IUPAC	2- (2-azocan-1-ylethyl) guanidine
Gross formula	C 10 H 22 N 4
Mol. weight	198.309 g / mol
CAS
PubChem
DrugBank
Classification
Farm. Group	Sympatholytic
ATX
Pharmacokinetics
Half-life		36 hours
Dosage forms
powder; tablets of 0.025 g (25 mg)
Trade names
Abapressin, Isobarin, Ismelin, Sanotensin, Abapressin, Antipres, Azetidin, Declidin, Eutensol, Guanethidini sulfas, Guanexil, Guanisol, Ipoctal, Ipoguanin, Iporal, Ismelin, Isobarin, Octatenzine, Presaltalmotonsedin, others.

Octadine (Octadinum, b- (N-Azacyclooctyl) -ethylguanidine sulfate) is a drug of the sympatholytic group. It is used to treat hypertension.

general information

The sympatholytic effect of octadine is due to the fact that it selectively accumulates in the granules of sympathetic nerve endings and displaces the adrenergic mediator norepinephrine from them. Part of the released mediator reaches postsynaptic a-adrenergic receptors and has a short-term pressor effect, but the main part of the mediator is destroyed under the influence of axonal monoamine oxidase. As a result of depletion of norepinephrine reserves in adrenergic endings, the transmission of nervous excitation to them is weakened or stopped.

Violation of the transmission of nervous excitement is associated, in addition, with the fact that, accumulating in the nerve endings, octadine has a local anesthetic effect on them. On cardiovascular system octadine affects in two phases: first, a transient pressor reaction develops with tachycardia and an increase cardiac output, then there is a progressive decrease in systolic and diastolic blood pressure, the heart rate, minute volume and pulse pressure decrease, and later (2-3 days after oral administration) persistent hypotension occurs. The initial pressor reaction can last up to several hours. With prolonged use of the drug, the hypotensive effect may decrease due to a gradual increase in cardiac output.

Octadine is used as an antihypertensive agent. The drug has a strong hypotensive effect and, with the correct selection of doses, can cause a decrease in blood pressure in patients with hypertension at various stages, including severe forms with high and persistent pressure.

Octadine is effective when taken orally. Absorbed slowly. The hypotensive effect in hypertension develops gradually; it begins to manifest itself 2-3 days after the start of taking the drug, reaches a maximum on the 7-8th day of treatment, and after stopping the intake it continues for another 4-14 days. The drug causes a decrease in heart rate, a decrease in venous pressure, and in some cases, peripheral resistance. At the beginning of treatment, a decrease in the filtration function of the kidneys and renal blood flow is possible, however, with further treatment and a persistent decrease in blood pressure, these indicators level out (N.A.Ratner et al.).

For the treatment of hypertension, octadine is prescribed orally in the form of tablets. Doses should be selected individually, depending on the stage of the disease, the general condition of the patient, the tolerability of the drug, etc. Start with a small dose - 0.01-0.0125 g (10-12.5 mg) 1 time per day, then the dose gradually increase (usually weekly by 10-12.5 mg) to 0.05-0.075 g per day. Usually smaller doses are sufficient: in severe cases up to 60 mg per day, in lighter cases - 10-30 mg. The daily dose can be taken in 1 dose (in the morning). After the therapeutic effect is achieved, an individual maintenance dose is selected. The treatment is carried out for a long time.

It is preferable to start treatment with octadine in a hospital. In outpatient settings, the drug should be used with caution, with constant medical supervision. It is necessary to take into account the possibility of individual fluctuations in the sensitivity of patients to octadine.

Sick elderly and old age the drug is prescribed in smaller doses, starting from 6.25 mg (1/4 tablet) 1 time per day, then gradually increasing the dose by 6.25 mg to a daily dose of 25-50 mg.

Side effect

Dizziness, general weakness, weakness, nausea, vomiting, swelling of the nasal mucosa, pain in the parotid gland, diarrhea (due to increased intestinal motility due to suppression of the influence of sympathetic innervation), tissue fluid retention. Daily fluctuations in blood pressure may increase. The hypotensive effect of the drug is often accompanied by the development of orthostatic hypotension, in some cases orthostatic collapse is possible (especially in the first weeks of treatment). To prevent collapse, patients should be in a horizontal position within 1.5-2 hours after taking the drug and slowly move from a lying position to a standing position; in some cases it is necessary to reduce the dose.

Before the advent of new antihypertensive drugs (clonidine, b-blockers, etc.), octadine was one of the main drugs for the treatment of hypertension. However, even now it has not lost its significance and is being used, especially in severe forms of arterial hypertension. The drug has a long-term effect. Side effects can be reduced by choosing the right dose. Diarrhea can be relieved by taking anticholinergic drugs. Octadine can be administered together with other antihypertensive drugs (reserpine, apressin, diuretics); simultaneous use with diuretics enhances the hypotensive effect and prevents fluid retention in tissues. When combined use with other drugs, the dose of octadine is reduced.

Contraindications

Severe atherosclerosis, acute cerebrovascular accident, myocardial infarction, hypotension, severe renal failure. Octadine should not be prescribed for pheochromocytoma, since at the beginning of the action, the drug can cause an increase in blood pressure. Octadine should not be administered concurrently with tricyclic antidepressants: chlorpromazine, ephedrine. In patients receiving MAO inhibitors, a break of 2 weeks should be taken before taking octadine. Patients subject to surgery should stop taking the drug a few days before surgery.

In ophthalmic practice, octadine is sometimes used for instillation into the conjunctival sac (1-2 drops of a 5% solution 1-2 times a day) for primary open-angle glaucoma. The drug causes moderate miosis, facilitates the outflow of aqueous humor, reduces its production and lowers intraocular pressure. Unlike cholinomimetic substances (pilocarpine, etc.), octadine does not affect accommodation; less impairment of visual acuity and the ability of patients to see in poor light. In patients with a closed and narrow chamber angle, octadine is not used, since an increase in ophthalmotonus may occur. In acute glaucoma, the drug is not indicated.

Physical properties

White crystalline powder of bitter taste. Let's slightly dissolve in water.

Release form

Method of production: powder; tablets of 0.025 g (25 mg).

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Excerpt Characterizing Guanethidine

And this one passed with a cart. This was followed by cheerful and, apparently, drunk soldiers.
“How can he, my dear man, blaze with a butt in the very teeth…” said one soldier in a high-tucked greatcoat, waving his hand widely.
- That is it, that sweet ham. - answered the other with a laugh.
And they passed, so that Nesvitsky did not recognize who had been hit in the teeth and what the ham belonged to.
- Ek are in a hurry that he let the cold one, you think so, they will kill everyone. Said the non-commissioned officer angrily and reproachfully.
- As it flies past me, uncle, the core is that, - said, barely holding back from laughing, with a huge mouth, a young soldier - I just died out. Really, by God, I was so frightened, trouble! Said the soldier, as if bragging that he was frightened. And this one passed. He was followed by a wagon unlike any that had passed before. It was a steam-powered German foreskin, which seemed to be loaded with a whole house; behind the foreskin, which the German was carrying, was tied to a beautiful, motley, with a huge udder, cow. A woman sat on the feather beds with baby, an old woman and a young, crimson-faced, healthy German girl. Apparently, these evicted residents were allowed through by special permission. The eyes of all the soldiers turned to the women, and as the carriage passed, moving step by step, and all the soldiers' remarks referred to only two women. On all faces there was almost the same smile of obscene thoughts about this woman.
- Look, the sausage is also removed!
“Sell your mother,” another soldier said, striking on the last syllable, addressing the German, who, with his eyes downcast, walked angrily and frightenedly with a wide step.
- Ek got away like! Then the devils!
“I wish you could stand by them, Fedotov.
- We did, brother!
- Where are you going? Asked the infantry officer, who was eating an apple, also half smiling and looking at the beautiful girl.
The German closed his eyes and showed that he did not understand.
“If you want, take it for yourself,” the officer said, giving the girl an apple. The girl smiled and took it. Nesvitsky, like everyone else on the bridge, did not take his eyes off the women until they passed. When they passed, the same soldiers were walking again, with the same conversations, and finally everyone stopped. As is often the case, at the exit of the bridge, the horses in the company carriage got stuck, and the whole crowd had to wait.
- And what do they become? There is no order! - said the soldiers. - Where are you going? Damn! There is no way to wait. Even worse will be how he sets fire to the bridge. You see, they've pinned the officer too, - said the stopped crowds from different sides, looking at each other, and they all huddled forward towards the exit.
Looking back under the bridge at the Ens water, Nesvitsky suddenly heard a sound that was still new for him, rapidly approaching ... something big and something plopping into the water.
- Look where he is! - Sternly said a soldier standing nearby, looking around at the sound.
“Encourages us to pass it quickly,” said the other uneasily.
The crowd started again. Nesvitsky realized that this was the core.
- Hey, Cossack, give me a horse! - he said. - Well you! stay away! step aside! road!
With great effort he reached the horse. Without ceasing to scream, he started forward. The soldiers shrugged to give him way, but again pressed on him so that they crushed his leg, and the nearest ones were not to blame, because they were pressed even harder.
- Nesvitsky! Nesvitsky! You, g "ozhha!" - a hoarse voice was heard from behind.
Nesvitsky looked around and saw, fifteen paces away, separated from him by a living mass of moving infantry red, black, shaggy, wearing a cap on the back of his head and valiantly draped over his shoulder Vaska Denisov.
- Tell them, why "tam, devils, give the dog" ogu, - shouted. Denisov, apparently in a fit of fervor, shining and moving his eyes, black as coal, in inflamed squirrels and waving a saber that was not drawn from its scabbard, which he held with his bare little hand as red as his face.
- Eh! Vasya! - answered Nesvitsky happily. - What are you?
- The squadron "onu pg" cannot be walked, - shouted Vaska Denisov, angrily opening his white teeth, spurring his handsome black, blooded Bedouin, who, blinking his ears from the bayonets, which he stumbled upon, snorting, splashing around him with foam from the mouthpiece, ringing, kicked the planks of the bridge with his hooves and seemed ready to jump over the railing of the bridge, if the rider would allow him. - What is it? like a bug "any! exactly the same bug" ana! Pg "oh ... give me a dog" oh! ... Stay there! you a cart, chog "t! saber exiled" I will kill! - he shouted, really taking out his saber bald and starting to wave it.
The soldiers with frightened faces pressed against each other, and Denisov joined Nesvitsky.
- Why are you not drunk today? - Nesvitsky said to Denisov when he drove up to him.
"And they won't let you get drunk!" Answered Vaska Denisov. "All day long, they drag a regiment here and there. Dg" fuck - so go. "And then chog" t knows what it is!
- What a dandy you are today! - Looking at his new mentik and saddle cloth, said Nesvitsky.
Denisov smiled, took out a handkerchief from the tashka, spreading the smell of perfume, and thrust it into Nesvitsky's nose.
- I can't, I'm going into business! vyg "washed, cleaned his teeth and perfumed.
The dignified figure of Nesvitsky, accompanied by the Cossack, and the decisiveness of Denisov, waving his saber and desperately shouting, acted in such a way that they squeezed over to the other side of the bridge and stopped the infantry. Nesvitsky found a colonel at the exit, to whom he had to convey the order, and, having fulfilled his order, drove back.
Having cleared the road, Denisov stopped at the entrance to the bridge. Casually restraining the stallion rushing to his own and kicking, he looked at the squadron moving towards him.
The transparent sounds of hooves were heard along the planks of the bridge, as if several horses were galloping, and the squadron, with officers in front of four in a row, stretched out across the bridge and began to go out to the other side.
The stopped infantry soldiers, crowding in the mud trampled down by the bridge, with that particular malevolent feeling of aloofness and ridicule, with which various types of troops are usually encountered, looked at the clean, dapper hussars who were gracefully passing by them.
- Smart guys! If only to Podnovinskoe!
“What's the use of them! Only for show and drive! - said another.
- Infantry, no dust! - joked the hussar, under which the horse, playing, splashed mud at the infantryman.
- I would have chased you off with a knapsack two, the laces would have worn out, - the infantryman said, wiping the dirt off his face with his sleeve; - and then not a man, but a bird sitting!
“That would have put you on a horse, Zikin, if you were dexterous,” the corporal joked over the thin soldier twisted from the weight of his knapsack.
- Take a club between your legs, here's a horse for you, - replied the hussar.

1 tablet contains 10 or 25 mg of guanethidine sulfate (β-guanidine sulfate).

Pharmacodynamics of the drug:

ismelin has a selective inhibitory effect on the transmission of excitation in the terminal branches of the sympathetic part of the autonomic nervous system, without limiting the activity of its parasympathetic part. Ismelin does not affect

CNS and has no sedative effect. Ismelin causes an intense, persistent and long-term hypotensive effect.

Pharmacokinetics of the drug GUANETIDINE MONOSULFATE:

when taking guanethidine sulfate by mouth

35-50% of the dose is slowly resorbed from the gastrointestinal tract. Guanethidine is extensively metabolized in the liver. In patients with high blood pressure, but without renal pathology, the highest concentration of unchanged guanethidine in plasma (approximately 24 ng / ml) was observed 2-4 hours after a single oral ingestion of 41 mg of guanethidine base. After absorption, guanethidine accumulates in tissues, and especially in tissues with well-developed adrenergic innervation. Active substance the drug does not bind to serum proteins. Within 3 days, 35% of a single dose is excreted in the urine, approximately 1/3 of guanethidine in unchanged form and 2/3 in the form of inactive metabolites. Only traces of guanethidine were found in the bile. Repeated administration leads to the accumulation of the drug in the blood plasma. After discontinuation of ismelin, the half-life of unchanged guanethidine is approximately 1.5 days.

In patients with high blood pressure and renal failure (creatinine clearance within 10-20 ml / min), guanethidine is excreted in the urine much more slowly, as a result of which, despite intensive metabolism, the drug is accumulated to a greater extent.

Indications for the use of the drug:

middle and extreme stages of essential, renal and malignant hypertensionwhen other antihypertensive drugs do not provide an adequate therapeutic effect.

Ismelin is desirable to prescribe as adjunctive therapy in combination with other antihypertensive drugs (for example, with diuretics).

Dosage of the medicinal product:

the dose of ismelin should be selected individually, and the smallest, but still quite effective dose should be adhered to. Blood pressure is measured to the patient both in a standing position and after physical activity... The daily dose can be taken in 1 dose, preferably in the morning.

In clinical practice, it is recommended to adhere to the following scheme - at the beginning of therapy, 1 tablet of 10 mg per day is sufficient. The daily dose is increased by 10 mg at intervals of about 1 week until the desired decrease in blood pressure is achieved (the usual daily dose is 30-75 mg). In hospitalized patients under constant medical supervision, the initial dose may be higher and can be increased at shorter intervals.

When combining ismelin with other antihypertensive drugs, for example, diuretics, the dose of ismelin can be reduced.

Contraindications:

pheochromocytoma, as well as previous treatment with MAO inhibitors, since it is possible to release a large amount of catecholamines, which, under certain circumstances, can cause a temporary, but very sharp increase

HELL. MAO inhibitors should be discontinued at least one week before starting treatment with ismelin.

Caveats:

with coronary sclerosis, sclerosis of cerebral vessels and severe renal failure it is necessary to avoid a sharp decrease in blood pressure. The drug should be prescribed with caution to patients with a history of gastrointestinal ulcers.

Alcohol enhances the hypotensive effect of ismelin.

Before surgery, the surgeon or anesthesiologist should be informed in advance that the patient is taking Ismelin, since it may be necessary to discontinue the drug for several days before the operation. For premedication in emergency operations to prevent excessive bradycardia, atropine can be prescribed.

Pregnancy and breastfeeding:

in the first trimester of pregnancy, ismelin should be prescribed only on strict indications. The active substance of the drug ismelin penetrates into breast milk, but in minimal amounts safe for the child.

Side effect:

postural disorders after getting up suddenly or exerting themselves; bradycardia, diarrhea, fatigue, dizziness, nasal congestion, tendency to salt and water retention. Sometimes ismelin suppresses ejaculation, however, potency remains.

Interaction with other medicines:

the appointment of ismelin against the background of previous treatment with MAO inhibitors can cause a temporary, but very sharp increase in blood pressure. With the simultaneous appointment of tricyclic antidepressants, amphetamine and phenothiazine, the hypotensive effect of ismelin may decrease.

The sympathomimetic effects of such vasoactive substances as ephedrine, norephedrine and phenylephrine, which are part of ophthalmic and antitussive drugs, as well as nasal agents, may be more pronounced in patients taking ismelin (increased blood pressure, cardiac arrhythmia).

Drug overdose:

symptoms - postural hypotension, collapse, bradycardia, diarrhea.

Treatment - in case of signs of postural hypotension, the patient should be placed with his legs raised high and measures should be taken to stop hypovolemia. With insufficient increase in blood pressure

despite the increase in BCC, the careful use of vasoactive substances is allowed. For diarrhea, an anticholinergic agent (for example, antrenyl) is prescribed, and for severe bradycardia, atropine.

Release form of the drug GUANETIDINE MONOSULFATE:

40 white tablets (10 mg) or 30 red tablets (25 mg) per pack.

pharmachologic effect

A sympatholytic agent that inhibits the transmission of excitation from adrenergic neurons. Selectively accumulates in the granules of sympathetic postganglionic nerve endings and displaces norepinephrine from them. Part of the released norepinephrine reaches postsynaptic alpha-adrenergic receptors and has a short-term pressor effect, but the main part is inactivated by MAO. As a result of depletion of norepinephrine reserves in adrenergic endings, the transmission of nervous excitation to them is weakened or stopped. Guanethidine has a short-term ganglion blocking effect and some stimulating effect on beta2-adrenoreceptors. Virtually no effect on the level of catecholamines in the central nervous system and the adrenal medulla. The hypotensive effect of guanethidine develops in two phases. Initially, a transient pressor reaction occurs, accompanied by tachycardia and an increase in cardiac output, then a gradually developing persistent decrease in systolic and diastolic blood pressure, a decrease in heart rate and minute volume occurs. By inhibiting the adrenergic innervation of the PS, guanethidine enhances intestinal motility. The drug causes miosis (constriction of the pupil) and reduces IOP by improving the outflow from the anterior chamber of the eye and reducing the production of intraocular fluid. Does not affect accommodation.

Indications

primary open-angle glaucoma.

Application

When taken orally, the initial dose is 10-12.5 mg 1 r / day, then the dose is gradually increased to 50-75 mg / day. After achieving a therapeutic effect, an individual maintenance dose is selected. For elderly and senile patients, the initial dose is 6.25 mg 1 r / day, then the dose is gradually increased to 25-50 mg / day. Locally apply 1-2 drops in the lower conjunctival sac of each eye 1-2 r / day. Guanethidine is used with caution in patients with coronary artery disease, IUD, recent MI, sinus bradycardia, diabetes mellitus, diarrhea, asthma, peptic ulcer, impaired liver function. In the case of the alleged surgical intervention you should stop taking guanethidine a few days before surgery. It should be borne in mind that an increase in body temperature can lead to an increase in the hypotensive effect of guanethidine. Therefore, in diseases accompanied by hyperthermia, it is necessary to reduce the dose of guanethidine.

Side effects

Orthostatic hypotension, orthostatic collapse, bradycardia, dry mouth, diarrhea, nausea, vomiting, dizziness, weakness, fatigue, depression, swelling of the nasal mucosa, pain in the area parotid gland, edema, decreased ejaculation, anemia, thrombocytopenia, leukopenia, myalgia, muscle tremor, paresthesia, hair loss, impaired urination, exacerbation of asthma and peptic ulcers. When topical application possible conjunctival hyperemia, miosis, burning sensation, ptosis, superficial punctate keratitis (with prolonged use of concentrated solutions).