inotropic drugs. Classification and mechanism of action of inotropic drugs

Heart - plentiful innervated organ. Among the sensitive formations of the heart, two populations of mechanoreceptors, concentrated mainly in the atria and left ventricle, are of primary importance: A-receptors respond to changes in the tension of the heart wall, and B-receptors are excited when it is passively stretched. Afferent fibers associated with these receptors are part of the vagus nerves. Free sensory nerve endings, located directly under the endocardium, are the terminals of afferent fibers that pass through the sympathetic nerves.

Efferent innervation of the heart carried out with the participation of both departments of the autonomic nervous system. The bodies of sympathetic preganglionic neurons involved in the innervation of the heart are located in gray matter lateral horns of the three upper thoracic segments spinal cord. Preganglionic fibers are sent to the neurons of the upper thoracic (stellate) sympathetic ganglion. Postganglionic fibers of these neurons along with parasympathetic fibers vagus nerve form the upper, middle and lower cardiac nerves. Sympathetic fibers permeate the entire organ and innervate not only the myocardium, but also elements of the conduction system.

The bodies of parasympathetic preganglionic neurons involved in innervation of the heart, located in medulla oblongata. Their axons are part of the vagus nerves. After the vagus nerve enters the chest cavity, branches depart from it, which are included in the composition of the cardiac nerves.

The processes of the vagus nerve, passing through the cardiac nerves, are parasympathetic preganglionic fibers. From them, excitation is transmitted to intramural neurons and then - mainly to the elements of the conduction system. The influences mediated by the right vagus nerve are addressed mainly to the cells of the sinoatrial node, and the left - to the cells of the atrioventricular node. The vagus nerves do not have a direct effect on the ventricles of the heart.

Innervating pacemaker tissue, autonomic nerves are able to change their excitability, thereby causing changes in the frequency of generation of action potentials and heart contractions ( chronotropic effect ). Nervous influences change the rate of electrotonic transmission of excitation and, consequently, the duration of the phases of the cardiac cycle. Such effects are called dromotropic.

Since the action of mediators of the autonomic nervous system is to change the level of cyclic nucleotides and energy metabolism, autonomic nerves in general are able to influence the strength of heart contractions ( inotropic effect). Under laboratory conditions, the effect of changing the value of the excitation threshold of cardiomyocytes under the action of neurotransmitters was obtained, it is designated as bathmotropic.

Listed pathways of the nervous system on the contractile activity of the myocardium and the pumping function of the heart are, although extremely important, modulating influences secondary to myogenic mechanisms.

Training video of the innervation of the heart (nerves of the heart)

Adrenalin. This hormone is formed in the adrenal medulla and adrenergic nerve endings, is a direct-acting catecholamine, causes stimulation of several adrenergic receptors at once: a 1 -, beta 1 - and beta 2 - Stimulation a 1-adrenergic receptors is accompanied by a pronounced vasoconstrictor effect - a general systemic vasoconstriction, including precapillary vessels of the skin, mucous membranes, kidney vessels, as well as a pronounced narrowing of the veins. Stimulation of beta 1 -adrenergic receptors is accompanied by a distinct positive chronotropic and inotropic effect. Stimulation of beta 2 -adrenergic receptors causes bronchial dilatation.

Adrenalin often indispensable in critical situations, since it can restore spontaneous cardiac activity during asystole, increase blood pressure during shock, improve the automatism of the heart and myocardial contractility, increase heart rate. This drug stops bronchospasm and is often the drug of choice for anaphylactic shock. It is used mainly as a first aid and rarely for long-term therapy.

Solution preparation. Adrenaline hydrochloride is available as a 0.1% solution in 1 ml ampoules (diluted 1:1000 or 1 mg/ml). For intravenous infusion, 1 ml of a 0.1% solution of epinephrine hydrochloride is diluted in 250 ml of isotonic sodium chloride solution, which creates a concentration of 4 μg / ml.

Doses for intravenous administration:

1) in any form of cardiac arrest (asystole, VF, electromechanical dissociation), the initial dose is 1 ml of a 0.1% solution of adrenaline hydrochloride diluted in 10 ml of isotonic sodium chloride solution;

2) when anaphylactic shock and anaphylactic reactions - 3-5 ml of a 0.1% solution of adrenaline hydrochloride diluted in 10 ml of isotonic sodium chloride solution. Subsequent infusion at a rate of 2 to 4 mcg / min;

3) with persistent arterial hypotension, the initial rate of administration is 2 μg / min, if there is no effect, the rate is increased until the required level of blood pressure is reached;

4) action depending on the rate of administration:

Less than 1 mcg / min - vasoconstrictor,

From 1 to 4 mcg / min - cardiostimulating,

5 to 20 mcg/min - a- adrenostimulating,

More than 20 mcg / min - the predominant a-adrenergic stimulant.

Side effect: adrenaline can cause subendocardial ischemia and even myocardial infarction, arrhythmias and metabolic acidosis; small doses of the drug can lead to acute renal failure. In this regard, the drug is not widely used for long-term intravenous therapy.

Norepinephrine . Natural catecholamine, which is the precursor of adrenaline. It is synthesized in the postsynaptic endings of the sympathetic nerves and performs a neurotransmitter function. Norepinephrine stimulates a-, beta 1 -adrenergic receptors, almost no effect on beta 2 -adrenergic receptors. It differs from adrenaline in a stronger vasoconstrictor and pressor action, less stimulating effect on automatism and contractile ability of the myocardium. The drug causes a significant increase in peripheral vascular resistance, reduces blood flow in the intestines, kidneys and liver, causing severe renal and mesenteric vasoconstriction. The addition of small doses of dopamine (1 µg/kg/min) helps to preserve renal blood flow when norepinephrine is administered.

Indications for use: persistent and significant hypotension with a drop in blood pressure below 70 mm Hg, as well as a significant decrease in OPSS.

Solution preparation. The contents of 2 ampoules (4 mg of norepinephrine hydrotartrate are diluted in 500 ml of isotonic sodium chloride solution or 5% glucose solution, which creates a concentration of 16 μg / ml).

The initial rate of administration is 0.5-1 μg / min by titration until the effect is obtained. Doses of 1-2 mcg/min increase CO, more than 3 mcg/min - have a vasoconstrictor effect. With refractory shock, the dose can be increased to 8-30 mcg / min.

Side effect. With prolonged infusion, renal failure and other complications (gangrene of the extremities) associated with the vasoconstrictor effects of the drug may develop. With extravasal administration of the drug, necrosis may occur, which requires chipping the extravasate area with a solution of phentolamine.

dopamine . It is the precursor of norepinephrine. It stimulates a- and beta receptors, has a specific effect only on dopaminergic receptors. The effect of this drug is largely dependent on the dose.

Indications for use: acute heart failure, cardiogenic and septic shock; the initial (oliguric) stage of acute renal failure.

Solution preparation. Dopamine hydrochloride (dopamine) is available in 200 mg ampoules. 400 mg of the drug (2 ampoules) are diluted in 250 ml of isotonic sodium chloride solution or 5% glucose solution. In this solution, the concentration of dopamine is 1600 µg/ml.

Doses for intravenous administration: 1) the initial rate of administration is 1 μg / (kg-min), then it is increased until the desired effect is obtained;

2) small doses - 1-3 mcg / (kg-min) are administered intravenously; while dopamine acts mainly on the celiac and especially the renal region, causing vasodilation of these areas and contributing to an increase in renal and mesenteric blood flow; 3) with a gradual increase in speed to 10 μg/(kg-min), peripheral vasoconstriction and pulmonary occlusive pressure increase; 4) high doses - 5-15 mcg / (kg-min) stimulate beta 1-receptors of the myocardium, have an indirect effect due to the release of norepinephrine in the myocardium, i.e. have a distinct inotropic effect; 5) in doses above 20 mcg / (kg-min), dopamine can cause vasospasm of the kidneys and mesentery.

To determine the optimal hemodynamic effect, it is necessary to monitor hemodynamic parameters. If tachycardia occurs, it is recommended to reduce the dose or discontinue further administration. Do not mix the drug with sodium bicarbonate, as it is inactivated. Long-term use a- and beta-agonists reduces the effectiveness of beta-adrenergic regulation, the myocardium becomes less sensitive to the inotropic effects of catecholamines, up to the complete loss of the hemodynamic response.

Side effect: 1) increase in DZLK, the appearance of tachyarrhythmias is possible; 2) in high doses can cause severe vasoconstriction.

Dobutamine(dobutrex). It is a synthetic catecholamine that has a pronounced inotropic effect. Its main mechanism of action is stimulation. beta receptors and increased myocardial contractility. Unlike dopamine, dobutamine does not have a splanchnic vasodilating effect, but tends to systemic vasodilation. It increases heart rate and DZLK to a lesser extent. In this regard, dobutamine is indicated in the treatment of heart failure with low CO, high peripheral resistance against the background of normal or elevated blood pressure. When using dobutamine, like dopamine, ventricular arrhythmias are possible. An increase in heart rate by more than 10% of the initial level can cause an increase in the zone of myocardial ischemia. In patients with concomitant vascular lesions, ischemic necrosis of the fingers is possible. In many patients treated with dobutamine, there was an increase in systolic blood pressure by 10-20 mm Hg, and in some cases, hypotension.

Indications for use. Dobutamine is prescribed for acute and chronic heart failure caused by cardiac (acute myocardial infarction, cardiogenic shock) and non-cardiac causes (acute circulatory failure after injury, during and after surgery), especially in cases where the mean blood pressure is above 70 mm Hg. Art., and the pressure in the system of a small circle is above normal values. Assign with increased ventricular filling pressure and the risk of overloading the right heart, leading to pulmonary edema; with a reduced MOS due to the PEEP regimen during mechanical ventilation. During treatment with dobutamine, as with other catecholamines, careful monitoring of heart rate, heart rate, ECG, blood pressure and infusion rate is necessary. Hypovolaemia must be corrected before starting treatment.

Solution preparation. A vial of dobutamine containing 250 mg of the drug is diluted in 250 ml of 5% glucose solution to a concentration of 1 mg / ml. Saline dilution solutions are not recommended as SG ions may interfere with dissolution. Do not mix dobutamine solution with alkaline solutions.

Side effect. Patients with hypovolemia may experience tachycardia. According to P. Marino, ventricular arrhythmias are sometimes observed.

Contraindicated with hypertrophic cardiomyopathy. Due to its short half-life, dobutamine is administered continuously intravenously. The effect of the drug occurs in the period from 1 to 2 minutes. It usually takes no more than 10 minutes to create its stable plasma concentration and ensure the maximum effect. The use of a loading dose is not recommended.

Doses. The rate of intravenous administration of the drug, necessary to increase the stroke and minute volume of the heart, ranges from 2.5 to 10 μg / (kg-min). It is often necessary to increase the dose to 20 mcg / (kg-min), in more rare cases - more than 20 mcg / (kg-min). Dobutamine doses above 40 µg/(kg-min) may be toxic.

Dobutamine can be used in combination with dopamine to increase systemic BP in hypotension, increase renal blood flow and urine output, and prevent the risk of pulmonary congestion seen with dopamine alone. The short half-life of beta-adrenergic receptor stimulants, equal to several minutes, allows you to very quickly adapt the administered dose to the needs of hemodynamics.

Digoxin . Unlike beta-adrenergic agonists, digitalis glycosides have a long half-life (35 hours) and are eliminated by the kidneys. Therefore, they are less manageable and their use, especially in intensive care units, is associated with the risk of possible complications. If sinus rhythm is maintained, their use is contraindicated. With hypokalemia, renal failure against the background of hypoxia, manifestations of digitalis intoxication occur especially often. The inotropic effect of glycosides is due to the inhibition of Na-K-ATPase, which is associated with the stimulation of Ca 2+ metabolism. Digoxin is indicated for atrial fibrillation with VT and paroxysmal atrial fibrillation. For intravenous injections in adults, it is used at a dose of 0.25-0.5 mg (1-2 ml of a 0.025% solution). Introduce it slowly into 10 ml of 20% or 40% glucose solution. In emergency situations, 0.75-1.5 mg of digoxin is diluted in 250 ml of a 5% dextrose or glucose solution and administered intravenously over 2 hours. The required level of the drug in the blood serum is 1-2 ng / ml.

VASODILATORS

Nitrates are used as fast-acting vasodilators. The drugs of this group, causing the expansion of the lumen of the vessels, including the coronary ones, affect the state of pre- and afterload and during severe forms heart failure with high filling pressure significantly increase CO.

Nitroglycerine . The main action of nitroglycerin is the relaxation of vascular smooth muscles. In low doses, it provides a venodilating effect, in high doses it also dilates arterioles and small arteries, which causes a decrease in peripheral vascular resistance and blood pressure. Having a direct vasodilating effect, nitroglycerin improves the blood supply to the ischemic area of ​​the myocardium. The use of nitroglycerin in combination with dobutamine (10-20 mcg/(kg-min) is indicated in patients at high risk of myocardial ischemia.

Indications for use: angina pectoris, myocardial infarction, heart failure with an adequate level of blood pressure; pulmonary hypertension; high level of OPSS with elevated blood pressure.

Solution preparation: 50 mg of nitroglycerin is diluted in 500 ml of solvent to a concentration of 0.1 mg / ml. Doses are selected by titration.

Doses for intravenous administration. The initial dose is 10 mcg / min (low doses of nitroglycerin). Gradually increase the dose - every 5 minutes by 10 mcg / min (high doses of nitroglycerin) - until a clear effect on hemodynamics is obtained. The highest dose is up to 3 mcg / (kg-min). In case of overdose, hypotension and exacerbation of myocardial ischemia may develop. Intermittent administration therapy is often more effective than long-term administration. For intravenous infusions, systems made of polyvinyl chloride should not be used, since a significant part of the drug settles on their walls. Use systems made of plastic (polyethylene) or glass vials.

Side effect. Causes the conversion of part of hemoglobin into methemoglobin. An increase in the level of methemoglobin up to 10% leads to the development of cyanosis, and a higher level is life-threatening. To lower the high level of methemoglobin (up to 10%), a solution of methylene blue (2 mg / kg for 10 minutes) should be administered intravenously [Marino P., 1998].

With prolonged (from 24 to 48 hours) intravenous administration of a nitroglycerin solution, tachyphylaxis is possible, characterized by a decrease in therapeutic effect in cases of re-introduction.

After the use of nitroglycerin with pulmonary edema, hypoxemia occurs. The decrease in PaO 2 is associated with an increase in blood shunting in the lungs.

After using high doses of nitroglycerin, ethanol intoxication often develops. This is due to the use of ethyl alcohol as a solvent.

Contraindications: increased intracranial pressure, glaucoma, hypovolemia.

Sodium nitroprusside is a fast-acting balanced vasodilator that relaxes the smooth muscles of both veins and arterioles. No significant effect on heart rate and heartbeat. Under the influence of the drug, OPSS and blood return to the heart are reduced. At the same time, coronary blood flow increases, CO increases, but myocardial oxygen demand decreases.

Indications for use. Nitroprusside is the drug of choice in patients with severe hypertension associated with low CO. Even a slight decrease in peripheral vascular resistance during myocardial ischemia with a decrease in the pumping function of the heart contributes to the normalization of CO. Nitroprusside has no direct effect on the heart muscle, it is one of the best drugs in the treatment of hypertensive crises. It is used for acute left ventricular failure without signs of arterial hypotension.

Solution preparation: 500 mg (10 ampoules) of sodium nitroprusside are diluted in 1000 ml of solvent (concentration 500 mg/l). Store in a place well protected from light. Freshly prepared solution has a brownish tint. The darkened solution is not suitable for use.

Doses for intravenous administration. The initial rate of administration is from 0.1 μg / (kg-min), with a low CO - 0.2 μg / (kg-min). At hypertensive crisis treatment begins with 2 mcg/(kg-min). The usual dose is 0.5 - 5 mcg / (kg-min). The average rate of administration is 0.7 µg/kg/min. The highest therapeutic dose is 2-3 mcg / kg / min for 72 hours.

Side effect. With prolonged use of the drug, cyanide intoxication is possible. This is due to the depletion of thiosulfite reserves in the body (in smokers, with malnutrition, vitamin B 12 deficiency), which is involved in the inactivation of cyanide formed during the metabolism of nitroprusside. In this case, the development of lactic acidosis, accompanied by headache, weakness and arterial hypotension, is possible. Intoxication with thiocyanate is also possible. Cyanides formed during the metabolism of nitroprusside in the body are converted to thiocyanate. The accumulation of the latter occurs in renal failure. The toxic concentration of thiocyanate in plasma is 100 mg/l.

General provisions

• The goal of inotropic support is to provide maximum tissue oxygenation (assessed by plasma lactate concentration and mixed venous blood oxygenation), and not to increase cardiac output.
• AT clinical practice catecholamines and their derivatives are used as inotropes. They have a complex hemodynamic effect due to α- and β-adrenergic effects and differ in their predominant effect on certain receptors. Below is a description of the hemodynamic effects of the main catecholamines.

Isoprenaline

Pharmacology

Isoprenaline is a synthetic agonist of β-adrenergic receptors (β 1 and β 2) and does not affect α-adrenergic receptors. The drug dilates the bronchi, during blockade it acts as a pacemaker, affecting the sinus node, increases conductivity and reduces the refractory period of the atrioventricular node. It has a positive inotropic effect. It has an effect on skeletal muscles and blood vessels. The half-life is 5 minutes.

Drug Interactions

• The effect increases when co-administered with tricyclic antidepressants.
• β-blockers are isoprenaline antagonists.
• Sympathomimetics may potentiate the action of isoprenaline.
• Gaseous anesthetics, by increasing the sensitivity of the myocardium, can cause arrhythmias.
• Digoxin increases the risk of tachyarrhythmias.

epinephrine

Pharmacology

• Epinephrine is a selective β 2 -adrenergic agonist (the effect on β 2 -adrenergic receptors is 10 times greater than the effect on β 1 -adrenergic receptors), but also acts on α-adrenergic receptors, without differentially affecting α 1 - and α 2 -adrenergic receptors.
• It usually has little effect on the level of mean blood pressure, except in cases of prescribing the drug against the background of non-selective blockade of β-adrenergic receptors, in which the vasodilatory effect of epinephrine mediated by the action on β 2 -adrenergic receptors is lost and its vasopressor effect sharply increases (α 1 -selective blockade does not cause such an effect ).

Application area

• Anaphylactic shock, angioedema and allergic reactions.
• The scope of epinephrine as an inotropic drug is limited only to septic shock, in which it has advantages over dobutamine. However, the drug causes a significant decrease in renal blood flow (up to 40%) and can only be administered together with dopamine in the renal dose.
• Heart failure.
• Open angle glaucoma.
• As an adjunct to local anesthetics.

Doses

• 0.2-1 mg intramuscularly for acute allergic reaction and anaphylaxis.
• 1 mg in cardiac arrest.
• In case of shock, 1-10 mcg / min is administered drip.

Pharmacokinetics

Due to rapid metabolism in the liver and nervous tissue and 50% plasma protein binding, the half-life of epinephrine is 3 minutes.

Side effects

• Arrhythmias.
• Intracerebral hemorrhage (with overdose).
• Pulmonary edema (with overdose).
• Ischemic necrosis at the injection site.
• Restlessness, dyspnea, palpitations, tremors, weakness, cold extremities.

drug interaction

• Tricyclic immunosuppressants.
• Anesthetics.
• β-blockers.
• Quinidine and digoxin (arrhythmia often occurs).
• α-Adrenergic agonists block the α-effects of epinephrine.

Contraindications

• Hyperthyroidism.
• Hypertension.
• Angle-closure glaucoma.

dopamine

Pharmacology

Dopamine affects several types of receptors. In small doses, it activates α 1 - and α 2 dopamine receptors. α 1 dopamine receptors are localized in vascular smooth muscle and are responsible for vasodilation in the renal, mesenteric, cerebral and coronary circulation. α 1 dopamine receptors are located in the postganglionic endings of the sympathetic nerves and ganglia of the autonomic nervous system. At an average dose, dopamine activates β 1 -adrenergic receptors, having positive chronotropic and inotropic effects, and at high doses, it additionally activates α 1 - and α 2 -adrenergic receptors, eliminating the vasodilating effect on the renal vessels.

Application area

Used to improve renal blood flow in patients with impaired renal perfusion, usually against the background of multiple organ failure. There is little evidence regarding the effect of dopamine on the clinical outcome of the disease.

Pharmacokinetics

Dopamine is taken up by sympathetic nerves and is rapidly distributed throughout the body. The elimination half-life is 9 minutes, and the volume of distribution is 0.9 l / kg, but the state of equilibrium occurs within 10 minutes (ie, faster than expected). Metabolized in the liver.

Side effects

• Arrhythmias are rarely seen.
• Hypertension at very high doses.
• Extravasation can cause skin necrosis. In this case, phentolamine is injected into the ischemic zone as an antidote.
• Headache, nausea, vomiting, palpitations, mydriasis.
• Increased catabolism.

Drug Interactions

• MAO inhibitors.
• α-Adrenergic blockers may enhance the vasodilatory effect.
• β-blockers may enhance the hypertensive effect.
• Ergotamine enhances peripheral vasodilation.

Contraindications

• Pheochromocytoma.
• Tachyarrhythmia (without treatment).

Dobutamine

Pharmacology

Dobutamine is a derivative of isoprenaline. In practice, a racemic mixture of a dextrorotatory isomer selective for β 1 and β 2 adrenoreceptors and a levorotatory isomer having an α 1 selective effect is used. The effects on β2-adrenergic receptors (vasodilatation of mesenteric and musculoskeletal vessels) and α 1 -adrenergic receptors (vasoconstriction) suppress each other, so dobutamine has little effect on blood pressure unless given at a high dose. It has less, compared with dopamine, arrhythmogenic effect.

Application area

• Inotropic support for heart failure.
• In septic shock and liver failure, it can cause vasodilation, therefore it is not the most preferred inotropic drug.
• Used in functional diagnostics for cardiological stress tests.

Pharmacokinetics

Rapidly metabolized in the liver. It has an elimination half-life of 2.5 minutes and a volume of distribution of 0.21 l/kg.

Side effects

• Arrhythmias.
• With an increase in cardiac output, myocardial ischemia may occur.
• The hypotensive effect can be minimized by the simultaneous administration of dopamine in a vasoconstrictive dose. This combination of drugs may be required to treat patients with sepsis or liver failure.
• Allergic reactions are extremely rare.
• Skin necrosis may occur at the injection site.

drug interaction

α-Adrenergic agonists increase vasodilation and cause hypotension.

Contraindications

• Low filling pressure.
• Arrhythmias.
• Cardiac tamponade.
• Heart valve defects (aortic and mitral stenosis, hypertrophic obstructive cardiomyopathy).
• Established hypersensitivity to the drug.

norepinephrine

Pharmacology

Norepinephrine, like epinephrine, has an α-adrenergic effect, but to a lesser extent affects most β 1 -adrenergic receptors and has a very low β 2 -adrenergic activity. The weakness of β 2 -adrenergic influence leads to the predominance of the vasoconstrictor effect, more pronounced than that of epinephrine. Norepinephrine is prescribed for acute hypotension, but due to its negligible effect on cardiac output and the ability to cause pronounced vasospasm, this drug can significantly increase tissue ischemia (especially in the kidneys, skin, liver and skeletal muscles). Norepinephrine infusion should not be interrupted suddenly, as this is dangerous with a sharp drop in blood pressure.

drug interaction

Tricyclic antidepressants (blocking the re-entry of catecholamines into nerve endings) increase the sensitivity of receptors to epinephrine and norepinephrine by 2-4 times. MAO inhibitors (for example, tranylcyprominr and pargyline) significantly potentiate the effect of dopamine, so it should be started with a dose equal to 1/10 of the usual initial dose, i.e. 0.2 µg/(kghmin).

Dobutamine is not a substrate for MAO.

Milrinone

Milrinone belongs to the group of phosphodiesterase (type III) inhibitors. Its cardiac effects may be due to its effect on calcium and fast sodium channels. β-Adrenergic agonists enhance the positive inotropic effect of a million.

Side effects

Enoximonr

Enoximone is a phosphodiesterase (type IV) inhibitor. The drug is 20 times more active than aminophylline, its half-life is approximately 1.5 hours. It is broken down to active metabolites with 10% enoximonar activity with a half-life of 15 hours. Used to treat congestive heart failure, it can be prescribed both in tablet form, as well as intravenously.

Side effects

Patients with hypovolemia may develop hypotension and/or cardiovascular collapse.

Bicarbonate of soda

Pharmacology

Sodium bicarbonate plays an important role as a buffer in the body. Its effect is short-lived. The administration of sodium bicarbonate results in sodium overload and carbon dioxide formation, which leads to intracellular acidosis and reduces the force of myocardial contraction. Therefore, the drug should be administered with great caution. Along with this, sodium bicarbonate shifts the oxyhemoglobin dissociation curve to the left and reduces the effective delivery of oxygen to tissues. Moderate acidosis causes vasodilation of the brain, so its correction may impair cerebral blood flow in patients with cerebral edema.

Application area

• Severe metabolic acidosis (there are conflicting data regarding use in diabetic ketoacidosis).
• Severe hyperkalemia.
• The use of sodium bicarbonate in cardiopulmonary resuscitation is best avoided, since cardiac massage and artificial respiration are quite sufficient.

Dose

Released in the form of 8.4% solution (hypertonic, 1 ml contains 1 mmol bicarbonate ion) and 1.26% solution (isotonic). Usually administered as a bolus of 50-100 ml under pH control arterial blood and hemodynamic monitoring. According to the recommendations of the British Council for Resuscitation, an approximate dose of 8.4% sodium bicarbonate solution can be calculated as follows:
Dose in ml (mol) = [BExt (kg)]/3, where BE is the base deficiency.

Thus, a patient with a body weight of 60 kg, having a base deficiency of -20, needs 400 ml of 8.4% sodium bicarbonate solution to normalize the pH. This volume contains 400 mmol sodium. From our point of view, this is very high, so it is desirable to adjust the pH to a level of 7.0-7.1 by prescribing 50-100 ml of sodium bicarbonate, followed by an assessment of arterial blood gases and repeated administration of the drug if necessary. This allows you to gain enough time to conduct more effective and safer diagnostic and treatment measures and treat the disease that led to the development of acidosis.

Side effects

• Extravasation results in tissue necrosis. If possible, the drug is administered through a central catheter.
• With simultaneous administration with calcium preparations, calcifications are formed in the catheter, which can lead to microembolism.

13891 0

Positive inotropic drugs affect preload and afterload correction. The main principle of their action is to increase the force of myocardial contraction. It is based on a universal mechanism associated with the effect on intracellular calcium.

The following requirements are put forward for drugs in this group:

• intravenous route of administration;
• the possibility of dose titration under the control of hemodynamic parameters;
• short half-life (for quick correction of side effects).

Classification

In modern cardiology, in the group of drugs with a positive inotropic mechanism of action, it is customary to distinguish two subgroups.

cardiac glycosides.

Non-glycoside inotropic drugs (stimulants):

• β1-adrenergic stimulants (norepinephrine, isoprenaline, dobutamine, dopamine);
• phosphodiesterase inhibitors;
• calcium sensitizers (levosimendan).

Mechanism of action and pharmacological effects

Stimulants of β1-adrenergic receptors. When β-adrenergic receptors are stimulated, G-proteins of the cell membrane are activated and a signal is transmitted to adenylate cyclase, which leads to the accumulation of cAMP in the cell, which stimulates the mobilization of Ca2+ from the sarcoplasmic reticulum. Mobilized Ca²+ leads to increased myocardial contraction. Derivatives of catecholamines have a similar effect. In clinical practice, dopamine (a natural precursor of catecholamine synthesis) and the synthetic drug dobutamine are prescribed. The drugs of this group, administered intravenously, affect the following receptors:

• β1-adrenergic receptors (positive inotropic and chronotropic action);
• β2-adreioreceptors (bronchodilation, expansion of peripheral vessels);
• dopamine receptors (increased renal blood flow and filtration, dilatation of the mesenteric and coronary arteries).

Thus, the main effect of β1-adrenergic stimulants - a positive inotropic effect - is always combined with others. clinical manifestations which can have both positive and negative effects on clinical picture acute heart failure.

Phosphodiesterase inhibitors. In clinical practice, another mechanism for enhancing myocardial contractility is also used, based on a decrease in the breakdown of cAMP. Thus, the basis is to maintain a high level of cAMP in the cell, either by increasing synthesis (dobutamine) or by reducing decay. Reducing the breakdown of cAMP can be achieved by blocking the enzyme phosphodiesterase.

AT last years another effect of these drugs was discovered (in addition to the blockade of phosphodiesterase) - an increase in the synthesis of cGMP. An increase in the content of cGMP in the vessel wall leads to a decrease in its tone, that is, to a decrease in OPSS.

So, drugs of this subgroup, increasing myocardial contractility (due to blockade of cAMP destruction), also lead to a decrease in OPSS (due to cGMP synthesis), which allows you to simultaneously influence preload and afterload in acute heart failure.

calcium sensitizers. The classic representative of this subclass is levosimendan. The drug does not affect Ca²+ transport, but increases its affinity for troponin C. As is known, Ca²+ released from the sarcoplasmic reticulum destroys the troponin-tropomyosin complex, which inhibits contraction, and binds to troponin C, which stimulates myocardial contraction.

Arutyunov G.P.

Inotropic drugs