Adrenergic drugs. Adrenergic drugs
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Adrenergic drugs are drugs that affect adrenergic synapses located at the end of the sympathetic nerves. Since adrenergic receptors are divided into several types and adrenergic receptors are postsynaptic, presynaptic and postsynaptic, and among adrenergic receptors similar adrenergic receptors are distinguished, all means that influence the transmission of excitation in adrenergic synapses are divided into three main groups:
1) excitatory adrenergic receptors - adrenergic agonists;
2) blocking adrenergic receptors - adrenergic blockers (adrenolytics);
3) affecting metabolism, deposition and release of mediators (sympatholytics).
Adrenergic agonists include drugs that stimulate adrenergic receptors. Based on their effect on a specific type of adrenergic receptors, adrenergic agonists are divided into three groups:
1) stimulating predominantly adrenergic receptors (adrenergic agonists);
2) stimulating predominantly adrenergic receptors (adrenergic agonists);
3) stimulating – and adrenergic receptors (adrenergic agonists).
adrenomimetics.
This group includes norepinephrine, the main mediator of adrenergic synapses, secreted by the adrenal medulla and having a predominantly stimulating effect on adrenergic receptors, to a small extent on and to a lesser extent on -adrenergic receptors.
Norepinephrine hydrotartate(Noradrenaiini hydrotartas).
Stimulates adrenergic receptors, has a strong vasopressor effect, stimulates heart contraction, and has a weak bronchodilator effect.
Application: acute decrease in blood pressure during injuries, surgical interventions, poisoning, cardiogenic shock. 2–4 mg of the drug (1–2 ml of 0.2% solution) in 500 ml of 5% glucose solution is administered intravenously (drip).
Side effects: headache, chills, palpitations; if it gets under the skin, necrosis is possible.
Contraindications: fluorotane anesthesia. Caution is required in cases of severe atherosclerosis, circulatory failure, and complete atrioventricular block.
Release form: 1 ml of 0.2% solution No. 10. List B.
Mezaton(Mesatonum).
It acts predominantly on adrenergic receptors, it is more stable than norepinephrine, and is effective when administered orally, intravenously, intramuscularly, subcutaneously and locally. It is used in the same way as norepinephrine.
Side effects and contraindications: the same.
Release form: powder and ampoules of 1 ml of 1% solution. List B.
Fethanol(Phetanolum).
Increases blood pressure compared to mezaton for a longer period.
Application, side effects and contraindications: the same as that of mesatone.
Release form: powder, tablets of 0.005 g, in ampoules of 1 ml of 1% solution.
Naphthyzin(Naphthyzinum).
Synonym: Sanorine.
Application: acute rhinitis, sinusitis, allergic conjunctiva. The vasoconstrictor effect is longer lasting than that of norepinephrine and mesatone, and the sanorin emulsion lasts longer than an aqueous solution of naphthyzine.
Release form: bottles of 10 ml of 0.05-0.1% solution.
Galazolin(Halazolinum).
Close to naphthyzin in action and application.
adrenomimetics
Drugs in this group have a direct stimulating effect on α1- or α1- and β2-adrenergic receptors. Stimulation of α2-adrenergic receptors has a rapid and pronounced bronchodilator effect, reduces swelling of the bronchial mucosa. Increases the functional activity of ?1 receptors in the myocardium, enhances cardiac activity.
Izadrin(Isadrinum).
Application: emphysema, bronchial asthma, pneumosclerosis. Prescribed orally 1-2 tablets 3-4 times a day sublingually, in the form of inhalations - 0.5-1 ml of a 0.5-1% solution 2-4 times a day.
Side effects: tachycardia, arrhythmia, nausea.
Contraindications: severe atherosclerosis, arrhythmia, pain in the heart area.
Release form: tablets of 0.005 g No. 20; in ampoules of 1 ml of 0.5% solution No. 5, aerosol of 25 g. List B.
Alupent(Alupent).
Close to isadrin, but in bronchial asthma it acts longer.
Release form: ampoules of 1 ml of 0.05% solution and bottles of 20 ml of 2% aerosol solution containing 400 single doses, tablets of 0.02 g.
Synonym: Asthmopent.
Release form: bottles of 20 ml of 1.5% aerosol solution containing 200 and 400 single doses.
Dobutamine(Dobutaminum).
Increases coronary blood flow, improves blood circulation.
Side effects: Tachycardia, arrhythmia, increased blood pressure, pain in the heart, nausea.
Contraindications: subaortic stenosis.
Release form: 20 ml bottles (250 mg dobutamine). It is administered intravenously, having previously been dissolved in a 0.9% sodium chloride solution.
Fenoterol(Fenoterolum).
Synonyms: Berotec. Close to asthmapent, but lasts longer. Better tolerated.
Application: bronchial asthma.
Release form: aerosol with a metering valve, one press – 0.2 mg of the drug; 1 breath 2-3 times a day. Under the name partusisten, it is used as a means of relaxing the muscles of the uterus.
Salbutamol(Salbutamolum).
Synonym: Ventolin. Gives a pronounced bronchodilator effect. Administration: orally and inhalation for bronchial asthma.
Release form: aerosol cans and tablets of 0.002 g.
adrenomimetics.
These drugs improve the conduction of nerve impulses at postganglionic synapses of sympathetic nerve fibers. The main effects are associated with direct or indirect stimulating effects on both α- and β-adrenergic receptors.
Adrenaline hydrochloride(Adrenalini hydrochloridum).
Used for bronchial asthma, hypoglycemia, allergic reactions 1.0 ml of 0.1% solution, for acute cardiac arrest - intracardiacly, for glaucoma - 1-2% solution in drops.
Side effects: tachycardia, increased cardiac output, increased blood pressure, deterioration of myocardial oxygen supply.
Contraindications: arterial hypertension, severe atherosclerosis, diabetes mellitus, thyrotoxicosis, pregnancy, angle-closure glaucoma.
Ephedrine hydrochloride(Ephedrini hydrochloridum).
It has a weaker effect, but lasts longer.
Application: bronchial asthma, allergic diseases, poisoning with sleeping pills, drugs, hypotension, enuresis, injuries, blood loss, infectious diseases, myasthenia gravis. Locally as a vasoconstrictor, to dilate the pupil for diagnostic purposes. Prescribed orally 0.025 g 2-4 times a day.
Administered parenterally (0.5–1.0 ml of 5% solution) and dropwise (2 ml of 5% solution in 500 ml of 5% glucose solution or 0.9% sodium chloride solution). Do not take at the end of the day or before bedtime.
Side effects: palpitations, nausea, sweating, insomnia, nervous agitation, urinary retention, rash, trembling limbs.
Contraindications: hypertension, atherosclerosis, severe organic heart disease, hyperthyroidism, insomnia.
Release form: tablets of 0.025 No. 10, ampoules of 2, 3 and 5% solution of 1 ml. List A.
Ephedrine is included in the Teofedrine tablets ( Teophedrinum) and the drug "Solutan" ( Solutan).
(DRUGS AFFECTING THE TRANSMISSION OF EXCITATION IN ADRENERGIC SYNAPSES) (ADRENOMIMETIC AND ADRENOBLOCKING DRUGS)
Let us recall that in adrenergic synapses the transmission of excitation is carried out through the mediator norepinephrine (NA). Within peripheral innervation, norepinephrine takes part in the transmission of impulses from adrenergic (sympathetic) nerves to effector cells.
In response to nerve impulses, norepinephrine is released into the synaptic cleft and its subsequent interaction with adrenergic receptors of the postsynaptic membrane. Adrenergic receptors are found in the central nervous system and on the membranes of effector cells innervated by postganglionic sympathetic nerves.
The adrenergic receptors existing in the body have unequal sensitivity to chemical compounds. With some substances, the formation of a drug-receptor complex causes an increase (excitation), with others a decrease (inhibition) of the activity of the innervated tissue or organ. To explain these differences in the reactions of different tissues, in 1948 Ahlquist proposed the theory of the existence of two types of receptors: alpha and beta. Typically, stimulation of alpha receptors causes excitation effects, and stimulation of beta receptors is usually accompanied by inhibitory effects. Although in general, alpha receptors are excitatory receptors, and beta receptors are inhibitory receptors, there are certain exceptions to this rule. Thus, in the heart, in the myocardium, the predominant beta-adrenergic receptors are stimulating in nature. Excitation of beta receptors of the heart increases the speed and strength of myocardial contractions, accompanied by an increase in automaticity and conductivity in the AV node. In the gastrointestinal tract, both alpha and beta receptors are inhibitory. Their stimulation causes relaxation of the smooth muscles of the intestine.
Adrenergic receptors are localized on the cell surface.
All alpha receptors are subdivided based on the comparative selectivity and potency of the effects of both agonists and antagonists on the alpha 1 and alpha 2 receptors. If alpha-1-adrenergic receptors are localized postsynaptically, then alpha-2-adrenergic receptors are localized on presynaptic membranes. The main role of presynaptic alpha-2 adrenergic receptors is their participation in the NEGATIVE FEEDBACK system that regulates the release of the neurotransmitter norepinephrine. Excitation of these receptors inhibits the release of norepinephrine from varicose thickenings of the sympathetic fiber.
Among the postsynaptic beta-adrenergic receptors, beta-1-adrenergic receptors (localized in the heart) and beta-2-adrenergic receptors (in the bronchi, skeletal muscle vessels, pulmonary, cerebral and coronary vessels, in the uterus) are distinguished.
If the stimulation of beta-1 receptors of the heart is accompanied by an increase in the strength and frequency of heart contractions, then with stimulation of beta 2-adrenergic receptors a decrease in organ function is observed - relaxation of the smooth muscles of the bronchi. The latter means that beta-2 adrenergic receptors are classical inhibitory adrenergic receptors.
The quantitative ratio of alpha and beta receptors in different tissues is different. Alpha receptors are predominantly concentrated in the blood vessels of the skin and mucous membranes, brain and vessels of the abdominal region (kidneys and intestines, gastrointestinal sphincters, trabeculae of the spleen). As you can see, these vessels belong to the category of capacitive vessels.
Mainly beta-1-stimulating adrenergic receptors are localized in the heart; beta-2-inhibitory adrenergic receptors are mainly located in the muscles of the bronchi, cerebral, coronary, and pulmonary vessels. This arrangement is evolutionarily developed, it runs away when danger arises: it is necessary to expand the bronchi, increase the lumen of the blood vessels of the brain, and increase the work of the heart.
The effect of norepinephrine on adrenergic receptors is short-lived, since up to 80% of the released mediator is quickly captured and absorbed through active transport by the endings of adrenergic fibers. Catabolism (destruction) of free norepinephrine is carried out by oxidative deamination in adrenergic endings and is regulated by the enzyme monoamine oxidase (MAO), localized in mitochondria and membrane vesicles. Metabolism of norepinephrine released from nerve endings is carried out by methylation by the cytoplasmic enzyme of effector cells - CATECHOL-O-METHYLTRANSFERASE (COMT). COMT is also present in synapses, and in plasma and cerebrospinal fluid.
The possibilities of pharmacological effects on adrenergic transmission of nerve impulses are quite diverse. The direction of action of substances can be as follows:
1) influence on the synthesis of norepinephrine;
2) impaired deposition of norepinephrine in vesicles;
3) inhibition of enzymatic inactivation of norepinephrine;
4) influence on the release of norepinephrine from the endings;
5) disruption of the process of reuptake of norepinephrine by presynaptic endings;
6) inhibition of extraneuronal neurotransmitter uptake;
7) direct effect on adrenergic receptors of effector cells.
CLASSIFICATION OF ADRENERGIC DRUGS
Taking into account the preferential localization of action, all the main means influencing the transmission of excitation in adrenergic synapses are divided into 3 main groups:
I. ADRENOMIMETIKS, that is, drugs that stimulate adrenergic receptors, acting like the neurotransmitter, imitating it.
II. ADRENO BLOCKERS - drugs that inhibit adrenergic receptors.
III. SYMPATHOLYTICS, that is, agents that have a blocking effect on adrenergic transmission using an indirect mechanism.
In turn, among ADRENOMIMETICS there are:
1) CATECHOLAMINES: adrenaline, norepinephrine, dopamine, isadrin;
2) NON-CATECHOLAMINES: ephedrine.
CATECHOLAMINES are substances containing a catechol or ortho-dioxybenzene nucleus (ortho is the top position of the carbon atom).
Group I of drugs, ADRENOMIMETICS, consists of 3 subgroups of drugs.
First of all, there are:
1) DRUGS THAT SIMULTANEOUSLY STIMULATE ALPHA AND BETA ADRENO RECEPTORS, that is, ALPHA, BETA ADRENO MIMETICS:
a) ADRENALINE - as a classic, direct alpha, beta-adrenergic agonist;
b) EPHEDRINE - indirect alpha, beta-adrenergic agonist;
c) NORADRENALINE - acting as a mediator on alpha, beta adrenergic receptors, as a medicine - on alpha adrenergic receptors.
2) DRUGS STIMULATING PRIMARILY ALPHA-ADRENORESCEPTORS, that is, ALPHA-ADRENOMIMETIICS: MEZATONE (alpha-1), NAPHTHYZIN (alpha-2), GALAZOLIN (alpha-2).
3) DRUGS THAT STIMULATE PRIMARILY BETA-ADRENORESCEPTORS, BETA-ADRENOMIMETICS:
a) NON-SELECTIVE, that is, acting on both beta-1 and beta-2 adrenergic receptors - IZADRIN;
b) SELECTIVE - SALBUTAMOL (mainly beta-2 receptors), FENOTEROL, etc.
II. ADRENO BLOCKING DRUGS (ADRENO BLOCKERS)
The group is also represented by 3 subgroups of drugs.
1) ALPHA BLOCKERS:
a) NON-SELECTIVE - TROPAPHEN, FENTOLAMINE, as well as dihydrogenated ergot alkaloids - DIHYDROERGOTOXIN, DIHYDROERGOCHRISTINE, etc.;
b) SELECTIVE - PRAZOSIN;
2) BETA BLOCKERS:
a) NON-SELECTIVE (beta-1 and beta-2) - ANAPRILINE or PROPRANOLOL, OXPRENOLOL (TRAZICOR) ETC.;
b) SELECTIVE (beta-1 or cardioselective) - METOPROLOL (BETALOK).
III. SYMPATHOLYTICS: OCTADINE, RESERPINE, ORNID.
We will begin the analysis of the material with drugs acting on alpha and beta adrenergic receptors, that is, with drugs from the alpha group, beta adrenergic agonists.
The most typical, classic representative of alpha, beta-adrenergic agonists is ADRENALINE (Adrenalini hydrochloridum, in amp. 1 ml, 0.1% solution).
Adrenaline is obtained synthetically or by isolating it from the adrenal glands of slaughtered cattle.
MECHANISM OF ACTION: has a direct, immediate, stimulating effect on alpha and beta adrenergic receptors, therefore it is a direct adrenergic agonist.
Kirov State Medical Institute
Department of General and Clinical Pharmacology
Methodological development for self-training of 3rd year students of the medical and pediatric faculties.
G. Kirov, 1998
Compiled by: Vorobyov's assistant V.V.
ADRENERGIC DRUGS
The concept of adrenergic systems first appeared in 1948, when Ahlquist proposed that the stimulating effect of adrenaline on the cardiovascular system is determined by two types of adrenergic receptors, alpha and beta. In this case, alpha-adrenergic receptors cause a vasoconstrictor effect, and beta-positive ino- and chronotropic effects.
In the late 50s, attempts were made to create drugs that would inhibit the stimulatory effects of catecholamines on the heart. After repeated attempts, reports of the successful use of propronalol for the treatment of angina and hypertension have emerged.
So, what are adrenergic drugs?
These are drugs that affect the transmission of excitation at adrenergic synapses of the sympathetic nervous system (SNS). The SNS controls such important involuntary functions of the body as blood pressure, heart rate, vascular tone, myocardial contractility, bronchial tone, as well as a number of metabolic processes. Therefore, pharmacological intervention on the SNS opens up enormous possibilities for regulating many important functions and treating such widespread diseases as arterial hypertension, asthma and a number of others.
Adrenergic axons, approaching effector cells, form structural and functional formations - synapses, in which the electrical potential coming from the central nervous system causes the release of the chemical transmitter norepinephrine, that is, the electrical signal is converted into a chemical one, which is norepinephrine. Norepinephrine interacts with receptors on the postsynaptic membrane. The binding of a mediator to adrenergic receptors leads to a chain of intracellular, enzymatic and ionic processes, causing a typical pharmacological effect.
Norepinephrine is synthesized at the endings of sympathetic fibers, where it is deposited in special vesicles in an inactive bound state. Under the influence of a nerve impulse, norepinephrine is released into the synaptic cleft, where it interacts with adrenoreceptors of effector cells and exerts its effect.
Having fulfilled its functions, norepinephrine is partially destroyed, and partially, up to 80%, is captured by vesicles for reuse. The process of inactivation of norepinephrine occurs with the participation of two enzymes catecholamine northomethyltransferase (COMT) and monoamine oxidase (MAO), as a result of which it turns into a biologically inactive substance.
Pharmacologically, it is possible to influence the following 3 stages of impulse transmission from the adrenergic neuron to the cell:
1. At the presynaptic stage, including storage and reverse use of the transmitter.
2. At the stage of enzymes that destroy the neurotransmitters MAO and COMT, which makes it difficult to destroy norepinephrine and prolongs its action.
3. At the stage of adrenergic receptors of the postsynaptic membrane. This is the most widely used route for pharmacological intervention in the SNS.
Pharmacological substances acting on postsynaptic receptors are close in chemical structure to the natural transmitter, but have some structural differences, making their effect different from the natural transmitter. Those drugs that cause stimulation of adrenergic receptors are called adrenergic stimulants (adrenomimetics or adrenergic receptor agonists). They are close in their main pharmacological effects to the natural neurotransmitter norepinephrine. There are direct-acting adrenergic stimulants, which directly act on receptors (adrenaline, norepinephrine) and indirect ones (ephedrine, phenamine), which cause the release of norepinephrine, which has an effect.
The distribution density of adrenergic receptors in the body is heterogeneous, which causes different effects on the organs of sympathetic innervation. In addition, these receptors themselves are heterogeneous.
There are two main types of receptors: a and b. In turn, b are divided into b1-cardiac and b2-peripheral.
Stimulation of b1-adrenergic receptors causes the following main effects:
- heart: increased contractility, increased conductivity, increased automaticity and increased excitability.
- kidneys: increased release of renin and blood pressure.
- adipose tissue: increased lipolysis.
Stimulation of b2-adrenergic receptors has the following effects:
- heart: increased automaticity.
- peripheral vessels: vasodilation.
- bronchial muscles: relaxation.
- uterus: relaxation.
- pancreas: Increased insulin release.
Stimulation of a-receptors has the following effects:
- peripheral vessels: vasoconstriction.
- bronchial muscles: reduction.
All drugs acting on postsynaptic adrenergic receptors differ in their activity with respect to the selectivity of action on a- and b-adrenergic receptors. There are drugs with a predominantly a-stimulating effect (mezaton) and drugs acting on a and b receptors (adrenaline and norepinephrine). In turn, b-adrenergic stimulants are divided into non-selective, acting on b1 and b2-adrenergic receptors (isoproterenol) and selective b2-adrenergic stimulants (Berotec, salbutamol).
In adrenergic synapses, the transmission of excitation is carried out through norepinephrine. Within peripheral innervation, norepinephrine takes part in the transmission of impulses from postganglionic adrenergic fibers to effector cells.
The biosynthesis of norepinephrine occurs in adrenergic neurons from tyrosine with the participation of a number of enzymes. In response to nerve impulses, norepinephrine is released into the synaptic cleft and its subsequent interaction with adrenergic receptors of the postsynaptic membrane.
The effect of norepinephrine on adrenergic receptors is short-lived.
Under the influence of MAO, oxidative deamination of norepinephrine occurs.
The adrenergic receptors existing in the body have unequal sensitivity to chemical compounds. Based on this principle, a- and b-adrenergic receptors are distinguished. The main a-adrenergic receptors are represented by a 1 - and a 2 - adrenergic receptors. b- receptors - b 1 -, b 2 -, b 3 - adrenergic receptors. The quantitative ratio of a- and b-receptors in tissues is different. Thus, a-adrenergic receptors predominate in the vessels of the skin, kidneys, intestines, sphincters of the gastrointestinal tract, trabeculae of the spleen, and the radial muscle of the iris. Excitation of a 1 - receptors leads to a stimulating effect of these organs (except the intestines), and a 2 - receptors lead to an inhibitory effect, since their stimulation inhibits the release of norepinephrine. In the heart (b 1), bronchi, blood vessels, uterus (b 2), in adipose tissue, in the smooth muscles of the digestive tract, gall bladder (b 3) there are mainly b - adrenergic receptors. Excitation of b 1 receptors leads to an increase in the strength and frequency of heart contractions, increased automaticity and facilitation of atrioventricular conduction in the heart. When b 2 receptors are stimulated, a decrease in the function of the effector organ is observed.
However, different types of receptors coexist in many tissues.
The localization and ratio of a- and b-adrenergic receptors determines the effect of irritation of adrenergic nerves, as well as the reaction to adrenomimetic substances that excite a- and b-adrenergic receptors.
Adrenergic receptors take part in the regulation of carbohydrate and fat metabolism. Excitation of adrenergic receptors by adrenomimetics is accompanied by activation of adenylate cyclase, which leads to the breakdown of glycogen and the release of free fatty acids from adipose tissue.
Pharmacological effects on adrenergic transmission of nerve impulses can occur through the influence on the synthesis, deposition, inhibition of enzymatic inactivation of norepinephrine, the release of norepinephrine from the endings, disruption of the process of reuptake of norepinephrine by presynaptic endings and through a direct effect on adrenergic receptors.
Most often in medical practice, substances that affect adrenergic receptors are used.
Substances that stimulate them are called adrenergic agonists, and those that inhibit them are called adrenergic blockers.
Taking into account the preferential localization of action, the main means influencing the transmission of excitation in adrenergic synapses are divided into:
1. Substances acting directly on adrenergic receptors:
a) direct-acting adrenergic agonists - norepinephrine hydrotartrate, adrenaline hydrochloride, isadrin, etc.;
b) Adrenergic blockers - phentolamine, anaprilin;
2. Substances affecting the release and/or deposition of norepinephrine:
a) sympathomimetics or adrenergic agonists of indirect action - ephedrine hydrochloride;
b) sympatholytics - octadine, reserpine.
Medicines that excite adrenergic structures (adrenergic agonists)
Adrenomimetic or sympathomimetic drugs are drugs that excite adrenergic receptors, i.e., they improve the conduction of excitation in the area of adrenergic innervation.
They are classified:
1. Stimulating a- and b-adrenergic receptors. Adrenaline hydrochloride (hydrotartrate) (b 1, b 2, a 1, a 2), norepinephrine hydrotartrate (a 1, a 2, b 1);
2. Predominantly stimulating b-adrenergic receptors: isadrin (b 1, b 2); salbutamol (b 2); dobutamine (b 1).
3. Stimulating predominantly a-adrenergic receptors: vesaton (a 1); naphthyzine (a 2); galazolin (a 2).
Under the influence of adrenergic agonists, the following main pharmacological effects develop in the body:
a) When stimulating a-adrenergic receptors:
1. Vasoconstriction (especially blood vessels of the skin, kidneys, intestines, coronary vessels, etc.);
2. Contraction of the radial muscle of the iris (mydriasis);
3. Decreased intestinal motility and tone;
4. Contraction of the sphincters of the gastrointestinal tract;
5. Contraction of the spleen capsule;
6. Contraction of the myometrium.
b) When stimulating b - adrenergic receptors:
1. Vasodilation (especially the vessels of skeletal muscles, liver, coronary vessels, etc.);
2. Increased strength and heart rate;
3. Decreased bronchial muscle tone;
4. Decreased intestinal motility and tone;
5. Decreased myometrial tone;
6. Increased glycogenolysis and lipolysis.
The most typical representative of adrenomimetics is adrenaline (Adrenalinum).
It is a biogenic catecholamine. Contained in chromaffin cells, mainly in the adrenal medulla. L-adrenaline salts are used in medical practice. It is obtained synthetically or isolated from the adrenal glands of slaughtered cattle.
Available in the form of adrenaline hydrochloride Adrenalini hydrochloridum - 0.1% solution in ampoules of 1 ml and 0.1% solution in bottles of 10 ml and adrenaline hydrotartrate Adrenalini hydrotartras - 0.18% solution in ampoules of 1 ml and bottles of 10 ml.
Adrenaline has a direct stimulating effect on a- and b-adrenergic receptors. All of the above effects are observed with the administration of adrenaline.
The effect of adrenaline on the cardiovascular system is especially pronounced. By stimulating the b-adrenergic receptors of the heart, adrenaline increases the strength and frequency of heart contractions and, in connection with this, the stroke and minute volume of the heart increases. At the same time, myocardial oxygen consumption increases. There is a reflex excitation of the center of the vagus nerve, which has an inhibitory effect on the heart; as a result, cardiac activity may slow down, and arrhythmias may occur, especially under conditions of hypoxia.
Adrenaline constricts the blood vessels of the abdominal organs, skin and mucous membranes, and, to a lesser extent, the vessels of skeletal muscles. Blood pressure rises.
By stimulating b-adrenergic receptors of the bronchi, it relaxes the smooth muscles of the bronchi and eliminates bronchospasm.
The tone and motility of the gastrointestinal tract under the influence of adrenaline are reduced, the sphincters are toned. The bladder sphincter also contracts.
Ardenaline causes pupil dilation (due to contraction of the radial muscle of the iris, which has adrenergic innervation), increases blood glucose and enhances tissue metabolism, improves the functional ability of skeletal muscles (especially during fatigue).
It usually does not have a pronounced effect on the central nervous system in therapeutic doses. However, anxiety and tremor may occur.
Adrenaline is prescribed subcutaneously, intramuscularly and locally (on the mucous membranes), sometimes intravenously (drop method); in case of acute cardiac arrest, a solution of adrenaline is sometimes administered intracardially. It is not prescribed internally, because it is destroyed in the gastrointestinal tract.
It acts for a short time (with intravenous injection - 5 minutes, with subcutaneous injection - up to 30 minutes), since there is a rapid neuronal uptake of it, as well as enzymatic expansion with the participation of catechol - O - methyltransferase and partly MAO.
Metabolites and small amounts of unchanged adrenaline are excreted by the kidneys.
Used to increase blood pressure and restore heart function in case of threatened weakening or cardiac arrest, collapse, poisoning with drugs and sleeping pills. Used in the diagnosis and treatment of urticaria and other anaphylactic reactions. As a local vasoconstrictor and hemostatic agent for bleeding from the mucous membranes of the nose, eyes, throat by tamponing with a solution of 1: 10,000 for large and 1: 20,000 for small animals. To constrict blood vessels in order to enhance and prolong the effect of local anesthetics, add one drop of official adrenaline solution (0.1%) to 5-10 ml of anesthetic solution. Used to relax bronchial muscles in case of pulmonary emphysema, eliminate hypoglycemic shock in case of insulin overdose (better in combination with glucose).
Contraindicated in hypertension, severe atherosclerosis, aneurysms, thyrotoxicosis, diabetes mellitus, pregnancy, under anesthesia with fluorotane, cyclopropane (arrhythmias are possible).
Doses subcutaneously and intramuscularly (0.1% solution): horses and cattle 3 - 10 ml; sheep and pigs 0.5 - 3 ml; dogs 1 - 5 ml of solution 1: 10000; foxes 0.05 - 0.3 ml.
It should be administered intravenously at a dilution of 1: 10,000 in doses of slightly smaller IM doses.
The use of adrenaline solutions can be repeated after 20 - 30 minutes, since it is quickly destroyed.
Norepinephrine hydrotartrate
Noradrenalini hydrotartras.
White crystalline powder, odorless, easily soluble in water.
The action is associated with a predominant effect on a 1 - adrenergic receptors of blood vessels.
It differs from adrenaline in having a stronger vasoconstrictor and pressor effect, a lesser stimulating effect on heart contraction, a weak bronchodilator effect, and a weak effect on metabolism.
It is used to increase blood pressure during an acute decrease, as well as to stimulate blood pressure during surgical interventions on the sympathetic system.
Administer intravenously (drip). The ampoule solution is diluted in a 5% glucose solution or 0.85% sodium chloride solution so that 1 ml of solution contains 2 - 4 ml of a 0.2% solution (4 - 8 mg).
In case of subcutaneous and intramuscular contact - necrosis.
Release form - 0.2% solution in ampoules of 1 ml.
Mezaton
White or white with a yellowish tint, crystalline powder, odorless. Easily soluble in water and alcohol.
Release form: powder, 1% solution in ampoules of 1 ml.
Mezaton exhibits a longer-lasting effect. It is effective when taken orally.
Used to increase blood pressure. Administered intravenously with glucose solution or isotonic sodium chloride solution.
Subcutaneously and intramuscularly in the form of a 1% solution.
To constrict blood vessels locally.
Izadrin
b-adrenergic stimulator.
White crystalline powder, easily soluble in water.
Release form - 0.5% and 1% solution in bottles of 25 ml and 100 ml (for inhalation); tablets 0.005 g.
It relaxes the bronchi well, but does not cause constriction of peripheral vessels and an increase in blood pressure; at the same time, like adrenaline, it causes increased heart rate and intensification.
It is not widely used in veterinary practice; it can be used for small pets as a bronchodilator in the form of a 0.5% or 1% solution for inhalation.
May cause tachycardia and arrhythmia.
Naphthyzin
a-adrenergic agonist.
Release form: 0.05% and 0.1% solution in 10 ml bottles.
Compared to norepinephrine and mesaton, it causes a longer constriction of peripheral vessels. Increases blood pressure, dilates the pupil. When applied to mucous membranes, it has an anti-inflammatory (decongestant) effect. For rhinitis, it facilitates nasal breathing, reducing blood flow to the venous sinuses.
Prescribed mainly for acute rhinitis, as well as to facilitate rhinoscopy, for inflammation of the maxillary cavities, to stop nosebleeds, for allergic conjunctivitis in the form of 0.05 - 0.1% solutions.
The drug “Sanorin” (Sanorinum) is produced abroad - a white emulsion containing 0.1% naphthyzine (10 ml bottle).
Fethanol
a- and b- adrenomimetic.
Release form - tablets of 0.005 g; 1% solution in ampoules of 1 ml.
White or off-white crystalline powder. Easily soluble in water and alcohol.
Used to increase blood pressure in various hypotensive conditions.
Ephedrine
Ephedra alkaloid.
Used in the form ephedrine hydrochloride - Ephedrine hydrochloride.
Release form - powder, tablets of 0.025; 0.001; 0.002 and 0.003 g; 5% solution for injection in ampoules of 1 ml; 2% and 3% solutions in 10 ml vial for otorhinolaryngological practice.
White needle-shaped crystals and white crystalline powder with a bitter taste. Easily soluble in water.
Its peripheral sympathomimetic effect is similar to that of adrenaline. In contrast, it has a specific stimulating effect on the central nervous system.
It is used to constrict blood vessels and reduce inflammation in rhinitis, as a means to increase blood pressure during surgery, for injuries, blood loss, infectious diseases, and hypotension.
Drugs that inhibit adrenergic structures (adrenergic blockers)
The mechanism of action of adrenolytic drugs is that they block adrenergic receptors of effector organs and the latter lose the ability to interact with the adrenergic mediators norepinephrine and adrenaline, causing the transmission of excitation to effector organs and tissues to temporarily stop. They do not affect the transmission of excitation in the ganglia.
It is easier to block the action of adrenaline than norepinephrine.
Adrenergic blockers, depending on the predominance of their effect on a- and b-adrenergic receptors, are divided into two groups:
1)a - adrenergic blockers;
2)b - adrenergic blockers.
There are drugs that block both a- and b-adrenergic receptors.
Phentolamine
a- adrenergic blocker.
Phentolamine hydrochloride is used.
Release form: powder and tablets of 0.025 g (25 mg).
White or slightly creamy crystalline powder, slightly soluble in water.
They simultaneously block post- and presynaptic a-adrenergic receptors, which causes tachycardia and increases the tone of the gastrointestinal tract. Strengthens the secretion of gastric glands and dilates the pupil.
Dilates peripheral vessels, which increases blood supply to muscles, skin, and mucous membranes. Blood pressure decreases.
Used for the treatment of trophic ulcers of the extremities, flaccid granulating wounds, bedsores, frostbite.
Prescribed orally after feeding, the dose for dogs is 0.025 g per dose 3 - 4 times a day.
Phenthalamine methosulfonate - dilates blood vessels, blood pressure decreases. Used for hypertension.
Tropaphen
a- adrenergic blocker.
White or white with a faint grayish-creamy tint crystalline powder. Easily soluble in water.
Release form: powder in ampoules containing 0.02 g of lyophilized tropafene.
Strongly dilates peripheral blood vessels and causes a decrease in blood pressure.
Used for the treatment of diseases associated with impaired peripheral circulation (endarteritis, trophic ulcers of the extremities and slow-healing wounds).
Ergot alkaloid derivatives.
A large group of dihydrogenated derivatives of ergot alkaloids (dihydroergotamine, dihydroergotoxin, etc.) has a-adrenergic blocking properties.
Used for peripheral circulation disorders.
Uterine drugs
Uterine products are substances that affect motility, tone and rhythmic contractions of the muscles of the uterus.
Contractile activity and myometrial tone are regulated by neurohumoral mechanisms. The myometrium contains M-cholinergic receptors, as well as a- and b2-adrenergic receptors. Stimulation of M-cholinergic receptors and a - adrenergic receptors causes a stimulating effect, and b 2 - adrenergic receptors - an inhibitory effect. In addition, female sex hormones - estrogens, the hormone of the posterior pituitary gland - oxytocin, as well as prostaglandins - have a significant stimulating effect on contractile activity. At the same time, there are endogenous substances that inhibit the contractile activity of the myometrium (progesterone).
Substances that primarily affect the contractile activity and tone of the uterus are divided into:
1. Drugs that primarily increase myometrial tone
Herbal preparations (alkaloids and ergot preparations: ergometrine maleate, thick ergot extract, ergotal, etc.)
Synthetic products
Cotarnine chloride.
II. Drugs that primarily affect the contractile activity of the myometrium:
Strengthening contractile activity
oxytocin, pituitrin, dinoprost.
Weakening contractile activity
a) substances that primarily stimulate b 2 - adrenergic receptors
fenoterol, solbutamol.
b) drugs for anesthesia
sodium hydroxybutyrate
c) different means
magnesium sulfate.
III. Drugs that lower cervical tone
Atropine sulfate, dinoprost, dinoprostone.
By origin:
1. Herbal (preparations of ergot, shepherd's purse, water pepper, Sophora thickcarp, Spherophysa salina);
2. Hormonal (pituitrin, oxytocin);
3. Preparations of the prostaglandin group (dinoprost, dinoprostone);
4. Synthetic (cotarnine chloride).
Uterine remedies are used for weak labor, uterine bleeding, to remove the placenta, accelerate the reverse development of the uterus in the postpartum period, and remove dead and mummified fetuses.
Drugs that primarily increase myometrial tone are used mainly to stop uterine bleeding. The principle of their action is a persistent increase in myometrial tone and, as a result, mechanical compression of small vessels. For this purpose, ergot alkaloids, its galenic and novogalenic preparations and some synthetic agents are widely used.
Ergot (uterine horns)
Secale cornutum.
Contains alkaloids that are derivatives of lysergic acid (ergotamine, ergosine, ergocristine, ergocornine, ergometrine, etc.).
Ergot alkaloids increase the tone of the myometrium, as well as the smooth muscles of internal organs and blood vessels, have a-adrenergic blocking properties (ergocristine, ergocornine), have a calming effect on the central nervous system, inhibit the vasomotor center, stimulate the centers of the vagus nerves, and the vomiting center.
With long-term use or administration in large doses, they cause vasospasm and endothelial damage, chronic poisoning (ergotism).
Used to stop uterine bleeding, facilitate separation of the placenta, and to remove a dead fetus. It is administered orally in the form of mixtures, powders, boluses, pills, porridges, and less commonly, infusions and decoctions.
Doses: horses 12 - 25 g; cattle 15 - 50 g; small cattle 5 - 15 g; pigs 2 - 10 g; birds 0.2 - 0.5 g.
Galenic and novogalenic preparations:
Extractum Secalis cornuti fluidum.
Extractum Secalis cornuti spissum.
Ergotalum - tablets of 0.0005 and 0.001; 0.05% solution for injection in amp. 1 ml each;
Ergotalum (hydrotartrate) 0.05% solution in ampoules of 1 ml; 0.1% solution in 10 ml bottles; tablets, dragees 0.001 g;
Ergometrine maleate - tablets 0.0002 g; 0.02% solution in ampoules of 0.5 and 1 ml;
Methylergometrine - 0.02% solution in ampoules of 1 ml; tablets of 0.000125 g.
Shepherd's purse grass
Herba Bursae pastoris.
Contains choline, acetylcholine, tyramine, organic acids, saponins, etc.
Used in the form of infusions and liquid extract (Extractum Bursae pastoris fluidum) for uterine atony and uterine bleeding.
Doses: horses and cattle 15 - 60 g; small cattle 5 - 12 g; pigs 3 - 10 g; dogs 0.5 - 2 g; poultry 0.2 - 0.5 g.
Water pepper herb
Herba polygoni hydropiperis.
Contains rutin, quercetin and other flavonol derivatives (2 - 2.5%), tannins (3.8%), essential oil, organic acids.
Doses for pigs 1 - 5 g, dogs 0.5 - 2 g.
Extractum Stachydis betonicaeflorae fluidum.
Tincture of leaves of barberry (Tinctura foliorum Berberis.
Hormonal uterine products .
Oxytocin
A hormone produced by neurosecretory cells of the hypothalamus and accumulated in the posterior lobe of the pituitary gland, from which it is released into the blood. Obtained synthetically.
Release form: ampoules of 1 ml, bottles of 100 ml, solution containing 5 or 10 ED oxytocin in 1 ml.
Stimulates labor in the uterus, causing powerful regular contractions of its muscles, and stimulates the release of milk from the mammary gland in lactating animals.
Used for weak labor attempts (when the cervix is dilated, otherwise uterine rupture is possible), for stimulation of the uterus after cesarean section, for atony, hypotension and inflammation of the uterus, for removing the placenta, stopping bleeding and accelerating the involution of the uterus, for agalactia of pigs, cows, for treatment of mastitis.
Administered intravenously, subcutaneously, epidurally, intramuscularly.
Doses in units: subcutaneous intravenous epidural
cows and mares 30 - 60; 20 - 40; 15 - 30;
sows up to 200 kg 30; 20; 10 - 15;
sheep and goats 10 - 15; 8 - 10;
dogs 5 - 10; 2 - 10.
cats 3 2
Pituitrin for injection
Pituitrinum pro injectionibus.
Aqueous extract of the posterior lobe of the pituitary gland of slaughter cattle.
Colorless transparent liquid with the smell of phenol (preservative).
Release form - in ampoules of 1 ml containing 5 and 10 units of pituitrin.
The active ingredients of pituitrin are the hormones of the posterior pituitary gland - vasopressin and oxytocin. Vasopressin constricts arterioles and capillaries, increases blood pressure, and acts as an antidiuretic, stimulating the reabsorption of water in the renal tubules. Oxytocin enhances the contraction of the smooth muscles of the uterus and gastrointestinal tract, and stimulates the secretion of milk from the mammary glands.
Used to enhance uterine contractions during weak pushing, uterine bleeding, and intestinal atony.
Injected subcutaneously.
Doses: horses and cattle 3 - 5 ml; small cattle 0.5 - 1 ml; pigs 0.5 - 1 ml; dogs 0.1 - 0.3 ml.
Prostaglandins have received much attention in recent years. These are active biogenic compounds found in many tissues and organs. They are designated by letter indices (E, F, etc.). Many of the prostaglandins have a pronounced stimulating effect on the myometrium, which manifests itself in the pregnant uterus at all stages of pregnancy, and for some prostaglandins in the non-pregnant uterus.
Dinoprost (Enzaprost)
Dinoprost (prostoglanid F 2 a).
Release form: liquid in ampoules of 1 ml and 5 ml.
It has a pronounced stimulating effect on the myometrium. Causes rhythmic contractions and increased tone of the pregnant and non-pregnant uterus, along with dilation of the cervix, shortens the period of functioning of the cyclic corpus luteum and pregnancy.
Used in animal husbandry to synchronize heat in horses, cows, sheep, pigs in combination with FFA, in the biotechnology of embryo transfer, to normalize uterine involution in the postpartum period; for chronic endometritis, removal of a mummified fetus, delayed calving, corpus luteum cyst, lack of heat and estrus.
Doses IM: horses 1 ml; cows 4 ml; heifers 3 ml; pigs 4 ml; dogs 1 ml.
Estrofan
Synthetic analogue of prostaglandin F 2 a.
Release form: liquid in 2 ml ampoules containing 250 mcg of the drug per 1 ml.
Indications are the same as for dinoprost.
However, estrofan exhibits a more pronounced luteolytic effect. During the sexual cycle, it causes regression of the corpus luteum and promotes the development of follicles, which causes a faster (after 46 - 70 days) onset of heat and estrus.
Subcutaneous doses: cows 2 ml; sows 0.7 ml.
Spherophysin benzoate
Sphaerophysini benzoas.
An alkaloid isolated from the plant Spherophysa salsa.
White crystalline powder, bitter taste, easily soluble in water.
Has ganglion-blocking activity. One of the features of the drug is its stimulating effect on the muscles of the uterus.
Release form: powder, tablets, 0.03 g; 1% solution in ampoules of 1 ml.
Isoverine
White or white with a slightly creamy tint crystalline powder. Easily soluble in water.
Its pharmacological properties are similar to spherophysin.
Release form - amp. 1 ml of 2% and 5% solution and tab. 0.1 g each
Cotarnine chloride (Cotarnini chloridum - powder, tablet 0.05 g) also has a stimulating effect on the muscles of the uterus.
Drugs that relax the muscles of the uterus (tocolytics).
To reduce the contractile activity of the uterus (mainly when there is a threat of premature birth), various drugs with neurotropic and myotropic effects (sedatives, anticholinergics, antispasmodics, etc.) are used.
In recent years, beta-agonists have also been prescribed for this purpose.
They also improve uteroplacental blood circulation (not only by relaxing the myometrium, but also by dilating arterioles and increasing blood flow).
Hanegif(isoxsuprine).
Relaxation of the uterus begins 10 - 15 minutes after application and continues for 1.5 - 2 hours. Used for spontaneous contractions of the uterus, premature contractions and pushing, obstetrics (improper position of the fetus) and operations on the uterus, including cesarean section . The effect of the drug can be removed by intravenous administration of oxytocin.
In addition, partusisten, salbupart, ritodrine, and giniprol are used.
Adrenergic drugs stimulate the sympathetic nervous system. Adrenergic drugs are also called sympathomimetic drugs.
The sympathetic nervous system is part of the autonomic nervous system, which begins in the thoracic region (chest) and extends to the lumbar spinal cord (low back). The sympathetic nervous system stimulates heart rate, sweating, breathing rate, and other stress-related processes in the body.
Use of adrenergic drugs
Adrenergic drugs have many uses. They are used, for example, to raise low blood pressure, or increase urine flow as part of the treatment of certain conditions. Adrenergic agents are also used as cardiac stimulants. They may be prescribed to prevent the drop in blood pressure that is sometimes caused by general anesthesia or may be used to stop bleeding by causing blood vessels to constrict. This ability to constrict blood vessels makes adrenergic drugs useful in combating nasal congestion associated with colds and allergies. Adrenergic agents may also be recommended in the treatment of asthma and chronic obstructive pulmonary disease (COPD).
Types of adrenergic drugs
There are several types of adrenergic receptors in the human body, and although all types of nerve endings respond to adrenergic drugs, the effect depends on whether specific receptors are properly stimulated.
So alpha receptors make the heart beat faster, the pupils of the eyes dilate, and the muscles contract. At the same time, beta receptors have similar effects, but also lead to bronchodilation. Alpha and beta receptors are divided into subgroups - alpha 1, alpha 2, beta 1 and beta 2, each of which has its own specific effects. A hormone called norepinephrine, which is secreted in the body, affects all types of adrenergic receptors; drugs used in medicine and surgery are designed to affect only certain types of receptors.
Based on the above, several adrenergic drugs of general use can be distinguished:
- albuterol and domestic analogues: taken orally, also available in the form of a nasal spray to ease breathing,
- dobutamine and related forms: used to stimulate the heart during surgery, after a heart attack or cardiac arrest,
- dopamine: used to increase cardiac output, blood pressure and urine flow in the treatment of patients with shock,
- epinephrine: used locally to control bleeding from arterioles and capillaries during surgery, to treat shock as a cardiac stimulant and as a decongestant,
- phenylephrine and Russian analogues: used to treat shock and low blood pressure, and as nasal drops or sprays to relieve nasal congestion from colds and allergies,
- Metaraminol and drugs containing it: used to increase blood pressure and stimulate the heart in the treatment of patients with shock,
- norepinephrine (norepinephrine): used to increase heart performance and raise blood pressure as part of the treatment of shock.
Recommended dosages of adrenergic drugs depend on the specific compound used, the purpose for which it is intended, and the route of administration (oral or intravenous). People who use adrenergic drugs to treat breathing problems or conjunctivitis should not use them on an ongoing basis as an alternative to professional therapy. Adrenergic drugs may only temporarily relieve the symptoms of some diseases, but they do not treat the underlying problems, which can be quite serious.
Precautionary measures
The use of adrenergic drugs during surgery is supervised by an anesthesiologist or other medical professional in the field. The following are just some of the dangers associated with the use of adrenergic drugs. Patients under anesthesia may not be aware of the side effects they experience.
Adrenergic drugs may cause:
- fast heartbeat,
- arrhythmia,
- chest pain,
- dizziness,
- dry mouth,
- headache,
- nausea,
- vomiting
- weakness.
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Before undergoing procedures that may involve the use of adrenergic drugs, patients should tell their doctor if they have:
- glaucoma,
- liver diseases,
- enlarged heart
- disorders affecting arteries and veins,
- diseases and disorders affecting the blood supply to the brain.
Side effects and interactions
The most common side effects of adrenergic drugs are nervousness, agitation, and sleep disturbances. These side effects usually do not cause problems when the drugs are used once during surgery or in combination with local anesthetics. When adrenergic drugs are used to treat nasal congestion due to allergies or infections, the following side effects may occur:
Other less common side effects may also occur with adrenergic drugs.
Adrenergic agents can interact with many different types of drugs. You should discuss the use of these medications with your pharmacist or doctor. Some drugs that interact with adrenergic drugs should not be taken several days before surgery.
Drugs that may interact with adrenergic drugs include:
- furazolidone,
- tricyclic antidepressants,
- guanethidine and its varieties,
- methyldopa (dopegyt).
Medicinal herbs may also interact with adrenergic drugs and include ephedra, St. John's wort, alfalfa, hibiscus, ginseng, angelica, and yohimbe.
The above lists do not include all drugs or herbs that may interact with adrenergic drugs. You should consult your doctor or pharmacist before taking adrenergic drugs and any other medicine together.
Denial of responsibility: The information presented in this article about adrenergic agents is intended to inform the reader only. It is not intended to be a substitute for advice from a healthcare professional.
