Medicines that affect the functions of the respiratory system. Respiratory stimulants (respiratory analeptics) Reflex-type breathing stimulant drug

Respiratory stimulants are a group of drugs used for respiratory depression. Based on their mechanism of action, respiratory stimulants can be divided into three groups:

1. central action: bemegride, caffeine (see Chapter 16 “Analeptic drugs”);
2. reflex action: lobelia, cytisine (see page 106);
3. mixed type of action: niketamide (cordiamin), carbon dioxide (see Chapter 16 “Analeptic drugs”).

1. 7% CO2 and 93-95% oxygen). The stimulating effect of carbogen on breathing develops within 5-6 minutes.

Department of Pharmacology

Lectures on the course “Pharmacology”

Topic: Drugs affecting respiratory function

Assoc. ON THE. Anisimova

In the treatment of acute and chronic respiratory diseases, which are widespread in medical practice, drugs from various groups can be used, including antimicrobial, antiallergic and other antiviral.

In this topic, we will consider groups of substances that affect the functions of the respiratory apparatus:

1. Breathing stimulants;

2. Bronchodilators;

3. Expectorants;

4. Antitussives.

I. Respiratory stimulants (Respiratory analeptics)

Respiratory function is regulated by the respiratory center (medulla oblongata). The activity of the respiratory center depends on the content of carbon dioxide in the blood, which stimulates the respiratory center directly (directly) and reflexively (through the receptors of the carotid glomerulus).

Causes of respiratory arrest:

a) mechanical blockage of the respiratory tract (foreign body);

b) relaxation of the respiratory muscles (muscle relaxants);

c) direct inhibitory effect on the respiratory center of chemical substances (anesthetics, opioid analgesics, hypnotics and other substances that depress the central nervous system).

Breathing stimulants are substances that stimulate the respiratory center. Some means stimulate the center directly, others reflexively. As a result, the frequency and depth of breathing increases.

Substances of direct (central) action.

They have a direct stimulating effect on the respiratory center of the medulla oblongata (see the topic “Analeptics”). The main drug is etimizol . Etimizole differs from other analeptics:

a) a more pronounced effect on the respiratory center and a lesser effect on the vasomotor;

b) longer action – intravenous, intramuscular – the effect lasts for several hours;

c) fewer complications (less tendency to depletion of function).

Caffeine, camphor, cordiamine, sulfocamphocaine.

Substances of reflex action.

Cititon, lobeline – stimulate the respiratory center reflexively due to the activation of N-XP of the carotid glomerulus. They are effective only in cases where the reflex excitability of the respiratory center is preserved. Administered intravenously, the duration of action is several minutes.

The drug can be used as a respiratory stimulant carbogen (a mixture of 5-7% CO 2 and 93-95% O 2) by inhalation.

Contraindications:

Asphyxia of newborns;

Respiratory depression due to poisoning with substances that depress the central nervous system, CO, after injuries, operations, anesthesia;

Restoring breathing after drowning, muscle relaxants, etc.

Currently, breathing stimulants are rarely used (especially reflex ones). They are used if there are no other technical possibilities. And more often they resort to the help of an artificial respiration apparatus.

The introduction of an analeptic gives a temporary gain in time, which is necessary to eliminate the causes of the disorder. Sometimes this time is enough (asphyxia, drowning). But in case of poisoning or injury, a long-term effect is required. And after analeptics, after a while the effect wears off and the respiratory function weakens. Repeated injections →PbD + weakening of respiratory function.

II. Bronchodilators

These are substances that are used to eliminate bronchospasms, as they dilate the bronchi. Used for bronchospastic conditions (BSS).

BSS associated with increased bronchial tone can occur in various diseases of the respiratory tract: chronic bronchitis, chronic pneumonia, some lung diseases (emphysema); in case of poisoning with certain substances, inhalation of vapors or gases. Bronchospasm can be caused by drugs, chemotherapy, V-AB, reserpine, salicylates, tubocurarine, morphine...

Bronchodilators are used in the complex treatment of bronchial asthma (attacks of suffocation due to bronchospasm; infectious-allergic and non-infectious-allergic (atopic) forms are distinguished).

Substances from various groups have the ability to expand the bronchi:

β 2 -AM (α,β-AM),

Myotropic antispasmodics,

Various means.

Bronchodilators are usually used by inhalation: aerosols and other dosage forms (capsules or discs + special devices). But they can be used enterally and parenterally (tablets, syrups, ampoules).

1. Widely used adrenomimetics , which influence β 2 -AR , the activity of the sympathetic nervous system increases, there is a decrease in smooth muscle tone and dilation of the bronchi (+ ↓ release of spasmogenic substances from mast cells, since ↓ Ca ++ and no degranulation).

Selective β 2 -AMs are of greatest practical importance:

Salbutamil (Ventolin),

Fenoterol (Berotek),

Terbutaline (Bricanil).

Less selectivity: Orciprenaline sulfate (asthmopent, alupent).

PC: relief and prevention of bronchial asthma attacks - 3-4 times a day.

When used inhalation in the form of aerosols, as a rule, there are no side effects. But in high doses (orally), headaches, dizziness, and tachycardia may occur.

With long-term treatment with β 2 -AM, addiction may develop, since the sensitivity of β 2 -AR decreases and the therapeutic effect is weakened.

Complex preparations: “Berodual”, “Ditek”, “Intal plus”.

Non-selective AMs can be used to eliminate bronchospasm, but they have many side effects:

Izadrin – β 1 β 2 -AR – effect on the heart, central nervous system; solution / inhalation; pills; aerosols;

Adrenalin - α,β-AM – ampoules (relief of attacks);

Ephedrine - α,β-AM – ampoules, tablets, combined aerosols.

PbD: blood pressure, heart rate, central nervous system.

Breathing is regulated by the respiratory center located in the medulla oblongata. The activity of the respiratory center depends on the content of carbon dioxide in the blood, which stimulates the respiratory center directly and reflexively, stimulating the receptors of the sinocarotid zone. Respiratory cessation can occur as a result of mechanical blockage of the respiratory tract (aspiration of liquids, entry of foreign bodies, spasm of the glottis), relaxation of the respiratory muscles under the influence of muscle relaxants, sharp depression (paralysis) of the respiratory center by various poisons (anesthetics, sleeping pills, narcotic analgesics, etc. ).

If breathing stops, urgent help is required, otherwise severe asphyxia occurs and death occurs. Of particular interest to pharmacology is the danger of depression of the respiratory center during poisoning with medicinal substances. In such cases, respiratory stimulants are prescribed that directly excite the respiratory center: corazol, etc. (see).

Respiratory analeptics of reflex action (,) in such cases are ineffective, since the reflex excitability of the respiratory center is impaired. Cititon and lobelia are used, for example, for asphyxia of newborns and carbon monoxide poisoning.
Etimizole occupies a special place among respiratory stimulants. It activates the centers of the medulla oblongata and has a sedative effect on the cerebral cortex and reduces anxiety.

In mixed-type analeptics (carbon dioxide), the central effect is supplemented by a reflex effect with the participation of chemoreceptors of the carotid glomerulus. In medical practice, a combination of C02 (5-7%) and 02 (93-95%) is used. This mixture is called carbogen.

The use of analeptics to stimulate breathing in cases of poisoning with drugs that depress the respiratory center is currently limited. This is due to the fact that with severe respiratory depression, the administration of analeptics can cause an increase in the need of brain cells for oxygen and aggravate the state of hypoxia. It is advisable to use analeptics in small doses for mild to moderate poisoning.

Respiratory analeptics- these are substances that directly or reflexively stimulate the respiratory and vasomotor centers.

Classification of respiratory analeptics.

I. Direct acting drugs. Direct-acting analeptics that directly stimulate the respiratory and/or vasomotor centers

• bemegrid
• etimizol
• caffeine

II. Reflex drugs (N - cholinomimetics). Analeptics of reflex action, which can have a stimulating effect on the ganglia of the autonomic nervous system and carotid glomeruli

• lobeline
• cititon

III. Mixed-action drugs.

• cordiamine
• camphor
• sulfocamphocaine

Mechanism of action of analeptics.

1. N-cholinomimetics.
They activate the chromaffin cells of the carotid glomeruli and reflexively stimulate the respiratory center along the Hering nerves, as a result of which the frequency and depth of respiratory movements increases.
2. Direct acting drugs.
The drugs directly increase the excitability of the cells of the respiratory center.
Etimizole inhibits phosphodiesterase, which leads to increased
c-AMP, and this in turn increases the metabolism of neurons of the respiratory center, stimulates the process of glycogenolysis, and increases the release of calcium ions from the endoplasmic reticulum.

Pharmacodynamics.

1. Stimulates breathing. It manifests itself in conditions of suppression of the functions of the respiratory center and a decrease in its activity to physiological stimulation (CO 2). Restoration of external respiration functions is usually unstable. Repeated administration may cause convulsive reactions.
2. Stimulate the vasomotor center. The tone of resistive and capacitive vessels increases, which leads to increased venous blood return and increased blood pressure. This effect is most pronounced in camphor and cordiamine.
3. Anti-drug effect. The effect is manifested in a temporary weakening of the depth of depression of the central nervous system, clarification of consciousness and improved coordination of movement. Drugs are indicated if depression does not reach the level of anesthesia. The most pronounced effect is found in bemegride and corazole.

Indications for use.

1. Exacerbation of chronic lung diseases, occurring with symptoms of hypercapnia, drowsiness, loss of coughing.
2. Respiratory arrest in premature newborns (Etimizol is used)
3. Hypoventilation of the lungs in case of poisoning with drugs that depress the central nervous system, carbon monoxide, during drowning, in the postoperative period.
4. Collaptoid state.
5. Poor cerebral circulation (fainting).
6. Weakening of cardiac activity in older people.

§ Direct-acting analeptics stimulate the respiratory and/or vasomotor centers by reducing the threshold of excitability of these centers, which leads to an increase in their sensitivity to humoral and nervous stimuli.

Analeptics of reflex action excite the ganglia of the autonomic nervous system and carotid glomeruli. From the receptors of the syncarotid zone, impulses travel along afferent pathways to the medulla oblongata and stimulate the respiratory and vasomotor centers.

An analeptic of mixed action, Niketamide has a direct activating effect on the vasomotor center (especially when its tone decreases), and also indirectly (due to stimulation of the chemoreceptors of the carotid sinus) is able to excite the respiratory center.

With the use of analeptics, breathing is stimulated and cardiovascular activity is enhanced.

§ Pharmacokinetics

Niketamide is well absorbed from the gastrointestinal tract and from parenteral administration sites. Subject to biotransformation in the liver. Excreted by the kidneys.

Sulfocamofcaine is rapidly absorbed after subcutaneous and intramuscular administration.

§ Place in therapy

§ Acute and chronic heart failure (in complex therapy).

§ Acute and chronic respiratory failure (in complex therapy).

§ Cardiogenic and anaphylactic shock.

§ Respiratory depression due to pneumonia and other infectious diseases.

§ Asphyxia (including newborns).

§ Poisoning with sleeping pills (barbiturates) and narcotic drugs.

§ Removal from anesthesia (caused by the use of barbiturates and other drugs).

§ Camphor preparations for topical use are prescribed for myalgia, rheumatism, arthritis, and bedsores.

§ Contraindications

§ Hypersensitivity.

§ Tendency to convulsive reactions.

§ Epilepsy.

§ Side effects

§ Nausea.

§ Muscle twitching.

§ In case of overdose, the following are possible:

§ Convulsions.

§ Precautionary measures

Analeptics are used under medical supervision.

When administering bemegride to children, the dose of the drug should be reduced by as many times as the child’s weight is less than the average body weight of an adult.

SC and IM injections of niketamide are painful. To reduce pain, novocaine can be injected into the injection site.

Caution must be exercised when administering sulfocamphocaine to patients with low blood pressure due to the possibility of developing the hypotensive effects of this drug.

§ Interactions

Niketamide enhances the effects of psychostimulants and antidepressants. Weakens the effect of narcotic analgesics, sleeping pills, neuroleptics, tranquilizers and anticonvulsants.

Bemegride injections can be combined with the administration of mezatone and caffeine.

Analeptics: Cititon, Lobelia, Camphor, Strychnine, Securenine

Analeptics(from the Greek analepsis - restoration, revival) are called medicinal substances that primarily excite the centers of the medulla oblongata - vasomotor and respiratory. In large (toxic) doses, they also stimulate the motor areas of the brain and cause seizures. The main representatives of this group are cordiamine, camphor, bemegride, carbon dioxide. Psychostimulants and strychnine have moderate analeptic properties. Respiratory analeptics also include cititon, lobelia, and etimizol.

There is mutual antagonism between analeptics and drugs that depress the central nervous system (anesthetics, sleeping pills, narcotics, analgesics). The differences between these analeptics lie in their activity, mechanism of action, its duration and the presence of individual pharmacological properties.

Corazol, bemegride, camphor, strychnine, cordiamine, and caffeine have a direct stimulating effect on the respiratory and vascular centers. Therefore, they are often called direct-acting analeptics. Among them, the most active are corazol and bemegride. In case of poisoning with narcotic and hypnotics (especially barbiturates), bemegride is the most active analeptic.

Carbon dioxide has a direct and reflex (through receptors of the sinocarotid zone) effect on the centers of the medulla oblongata. Constantly formed in the body during the metabolic process, it is a physiological stimulator of the respiratory center. In medical practice, carbon dioxide is used for inhalation in a mixture with oxygen or air. A mixture of carbon dioxide (5-7%) and oxygen (95-93%) is called carbogen.

Respiratory analeptics cititon And lobelia excite the respiratory center reflexively (through receptors of the sinocarotid zone), act for a short time and are effective only when administered intravenously and maintaining the reflex excitability of the respiratory center. In case of sharp depression of the latter, for example, in case of poisoning with sleeping pills or other substances, cititon and lobelia have no effect. However, by stimulating the ganglia of the autonomic nerves and the adrenal medulla, they contribute to an increase in blood pressure.

Etimizole has a direct stimulating effect on the respiratory center and, to a lesser extent, on the vasomotor center. Stimulation of breathing is prolonged and is especially pronounced when breathing is suppressed by morphine. In addition to analeptic properties, etimizol has a moderate tranquilizing effect and somewhat enhances the effect of narcotic and sleeping pills. Therefore, it can be used during and after surgical anesthesia. In connection with the stimulation of the adrenocorticotropic function of the pituitary gland, etimizol is also used as an anti-inflammatory and antiallergic agent.

Camphor along with the central analeptic effect, it has a direct stimulating effect on the heart and increases the sensitivity of the myocardium to the influence of sympathetic nerves and adrenaline. The local action of camphor is characterized by irritant and antimicrobial effects. Camphor alcohol is widely used for rubbing into the skin in the hope of a distracting effect for arthritis, myositis and other inflammatory diseases.

In medical practice, an oil solution of camphor is used for subcutaneous injection as an analeptic and cardiotonic agent, and also externally as a distracting agent. Camphor is relatively non-toxic to the body, and only when the dose is significantly exceeded (up to 10 g) can convulsions occur. Corazol is more toxic, causing characteristic clonic convulsions. In case of corazol poisoning, drugs that have an anticonvulsant effect (hypnotics, narcotics, etc.) are prescribed.

Drugs that stimulate the central nervous system also include substances that primarily tonic the cells of the spinal cord (strychnine, securenine), various herbal preparations and some organ preparations.

Strychnine- an alkaloid found in some plants of the genus Strychnos, growing in the tropics. In medical practice, strychnine nitrate is used, as well as chilibuha tincture and extract. The action of strychnine is directed mainly to the spinal cord. In therapeutic doses, it improves the conduction of impulses in the spinal cord and tones skeletal muscles. In addition, it stimulates the centers of the medulla oblongata (respiratory, vascular) and improves the function of the senses (hearing, vision, smell).

According to modern concepts, strychnine blocks the action of amino acid neurotransmitters, mainly glycine, which play the role of inhibitory factors in the transmission of excitation in postsynaptic nerve endings in the spinal cord.

In clinical practice, strychnine is used as a general tonic for hypotension, paralysis and other dysfunctions of the spinal cord and sensory organs. It should be noted that currently the clinical use of strychnine is limited due to its high toxicity. The alkaloid securenine is less toxic (and less active) (isolated from the Securinega subshrub that grows in our country).

Poisoning with strychnine or securenine causes severe attacks of tetanic convulsions. During an attack, the body arches (opisthotonus) and breathing stops. Death occurs from asphyxia. When providing assistance, it is necessary first of all to relieve seizures with narcotic drugs or muscle relaxants (with artificial respiration). After eliminating the convulsions, the stomach is washed (if the poison was taken orally) with a solution of potassium permanganate (1:1000), then activated charcoal and a laxative salt are injected into the stomach.

Related information.

Many medications stimulate breathing differently and their mechanism of action is different. Often, when the dose is increased, stimulation turns into respiratory depression up to apnea, for example, in case of poisoning with aminophylline (neophylline, etc.).

Depending on the place of action on the central nervous system, stimulants are divided into: spinal, brainstem, cerebral, and reflex-acting. Small doses of strychnine have no effect on breathing, but when the central nervous system is depressed with medications, it causes increased and deepening of breathing, although this effect is weaker than cardiazol and picrotoxin. Picrotoxin has a weak effect on the breathing of healthy people, but in case of poisoning, in particular with barbiturates, it increases the frequency and depth of breathing. Pentetrazole is preferred for poisoning with neobarbiturates (but not for poisoning with morphine, methadone, etc.) over picrotoxin. In acute barbiturate poisoning, pentetrazole is administered intravenously (5 ml of a 10% solution) in order to establish the depth of coma, as well as to treat poisoning. Based on experiments, it is argued that of the classical stimulants of the central nervous system, only picrotoxin and pentetrazole have a sufficient analeptic effect, and caffeine, ephedrine, amphetamine, cordiamine, strychnine are not able to counteract the effect of lethal doses of barbiturates and only in mild cases can bring them out of a coma. Of the newer stimulants, bemegrin (megimide), pretkamide, etc. should be mentioned, although they are rarely used for poisoning with barbiturates and other hypnotics, since their treatment is based on other principles.

Xanthines also stimulate the respiratory center and are useful for mild to moderate depression. In addition, they also have a bronchodilator effect (aminophylline has the most powerful effect) and are very useful for bronchospasm. It is claimed that atropine sometimes slightly stimulates respiration, but in humans this has only been conclusively proven when high doses of 5 mg are used. In atropine poisoning, on the other hand, coma with rapid and shallow breathing may occur in the later stages, followed by apnea. Atropine, as a weak respiratory stimulant, is not used in the treatment of poisoning with opiates and hypnotics, but is a specific antidote for central respiratory depression that occurs during poisoning with anticholinesterase drugs. Scopolamine stimulates the respiratory center in some people and depresses the respiratory center in others. It is also known that higher doses of cocaine cause centrally mediated tachynea, but respiratory depression occurs later.

Reflexively, through the carotid sinus, stimulation of breathing is caused by lobeline, hellebore alkaloids, etc. Lobelia, in addition, stimulates cough and pain receptors in the pleura. The clinical doses of hellebore alkaloids used do not cause serious respiratory problems. Only sometimes patients complain of a feeling of heaviness in the epigastric region and behind the sternum, and their breathing deepens a little (“sighing breathing”). Under experimental conditions, bradypnea or apnea, caused by a reflex pathway, occurred depending on the dose. The reflex probably occurs due to stimulation of pulmonary stretch receptors. Veratridine, applied locally to the carotid sinus receptors, stimulates respiration. Cholinergic drugs can also be included in this group. Acetylcholine and related cholinergic drugs administered intravenously alter breathing. The respiratory center is affected only with excessively high doses, and breathing is stimulated suddenly and for a short time by reflex with minimal quantities. Hypotension caused by acetylcholine irritates the hemoreceptors of the wall of the aorta and carotid sinus (they suffer from a lack of O2) and stimulates the respiratory center. Hemoreceptors are less sensitive than smooth muscle cells of arterioles, and they are excited directly by acetylcholine, but only administered intravenously in high doses.

Epinephrine and norepinephrine injected into a vein usually stimulate breathing. On the other hand, it is known that during an acute hypotensive reaction to the administration of adrenaline, apnea occurs in anesthetized animals. This was generally thought to be the result of a reflex caused by increased blood pressure. However, much evidence indicates that apnea is caused by direct inhibition of the respiratory center, similar to adrenalin inhibition of nerve transmission in the ganglia. Norepinephrine has a similar effect. The effect of adrenaline, however, on breathing is determined mainly by its bronchospasmolytic effect, which is more pronounced in pathological bronchospasm. In addition, apparently, adrenaline also has a direct effect - in small doses it stimulates, and in large doses it depresses the respiratory center. In case of adrenaline poisoning, in addition to pulmonary edema, breathing disorders without pulmonary edema occur - progressive tachypnea, which can develop into apnea. Dibenamine and other alpha-adrenergic blockers can also stimulate breathing. Hyperventilation becomes especially common when treating epilepsy with sultiam (ospolot), which also causes dyspnea. Direct stimulation of the respiratory center occurs during aspirin poisoning and, in general, during poisoning with salicylates. As a result of hyperventilation, large amounts of CO2 are removed from the body and respiratory alkalosis develops. Later, the direct effect of salicylates develops, in particular in relation to liver and kidney cells (depletion of glycogen, increased cellular metabolism, etc.). This leads to a change in the alkaline-acid balance of the body and disruption of the regulatory function of the kidneys - ketosis and acidosis can develop. The end result in severe poisoning may be oliguria with slightly acidic urine. In young children and infants, metabolite effects predominate from the very beginning. These opinions differ quite significantly from the classical concepts, according to which the toxic effect of salicylates is due to their direct acidotic effect, which is supported by a slight decrease in the alkaline reserve in the blood and “acidotic” Kussmaul respiration. The changes described above are complicated by dehydration, which is caused by hyperventilation. Dehydration leads to dry airway mucosa and can contribute to the development of respiratory infections.