RU2266116C1 - Method for treating the cases of tobacco addiction - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves delivering nicotine to patient organism and administering medicament by smearing internal surface of superior and inferior nasal passage part. Treatment is carried out with cigarette consumption being retained. Smell receptor canal blocker like rapid sodium canal blocker lidocaine is used as the medicament. Its aerosol is introduced immediately before smoking action as single jet in each nasal passage. Medicament introduction is localized with epithelial smell receptor cells arrangement.

EFFECT: enhanced effectiveness of treatment.

2 cl, 2 tbl

Description

The present invention relates to the field of medicine and healthcare and can be used in the treatment of nicotine addiction.

Known methods for the treatment of nicotine addiction are given in a review article by O. V. Vikhireva [1]. With nicotine replacement therapy, the patient should completely give up smoking for the entire course of treatment. Nicotine replacement therapy is the introduction of drugs into the body that are structurally or functionally similar to nicotine or nicotine itself. This replacement therapy relieves withdrawal symptoms that occur when smoking is stopped. A gradual decrease in the dose of a medication intended for substitution therapy ensures, over time, the patient quits smoking tobacco. One way to administer nicotine-containing medications is by aerosol irrigation of the nasal cavity (see page 36 [1]). This method of introducing nicotine ensures its rapid absorption through the mucous membrane of the nasopharynx and oral cavity, stopping attacks of cravings for cigarettes. The dosage of these drugs is directly proportional to the number of cigarettes smoked per day. For a nasal spray, the daily dose is from 8 to 40 single doses, with a maximum of 5 doses per hour. The course of treatment is from three to six months.

The disadvantage of nicotine replacement therapy is the need for the patient to completely stop smoking for the entire course of treatment, which is a strong negative psychoemotional factor for the patient. This affects his psyche and causes early termination of treatment, so many patients do not complete the course of treatment and return to smoking. For those patients who are undergoing a full course of treatment and quit smoking, after it cannot be reliably considered that the reason for quitting smoking was the use of drugs, and not prolonged abstinence from addiction with the help of emotional-volitional effort. Nicotine replacement therapy has a number of contraindications, in particular, it is contraindicated for persons in the acute period of myocardial infarction, with severe cardiac arrhythmias, unstable angina, since nicotine, being a vasoactive drug acting on blood vessels, will undoubtedly worsen the functions of the circulatory system at all levels and can lead to irreversible consequences. Any medication for the treatment of tobacco dependence is contraindicated for smoking patients with severe cardiovascular pathology, since it is impossible to fully predict their possible effect on the patient's body with decompensated activity of the circulatory system.

The closest analogue is a method of treating tobacco dependence by administering nicotine-containing drugs aerosolized into the nasal cavity, from which nicotine is absorbed into the blood using a nicotine spray (see ibid., P. 36 [1]), followed by a decrease in the daily dose to a complete failure from smoking. The route of administration of the drug through the nasopharynx is explained by intensive vascularization of the nasal mucosa, which accelerates the absorption of the drug, on the one hand, and the maximum absorption from the anatomical zone where this occurs under normal conditions, i.e. when smoking, on the other hand (the patient’s habit of absorbing nicotine from the mouth and nose). The disadvantages of this method are all the disadvantages noted above.

The objective of the present invention is to expand the arsenal of methods and means of treating nicotine addiction for a wide range of patients, to facilitate the psychological process of treatment for patients.

To solve this problem, it is necessary first of all to reveal in detail the mechanism of formation of nicotine addiction.

Tobacco dependence in a person is caused by nicotine contained in tobacco. It is rapidly absorbed by the mucous membranes and skin and spreads throughout the body, causing a short-term increase in the activity of brain neurons. The short-term expansion of cerebral vessels and the stimulating effect of ammonia on it, which occurs in parallel with this, create a sensation of a surge of strength, high spirits and calming (see [2]). At the same time, nicotine, being a poison, causes somatic reactions - nausea, dizziness, bradycardia. Thus, the process of forming an addiction to smoking consists of multidirectional mental and somatic reactions. Over time, mental reactions increase, and somatic ones decrease due to the quick adaptation of a person to poisons [3]. The seeming rise in energy, improvement, calmness with a smoked cigarette, gaining a foothold in the mind of a smoking person, pass into a conditioned reflex [2]. The key point in the scheme of formation of tobacco dependence is, according to the author, the constantly present strong smell of burning tobacco, which is a conditioned irritant.

The structural basis of reflex activity is the reflex arc [4]. It consists of receptors that perceive irritation, afferent pathways that carry excitation from the periphery to the central nervous system, intercalary neurons, efferent nerve fibers, and the executive organ. Since, during smoking, the intake of nicotine into the body is perceived only by the chemoreceptors of target organs, i.e. those organs in which the body is able to feel the effects of nicotine, the simultaneous stimulation of olfactory and taste receptors forms an arc of a conditioned reflex - smoking. If you break the reflex arc of the conditioned reflex of tobacco dependence, you can affect the conditioned reflex itself and cure the patient of tobacco dependence. Thus, the "decoding" of the conditioned reflex of smoking can occur by eliminating the constant stimulation of the limbic region of the brain, which is responsible for the formation of emotions, comfort, pleasure, namely the exception of the conditioned stimulus - the smell of burning tobacco. To eliminate the smell of tobacco during smoking, it is necessary to influence the olfactory receptors so that they do not respond to the smell of burning tobacco or change their reaction. Then the smoker during the smoking process will either not smell the tobacco at all or will not feel the usual smell, but a changed, unusual one.

The author’s research has established that temporary or permanent loss of smell to smokers reduces cravings for smoking and facilitates smoking cessation. Without support, the main stimulus - the smell - the reflex dies away. Smokers who persistently lose their sense of smell as a result of injuries and surgical interventions quit smoking on their own without any treatment in 90% of cases. This was established by the author by conducting a postal survey of patients of the Republican Clinical Hospital and the Republican Cancer Center of Tatarstan who lost their sense of smell due to surgical treatment. The research results are shown in Table 1. The reliability of the survey results is evidenced by the correspondence of the smoking / non-smoking distribution in the total number of respondents, the distribution of smokers by gender, social characteristics, and average statistics.

However, it is unreasonable to treat patients from smoking by completely violating their sense of smell, as was the case in the studies described. Based on the results of Table 1, the author has developed his own method of treatment for tobacco dependence. This method is based on the destruction of the conditioned reflex arc of the smoker by temporarily changing its olfactory sensitivity. The sense of smell should only be changed at the time of smoking. A longer change in sense of smell is not required. Accordingly, in order to achieve a result, it is necessary to apply a minimum dose of a short-acting preparation that can affect the olfactory receptors of a smoking person and repeat the administration as necessary until the final result is achieved.

Thus, the method of treatment for tobacco dependence, as in the prototype, includes the supply of nicotine into the patient’s body, using medications that are applied to the inner surface of the upper and middle parts of the nasal passages. The difference from the closest known method is that nicotine is not supplied in the form of medications, but in the usual way during the act of smoking, i.e. the patient is not required to quit smoking during treatment. As a medicament, a blocker of ion channels of the membranes of olfactory cells, in particular, fast sodium channels, which temporarily reduces all types of sensitivity, including olfactory, is used, and the blocker is administered immediately before smoking. Blocking of fast sodium channels is preferable in relation to other ion channels, since they create a receptor action potential, and it is their launch that initiates an excitation wave - a signal of adequate irritation received, propagating to the sensory center in the central nervous system [5]. Inactivation of the sodium channel contributes to the cessation of the action potential and the development of temporary non-excitability - refractoriness. In addition, drugs for their blockade have been developed for a long time and approved for use as medicines. To prevent the generation and conduction of excitation, the use of anesthetics is most acceptable, since it is believed that they act on the inner surface of the membrane of nerve fibers, reducing the membrane permeability to ions, for example sodium, i.e. are ion channel blockers. There is an assumption that the decrease in the ionic permeability of nerve fiber membranes is due to the fact that anesthetics increase the surface tension of membrane phospholipids, which closes the ion channels [6]. Sodium channel blocking agents are used in cardiology and are called membrane stabilizers (quinidine, novocainamide, disopyramide, lidocaine, diphenin, flecainide, propafenone), since they are used for arrhythmias associated with impaired automatism and conduction. Thus, the following medications can be used as blockers:

- lidocaine, 10% aerosol anesthetic;

- cocaine hydrochloride, 1-5% solution or fine powder;

- membrane stabilizing drugs - preventing the change in the membrane potential of the cell, and consequently, the spread of momentum: quinidine, disopyramide, procainamide, mexiletine, phenytoin, flecainide, encainide, propafenone, and other of the above drugs.

All these drugs can be used to block the olfactory receptors, however, the dosage form of lidocaine in the form of a spray makes its use more preferred and more affordable, and only it is available in aerosol packaging.

Calcium channel blockers (phenigidine, felodipine, isradipine, veropamide, diltiazem) also reduce automatism, significantly reduce conductivity and increase the effective refractory period, which makes them suitable for use as a blockade of olfactory receptors.

The preferred form of the anesthetic is aerosol, but in principle, drop solutions can be used to apply the desired effect by applying to the area of the olfactory epithelium by instillation in the nose or lubrication of the nasal cavity with a swab moistened with the drug. The use of powder forms for inhalation is also possible, however, the elimination period for the powder form is longer. The introduction of a medication is localized by the location of the epithelial cells of the olfactory receptors, namely the inner surface of the upper and middle nasal concha and upper sections of the nasal septum.

The duration of treatment is proportional to the length of smoking and the daily dose of tobacco. The dose of the drug is calculated based on the fact that one inhalation modifies (reduces and changes at the same time) olfactory sensations from five minutes to 1 hour, depending on which drug is chosen for treatment - quick or short action. The choice of the drug must be carried out on the basis of anamnestic data on the presence of allergies to anesthetics, individual sensitivity to them and individual average duration of action of the anesthetic. For any drug chosen, a single use implies a single inhalation into the nasal cavity immediately before smoking. The daily dose is equal to the number of cigarettes smoked per day: one cigarette - one inhalation, but should not exceed the maximum daily therapeutic dose. For example, the maximum dose of lidocaine is 40 exposures (irrigation) per day.

During irrigation of the nasal cavity with an anesthetic, the blockade of fast sodium channels temporarily paralyzes all types of sensitivity, including olfactory. The olfactory receptors do not respond to the smell present during smoking, and the patient does not feel it. Due to the exclusion of the main stimulus - the smell, the cessation of standard stimulation of the limbic region of the cerebral cortex during smoking, the inconsistency of sensations during smoking with stereotyped craving for smoking decreases and the reflex fades. The reflex arc breaks. Somatic manifestations: dizziness, cough, nausea, persisting regardless of the degree of violation of the sense of smell, serve as an additional incentive to stop craving for tobacco.

The method was tested in the Tatar Republican Oncology Center during the course of treatment for tobacco dependence of 20 people. The course of treatment consisted of 5 sessions. Each patient underwent preliminary testing of olfactory function for external stimuli and for those placed in the oral cavity. Then, lidocaine aerosol was sprayed with 10%, one dose in each nasal passage. Five minutes after inhalation, the smell functions were retested. All interventions were carried out with preliminary and current control of olfactory function using the olfactory method published in [7]. The dose and number of doses of 1-10 per day were calculated individually for each patient, depending on the form of tobacco dependence: dissociated, ideative, psychosomatic, smoking history, number of cigarettes smoked per day. The total amount of anesthetic administered was no more than 10% by weight of the anesthetic safe for the patient. A single injection provided an incomplete shutdown of the sense of smell within 1 hour. During the day, the spray was carried out during hours of maximum tobacco use. Patients were allowed to smoke when there was a desire to smoke only after an anesthetic was sprayed. In the event of a desire to smoke more than an hour after insufflation, the drug was repeated. After 1-1.5 hours, the sensitivity of the receptors was restored, which was controlled by the above method using an olfactory test kit. The treatment results are shown in Table 2. All patients received anesthetic insufflation 1 time per day. All patients noted changes in the taste of cigarettes during smoking and continued to feel this for 1 hour after insufflation. As can be seen from table 2 according to the results of treatment, with the number of sessions more than two, all patients reduced the number of cigarettes smoked per day. The prognosis of treatment outcome is positive.

None of the currently existing methods for treating tobacco dependence is associated with a change in the quality or intensity of olfactory reception, i.e. with suppression of an arch of a pathological reflex.

The duration of treatment - until the conditioned reflex is completely faded - craving for smoking, according to predicted data is from 2-3 weeks to 2 months.

Table 1 Total smokers Of which have lost their sense of smell Of those who quit smoking IN % 37 people thirty 27 people 90%

table 2 №№ Number of sessions Number of people Form of the disease The number of cigarettes smoked per day Before treatment After treatment 1. 1 session 7 pax (5 men, 2 women) Dissociated - 4
Ideator - 2
Psychosomatic - 1 twenty Without change 2. 2 sessions 5 pax (2 men., 3 women.) Dissociated - 2
Ideator - 2
Psychosomatic - 1 5-20 1 patient reduced the number of cigarettes in 2 times, the rest unchanged 3. 3 sessions 1 pax (1 women) Dissociated twenty Stopped smoking completely 4. 4 sessions 2 pax (2 husband.) Dissociated - 2 20; twenty 8; 6 5. 5 sessions 6 people (3 men., 3 women.) Dissociated - 1
Ideator - 4
Psychosomatic - 1 20-40 All reduced the number of cigarettes 3-4 times

Sources of information

1. O.V. Vikhireva. Modern drug treatments for tobacco dependence (literature review). Disease Prevention and Health Promotion, 2002, No. 3, p. 35, 36 - prototype.

2. Rudenko E.I. Legacy of Jean Nico. M .: Medicine, 1983, p. 32.

3. V.K. Smirnov. Clinic and therapy of tobacco dependence. M .: Soyuzinformbiology, 2000

4. Brief medical encyclopedia. M .: Soviet Encyclopedia, 1973, p. 573.

5. General course in the physiology of man and animals, book 1, M .: Higher school, ed. Nozdracheva A.D., pp. 36-58, 373-382.

6. D.A. Kharkevich. Pharmacology. M .: Medicine, 1999.

7. Bulletin of Otorhinolaryngology, 1988, No. 3. A.E. Kitser, I.M. Prokopiv "Clinical olfactometry."

Claims (2)

1. A method of treating tobacco dependence, comprising supplying nicotine to the patient’s body and using a medication that is applied to the inner surface of the upper and middle parts of the nasal passage, characterized in that the treatment is carried out while maintaining the consumption of cigarettes by blocking or reducing the sensitivity of the olfactory receptors, as medications use the olfactory receptor ion channel blocker - a fast sodium channel blocker in the form of a lidocaine anesthetic, its administration of lock lysed by the location of the olfactory receptor epithelial cells and injected immediately before the act of smoking. 2. The method according to claim 1, characterized in that the injected lidocaine aerosol in the form of a single injection in each nasal passage.