A dangerous complication when using opioids. Poisoning with morphine and other opiates, treatment

Opiates are opium, which is obtained from milk of the poppy capsules or substances synthesized from it - levamethadone, heroin, morphine. Aqueous solutions These substances are used as medicinal materials. These substances can be quite dangerous, since their uncontrolled use results in pronounced euphoria and pathological dependence. These drugs are among the most common drugs that lead to mental and physical dependence.

With the development of a pathological addiction to drugs of the opiate group, the dose of these substances constantly increases, which leads to their accumulation in the body. As a result, an overdose leads to poisoning, one of the main symptoms of which is respiratory paralysis.

Symptoms

Acute poisoning:

pallor, euphoria;

vomiting, nausea;

constriction of the pupils;

dilated pupils;

disruption of activity circulatory system and hearts;

respiratory depression;

Chronic opiate poisoning:

disturbance of consciousness;

urinary disturbance;

When the body is intoxicated with opiates, severe nausea immediately occurs, with persistent vomiting, constriction of the pupils, the skin turns pale and then acquires a bluish tint. Shallow breathing and a thread-like pulse appear. Further respiratory depression develops, disruption of the circulatory system and heart, dilation of the pupils and coma occurs.

There is only one reason for the development of drug poisoning - an overdose. In this case, drugs act through opioid receptors - specific nerve endings of brain neurons. When opioids bind to these receptors, all functions of the nervous system are disrupted, which explains the pain-relieving effect of these substances.

First aid

With the development of severe intoxication with opium derivatives, the main task is to provide artificial ventilation of the patient's lungs to prevent disorders that can be caused by respiratory paralysis. There is also an antidote for poisoning with these substances - “Naloxone”, the action of which is aimed at displacing toxins from the receptors mentioned above. If drugs were taken orally, gastric lavage and bladder catheterization should be performed.

In case of an overdose of narcotic drugs, it is quite difficult to do anything on your own, and it is often too late. When identifying the first signs of poisoning, you should immediately call an ambulance.

In most cases, drug overdose is the result of pathological dependence on them. Therefore, when the first signs of addiction appear, you should immediately contact a narcologist. Opiate poisoning in most cases indicates a person is addicted.

After the doctor eliminates the life-threatening symptoms of poisoning and the patient’s condition improves, the patient is referred for treatment to a narcologist.

How to avoid opiate poisoning?

First of all, you need to get rid of drug addiction. In this matter, the main thing is that a person realizes in time the full extent of the danger that threatens him and comes to the doctor on time. Below are the main stages of drug addiction:

pathological attraction to using drugs and acquiring them at any cost;

the emergence of a need for a constant increase in dose;

development of mental and physical dependence;

complete personality degradation.

Opiates are used in the treatment of acute and long-term pain. Let's consider why opiate poisoning occurs, its symptoms, and methods of providing first aid for such conditions.

What are opiates?

Opiates, or opioids, are medications used primarily to relieve pain. They have a narcotic effect and misuse can cause addiction in a person. Opiate overdose causes high-risk poisoning fatal outcome.

This group of drugs usually includes the alkaloids morphine and codeine and their analogs. They are obtained from poppy seeds. All these drugs bind to opiate receptors in the body, resulting in their specific effects.

These drugs can stimulate the central nervous system. The toxic dose varies widely, so opioid poisoning can occur even if the dosage is followed. Each organism has one or another individual sensitivity to such substances. This is why opiate poisoning is very common.

How do they affect the body?

Opiates have a selective psychotropic, neurotropic, and depressant effect. There are several types of receptors that perceive opioids:

Mu receptors - do not have selective perception narcotic substances.
Kappa receptors - when stimulated, an analgesic effect occurs.
Delta receptors.
OP-4 receptors - are involved in the formation of a pronounced analgesic effect.
Sigma receptors.

Each type of opiate receptor is associated with different systems body and have a specific effect on certain organs.

A few seconds after the introduction of these substances into the body, an immediate effect appears. It manifests itself, first of all, in a feeling of warmth in the lumbar region and abdomen. The following symptoms are observed:

constriction of the pupils;
facial hyperemia;
dry mouth;
itching in the chin and nose area;
changes mental activity: a person seems to “see the light”, everything that happens around him has no meaning, he focuses on his feelings.

After a few minutes, a person who has taken opiates experiences a feeling of pleasant languor spreading throughout the body. His limbs gradually become heavier, he becomes almost motionless. During this phase, a person experiences fantasies, sometimes hallucinations and delusions. The duration of this phase is about three hours.

Next, the patient is overcome by sleep, which, however, is intermittent. Its duration is no more than 4 hours. After it, some people may experience headache, anxiety, melancholy, and hand trembling. After a few hours, these signs disappear.

Causes of intoxication

Opiate poisoning occurs due to intentional or accidental use, as well as during a suicide attempt. There are cases of intoxication of children: it can happen if the parents improperly monitor the child, do not hide medicines in places inaccessible to him.

Poisoning in adults also occurs in the case of premedication, as well as if they have chronic pain syndrome, combined with disorders of the liver and kidneys. Sometimes bolus administration of opiates causes intoxication when hypersensitivity human body to such drugs.

Overdose of such drugs is possible in substance abusers due to the variability of opiate dosages. Many of them may experience a loss of tolerance after a break in use.

Provoking factors for the development of opiate intoxication - early initiation of injection, female gender, excessive use alcoholic drinks. Group poisonings with narcotic substances are often recorded.

Finally, acute opiate poisoning is also possible with a pathological addiction to such drugs. Often, an addicted person increases the dosage of such a drug to such a limit that a life-threatening overdose develops.

How does poisoning manifest itself?

Signs of opiate poisoning can appear with any method of introducing these drugs into the body. If a person has opiate poisoning, the symptoms may be as follows:

Impaired consciousness.
Coma.
Constriction of the pupils (and it can occur regardless of the dosage).
Cyanosis.
Toxic brain damage.
Breathing according to the Cheyne-Stokes type.
Brain swelling.
Mydriaz.
Pneumonia.
Insufficiency of cardiac activity.
Cramps.
Oxygen starvation of the myocardium.
Fluctuations in body temperature.
Vomiting (and it can even be in an unconscious state).
Oliguria.

In the early stages of opioid use, a feeling of euphoria occurs. It manifests itself due to the stimulation of dopamine receptors. All similar narcotic drugs have a similar effect.

The danger of opiate poisoning is the development of dangerous complications. So, a person may develop the following phenomena:

postanoxic encephalopathy;
paresis, paralysis, polyneuropathy;
affective states;
pneumonia - aspiration and inhalation;
acute kidney damage.

The patient may experience opium withdrawal. In addition, systematic use of opioids leads to the development of drug addiction. This most dangerous disease goes through 4 successive stages in its development:

A pronounced craving for the use of narcotic substances, the desire to acquire them at any price.
Development of the need to use this product and increase the dosage of the drug.
The emergence of persistent physical and psychological dependence from opiates.
Persistent degradation of a person's personality.

These stages will follow each other until the person suffering from drug addiction begins treatment.

Stages of acute poisoning

In total, there are 4 stages of acute opiate poisoning. At the first stage of development of the pathology, patients are inhibited, drowsy and stunned. Neurological symptoms at this stage are:

significant reduction in pupils;
nystagmus;
ptosis;
decreased muscle tone.

During the second stage of poisoning, a person develops a coma. Blood pressure decreases, there is no response to pain.

In the third stage, the patient develops a deep coma. Appears:

Bradypnea.
Brain swelling.
Intermittent breathing.

If first aid for an opiate overdose is not provided at this stage, then death may occur.

In the fourth stage, the coma is recovered. The patient resumes breathing and breathing gradually returns.

Signs of withdrawal syndrome

Clinical manifestations of withdrawal syndrome depend on the degree of formation and duration of drug use. The severity of withdrawal symptoms also depends on the duration of a person’s deprivation of this dangerous substance.

The first phase of withdrawal syndrome is characterized by the following manifestations:

uncontrollable craving for a drug;
severe tension and dissatisfaction;
yawn;
severe lacrimation;
development of so-called goose bumps;
pronounced decrease in appetite.

Subsequently, withdrawal symptoms become more pronounced:

Chills followed by a feeling of heat.
Sudden attacks of sweating, fever.
Goose pimples.
Inconvenience and discomfort in the legs.
Cramps.

Victims feel pain; they cannot find a place for themselves, they spin in bed. Patients become angry and develop depression. The craving for the drug intensifies even more.

In the third phase of the development of withdrawal syndrome, a person begins to experience sharp and severe muscle pain. Diarrhea appears, sometimes its frequency can increase to 10 or even 15 times a day. Tenesmus occurs against the background of diarrhea. Blood pressure rises, tachycardia occurs, and some people may develop high blood sugar.

How is poisoning diagnosed?

Differential diagnosis is necessary. By clinical manifestations the picture of poisoning is similar to hypoglycemia, metabolic disorders, oxygen starvation, hypothermia, and benzodiazepine intoxication. For differential diagnosis Laboratory blood tests are indicated. Laboratory diagnostics make it possible to identify opiates even after their effects have worn off.

Determining the presence of opiates in the blood is possible by administering liquid chromatography. Morphine can be detected in the blood within 2 days, codeine - within 3 days.

Crucial To diagnose poisoning, it has an analysis of the clinical picture. Manifestations of intoxication before and after the administration of the antidote are analyzed. Such diagnostics are very important for carrying out high-quality and highly effective treatment of opium intoxication. It is advisable to detect signs of compression of the soft tissues of the body (for example, changes in the volume and size of the limb).

In case of death, a submedical examination is prescribed.

Features of treatment

If a patient is discovered with obvious signs of opiate poisoning, it is strictly forbidden to take any measures. First aid for poisoning should only be provided by an experienced doctor. It is prohibited to give alcohol, coffee and any other drugs that affect the central nervous system.

The main task of a doctor providing assistance with opium intoxication is to ensure normal respiratory function person. This may require transferring the patient to mechanical ventilation. If administered orally, emergency urinary catheterization may be used.

In case of acute opiate poisoning, it is necessary urgent Care. The antidote is naloxone hydrochloride. It is a pure antagonist of opiates, opioids. This antidote has no effect in cases of respiratory depression. Naloxone is diagnosed for overdose of this substance.

This antidote has a short duration of action - no more than 45 minutes. During the treatment of NVDO, constantly monitor the poisoned person to prevent the resumption of symptoms of morphinization. If an opiate antagonist is administered intramuscularly, you can expect a longer lasting effect.

Artificial ventilation using an Ambu bag is indicated. In severe cases, tracheal intubation is indicated. Additionally, the following drugs are administered:

glucose;
Mexidol;
Pyridoxine hydrochloride;
nootropic drugs;
Thiamide bromide;
antibiotic therapy;
prescription of glucocorticosteroid drugs.

For positional compression, plasmapheresis, hemodiafiltration, and hemodialysis are prescribed. Warming of the patient is indicated.

Video: Basic pharmacology of opioid analgesics.

For intensive detoxification, the method of forced diuresis and gastric lavage are used. When performing first aid, precautions must be taken to eliminate the risk of infection with the human immunodeficiency virus.

As an initial dose of therapy, 0.42 g of Naloxone is administered intravenously. Its effect does not last long, so constant maintenance therapy is necessary. With the help of antidotes, the development of a coma can be prevented.

Physiotherapy for poisoning consists of active gastric lavage and the use of substances that can bind potent poisons.

Opiates, when used correctly, are safe to use. Side effects occur with overdose and excessive use of opiates and codeine. When the first signs of opiate intoxication appear, self-medication is prohibited.

With the systematic use of narcotic substances, a person develops severe drug addiction. It must be treated as early as possible in order to avoid complete degradation of the human personality.

Opiates are widely used in medicine to treat acute and chronic pain. Various dosage forms for any route of administration.

Opiates are the natural alkaloids obtained from the opium poppy: morphine, codeine and, to some extent, thebaine and noscapine. The term "opioids" is used to refer to a wide range of substances that bind to opiate receptors and have similar effects to opiates. Semi-synthetic opioids (heroin, oxycodone) were created by chemically modifying opiates. Synthetic opioids are chemicals that are not related to opiates, but can bind to opiate receptors and have similar effects. The term "drugs" originally referred to substances with hypnotic effects, mainly opioids. Currently, drugs are often called any psychoactive substances prohibited for free use.

Pharmacodynamics

Types of opiate receptors

There are several types of opiate receptors, each with several subtypes. Activation of different receptors leads to different effects.

Mu receptors

Almost all known endogenous opioids bind to mu receptors, but also act on other receptors. Two subtypes of mu receptors are known, but this fact has no clinical significance due to the lack of drugs that are sufficiently selective for one or another subtype.

Kappa receptors

Kappa receptors are found in the spinal cord of higher vertebrates, as well as in the antinociceptive centers of the brain and substantia nigra. When they are stimulated, pain relief develops at the level spinal cord, miosis and polyuria (due to inhibition of ADH production). In contrast to the effects of mu-receptor stimulation, respiratory depression is uncommon.

Delta receptors

Little is known about these receptors. Their endogenous ligands are enkephalins.

OP4 receptors

These receptors were discovered in 1994 by identifying nucleotide sequences homologous to opiate receptor gene sequences from complementary DNA libraries. They have been shown to be involved in the formation of anxiolytic and analgesic effects, but the clinical significance of these receptors has not yet been determined.

Sigma receptors

It was initially believed that c-receptors were a subtype of opiate receptors, but this theory was subsequently disproved and these receptors were not designated by the Committee on Nomenclature of the International Union of Pharmacologists.

Mechanisms of signal transduction from opiate receptors

The results of studies of these mechanisms are contradictory. Initially, it was believed that each receptor is associated with a specific system of intracellular signal transmission, but later it turned out that the same receptors can be associated with different systems depending on many factors, on the localization of the receptor (for example, pre- and postsynaptic).

Symptoms of Opiate Poisoning

It is traditionally believed that the analgesic effects of opiates are due solely to their effects on the brain, but in reality they appear to have antinociceptive effects at the level of the brainstem, spinal cord and nerve fibers. Mu receptors located in the brain, spinal cord, and other organs and tissues (for example, in joints) are responsible for this effect. Delta and κ receptors also mediate the analgesic effects of opioids, but mainly at the level of the spinal cord. They influence the transmission of impulses from pain receptors along the spinothalamic pathway to the thalamus and weaken the perception of pain in the central nervous system. Reluctance to use opiates for pain management is often due to fear of addiction or abuse. However, despite numerous studies, this opinion has not been confirmed. In addition, opioids are generally easier to tolerate, safer, and less expensive than other analgesics (eg, NSAIDs).

Euphoria

Euphoria occurs in the early stages of opiate poisoning. Many drugs produce feelings of pleasure by releasing dopamine in the mesolimbic system. All opioids have a similar effect.

Exogenous opioids affect mood in different ways. Some substances, especially highly fat-soluble ones (heroin), cause euphoria, while morphine is practically devoid of such properties, but has analgesic, anxiolytic and sedative effects. Heroin has a low affinity for opiate receptors and its effects are due to 6-monoacetylmorphine and morphine formed by deacetylation. Apparently, significant differences in the effects of heroin and morphine are due to the different ability of these drugs to penetrate the blood-brain barrier. The effect of fentanyl subjective feelings drug addicts, similar to that of heroin.

Antitussive effect

Codeine and dextromethorphan have this effect. It is believed that the antitussive effect is due to stimulation of p2- or k-receptors and blockade of 5-receptors.

Toxic effect

At correct use V medical purposes Opiates are highly safe and effective, but opiate poisoning can lead to serious complications. Most side effects can be predicted from the general mechanisms of action of opioids (eg, respiratory depression), but a number of drugs have specific toxic effects. Although there are some differences, opiate poisoning is characterized by a constellation of symptoms known as opioid syndrome. The most characteristic of these symptoms of opiate poisoning are depression of consciousness, hypoventilation, miosis and impaired intestinal motility.

Respiratory depression

In experiments with the study of stimulants and blockers of opiate receptors, it was shown that morphine depresses respiration due to its effect on beta receptors. Stimulators of these receptors reduce ventilation of the lungs, reducing the sensitivity of the medulla oblongata chemoreceptors to hypercapnia. In addition, opiates also reduce the ventilatory response to hypoxia. As a result, in case of opiate poisoning, stimulation of the respiratory center is eliminated and apnea develops. Analgesic doses of most available opioids produce equivalent doses of respiratory depression. With long-term use, partial tolerance to this action opioids. Decreased ventilation may be due to a decrease in respiratory rate and tidal volume, so both of these indicators must be taken into account when diagnosing hypoventilation.

Acute lung injury syndrome

The development of this syndrome has been described after the prescription of almost all opiates and in different clinical situations. In a typical case of opiate poisoning, after deep respiratory depression, normal ventilation is restored (on its own or after administration of opiate receptor blockers), but after a few minutes or hours hypoxemia develops, moist rales appear in the lungs, and pink foamy sputum appears. The development of acute lung injury syndrome cannot be explained by any one mechanism, but hypoxic damage to the alveoli and barotrauma due to negative alveolar pressure (attempts to inhale during a closed glottis). The syndrome of acute lung injury after the use of naloxone is probably similar in pathogenesis to neurogenic lung injury, in which acute left ventricular failure develops due to a sharp increase in the activity of the sympathoadrenal system and the damaging effect of catecholamines on the myocardium.

Cardiovascular complications

Opiates cause dilation of arterioles and veins, and a slight decrease in blood pressure. This effect appears to be mediated by histamine. Dextropropoxyphene has a pronounced toxic effect on the cardiovascular system, causing a decrease in contractility due to blockade of fast sodium channels. Some opioids in normal doses (especially methadone) impair myocardial repolarization, which increases the risk of torsades de pointes.

Epileptic adjustments

Epileptic seizures rarely occur with regular doses of opioids. In acute opiate poisoning, seizures most likely develop due to hypoxia. The risk of seizures is higher with an overdose of pethidine, dextrogropoxyphene and tramadol.

Diagnosis of opiate poisoning

Differential diagnosis

Common conditions with a clinical picture similar to opiate overdose include hypoglycemia, hypoxia, and hypothermia. These conditions are easy to diagnose, but their presence does not exclude opiate poisoning. A similar picture is observed in case of poisoning with clonidine, phencyclidine, phenothiazines, tranquilizers and sleeping pills (especially benzodiazepines). Poisoning with clonidine and other centrally acting antihypertensive drugs is especially difficult to distinguish from opiate overdose. Finally, similar symptoms are observed in a variety of injuries, metabolic disorders and infectious diseases. Moreover, all of these conditions can occur simultaneously with opiate poisoning.

Laboratory research

Opiates can be detected in body fluids for a long time after their effects have ceased, so laboratory results are only meaningful in conjunction with the clinical picture. To establish a diagnosis of opiate poisoning, anamnesis and examination are usually sufficient; sometimes a reaction to naloxone helps. In acute cases laboratory research are almost always useless because they are too long wait results.

Cross reactions

Standard laboratory methods Diagnosis of opiate poisoning is based on determining the structure of the substance, so drugs similar in structure to opioids may give cross-reactions. The accuracy of the results depends on the sensitivity and specificity of the method, as well as on the serum concentration of the opioid. The main methods are designed for the determination of morphine, so its derivatives and drugs with similar structures often give cross-reactions. On the other hand, these methods do not detect most semi-synthetic and synthetic analogues. For example, fentanyl (a powerful opioid that can cause fatal complications) does not cross-react with morphine, so an overdose may not be detected without further testing.

Treatment of opiate poisoning

Acute opiate poisoning leads to depression of the central nervous system and respiration. Early initiation of mechanical ventilation (using a bag air bag or tracheal intubation) and maintenance of oxygenation is usually sufficient to prevent death, but the duration of mechanical ventilation can be significantly reduced by prescribing opiate receptor blockers. These drugs, the most common of which is naloxone, competitively inhibit the binding of opioids to opiate receptors, allowing spontaneous breathing to be restored.

The purpose of prescribing naloxone for opiate poisoning is to restore spontaneous breathing, not consciousness. To reduce the risk of difficult-to-predict opioid withdrawal syndrome, which can worsen the patient's condition, start with a minimal dose of naloxone and then increase it based on the clinical picture. In most cases, the effect is observed with 0.05 mg naloxone administered intravenously, although the onset of action of the drug sometimes occurs later than with larger doses, and continued mechanical ventilation may be required for some time. This method avoids tracheal intubation and confirms or excludes opiate toxicity while minimizing the risk of withdrawal symptoms. With subcutaneous administration of naloxone, the patient's condition is restored more smoothly than with intravenous administration of large doses, but it is more difficult to control the onset of action of the drug. The duration of action of naloxone with subcutaneous administration also increases, which can lead to withdrawal syndrome.

In the absence of a history or clinical evidence of opiate poisoning, cautious administration of naloxone is both diagnostic and therapeutic. But in case of opioid addiction, naloxone can cause side effects, especially opioid withdrawal syndrome. One of its manifestations is vomiting, which can be especially dangerous if consciousness is not fully restored after the administration of naloxone (for example, while taking alcohol, tranquilizers or sleeping pills), since in the absence of tracheal intubation there is a high risk of aspiration of gastric contents.

To reduce the unnecessary risk of withdrawal symptoms in opioid addiction, it is necessary to determine the likelihood of a positive effect of naloxone. Shown, that best result gives the administration of naloxone to patients brought to the intensive care unit in an unconscious state, with a respiratory rate of 12 per minute or less. However, it is impossible to determine the indications for prescribing naloxone or mechanical ventilation based only on respiratory rate, since hypoventilation can be caused by hypopnea, and bradypnea develops only after some time.

It is important to determine the indications for discharge after restoration of consciousness as a result of naloxone administration. The patient can be discharged if there are only mild signs of opiate overdose, stable condition within several hours after administration of naloxone, and no conditions requiring special attention(for example, risk of suicide).

In most cases of opiate poisoning, the clinical picture can be predicted based on knowledge of the pharmacological properties of opiate receptors. However, some opioids cause atypical symptoms in overdose, so careful examination and, if indicated, individual empirical treatment are always necessary.

The article was prepared and edited by: surgeon

A) Toxicokinetics of opiates. The table below summarizes the toxicokinetic parameters and clinical data for some commonly used opioids.

b) Therapeutic dose. The table below shows doses of opioid analgesics for adults and children weighing at least 50 kg who have not previously received opioids.

IM - intramuscular; s/c - subcutaneously; q - every (for example, q 3-4 hours - every 3-4 hours).
* Published data regarding equianalgesic doses, i.e., equivalent in analgesic effect to a given dose of morphine, vary.
The criterion for each patient is the clinical effect, and depending on it, dose adjustment is necessary. Since complete cross-tolerance between these drugs does not exist, when changing medications, you should usually start with a lower than equivalent analgesic dose and adjust the dosage again depending on the patient's response.
** Recommended doses do not apply to patients with renal, hepatic insufficiency or other disorders affecting the metabolism and pharmacokinetics of drugs.
***For morphine, hydromorphone, and oxymorphone, rectal administration serves as an alternative for patients unable to take it orally; equianalgesic rectal doses may differ from those given in the table due to different pharmacokinetics.
A transdermal form of fentanyl is also used; the conversion factor relative to a single dose of morphine has not been determined. For appropriate calculations, use the package insert for the drug.
**** When aspirin or acetaminophen is used with an opioid-NSAID combination, dosages should be adjusted based on the patient's body weight. Aspirin is contraindicated in children with fever and other viral illnesses because it can cause Reye's syndrome.
***** Codeine doses above 65 mg are often inapplicable, since analgesia decreases stepwise with increasing doses, and nausea, constipation, etc. side effects intensify continuously.

V) Mechanism of action of opioids. U healthy men Those who run until they collapse without feeling any discomfort have increased levels of beta-endorphins (endogenous opioids). Such individuals can easily run to the point of confusion, dehydration, hyperthermia, and hypophosphatemia. Signs of opiate addiction, opioid receptor interactions, and physiological effects of opioids are in the tables below.

G) Clinical picture opioid poisoning. It is important to understand the difference between the maladaptive behavior associated with regular opiate use and the direct effects on the central nervous system. The first is opioid dependence and abuse. The second includes opioid intoxication and withdrawal syndromes. Acute overdose is a condition requiring emergency medical care and is a complication of acute intoxication.

- Opioid addiction. The American Psychiatric Association has established diagnostic criteria for opioid dependence of varying severity, as well as for opioid abuse.

- Opioid abuse. Opioid abuse is now considered a “residual” category of maladaptive opioid use that does not meet the criteria for opioid dependence. Its main symptom is regular drug use, despite persistent or recurrent problems of a social, professional, psychological or physical nature. The time factor is also important.

- Induction of seizures. Anecdotal evidence suggests that morphine, meperidine, fentanyl, sufentanil, and alfentanil induce seizures in non-epileptic individuals (morphine also in epileptics). Anticonvulsants (for example, phenytoin, phenobarbital and phenothiazines) stimulate the conversion of meperidine to normeperidine, which has pronounced proconvulsant properties.

Physiological effects of opioids by organ system:

1. Central nervous system:
Analgesia
Sedative effect
Nausea and vomiting
Miosis
Antitussive effect
Seizures
Dysphoria

2. Respiratory depression:
Reaction to CO2
Minute ventilation, respiratory rate, tidal volume

3. Cardiovascular system:
Bradycardia (fentanyl, morphine)
Tachycardia (meperidine)
Histamine release (morphine)

4. Digestive system:
Weakening of motility and peristalsis
Increased tone of the sphincters (hepatic-pancreatic ampulla, ileocolic)

e) The American Psychiatric Association's diagnostic criteria for opioid withdrawal are listed below.

Signs of opioid addiction:

1. Unusual changes in behavior: sudden mood swings, periods of depression, anger and irritability, alternating with periods of euphoria
2. Drug addiction is a state of loneliness and isolation from the world. Drug addicts quickly abandon family, friends and outdoor activities
3. Denial is the most characteristic symptom of drug addiction. If relatives directly express their suspicions, the addict may become defensive and passionately argue that the accusations are groundless.
4. There may be an increase in the frequency and intensity of family conflicts, quarrels and fights

5. The drug addict needs to be close to the source of the drug. If drug addiction or other drug addiction the medical worker suffers, he will stay at the workplace for a long time, even on someone else’s shift. Alcoholics often show up sick at work; they can, without informing anyone, “disappear” into a bar or secluded place with a drink
6. An increase in expenses that is incomprehensible to others, illegal actions (for example, driving while intoxicated), gambling, adultery and problems at work
7. There may be a significant decrease in libido
8. A drug addict usually has pills, syringes or bottles of alcohol in his house.

9. Bloody tampons or pieces of tissue in the house may indicate the presence of an injection drug user.
10. A sudden habit of locking yourself in the bathroom or other room (to inject drugs) may occur.
11. An obvious sign of alcoholism is the smell of alcohol on your breath.
12. Drug addicts often have narrowed pupils.

13. Drug addicts have obvious signs of withdrawal, especially heavy sweating and tremors.
14. Pallor and weight loss are common.
15. Unidentified drug addicts are found in a comatose state
16. Untreated drug addicts are found dead

* Relatives of a doctor or nurse suffering from drug addiction may notice some symptoms of addiction, both similar to those observed in the workplace, and additional.
Addiction to hard drugs progresses very quickly (in a matter of weeks - months), so identifying subjective symptoms on early stage difficult. Signs of drug addiction can take years to appear.

Diagnostic criteria for opioid dependence and its severity (presence of at least three):
1. Opioids are used in large quantities or longer than the person planned
2. The desire to take opioids persists, or the person repeatedly tries unsuccessfully to quit or limit their use
3. It takes a lot of time to get opioids (including stealing them), use them, or get back to normal after they take effect.
4. The person is often intoxicated or suffering from withdrawal symptoms while performing important duties at work, such as educational institution or at home (for example, playing truant, coming to work or school high, or caring for children while high) or when opioid use poses a physical danger (for example, driving while high)
5. Social, professional, or recreational activities that were important to the person in the past cease or decline
6. Marked tolerance: the need to significantly increase the dose (by at least 50%) to achieve the desired effect or a noticeable weakening of the effect when using the previous dose
7. Characteristic withdrawal symptoms
8. Opioids are often used to prevent or relieve withdrawal symptoms.
At least some of these symptoms persist for at least a month or recur repeatedly over a longer period

Severity of opioid addiction:
a) Weak. Apart from those necessary for diagnosis, there are few or no symptoms; professional quality suffer slightly, and general social activity and relationships with other people do not worsen
b) Moderate. A state intermediate between “weak” and “severe” addiction
c) Heavy. In addition to those necessary for diagnosis, many symptoms are present; they greatly interfere with work or study, as well as general social activity and relationships with other people
d) Partial remission. Over the past six months, the drug has been used occasionally and some symptoms of addiction are present.
d) Complete. In the last six months, opioids were either not used or used without symptoms of dependence

Diagnostic criteria for opioid withdrawal According to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Third Revised Edition (DSM-III-R):
A. Termination of long-term(over at least several weeks) moderate to heavy opioid use or reduction (or use of an antagonist after short-term use) followed by at least three of the following symptoms:
1. Opioid cravings
2. Nausea or vomiting
3. Muscle pain
4. Watery eyes or rhinorrhea
5. Pupil dilation, piloerection, or sweating
6. Diarrhea
7. Yawning
8. Fever
9. Insomnia
B. These symptoms not caused by a physical or other (except drug addiction) mental disorder

Typical screening flowchart Braithwaite et al. published:

Opiate Screening Flowchart.
TLC - thin layer chromatography; GC - gas chromatography;
HPLC - liquid chromatography high resolution; GC-MS - gas chromatography - mass spectrometry.

e) Treatment of withdrawal symptoms:

- Clonidine (Catapres) for opioid withdrawal. A preliminary study of clonidine and naltrexone hydrochlorides used in combination showed that with the help of this drug, 12 out of 14 heroin addicts successfully overcame opioid withdrawal syndrome (“withdrawal”).
Clonidine relieves symptoms mediated by noradrenergic mechanisms, including lacrimation, rhinorrhea, sweating, diarrhea, chills, and piloerection (gooseflesh). Neither clonidine nor its structural analogue lofexidine (licensed in the UK) reduces muscle and bone pain, insomnia and the craving for opioid-induced euphoria.

- Nitrous oxide for opioid withdrawal. Experiments with the treatment of alcohol and opioid withdrawal with inhaled nitrous oxide have yielded promising results. In one case, this gas was used according to the following scheme: 20 minutes - oxygen, 20 minutes - precisely dosed nitrous oxide, 20 minutes - cleaning the respiratory system with oxygen.
The patient remained conscious throughout the procedure. Before this method becomes routine, it needs to be further investigated and the potential risks assessed. So far it has only been used to treat adults.