Does tramadol cause liver damage? Explore the potential risks, precautions, and important information about the impact of tramadol on liver health.

Tramadol and Liver Health: Exploring the Potential Risks

Tramadol, a widely prescribed opioid medication, has come under scrutiny for its potential impact on liver health. While generally considered safe when used as directed, there have been reports that prolonged use or misuse of tramadol may lead to liver damage. This article will delve into the current understanding of the relationship between tramadol and liver health, discussing the risks, precautions, and steps individuals can take to protect their liver when using this medication.

Understanding the Potential Liver Damage Caused by Tramadol

Tramadol is an opioid analgesic used to treat moderate to severe pain. While it is generally considered safe when taken as prescribed, there have been some reports of tramadol causing liver damage, particularly in cases of overdose or prolonged use. A 2015 study found that long-term use of tramadol was associated with an increased risk of liver and kidney damage. Additionally, research has shown that combining tramadol with acetaminophen (a common pain relief medication) may lead to complications, including acute liver failure.

Opioids and Liver Health: Understanding the Relationship

Tramadol is a type of opioid, and researchers have found that opioids, in general, have an association with higher incidences of adverse effects in people with existing liver damage. Therefore, individuals with pre-existing liver conditions should exercise caution when using opioids, including tramadol, and consult their healthcare providers to ensure the appropriate course of treatment.

Minimizing the Risks: Precautions for Tramadol Users

To reduce the risk of liver damage while taking tramadol, individuals should take the lowest possible dose for the shortest duration, avoid consuming alcohol while using the medication, and steer clear of combining tramadol with other medications that may interact and cause further complications. Regularly monitoring liver function and following the guidance of healthcare professionals are also essential steps in safeguarding liver health.

Opioid Use and Associated Risks: Beyond Liver Damage

In addition to potential liver damage, the use of opioids like tramadol carries other risks, such as addiction, misuse, and withdrawal symptoms. Recognizing and addressing these issues is crucial for maintaining overall health and well-being. Individuals should be aware of the signs of addiction, the timeline for opioid withdrawal, and the potential for overdose, and seek medical assistance if necessary.

Navigating Drug Interactions: Ensuring Compatibility with Tramadol

Tramadol can interact with various other medications, potentially leading to fatal side effects. It is crucial for individuals taking tramadol to disclose their current medication regimen to their healthcare providers and follow their guidance to avoid any potentially dangerous drug interactions.

Serotonin Syndrome: A Rare but Serious Condition to Consider

Serotonin syndrome is a rare but potentially life-threatening condition that can occur when the body produces too much serotonin or when there is an interaction between tramadol and another medication or substance. Individuals should be aware of the symptoms of serotonin syndrome and seek immediate medical attention if they experience any concerning side effects.

In conclusion, while tramadol is generally considered safe when used as directed, there is the potential for liver damage, particularly in cases of overdose or prolonged use. By understanding the risks, following precautions, and closely monitoring their health, individuals can minimize the chances of experiencing adverse effects and protect their liver health while using this medication. Collaborating with healthcare professionals and being vigilant about the potential risks associated with opioid use is essential for ensuring safe and responsible management of pain relief treatment.

Does tramadol damage the liver?

Tramadol is a narcotic that can treat moderate to severe pain. There have been reports that tramadol may damage the liver. People can reduce the risk of liver damage by avoiding taking tramadol alongside alcohol and certain other drugs.

The reports state that taking this medication in high doses over an extended period may cause liver damage. People should not take tramadol without consulting a doctor.

This article looks at how tramadol affects the liver and the other risks of this medication. It also lists the steps that people can take to protect their liver health.

Tramadol is a prescription drug that can relieve moderate to severe pain. Healthcare professionals use it to treat chronic pain or pain following surgery. Tramadol works by changing how the brain perceives and responds to painful stimuli.

Tramadol is a controlled substance, and a person may only use it under the close supervision of a doctor. This is because tramadol has the potential to cause addiction, and people can misuse it.

Share on PinterestFRED TANNEAU/AFP via Getty Images

There is some debate as to whether tramadol is harmful to the liver. Tramadol is generally safe to use, but in some cases — such as overdose or prolonged use — it may damage the liver.

A 2015 study found that there was a risk of increased liver and kidney damage due to the long-term use of tramadol. Other research has shown that taking tramadol with acetaminophen may cause complications, including acute liver failure.

Tramadol is a type of opioid. Researchers have found that opioids, in general, have an association with higher incidences of adverse effects in people with existing liver damage. Therefore, people with liver damage should not use opioids unless other options are unsuitable.

Tramadol is mostly safe and rarely causes liver damage. However, in some cases, the drug has contributed to health problems such as seizures, high blood pressure, and heart problems.

Learn more about the side effects of tramadol.

There are some ways in which a person can protect their liver from damage when using tramadol.

• Dosage: Taking the lowest dose possible for the shortest period will reduce the risk of liver damage.
• Alcohol: A person should avoid drinking alcohol while taking tramadol, as this can cause liver damage.
• Other medications: There are many other medications that people should avoid combining with tramadol, including any that may cause drowsiness.

Opioid use has other associated risks.

Side effects

Whenever a person takes any medication, there is a risk of side effects. For people taking opioids, these include:

• constipation
• dry mouth
• fatigue
• headaches
• sleepiness
• sweating
• vomiting

Addiction or misuse

People who take opioids for too long can develop an addiction to the drug. This means that they will start to experience a persistent urge to use the drug, despite any negative effects it may have.

Opioids also have the potential for misuse. Misuse happens if a person takes the drug to experience a high or does not follow the prescribed dosage.

It is also possible to develop a tolerance to the drug, meaning that a person needs more of it to feel its effects. This is why it is important for people to stop taking the drug before their tolerance increases.

Withdrawal symptoms

When a person stops taking opioids after taking them for a while, they might experience withdrawal symptoms, such as shaking and sweating.

Learn about the timeline for opioid withdrawal.

Overdose

Taking a dosage of tramadol that is too high can result in an overdose. An overdose can cause respiratory depression, which is when a person’s breathing becomes dangerously slow and shallow. This can lead to death.

Learn how to recognize the signs of an opioid overdose and what to do.

Drug interactions

Tramadol is a drug that interacts with other medications and can cause fatal side effects if people do not take it properly. It is important to know what drugs are compatible with tramadol to avoid any complications.

A person should speak with a doctor about any current medications before they start taking tramadol.

Serotonin syndrome

Serotonin syndrome is a rare but potentially life threatening condition that occurs when the body produces too much serotonin, there is an interaction with another medication or substance, or both.

Serotonin syndrome can cause symptoms such as:

• agitation
• confusion
• hallucinations
• high blood pressure
• irregular heartbeat
• nausea and vomiting
• seizures
• sweating
• tremors

The liver is one of the most important organs in the body. It is responsible for transforming nutrients in food into substances that the body can use and for filtering toxins from the blood.

Many factors can affect the health of a person’s liver, such as genetics, diet, alcohol consumption, and lifestyle choices.

Liver health is important for the proper functioning of the whole body. There are many things that people can do to keep the liver healthy.

These include:

• eating a balanced diet, including plenty of fresh fruits and vegetables
• avoiding alcohol
• avoiding excess sugar and salt
• exercising regularly
• quitting smoking, if applicable

If the damage to the liver is not severe and doctors find it early, it can be reversible. However, if the damage is severe enough, it may be permanent.

Most of the time, taking tramadol will not cause liver damage. Additionally, because healthcare professionals regularly monitor people taking tramadol, they may notice any signs of liver damage early.

Blood tests can help healthcare professionals determine how well a person’s liver works. If the liver shows signs of damage, the doctor may lower the dosage of tramadol or prescribe an alternative medication.

Tramadol can cause liver damage if a person does not take it according to the prescription.

People should always ensure that they take the proper dosage of tramadol and avoid taking other drugs that may interact with it.

A person should not take tramadol if they have any type of kidney or liver disease.

Tramadol – LiverTox – NCBI Bookshelf

Last Update: November 24, 2020.

OVERVIEW

Introduction

Tramadol is an opioid analgesic used for the therapy of mild-to-moderate pain. Tramadol overdose can cause acute liver failure. Pharmacologic doses of tramadol has not been associated with cases of clinically apparent drug induced liver disease.

Background

Tramadol is a synthetic codeine analog that acts as a weak opioid agonist in addition to mildly inhibiting serotonin and norepinephrine reuptake. Tramadol is effective against mild-to-moderate pain, but is not as effective as standard opioids and not recommended for severe pain. Tramadol was approved for use in the United States in 1995 and is currently widely used, with more than 18 million prescriptions written yearly. Tramadol is available in 50 mg tablets in multiple generic forms and under the brand name Ultram. It is also available as tablets of 37.5 mg in combination with acetaminophen (325 mg) both generically and under the brand name Ultracet. The usual dose in adults is initially 25 mg daily, with titration based on effect and tolerance to 50 to 100 mg every 4 to 6 hours as needed for pain, but not to exceed 400 mg daily. Extended release formulations in capsules of 100, 200 and 300 mg are also available (ConZip and generics) and are given once daily. Physical dependence can occur, and while the potential for abuse is less than with more typical opioid analgesics, tramadol is classified as a schedule IV drug and is provided under a risk evaluation and mitigation strategy (REMS). Common side effects are nausea, dizziness, dry mouth, sedation and headache. Tramadol may increase the risk of seizures. It is considered contraindicated in children below the age of 12 because of risk of respiratory depression, and prolonged use should be avoided in pregnancy because of the risk of infant withdrawal syndrome. Rare but potentially severe adverse events include seizures, severe respiratory depression, serotonin syndrome, addiction, abuse and withdrawal syndrome.

Hepatotoxicity

Serum aminotransferase levels can be elevated in a small proportion of patients receiving tramadol, particularly with high doses. Intentional and accidental overdoses of tramadol can cause respiratory arrest as well as acute liver failure, several fatal instances of which have been reported. In these cases, however, the liver injury may have been caused by shock, hypoxia or ischemia secondary to the respiratory arrest. Liver injury attributed to tramadol overdose has also been associated with hyperammonemia, lactic acidosis and hepatic steatosis, suggestive of direct mitochondrial injury. In some situations, acute liver failure after tramadol overdose may be related to acetaminophen taken separately or in combination with tramadol. Clinically apparent idiosyncratic liver injury with recommended doses of tramadol has not been reported.

Likelihood score: E* (unproven cause of liver injury in therapeutic doses but reported to cause liver injury with overdose).

Mechanism of Injury

The mechanism of hepatotoxicity from overdoses of tramadol is not known, but is likely due to direct hepatocellular injury, either as a result of ischemia or mitochondrial toxicity. Tramadol is metabolized by the liver, predominantly by CYP 2D6 and 3A4 to its active form and it can result in troublesome drug-drug interactions.

Outcome and Management

The minor enzyme elevations that occur with tramadol use are usually mild, asymptomatic and self-limited, resolving even with continuation of therapy. Cases of acute liver failure due to tramadol overdose require intensive medical management and can be fatal. In acute overdoses, there may be interaction with other agents capable of causing liver injury (particularly acetaminophen).

Drug Class: Opioids

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 24 November 2020

• Zimmerman HJ. Nonsteroidal anti-inflammatory drugs. Drugs used to treat rheumatic and musculospastic disease. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 517-41.

  (Textbook of hepatotoxicity published in 1999; tramadol is not discussed).

• Yaksh T, Wallace M. Opioids, analgesia, and pain management. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 355-386.

  (Textbook of pharmacology and therapeutics).

• Lewis KS, Han NH. Tramadol: a new centrally acting analgesic. Am J Health Syst Pharm. 1997;54:643–52. [PubMed: 9075493]

  (Review of pharmacology, efficacy and side effects of tramadol in management of pain; extensively metabolized in the liver, largely through CYP 2D6; adverse events in 15%, but no mention of hepatic effects).

• Cossmann M, Kohnen C, Langford R, McCartney C. Drugs. 1997;53 Suppl 2:50–62. [Tolerance and safety of tramadol use. Results of international studies and data from drug surveillance] [PubMed: 9190325]

  (Extensive review of side effects of tramadol from phase II-IV studies in 21,000 patients from 1977-93; little evidence of respiratory depression or dependence with oral administration; no mention of hepatotoxicity).

• Bamigbade TA, Langford RM. Tramadol hydrochloride: an overview of current use. Hosp Med. 1998;59:373–6. [PubMed: 9722388]

  (Review of mechanism of action, pharmacology and uses of tramadol).

• Tolman KG. Hepatotoxicity of non-narcotic analgesics. Am J Med. 1998;105:13S–19S. [PubMed: 9715830]

  (Review of liver injury due to analgesics; states that tramadol has not been reported to cause hepatic injury).

• Musshoff F, Madea B. Fatality due to ingestion of tramadol alone. Forensic Sci Int. 2001;116:197–9. [PubMed: 11182272]

  (26 year old man found dead after tramadol overdose; autopsy showed brain edema, no mention of liver).

• Highlights of the 22nd French pharmacovigilance meeting. Prescrire Int. 2002;11:21–3. [PubMed: 11985373]

  (Tramadol reported to interact with warfarin leading to marked increases in INR and bleeding).

• Loughrey MB, Loughrey CM, Johnston S, O’Rourke D. Fatal hepatic failure following accidental tramadol overdose. Forensic Sci Int. 2003;134:232–3. [PubMed: 12850423]

  (Accidental tramadol overdose in 67 year old man taking ~1000 mg daily for 8 days, presenting with respiratory failure, stupor and liver injury [bilirubin 3. 3 mg/dL, ALT 1739 U/L, Alk P 89 U/L, lactic acidosis and hypoglycemia], dying after cardiopulmonary arrest and possibly ischemic hepatic injury).

• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, none were attributed to tramadol).

• De Decker K, Cordonnier J, Jacobs W, Coucke V, Schepens P, Jorens PG. Fatal intoxication due to tramadol alone: case report and review of the literature. Forensic Sci Int. 2008;175:79–82. [PubMed: 17875377]

  (28 year old man with acute tramadol overdose suffered cardiopulmonary arrest, was resuscitated, but died two days later with acute liver and renal failure and hyperammonemia; liver biopsy showed steatosis and centrolobular ischemic necrosis).

• Leppert W. Tramadol as an analgesic for mild to moderate cancer pain. Pharmacol Rep. 2009;61:978–92. [PubMed: 20081232]

  (Review of mechanism of action, pharmacology, efficacy and safety of tramadol in mild-to-moderate cancer pain; side effects occur in 1-6% of patients, but serious adverse effects are very rare; hepatotoxicity and ALT abnormalities are not discussed).

• Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, none of which were attributed to tramadol).

• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none were attributed to tramadol).

• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to tramadol, other opiates or opiate antagonists).

• FDA warns against use of codeine and tramadol in children and breastfeeding women. Med Lett Drugs Ther. 2017;59(1521):86–8. [PubMed: 28520700]

  (Concise summary of revised FDA recommendations on use of tramadol in children listing it as contraindicated in those below the age of 12 because of risk of severe respiratory depression, cautioning its use in adolescents because of addiction and abuse, and avoidance of prolonged use in pregnant women because of potential of withdrawal syndrome in newborns; no mention of ALT elevations or hepatotoxicity).

• Opioids for pain. Med Lett Drugs Ther. 2018;60(1544):57–64. [PubMed: 29664446]

  (Concise review of the mechanism of action, efficacy, safety and costs of opioids used for pain relief, discusses adverse events or short and long term use of tramadol, but makes no mention of ALT elevations or hepatotoxicity).

Phenazepam, clozapine, tramadol. Why the police did not notice the serial poisoner in the center of Moscow

Over the past month, at least 24 people have been poisoned in the center of Moscow. On a series of incidents on June 24, the city edition of The Village told. The scenario in all cases was similar: a certain young man treated Muscovites having a rest with a drink, in which he mixed strong drugs. When the victims fainted, he robbed them. NV found out how these substances work and why the police paid attention to these cases only after a wave of publications.

What happened?

In May and June, at least 24 people were poisoned in the center of Moscow. While the victims were unconscious, they were robbed, sometimes beaten. According to The Village, the attacks took place in squares near Chistye Prudy, as well as in the Pit (Khokhlovskaya Square), Gorka Park and the Zinziver bar.

At the beginning of June, passers-by saw a young man who was searching the bags of people lying on the ground. He tried to explain that his friends got sick, so he collects their things “so as not to be stolen.” Passers-by did not believe and called the police. The police, after initiating a theft case, released the alleged offender on bail. After this, the attacks continued, with some victims so severely affected that they lay in a coma for about two weeks. The case received a response when it became clear that the victims of the attacks were journalists – for example, the photo editor of The Village, Lyudmila Chizhova.

The next day after the publication in the media, the young man was detained again.

Who is blamed for the attacks?

Murat Sabanov, a 26-year-old native of Kabardino-Balkaria, was detained on suspicion of attacks. Police searched him and found phenazepam, clozapine and tramadol. In the criminal case of the suspect, which was initially initiated under the article on theft (Article 158 of the Criminal Code of the Russian Federation), then an article on robbery was added (Article 162 of the Criminal Code of the Russian Federation).

At the trial, while under restraint, Sabanov said that in Moscow he “worked unofficially” – “was engaged in cargo transportation.” The defendant’s profile on the profi.ru website indicates that he worked as a loader.

“Open media” found pages in social networks, possibly belonging to Sabanov: he served in the internal troops (now the Russian Guard) at least until 2014. In one of the photos on VKontakte, Sabanov is in military uniform against the backdrop of a shopping center in the city of Sosnovy Bor: not far from there is the military unit of the Russian Guard No. 3705. Moreover, in one of the photos Sabanov has epaulettes of a junior lieutenant.

During the trial, Sabanov said that he had lived in Moscow for five years in a hostel on Basmannaya Street. According to the interrogation protocols, the suspect did not deny that he had mixed phenazepam into the water. The Tagansky District Court of Moscow sent Sabanov to a pre-trial detention center for two months.

Later, the Investigative Committee announced the arrest of a suspect in a similar case. According to investigators, a resident of Tver poisoned a fellow traveler in the Podsolnechnaya-Moscow train with clozapine, who died a few hours later. The criminal case is being investigated under Part 4 of Article 111 of the Criminal Code of the Russian Federation (“Intentional infliction of grievous bodily harm resulting in death”) and Part 4 of Article 162 of the Criminal Code of the Russian Federation (“Robbery”). The investigation believes that the accused is involved in the commission of other crimes on the territory of Moscow, Moscow and Tver regions .

What do we know about the substances found at Sabanov’s?

Most often, such poisoning in the post-Soviet space is associated with clonidine – this is a common medicine for high blood pressure, but in case of an overdose it leads to fainting or even death. Judging by the court verdicts published on the aggregator website sudact.ru, in recent years, clonidine has been used less and less – but such drugs as phenazepam and clozapine have appeared in the prosecution materials.

During a search in Sabanov’s hostel, the police found exactly this set – phenazepam and clozapine, as well as tramadol.

Alexei Vodovozov, a toxicologist, and Oleg Toytman, a psychiatrist and narcologist, told NV what you need to know about these drugs.

It is easy to explain why these drugs were used. “Of course, I can’t know, but I think that this guy consulted either with a familiar pharmacist or with some medical student. And for medical purposes we have not been using clonidine for a long time, there are newer and more sensible drugs for pressure, here no one remembered him,” says Vodovozov.

Clozapine is a neuroleptic, it has “an unpleasant side effect – orthostatic hypotension: that is, a person tries to stand up, his pressure drops sharply, and after the pressure the person himself falls. ” It’s a strong drug used in so-called “big psychiatry” — in cases of schizophrenia or bipolar disorder, Vodovozov says.

“After all, it is better known in Russia under the name Azaleptin, it was he who caused the main toxic effect of these three drugs,” says psychiatrist-narcologist Oleg Toytman. Clozapine is used to treat schizophrenia and similar diseases, as a behavior corrector and a typical antipsychotic It is with its overdose that excessive drowsiness, weakness, confusion, muscle relaxation occur, and at high doses – depression, up to coma.0003

Phenazepam is “almost the first” benzodiazepine, quite heavy, “hitting the head and the entire nervous system.” This remedy inhibits the action of brain neurons, it may well be used as a sleeping pill. In large doses, it leads to stunning, confusion and coma, says Vodovozov.

“In principle, this is a very good tranquilizer, albeit a rather “old one”. At the same time, its effectiveness is much higher than any modern drugs. In terms of action, this is not a very potent drug, but at the same time it has a depressing effect on the nervous system,” adds Toytman .

Acute poisoning can lead to death, especially in combination with alcohol, specifies Vodovozov.

“About tramadol – I’m very surprised why it is needed. It is a synthetic opioid analgesic, a drug. Like any opioid, it has a euphoria-forming effect, however, none of the victims described this,” the toxicologist notes.

Indeed, none of the victims described euphoria, but they complained of shortness of breath. “The first thing a toxicologist might think of when they are told they are having difficulty breathing is opioids. And the second is a benzodiazepine, in our case, phenazepam.”

“This is the safest of the three because it is mainly used as an analgesic. It is quite strong in action, but in principle it can be prescribed to neurologists and therapists and oncologists and a bunch of other doctors. I must say right away that there can be no oppression of consciousness from it, but . .. when interacting with phenazepam and azaleptin, they enhance each other’s action and the toxic effect on the nervous system is significantly enhanced, ”explains Toytman.

“Why they put it all together is a mystery to me. Maybe, for reliability, they consulted with someone, they were given several different tips, and they combined them for reliability. In fact, each of these drugs separately is more than enough, considering that they were given in horse doses, if people immediately fell from one sip,” continues Vodovozov. The toxicologist is sure that the dose was powerful.

Phenazepam, clozapine and tramadol are strictly forbidden to be mixed with alcohol, but even without alcohol, an overdose of these substances is extremely dangerous and entails not only damage to the nervous system, but also multiple organ failure – that is, damage to the liver (where these substances are activated) and others internal organs. And for each of these drugs, the instructions say: in case of an overdose, coma or death is possible.

Therefore, all three drugs must be dispensed strictly by prescription. “In our country since 9In the early 1900s, there were so-called “station pharmacies” – strange establishments where you can buy almost everything you need. Pharmacy drug addicts have not gone anywhere, there are some pharmacies that almost specialize in this, the main turnover is made precisely at the expense of such clients, “explains Vodovozov.

I decided to try out the method I heard earlier on Chistoprudny Boulevard in Moscow. In this regard, I needed to purchase Phenozipam, which I purchased at the Strogino pharmacy, which was located on the street [address hidden], this pharmacy is not official, and has no signs, this pharmacy sells many medications without asking a prescription for their purchase,” Sabanov said during interrogation (the page of the protocol was published by the “Pravozaschita Otkryki”, spelling and punctuation as in the original).

It is now difficult to understand why these drugs could not be detected during tests during hospitalization. The toxicologist claims that benzodiazepines, like opioids, are routinely tested because they can be used as drugs. It is not always possible to name the exact drug, but the drug class is easy to identify.

“Perhaps the fact is that patients were not delivered to special toxicological hospitals. Our toxicological service was badly damaged during the cuts, there are practically only one department left in large cities. But we need to understand each specific case,” says Water carriers.

The old scheme

The terms “clofelin” or “clofelin” came into common use in the 80s – 90s, then mostly sex workers hunted for poisoning, who mixed the sedative to the client, after which they took valuable things from him . In the “zero” they were joined by taxi drivers, who treated lonely drunken customers to coffee from a thermos, after which the passenger lost consciousness.

After the publication of the incidents of recent weeks, two more people wrote to the NV correspondent who were victims of similar robberies over the past year. So, a young man, who wished to remain anonymous, said that back in September he was robbed when he was drinking in a bar in the evening. “The last thing I remember is how they spilled my cocktail and bought a new one. Then everything, emptiness,” he told NV.

According to the young man, he “was recovering for two days”, and only then discovered that not only had his bank card been stolen, but also “a decent amount” had been withdrawn from it. “There are cameras from an ATM where a person withdraws money. There is card data where the remaining money was transferred, but the case is still suspended, they are not looking for anyone,” the young man complains.

25-year-old Anastasia says that in December a similar story happened to her: “I was sitting at the bar, a man sat next to me and knocked my glass with his elbow. He was very apologetic and convinced that he would buy me a new drink.” After the first sip, the girl became very dizzy, and she went outside to recover in the cold.

“I remember that he came out after me and tried to hug my shoulders, took my purse from my hands. Then I immediately realized that there was something wrong with my new glass and, stumbling, ran,” Anastasia said. She was afraid that the man had slipped something into the glass to rape the girl, so she ran “as fast as she could.”

At home she immediately fell asleep, woke up the next evening and realized that the purse remained in the man’s hands. Anastasia could not remember his signs. “I didn’t go to the police, because I know what they would have answered me there,” the girl summed up.

What do the police say about it?

Artem Fayzulin, a former police captain from the Perm Territory, explained to an NV correspondent the complexity of such cases. According to Fayzulin, the “clofelinist” can walk free for quite a long time.

On the one hand, in most cases, the investigation has at least one victim, since the victims of “clofelins” rarely die, and it is impossible to calculate the dose in such a way as to accurately bring a person to memory loss. Moreover, the investigation often even has fingerprints of the criminal – on dishes or bottles.

“Unfortunately, an identikit is an extremely ineffective measure, making a recognizable portrait is more difficult than it seems. And fingerprints are good either as a reserve for the future, or if the person has already committed a crime and is in the police database,” says the former police officer.

The most effective and common method of catching is the criminal-to-crime investigation, says Faizulin. “First (for example, with the help of agents) they find people who they decide to hire, and then they look at what exactly they have done.

Even when the police know exactly which card the stolen money was transferred to, the chain often breaks here: the cardholder is usually a figurehead, a poor student or a marginal element who does not fully understand what he is involved in.

“They only come to him to take money, and they can come once a month, and once every six months – no one will sit in ambush for so long, if, again, it’s not about the series,” explains Faizulin. There is also a more complicated scheme: when a card is ordered through an online bank for false documents. “These cards are brought by a courier who rarely realizes that he has stolen or fake documents in front of him,” says the former police officer.

Articles of accusation for “clofelins” are chosen based on the decision of the Plenum of the Supreme Court “On judicial practice in cases of theft, robbery and robbery.” “The essence of this explanation of the Armed Forces, roughly speaking, is that if they tore off your hat from your head and ran away, this is robbery, and if you took out a knife and ordered to give your hat back, this is robbery.” That is, if violence dangerous to health is used, the Supreme Court defines this crime as robbery. Accordingly, if the “clofelinschik” deliberately used a dose of a substance dangerous to health or the victim’s health was seriously affected (for example, if the victim fell into a coma), the case qualifies as robbery.

“I assume that this Moscow guy of yours was released on bail so easily, because it didn’t occur to the police that he had used some kind of psychotropic substances. They decided that he simply turned the pockets of drunk people inside out,” Fayzulin said. The former policeman explains the inability of the Moscow police to combine such a number of similar poisonings with the poor work of the analytical department, which does not work “in the field”, but is engaged in comparing and identifying a series of crimes in the city.

“I’ve seen people like that: they bring more green ones and sort out pieces of paper right away – they haven’t been in the field, they haven’t sniffed the earth, they haven’t seen corpses. They would sort out the pieces of paper at least wisely,” says Faizulin. In his opinion, the questions are for analysts, and not for grassroots operatives.

An active member of the Moscow police agreed to talk to the NV correspondent on condition of anonymity. According to him, it is very difficult to work, since Moscow is a big city, “a lot is happening here,” but there is less and less trust in the police.

“A boy of about ten saw me on the street and ran away from me in the other direction! Was it like that in the Soviet Union?” – the 37-year-old policeman is indignant.

There is a lot of work and you have to “set priorities” – which things are more important, he complains. “Of course, you will excuse us, but drunken youth constantly get into some kind of story, we can’t flock to every sneeze all over the city.” According to the policeman, the police definitely could not have aimed to hush up the case or release the poisoner, since serial criminals are taken very seriously, but “it is very difficult to recognize them at first sight.”

A case of long-term treatment of chronic non-oncological pain with tramadol :: DIFFICULT PATIENT

L.P. Ananyeva

Institute of Rheumatology RAMS

According to the WHO, pain syndromes are one of the main reasons – from 11 to 40% – of visits to a doctor in the primary care system. Especially widespread among the adult population are chronic pain syndromes in the area of ​​the musculoskeletal system. Chronic pain is accompanied by impaired physiological functions and psychological problems and causes enormous economic damage to society. In Europe, disability costs associated with chronic pain amount to $5 billion annually. Of particular concern are moderate to severe chronic pain, with an average frequency of 19 in Europe.%. It is important that the vast majority are ill for a long time (more than two years), and the average duration of such a pain syndrome is 7 years [4]. At the same time, one in five patients lose their jobs, and one in five develop depression associated with chronic pain.
Due to the great importance of pain syndromes, pain is currently regarded as the fifth vital symptom. Along with the pulse, blood pressure, temperature and number of breaths, pain must also be measured. To measure the intensity of pain, it is proposed to use a 10-cm strip (ruler) – the so-called visual analog scale (VAS), according to which the pain intensity is determined by the patient in millimeters from 0 – “no pain” to 100 mm – “the most severe pain”. Conventionally, pain less than 40 mm is considered weak, more than 40 mm – moderate, pain 70-100 mm is considered strong. Medical professionals should consider cases of intractable pain as a “red flag” [3]. Despite worldwide efforts to better recognize and treat pain adequately, there is much evidence of undertreatment of pain. If an analgesic is prescribed that is insufficient to eliminate pain, the latter persists and begins to grow rapidly due to the summation of pain stimuli and overexcitation of the nerve structures that conduct pain, resulting in the formation of a chronic pain syndrome that is difficult to eliminate. Untreated and mistreated pain is still a significant public health problem.
According to the WHO pain pharmacotherapy regimen, widely available non-opioid analgesics – paracetamol, NSAIDs – are sufficient for mild pain and at high doses for moderate pain. With pain of moderate intensity, opioids with moderate analgesic potential are indicated – tramadol, codeine. For severe pain, strong opioids are indicated – morphine, buprenorphine, fentanyl. Non-opioid analgesics are the most common means of pain control, but sometimes the use of even the highest doses of NSAIDs does not provide adequate analgesia, for example, in severe pain. The development of known side effects also complicates the use of NSAIDs. Leading organizations such as the Food and Drug Administration in the United States and the European Medicines Agency in Europe in 2005 concluded that there was an undoubted increase in cardiovascular and gastrointestinal risk in patients taking NSAIDs, and recommended limiting the use of all NSAIDs based on the principle of prescribing as little as possible. doses for as short a period as possible [7, 8]. Therefore, when moderate or severe non-cancer pain persists, it is often necessary to use an opioid analgesic. As shown by a study of chronic pain in Europe, this need arises in approximately one in five or six patients. Thus, for the purpose of pain relief, doctors prescribed NSAIDs in 44% of cases, paracetamol in 23%, and weak opioids in 18% of cases [4].
The possibility of using opioid analgesics in rheumatology has ceased to be a subject of discussion. They are prescribed, but according to strict indications, mainly in cases where antirheumatic therapy has exhausted its possibilities, and there is no hope of reducing pain in other ways. In particular, opioids are prescribed for a long time for severe pain in patients with osteoarthritis, when inflammatory changes are minimal, and surgical treatment cannot be carried out. It is known that with long-term use, such a traditional “soft” opioid as codeine in patients with rheumatic diseases has a good analgesic effect even in small doses, is well tolerated, and addiction develops very rarely. In the latest European League Against Rheumatism (EULAR) guidelines for the treatment of osteoarthritis of the hip, opioid analgesics are considered as a useful alternative to NSAIDs and coxibs in cases of intolerance, ineffectiveness or contraindications to their prescription (bronchial asthma, high risk of cardiovascular events, ulcers, bleeding or intestinal perforation) [10]. These recommendations are based on literature data and expert opinions, which indicate that opioids do not have cardiovascular complications and negative effects on the kidneys and gastrointestinal mucosa, characteristic of NSAIDs [5]. The Working Group on Pain Management (WGPM), which has been operating over the past few years, has proposed its algorithm for the treatment of pain in osteoarthritis in patients with risk factors such as cardiovascular and gastrointestinal (figure). According to these recommendations, at the stage when paracetamol does not help, and NSAIDs are contraindicated, weak opioids are used first, when they are ineffective, more active opioid analgesics are used [cit. by 9].
In response to the increased interest in opioid analgesics for the treatment of non-cancer pain, there is a need to become more familiar with the features of their practical use. An important condition for the correct work with opioids is the doctor’s knowledge of the mechanism of their action. It is well known that opioid analgesics differ significantly both in the mechanisms of interaction with receptors of the endogenous opioid system and in their narcotic potential, i.e., the ability to cause drug dependence [2]. All known opioids are divided into classes depending on the nature of interaction with receptors. The main class is made up of opioid agonists of opioid μ-receptors, including strong analgesics – morphine, fentanyl, less strong ones – promedol, prosidol, as well as weak ones – tramadol, codeine. It is these opioids that are most commonly used to treat pain. All opioid agonists, except tramadol, have a specific ability to cause physical and mental dependence and therefore they are included in the category of controlled drugs by the International Narcotics Convention. They are subject to special rules for prescribing, dispensing, accounting, storage, etc. Tramadol, which is an exception, does not apply to drugs, since, according to extensive world and domestic experience, the development of dependence on tramadol is extremely rare, is well predicted and can be prevented if used correctly [6 ]. Tramadol is not included in the Convention on Drugs under International Control and is not subject to special registration as a narcotic analgesic. This drug is classified as a potent drug and is issued on a special prescription form (form 148-1/y) [1]. This makes it more affordable than narcotic opioids and tramadol can be prescribed by all types of physicians. Potent drugs are subject to quantitative accounting (i.e., a pharmacy, when reporting to regulatory authorities, must report prescriptions for each package of the drug dispensed). Tramadol hydrochloride is included both in the “List of vital drugs” and in the “preferential” lists for various categories of patients.
A characteristic property of strong opioids is also tolerance, i.e., a decrease in the analgesic effect with an increase in the duration of opioid administration into the body, which requires a gradual increase in the dose during long-term therapy to maintain pain relief [2]. Thus, the dose of morphine can increase tenfold compared to the initial dose during treatment for several months, reaching or even exceeding 1000 mg / day. This group of opioids has a number of side effects: sedation (rarely euphoria), general weakness, inhibition of the cough reflex, in large doses – respiratory depression (bradypnea, apnea) and blood circulation (hypotension, bradycardia). In tramadol, not only the property of dependence, but also other dangerous side effects of true drugs – depression of breathing, consciousness, blood circulation – is not expressed, therefore it belongs to safe drugs and can be used on an outpatient basis.
In clinical practice, there are often patients with chronic pain syndrome due to diseases of the musculoskeletal system, who take various analgesics for a long time, including Tramadol hydrochloride. The following is a rare example of taking tramadol hydrochloride for 10 years without the development of side effects, tolerance and dependence.

Patient S., Russian, born in 1957 (49 years old), was hospitalized in November 2006 with complaints of severe musculo-articular pain throughout the day, fluctuations in blood pressure, shortness of breath and retrosternal pain during exercise. Particularly pronounced pain was noted in the spine, as well as in the hip, knee, shoulder joints, pain and swelling of the first metatarsophalangeal joint of the right foot were disturbing.

Medical history
Childhood invalid due to spastic paraparesis after birth trauma (forceps). Due to changes in muscle tone, disorders of the musculoskeletal system arose immediately after birth. Since childhood, contractures of the joints of the arms and legs, shortening of the right leg were noted, he suffers from a violation of posture, gait, and limps on his right leg. Was observed with a diagnosis of “Little’s disease, right-sided hemiparesis.” At the age of 4, an Achilles tendon plasty was performed to correct the contracture of the right ankle joint. At 19At the age of 90 (33 years), pains appeared in the hip joints and in the spine, which gradually increased, especially during physical exertion. Later, pain in the knee and shoulder joints appeared. In 1990, he periodically took paracetamol and NSAIDs with effect, but gastralgia quickly arose, and then exacerbations of cholecystopancreatitis. In 1994, against the background of long-term wearing of weights, the pain in the joints increased so much that he was forced to take analgesics almost constantly. Tried to use different drugs (analgin, reopirin, paracetamol, ibuprofen, diclofenac, etc.). The intake of analgesics was effective, but was accompanied by the development of adverse reactions from the gastrointestinal tract. With severe adverse reactions, the patient was periodically prescribed 100-200 mg per day of tramadol. From 1996, due to poor tolerance and the development of complications on the background of long-term use of NSAIDs, he began to take tramadol constantly, first in capsules, then in retard form. The drug was purchased independently. Depending on the intensity of pain and the condition of the gastrointestinal tract, the daily dose of tramadol was 200-400 mg. When taking 200 mg of tramadol, pain was suppressed by 50-70%, to enhance analgesia, some NSAID was often added. With increased symptoms of damage to the gastrointestinal tract, NSAIDs canceled and increased the dose of tramadol. Suffered severe exacerbations of cholecystopancreatitis at 1999, 2001, 2004, 2006 with hospitalization due to the severity of the condition in 2001 and 2004. Since about 2000 (43 years) – fluctuations in blood pressure. Since 2001 – a constant intake of antihypertensive drugs, diuretics. In 2001 and 2006 was hospitalized with symptoms of unstable angina pectoris, the diagnosis of myocardial infarction was discussed. In 2004, he was hospitalized with a diagnosis: “Exacerbation of chronic cholecystopancreatitis. Hypertension 2 tbsp. Atherosclerotic cardiosclerosis. coronary artery disease, angina pectoris. 2 FC. Widespread osteochondrosis with pain syndrome. consequences of birth trauma. Lower spastic tetraparesis. An X-ray examination revealed a pronounced asymmetry of the pelvic bones, the phenomena of osteoarthritis of the hip joints, spondylosis and osteochondrosis of the lumbar spine. According to CT scan of the brain – severe internal post-traumatic asymmetric hydrocephalus. Consulted by a psychoneurologist: post-traumatic stress disorder. The conclusion of the neuropathologist: lower spastic paraparesis with a uniform revival of tendon reflexes. Babinsky’s symptom from 2 sides. Lassegue’s symptom at an angle of 30°, sensitivity is not impaired.
In the spring of 2006, there was an acute episode of swelling of the first right metatarsophalangeal joint, the second episode occurred a month before the present hospitalization. Self-administered allopurinol 300 mg/day.
Anamnesis of life. Higher education (historical and archival), worked in the specialty for many years. In 1990-1996 he was disabled of group III, since 1996 – group II, since 1999 – II for life. Married, has a daughter. My maternal uncle has psoriasis.
On admission, the patient’s condition was satisfactory. Body mass index = 32. Lower spastic paraparesis. Increased muscle tone in the right leg. Shortening of the right limb by 4 cm. Limited range of motion in the ankle joints, more on the right. Flexion contractures of the right elbow and left knee joint. Restriction of abduction in the right hip joint due to pain. Restriction of movements in the right knee joint due to fibrosis of periarticular tissues. Arthritis of the I right metatarsophalangeal joint with severe edema and cyanosis of the skin over the joint. Right side scoliosis. Palpation tenderness of the spinous processes of the thoracic and lumbar spine. The range of motion in all parts of the spine is sharply limited due to pain. Thomayer’s symptom – 50 cm. Hallux valgus, transverse flat feet. Subluxations of the II-IV metatarsophalangeal joints on both sides. Rubrophytosis of the nails of the feet. Breathing is vesicular, no wheezing. Heart sounds are sonorous, rhythmic, there are no noises. Pulse 90 beats / min, the rhythm is correct. BP 120/70 mm Hg. Art. The abdomen is soft and painless on palpation. The liver and spleen are not enlarged. Pasternatsky’s symptom is negative on both sides. Stool and diuresis are within normal limits.
Characteristics of pain syndrome: Suffering from pain syndrome since 1990 (16 years old). At the moment, the joint pains are assessed as severe, in the morning according to VAS at 87 mm. Due to pain 2-3 times a day, I have to stop any activity. The pain is constant, debilitating, periodically – excruciating, inspiring anxiety. In the lumbar spine, the pain is acute, restricting movement, in the region of the legs – hot-burning. The patient periodically has a fear – what will happen next?
According to the laboratory examination, no inflammatory activity was detected. Hemoglobin 158 g/l, leukocytes – 11.5 × 109/l, ESR = 13 mm/h. Glucose – 6.1 mmol/l (norm up to 5.8), cholesterol – 6.0 mmol/l, CRP – negative. Creatinine 94.5 µmol/l (40-82), Uric acid – 398.0 µmol/l (140-420), urea 3.9 mmol/l (2.5-8.3), Gamma-GTP – 110 .56 U / l (5-30), Bilirubin total – 22.6 μmol / l (0-20.5), Bilirubin direct 5.8 μmol / (0-5.1), ALT 38.3 (8- 30 units/l). AST is the norm.
Complete urinalysis without features.
ECG. Sinus arrhythmia 72 beats / min. Deviation of the electrical axis of the heart to the left. Changes in the myocardium of the left ventricle. Cicatricial changes in the myocardium in the posterior wall. Enlargement of the left side of the heart. Incomplete blockade of the right leg of the bundle of His and the anterior left leg of the bundle of His.
Chest x-ray. The apical pleura is thickened. Lung fields are transparent. The lung pattern is reinforced in the root zones. The roots are compacted and expanded, contain petrificates. The diaphragm is usually located. Sinuses are shallow. The heart is slightly dilated to the left, the waist is flattened. The aorta is expanded.
X-ray of the hands and distal feet. Osteoporosis. The joints of the wrists and fingers are slightly narrowed. Small osteophytes of articular surfaces. Valgus deviation and subluxations of the II-IV metatarsophalangeal joints (more on the left).
X-ray of the pelvis. Bone rupture. Narrowing of the hip joints. The sacroiliac joints are narrowed, the contours are indistinct, their mild subchondral sclerosis. Severe asymmetry of the pelvic bones. Deformity of the right pubic bone.
Radiography of the lumbar and thoracic spine in two projections. Scoliosis of the departments. Increased radiolucency of the vertebrae. Schmorl’s hernias in the area of ​​the supporting platforms of the bodies of some vertebrae. The anterior longitudinal ligament was sealed in the region of the lateral angles of adjacent bodies Th8-Th20. The anterovertical size of the bodies of some vertebrae is reduced. The height of the intervertebral spaces is unevenly reduced. The anterior and lateral angles of the bodies of some vertebrae are pointed.
Ultrasound of the internal organs. Liver: the right lobe is enlarged 95 mm (+ 2 cm), the left lobe is enlarged 164 mm (+ 2), the contours are even, clear, the edge is rounded, the structure is diffusely heterogeneous, echogenicity is increased. Changed according to the type of fatty hepatosis. The vascular pattern is depleted. The gallbladder is enlarged 93 × 37 mm, the walls are sealed, the contents are homogeneous. The pancreas is of normal size, the contours are uneven, clear, the structure is diffusely heterogeneous, echogenicity is increased. Spleen: the contours are even, clear, the echostructure is homogeneous, echogenicity is normal. Kidneys: CHLS is not dilated, calculi on the left side are 4 mm in diameter.
ECHOCG. Consolidation of the aorta. Dilatation of the left atrium. Violation of the diastolic function of both ventricles according to type I. Hypokinesis in the posterior basal segment of the left ventricle cannot be ruled out.
Ultrasound of the joints. Hip: narrowing of the cracks on both sides. Exostosis of the femoral neck on the left. Knee: osteophytes on the edges of the lateral condyles on the left.
Consultation with a narcologist (Moscow Scientific and Practical Center for Narcology). A patient with a polymorbid condition and chronic pain syndrome caused by damage to the musculoskeletal system takes analgesics for a long time, including tramadol hydrochloride. During the long-term treatment with tramadol, the patient did not exceed the therapeutic dose of 400 mg per day, periodically does without it, periodically reduces the dose to 200 mg per day, combined with other analgesics. In this case, continued treatment with tramadol (at a dose not exceeding the therapeutic dose) is possible to improve performance and maintain social status. It is advisable to take it in the retard form at 200-400 mg per day, a combination with sonapax 10-25-50 mg per day is possible.
Treatment included prestarium 4 mg/day, thromboASS 100 mg/day, arifon was replaced by kardiket 20 mg/day, the dose of allopurinol was reduced to 150 mg/day. Reception of tramadol-retard 100 mg twice a day was combined with the imposition of a transdermal system with 5% lidocaine (Versatis) on the lumbar spine. During therapy, it was possible to achieve a reduction in pain by 70%.
The patient was discharged with the diagnosis: “Common polyosteoarthrosis with a primary lesion of large joints, spondylosis and osteochondrosis of the spine, transverse-longitudinal flat feet. Chronic pain syndrome associated with damage to the musculoskeletal system. Gout, relapsing course, acute attack. arterial hypertension. ischemic heart disease. Postinfarction cardiosclerosis. Atherosclerosis of the vessels of the heart, brain, kidneys. Chronic cholecystopancreatitis in the stage of unstable remission. Consequence of birth trauma (lower spastic tetraparesis). At discharge, it was recommended to prolong all ongoing treatment. During a telephone survey a year later (October 2007): the state is without significant changes, severe generalized musculoskeletal pain persists, to the maximum in the spine. Pain is assessed by VAS from 80 to 100 mm before taking medication. Constantly takes tramadol capsules 150 mg 2 times a day (2-3 times a month increases the dose to 400 mg), allopurinol 100 mg. During treatment, pain decreases to 40 mm according to VAS. Notes the stabilization of blood pressure (against the background of antihypertensive drugs), there were no severe exacerbations of chronic diseases of the gastrointestinal tract, attacks of gouty arthritis did not recur.

Discussion
The case history of patient S. is an example of the development of a severe chronic pain syndrome of mixed genesis, the prerequisites for the development of which arose at birth. The consequences of a traumatic brain injury received during childbirth manifested themselves in the form of Little’s disease – a variant of cerebral palsy. Spastic tetraplegia, which arose in early childhood, with a predominant lesion of the lower extremities, was accompanied by the gradual formation of tendon-muscle contractures, joint stiffness, and skeletal deformities (scoliosis, pelvic asymmetry, shortening of the leg). The pathology of the musculoskeletal system began to progress from infancy, accompanied by the early development of functional insufficiency of a number of joints and hypodynamic deficiency, and subsequently obesity. It is known that cerebral palsy is associated not only with the exhaustion of mental processes, a smaller amount of adaptive resources and a decrease in working capacity, but also with disturbances in the functioning of internal organs, in particular the gastrointestinal tract. Sometimes with cerebral palsy there is a severe pain musculo-articular syndrome, the genesis of which remains unspecified.
Despite the illness, through the efforts of parents and doctors, the patient achieved good psychological and social adaptation, which allowed him to get a higher education, start a family and raise a daughter. However, against the background of a pathological neuromuscular spastic state, disorders of the musculoskeletal system continued to progress, a symptom complex of dorsopathy was formed, then a “twisted” pelvis.
It should be noted that by the time of the onset of pain in 19In 1990 and later in 1996 (when the patient began taking an opioid analgesic permanently), the joint dysfunction was not significant enough to fully explain the intensity of the pain. In this case, it is possible to draw an analogy with patients with rheumatoid arthritis, in whom the perception of pain is determined by the degree of violation of the psychological status, and not by the severity of objective changes in the musculoskeletal system. It is known that damage to pain endings (which appeared very early in our patient) leads first to functional restructuring, and then to structural (irreversible) changes in the pain transmission system. If the cause of increased peripheral impulses persists, the phenomenon of increased pain occurs in the central nervous system, which also maintains pain. The long course of diseases of the musculoskeletal system leads to the fact that chronic pain gradually loses its protective function inherent in physiological pain. Pain that has a pathogenic effect, causing maladaptation, is called pathological pain (G.N. Kryzhanovsky, 1997). The biological significance of pathological pain differs from the physiological one by the mechanisms of implementation and clinical and behavioral reactions. Pathological pain loses its signal value and becomes a pathogenic factor, disrupting the adaptive abilities of the body, causing disorders in the activity of the central nervous system, microcirculation, cardiovascular system, etc. Various autonomic and depressive disorders gradually appear against its background. Obviously, patient S. developed pathological pain, which can be considered as an independent disease requiring adequate therapy.
Unfortunately, the progression of the pathology of the musculoskeletal system was accompanied by physical inactivity and the development of obesity. These factors, and possibly long-term use of NSAIDs, contributed to the onset of arterial hypertension, and the intake of diuretics exacerbated metabolic disorders. All this led to the emergence of gouty arthritis, at this stage of the development of the disease – a relapsing character. Gout attacks complicate pain management and increase polypharmacy. The cicatricial changes of the myocardium and the probable zones of physical inactivity on the ECHO-cardiograms revealed during the last hospitalization indicate a complicated course of hypertension and are unfavorable prognostically. Forced long-term (more than 10 years) use of NSAIDs was accompanied by the development of serious adverse reactions. Currently, NSAIDs are contraindicated for the patient due to diseases of the gastrointestinal tract and due to a high degree of cardiovascular risk. Given the irreversibility of changes in the joints and the ongoing progression of the articular syndrome, which is the basis of chronic pain, it is safe to predict the persistence of severe pain. The drug of choice in this situation is tramadol hydrochloride in therapeutic doses, preferably in the retard form.
Conclusion
The opioid non-narcotic analgesic tramadol, classified as a potent drug, is prescribed when it is necessary to relieve a patient of pain that is not eliminated by non-opioid analgesics (articular, neuropathic and other non-oncological pain). It seems that patients suffering from severe pain should not be deprived of the effective and safe modern pain relief that this drug achieves.
The purpose of this demonstration was not to expand the indications for the use of opioid analgesics and call for their more frequent use, but to draw attention to the study and generalization of experience in their use in non-cancer pain. Perhaps this experience can be useful for their correct and adequate use.

Literature
1. Babayan EA, Gaevsky AV, Bardin EV Legal aspects of the turnover of narcotic, psychotropic, potent, poisonous substances and precursors. M. MTsFER, 2000; 438.
2. Osipova N.A., Novikov G.A., Prokhorov B.M. Chronic pain syndrome in oncology. M.: Medicine, 1998; 178.
3. American Pain Society. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain. Glenview, IL: American Pain Society, 1999.
4. Breivik H., Colett B., Ventafridda V., Cohen R., Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment // Eur J Pain. 2006; 10:287-333).
5. Chou R, Clark E, Helfand M. Comparative efficacy and safety of ling-acting oral opioids for chronic non-cancer pain: a systematic review // J Pain Symptom Manage. 2003; 26:1026-1048.
6. Cicero TJ, Inciardi JA, Adams EA et. al. Rates of abuse of Tramadol remain unchanged with the introduction of new branded and generic products: results of abuse monitoring system, 1994-2004 // Pharmacoepidemiol Drug Saf.