Table A6.2, Approximate potency of opioids relative to morphine; PO and immediate-release formulations unless stated otherwisea – WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents

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WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. Geneva: World Health Organization; 2018.

WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents.

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Table A6.2Approximate potency of opioids relative to morphine; PO and immediate-release formulations unless stated otherwise

^a

Source: Adapted with permission from Twycross et al. 2017:371 (Table 4) (3).

a

Multiply dose of opioid in the first column by relative potency in the second column to determine the equivalent dose of morphine sulfate/hydrochloride; conversely, divide morphine dose by the relative potency to determine the equivalent dose of another opioid.

b

Dependent in part on severity of pain and on dose; often longer-lasting in very elderly and those with renal impairment.

c

The numbers in parenthesis are the manufacturers’ preferred relative potencies.

d

A single 5 mg dose of methadone is equivalent to morphine 7.5 mg, but a variable long plasma half-life and broad-spectrum receptor affinity result in a much higher-than-expected relative potency when administered regularly – sometimes much higher than the range given above. Therefore, guidance from a specialist is recommended for conversions to regularly administered methadone.

From: ANNEX 6, Pharmacological Profiles and Opioid Conversion Tables

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Opioids: Listed From Strongest to Weakest

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Opioid addiction has dominated news headlines and flooded the treatment industry in the last few years. The problem is so severe that approximately 130 people die each day from an opioid-related overdose. Additionally, in 2017, 1.7 million people in the United States were addicted to prescription opioids and approximately 652,000 suffered from heroin addiction.[1]

Even though many of the opioids on this list can be prescribed by a physician, it doesn’t mean that they are safe. In fact, all opioids are highly addictive when abused. Despite the high potential for abuse, the CDC reports that in 2017, the average opioid prescribing rate was 58.7 prescriptions per every 100 people.[2]

Most opioids are controlled substances that have a high potential for abuse. When abused, a person’s tolerance increases and the body requires more and more of the drug. Then, the body becomes physically dependent on the drug to avoid going into opioid withdrawals. However, not all opioids are the same. Here are the most common opioids of abuse, listed from strongest to weakest. 

Fentanyl

Fentanyl is among the strongest and most dangerous opioids. It is 50 times more potent than heroin.[3] It is a synthetic opioid that is often prescribed after surgery to treat severe pain. However, it has become a very popular street drug of abuse. Due to its low cost and extremely high potency, street dealers often mix fentanyl with heroin, which can easily result in a fatal overdose. If a person with little to no tolerance to opioids consumes the smallest amount of the substance, they are at serious risk for overdose. 

Heroin

Heroin is derived from morphine and is the second strongest opioid. Although most opioids have a medical purpose – heroin does not. It is an illegal substance with a very high potential for abuse. 

Whether it is sold as a sticky black substance or a white or brown powder, heroin rapidly enters the bloodstream and causes intense feelings of euphoria. Regardless if it is snorted, injected, or smoked, it is extremely dangerous and can result in an overdose. Heroin is particularly dangerous because it is manufactured in clandestine laboratories. Sometimes, it is cut with fentanyl or other dangerous substances. It can be difficult to tell exactly what chemicals are in different batches of heroin until it is too late.

Hydromorphone (Dilaudid)

Hydromorphone, or Dilaudid, is prescribed as a pain reliever for severe pain. Since it is significantly stronger than morphine, it produces relaxation and extreme sedation. The drug can be dissolved and injected, causing instant effects similar to those of heroin. Consequently, many people who suffer from an opioid use disorder will use hydromorphone as a substitute for heroin. 

Oxymorphone (Opana)

Oxymorphone is sold under the brand name Opana. Although it has medicinal use in treating moderate to severe pain, it still has a high potential for abuse. It is usually dispensed in pill form, however, it also comes as a liquid made for injection. 

Those who abuse oxymorphone might swallow the pills, snort them, or inject them. They can also be obtained illicitly on the street. 

Methadone

Methadone is strictly regulated because it is prescribed to treat opioid addiction and to help reduce opioid withdrawal symptoms. Methadone can be swallowed or injected. However, abusing methadone against a physician’s orders is illegal. After all, it has a similar chemical structure to that of morphine and heroin. In addition, it can make users feel euphoric and sedated. 

Since methadone is used to treat opioid use disorders, some may believe that the drug is safe. Unfortunately, this is not the case. When methadone is abused, users are at risk of overdose and other adverse health reactions. Methadone should only be used under careful professional supervision. 

Oxycodone (Oxycontin, Roxicodone, Percocet)

Next on the list of the strongest opioids is Oxycodone. Oxycodone is sold under the brand names Percocet, Roxicodone, and Oxycontin. It is one of the most common opioids that is prescribed to treat moderate to severe pain. Despite the fact that it is prescribed often, it still has a high potential for abuse due to its calming and sedating side effects. 

Morphine

Morphine is derived naturally from the poppy plant. Even though it is not synthetic, it is still potent. The potency of morphine is similar to the potency of Oxycodone. It is usually prescribed in the place of other opioids if they are ineffective at treating pain. Morphine can be swallowed or injected, although injection is preferred among people who abuse it due to the near-instantaneous effects it can produce. 

Hydrocodone (Vicodin, Lortab)

Hydrocodone is similar in potency to morphine and oxycodone. It is, by far, the most commonly prescribed opioid medication in the United States. In 2017, approximately 83.6 million hydrocodone prescriptions were dispensed. [4] Additionally, there are staggering rates of hydrocodone diversion, street use, and polydrug abuse including drinking while under the influence of hydrocodone. In many instances of hydrocodone addiction, users will graduate to using stronger, more potent opioids.

Codeine

Codeine is commonly found in a prescription cough syrup that is used to reduce coughing. However, it can also be prescribed to treat mild to moderate pain when it comes in tablet form combined with Tylenol. Although it is weaker in potency than many other opioids, it still has a potential for abuse.  

Meperidine (Demerol)

Meperidine, or Demerol, was the first synthetic opioid to hit the market. It is weaker than the previous opioids on this list, but it still has a potential for abuse. Despite the fact that meperidine isn’t as potent as some opioids, physical dependence, and tolerance to the drug develops far quicker than some of the stronger opioids. As a result, it can be just as dangerous as the other opioids on the list.  

Tramadol (Ultram)

Tramadol is sometimes dispensed under its brand name, Ultram. Tramadol is similar in potency to meperidine, but it is less dangerous because there is a lower risk of tolerance, physical dependence, and abuse. Even though it is the weakest opioid, it can still be abused and can lead to addiction. 

Opioid Addiction Treatment 

Regardless of what type or potency of opioids is abused, there is always a risk for addiction. Unfortunately, approximately 80 percent of heroin users report that they began using prescription opioids before moving on to heroin.[5] It is evident that opioid abuse is dangerous, and can be deadly. 

Fortunately, recovery from opioid or painkiller addiction is possible. The best first step to take is to seek addiction treatment from a drug rehab near you.

References: 

1. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis
2. //www.deadiversion.usdoj. gov/drug_chem_info/hydrocodone.pdf
3. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis

The use of narcotic analgesics in the treatment of chronic non-cancer pain

Opioid analgesics are in the first line of treatment for severe pain, as they have the highest analgesic activity. Opioid analgesics are effective in the treatment of pain syndromes with different leading pathogenetic mechanisms: nociceptive and neurogenic. The widest area of ​​application of opioids is somatogenic pain syndromes resulting from the activation of nociceptors during trauma, inflammation, ischemia, tissue edema, and other injuries.

Particular examples of chronic nociceptive pain are such diseases of the musculoskeletal system as osteoarthritis, pain in the lower back, fibromyalgia, etc. The treatment of rheumatic diseases is aimed at limiting tissue damage as a result of systemic or local inflammation and includes biological agents, disease-modifying drugs , corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs). The suppression of the mediator response to inflammation and tissue damage by these agents is naturally accompanied by a decrease in pain. But sometimes in patients with chronic non-oncological pain of significant severity, the analgesic effect of antirheumatic therapy, including NSAIDs, may be insufficient. In these cases, the question arises of the use of stronger painkillers, in particular opioids. In recent years, the use of opioid analgesics in patients with non-cancer diseases has been actively discussed, and their use has expanded markedly.
Over the past decade, regulations and guidelines have emerged in many developed countries to allow and regulate the use of opioids for non-cancer pain [5,12,17]. Interest in opioid analgesics has also increased due to the emergence of new opioid drugs with an improved benefit / risk profile, as well as the forced restriction of the use of NSAIDs due to side effects. Thus, recently the American Society of Cardiology proposed a new algorithm for the pharmacotherapy of musculoskeletal pain in patients with a high degree of cardiovascular risk [4]. This algorithm is an inverted pyramid, on the broad base of which are first-line drugs – “simple” analgesics and opioids (Fig. 1). The steps of the pyramid tapering downwards mean limited indications for NSAIDs, which are located below opioids (even strong ones).
Recently, a large-scale study of chronic pain was undertaken in 16 countries in Europe, which opened a new chapter in understanding this problem. This pan-European study analyzed 46 thousand patients with moderate to severe pain (more than 5 points on a 10-point scale) and proved the high prevalence of severe chronic non-cancer pain in the population. It turned out that about one in five Europeans (19%) had to live with chronic pain for years, with two thirds experiencing moderate (5–7 points) and one third severe pain (8–10 points). One third of patients experience pain 24 hours a day, 365 days a year. The most common sources of pain are arthritis and osteoarthritis (35%) and back pain (24%). [6]. As it turned out, for the treatment of such severe chronic pain, non-steroidal anti-inflammatory drugs (44%) and paracetamol (23%), as well as opioid analgesics, are most often used. According to the strength of the analgesic effect, opioids are conditionally divided into weak (hydrocodone, propoxyphene, tramadol, codeine and combined preparations containing them), which are used to treat pain of moderate intensity, and strong (morphine, fentanyl, methadone, oxycodone, hydromorphone, etc.), used to treat severe pain. The frequency of weak and strong opioids was determined by answering the question: “What are you currently taking for pain relief?” It turned out that weak opioids take an average of 23% of those suffering from moderate to severe pain. At the same time, this figure is 50% in the UK, 36% in Sweden, 15-13% in Belgium and Spain, and 5% in Israel. Strong opioids were taken on average by 5% of the respondents. In different countries, the frequency of strong opioid use ranged from 12% and 11% in the UK and Denmark to 4% in Germany and France and 0% in Italy [6]. The results obtained allow us to conclude that in real practice, the prescription of opioids for the treatment of chronic non-cancer pain is no longer a rarity. This means that a much wider pool of physicians, previously inexperienced with their use, are prescribing opioids. The safe use of this group of analgesics for non-cancer pain requires knowledge of available drugs, relevant indications for use, dosage forms and routes of administration, as well as possible side effects and methods for their prevention and treatment.
The mechanism of action of opioid analgesics is well understood. Opioids interact with one or more opioid receptor subtypes, ie. mu, delta and kappa at the supraspinal, spinal and peripheral levels, causing analgesia and many other effects. Opioid receptors are localized both in the central nervous system and on primary nociceptive afferents in peripheral tissues. Current potent opioid analgesics are ?1-receptor agonists, although selective delta and kappa agonists can also cause analgesia. Opioids act by presynaptic inhibition of neurotransmitter production by C-fiber endings, postsynaptic suppression of evoked activity in nociceptive pathways, or removal of inhibition of other links in the regulation of nociceptive impulses. The supraspinal action of opioids is characterized by an increase in the transmission of downward inhibition of spinal nociceptive conduction. Opioid analgesics can be full agonists of specific opioid receptors, namely m-receptors, mixed agonist-antagonists with opposite effects on certain receptor subtypes, or partial m-agonists.
The effectiveness of opioids in chronic non-cancer pain (nociceptive and, to a lesser extent, neuropathic) has been proven in a number of controlled trials [3,8,14,16 and others] and demonstrated using a meta-analysis of trials using opioid analgesics [11].
The indications for prescribing opioids for non-cancer pain are rather narrow. Opioids for non-oncological pain are prescribed: 1) for severe chronic pain syndromes in patients with the ineffectiveness of all possible non-opioid analgesic therapy; 2) patients with toxic organ damage resulting from non-opioid therapy; 3) with contraindications to non-opioid analgesics (in patients with renal, hepatic insufficiency, gastropathy, a high degree of cardiovascular risk, bronchial asthma, with changes in the blood, etc. ).
All opioid agonists have a specific ability to cause physical and mental dependence and are therefore rated as dangerous drugs or narcotics. It is known that opioid analgesics differ significantly not only in the mechanisms of interaction with the receptors of the endogenous opioid system, but also in their narcotic potential, i.e. ability to cause drug dependence [1]. New drugs and new ways of administering opioids are constantly being developed to reduce the adverse effects of opioids. In recent years, new analgesics have appeared, differing in the strength of the analgesic effect and the severity of adverse reactions, in particular, in the degree of development of addiction and addiction. The better tolerability and safety profile of modern opioids is due to their low affinity for opiate receptors at therapeutic doses. Some of the new drugs have such a low narcotic potential that they are not included in the lists of narcotic drugs, but are classified as potent drugs. Non-narcotic opioids include tramadol hydrochloride, butorphenol tartrate and nalbuphine chloride. The division of opioid analgesics into non-narcotic and narcotic (morphine and all others) is important in social terms, since the use of all narcotic analgesics is under strict state control, which implies the legal responsibility of doctors and pharmacologists.
One of the problems associated with long-term use of narcotic analgesics is the development of tolerance. Tolerance to opioids is expressed in a decrease in the therapeutic effect over time, which requires a gradual increase in the initially effective analgesic dose. Tolerance to the analgesic action of a narcotic analgesic develops rather quickly and leads to a decrease in the duration and quality of analgesia. Factors leading to tolerance may be pharmacokinetic features (such as impaired distribution of the drug or stimulation of enzyme production) or pharmacodynamics (changes in receptor density, distribution and sensitivity). Recently, studies have appeared that indicate participation in the development of tolerance of NMDA receptors and nitric oxide. Long-term treatment with high doses of opioids can be unsafe and of little benefit, so increasing the dose should be very well justified, otherwise it should be avoided. When tolerance develops, it may sometimes be beneficial to switch drugs because cross-tolerance to opioids is not complete. The search and study of drugs that prevent the development of tolerance to narcotic analgesics is one of the priority tasks of pain pharmacotherapy. Tolerance, physical and mental dependence on the drug are the main dangerous consequences of its long-term use.
Physical dependence is manifested by the development of withdrawal symptoms (abstinence) when the patient suddenly stops receiving the drug. Opioid withdrawal syndrome includes pain throughout the body, diarrhea, goosebumps, loss of appetite, nervousness and restlessness, runny nose, sneezing, tremors, spasmodic stomach pain, nausea, insomnia, sweating, yawning, asthenia, tachycardia, and unexplained fever. Most opioid side effects other than “withdrawal” can be managed with the selective opioid antagonists naloxone and naltrexone (naloxone is used parenterally and naltrexone, a long-acting antagonist, is taken orally). In opioid treatment, physical dependence is closely related to tolerance. With the development of tolerance, as a rule, dependence also arises. Physical dependence appears to a small extent after a week of regular use of opioids. Psychological dependence is interpreted by some authors as a synonym for addiction, while others define it as the conscious desire of patients to take medication (addiction) and their subjective feeling that this will certainly restore their good health. Addiction is a pattern of drug use behavior characterized by a constant or periodic desire for repeated use with a compulsive (compulsory) search for the drug, irresistible involvement in the process of obtaining and using it, and with a high degree of relapsing course. Habituation should not be formed with the correct medical use of opioids. The problem arises when the diagnosis is wrong or when opioids are prescribed off-label. The clinical significance of the development of dependence is the use of the drug for non-therapeutic purposes. In this case, the drug is often taken in large quantities for a longer period, its use can continue despite complications. The social significance of addiction is to reduce professional and health-improving activity, when a lot of time and effort are spent on getting the drug. Drug dependence, tolerance and addiction can be a major problem in the use of opioids for both patients and physicians and nursing staff.
According to the literature, chronic pain syndrome not associated with terminal cancer can be successfully treated with opioids at a stable dose, with a minimal risk of addiction (dependence), without cognitive impairment when using medium doses (with a duration of treatment from several weeks to several months). At the same time, it is known that the risk of developing addiction in the treatment of chronic non-cancer pain with opioids is real and cases of addiction do occur. However, the addictive potential of opioids for non-cancer chronic pain is low. It is believed that addiction to narcotic analgesics, when used correctly for the treatment of severe pain, rarely develops. Thus, in the treatment of pain with opioids in a hospital in 11882 patients, the development of addiction was noted only in 4 [15].
In Mahowald M.L. et al., who observed patients with spinal pathology (spondylolisthesis, spinal stenosis, diseases of the intervertebral discs, etc.), who received strong opioids for back pain and were followed up for 9 months, signs of addiction developed in 2% of cases. In most patients, the dose of opioids remained stable, and dose increases (in rare cases) were associated with exacerbation of spinal disease. The authors conclude that opioid therapy in patients with orthopedic spinal problems is effective and safe [13].
In our country, there is a complex system for monitoring the prescription and use of narcotic analgesics (including tramadol and codeine), which serves as an obstacle to adequate opioid therapy for severe pain even for cancer patients [2], and in practice they are not used at all in non-cancer chronic pain syndromes. While the regulatory framework for prescribing opioids to patients with chronic non-oncological pain in our country exists and is currently determined by Order No. 110 of February 12, 2007 “On the procedure for prescribing and prescribing medicines, medical devices and specialized medical foods” . Writing prescriptions for narcotic drugs to preferential categories of patients with severe pain syndrome of non-tumor origin is carried out by the attending physician or specialist doctor by decision of the medical commission of the medical institution (Appendix No. 13, clause 2.4.2.). The appointment of narcotic drugs to other (non-preferential) categories of patients in outpatient treatment is carried out by the attending physician by decision of the medical commission (Appendix No. 12, clause 3.7.1.). It should be added that many doctors fear the development of drug addiction in patients and psychologically do not accept it. Therefore, at present, the choice of treatments for severe non-oncological pain is extremely limited, doctors do not prescribe strong opioid analgesics, and patients turn into “prisoners of the room”, left alone with their problems. At the same time, it is known that tissue damage leading to damage to nociceptive terminals 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. In the case of the appointment of an insufficient dose of analgesic to eliminate pain, the latter persists and begins to increase rapidly due to the summation of pain stimuli and overexcitation of the nerve structures that conduct pain. As a result of hyperexcitability of the central and peripheral nervous system, a difficult to eliminate chronic pain syndrome is formed. Therefore, severe pain should be treated, if indicated, with opioids, but it is good to know the features of their use in order to reduce the risk of adverse reactions.
Opioids have side effects but are not classified as organotoxic drugs. Traditional opioid-based pain relief is associated with side effects such as nausea, vomiting, constipation, respiratory depression, and sedation. Hypersensitivity to opioids may present as pruritus, urticaria, or bronchospasm. Serious adverse reactions such as serotonin syndrome may occur if fentanyl, pethidine or tramadol are given to patients receiving monoamine oxidase inhibitors, namely meclobemide, phenelzine, tranylcypromine. Other CNS depressant drugs, such as sedatives, hypnotics, phenothiazines, anesthetics, and alcohol, may increase the sedative and depressant effects of opioids. The combined use of opioids and anticholinergics may increase the risk of constipation and/or urinary retention.
The degree of analgesia, severity of side effects, and analgesic tolerance vary greatly among patients with pain, so opioid treatment is selected individually by trial and error. If pain persists at the beginning of treatment, and adverse reactions are very pronounced, it is advisable to change (rotate) to another opioid. Sometimes a patient does not tolerate one m-receptor agonist well and takes another without problems. Tables of opioid equivalent doses are used for adequate rotation.
In recent years, great efforts have been made to optimize the treatment of non-cancer pain with opioids. A number of recommendations have been developed for the rational use of opioid analgesics, aimed at preventing adverse reactions inherent in opioids. Of great importance for the prevention of addiction and dependence are developed risk identification programs. These controlled drug prescriber programs define the rules for treating patients with opioids. Such programs help to prevent or identify situations in which misuse of medicines may occur. Particular attention is paid to the prediction of possible aberrant (abuse) behavior and dependence [7,10,18]. A number of tests and questionnaires have been developed for patients to suspect the possible development of these complications. Risk factors for developing addiction to opioids include a history of drug addiction or problem behavior, a family history of drug abuse, alcohol abuse; mental illness in the family, a history of criminal situations, especially related to drugs, regular contact with high-risk groups, getting into car accidents. Particular attention should be paid to patients with pre-existing alcohol and / or drug dependence, with chronic pain syndromes when the pain exists for a long time (migraine, back pain, complex regional syndromes), and patients with chronic pancreatitis and frequent renal colic. These conditions require good communication between the general practitioner and medical professionals who provide emergency care to patients from time to time, including for pain. If the fact of abuse of any drug is established, the situation with the intake of other medications should also be clarified, since in such cases polyvalent dependence is characteristic. It should also be taken into account that among addictive patients there are relatively many people with mental disorders: depression, various phobias, depersonalization, etc.
For example, one of the questionnaires, which takes approximately 5 minutes to complete before a doctor’s examination, consists of only a few questions. These questions include the patient’s family history and history of alcohol use and psychiatric illness, whether there was sexual contact before adolescence, whether illegal drugs or drugs prescribed by a doctor on special forms were used. The doctor evaluates the answers in points, the sum of which reflects the risk of developing addiction.
Conducting a questionnaire in practice among 185 patients showed that in the low-risk group, 17 (94.4%) of 18 opioid users did not develop aberrant behavior. On the contrary, in the high-risk group, 40 (90.9%) of 44 patients developed aberrant behavior [18].
Opioids in rheumatic diseases can significantly improve the quality of life of patients suffering from severe pain, but their use requires special precautions regarding the choice of a specific opiate and the identification of patients at high risk of drug abuse.
Currently, a standardized approach to prescribing opioids for long-term treatment of chronic non-cancer pain has been developed abroad. Where possible, one physician and one pharmacist are involved in opioid treatment. In opioid treatment, it is important to create a complete understanding between the patient and physician regarding the benefits and risks of long-term opioid use. The participation of the patient in the treatment process (his rights and obligations) is essential. The following are recommendations for practitioners prescribing opioid analgesics. The main purpose of these recommendations is to help the doctor correctly and as safely as possible to use narcotic drugs.
Key steps in opioid treatment
chronic non-cancer pain
(with modifications, according to Coluzzi et al. [9])
Step 1. Justify the indications for starting opioid therapy. Since opioids are prescribed under the condition that adequate therapy by other therapeutic methods is ineffective, it is necessary to clarify the diagnosis of the underlying disease and ongoing therapy, confirming the ineffectiveness of previous non-opioid analgesic therapy, study the history and familiarize yourself with medical documents (if necessary, make a request to the institution where the patient was treated before).
Stage 2A. Development of an individual treatment plan together with the patient.
• Perform a thorough examination of the patient, assess the severity of pain and the degree of functional impairment, and outline the scheme of initial opioid therapy.
• Determine mood changes, sleep disturbances, work capacity and skill levels. The physician prescribing opioids must be familiar with the patient’s psychosocial status.
Stage 2B. Prediction of possible complications and dependence.
• Identify “red flags” of possible inappropriate attitudes towards treatment (aberrant behavior). If these flags are identified, a consultation with a narcologist is indicated. If there is a high risk of developing maladaptive behavior, it is advisable to refuse opioid treatment and discuss alternative treatment regimens.
Stage 3: Opioid therapy.
• It is necessary to familiarize the patient and his family members with the features of opioid therapy.
• It should be explained that problems of tolerance, physical and psychological dependence are not the main thing in opioid treatment. Together they can be warned.
• It is important to obtain informed consent from the patient for opioid treatment.
• The inadmissibility of violations of medical recommendations should be explained and situations that will lead to the termination of treatment should be discussed.
• Set realistic treatment goals and agree on them with the patient. These goals can be modest, such as being able to live with pain, reducing pain by 20% and improving sleep, etc. Depending on the clinical situation, it is possible to plan for a more significant reduction in pain, as well as an improvement in function or quality of life.
• Choice of initiation of therapy. It is recommended to start with short-acting opioids and then switch to long-acting ones. The most appropriate use of prolonged forms of opioids (slowly released), as well as patches and transdermal therapeutic systems.
• For optimal effect, treatment should begin with titration – a gradual, slow increase in dose.
• The use of opioids by patients should be closely monitored. Against the background of treatment, regular (monthly at the beginning of treatment) monitoring of the patient’s status is carried out according to the most important parameters – the degree of analgesia, daily activity, aberrant behavior, side effects, etc. It is desirable to use available methods for assessing parameters (for example, pain assessment on a visual analogue scale). If necessary, the goals and objectives are adjusted.
• The physician using opioids in the treatment of patients must recognize and be able to treat tolerance, withdrawal, abnormal behavior, addiction, dependence and pseudo-dependence, and other adverse reactions.
• Recording in medical records of all stages of opioid treatment is mandatory.
• Opioid treatment should not be considered lifelong.
In the course of opioid treatment, there may be indications for interruption of opioid treatment or an opportunity to withdraw them. The rate of opioid withdrawal depends on the duration of the drug. Gradual dose reduction by 20% per day significantly reduces the likelihood of withdrawal symptoms. If withdrawal does occur, the most prudent course of action is to resume small doses of opioids. Another option may be to use benzodiazepines and clonidine. In difficult cases, consultation with a narcologist is necessary.
Opioids are highly effective in the treatment of severe non-oncological pain syndromes. However, their use in the practice of general practitioners is associated with a number of problems: low availability of drugs, strict control measures, etc. These problems are of a social nature, and their solution does not depend on the attending physician. The practical doctor’s problems are narrower and more specific. The main therapeutic problems in the use of narcotic analgesics in wide practice are the prediction of possible complications of therapy and the need for careful monitoring. As extensive clinical experience shows, routine prevention, diagnosis, prevention and treatment of complications arising from opioid treatment are now possible. Proper use of narcotic analgesics according to strict medical indications makes it possible to provide adequate assistance to seriously ill patients with severe non-oncological pain.

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Narcotic analgesics in Anesthesiology. Classification and mechanism of action. Indications and contraindications. Application. Side effects.

Narcotic analgesics in anesthesiology — group of drugs used as a component of general anesthesia, sedation and premedication . In resuscitation, drugs are used mainly to relieve pain , less often with prolonged mechanical ventilation in order to synchronize the patient with the respiratory apparatus. Modern narcotic analgesics in anesthesiology include: fentanyl, sufentanil, alfentanil, remifentanil, morphine and tramadol. Some of them are not registered in the Russian Federation.
The classification and effects of these drugs are based on the mechanism of action of opioids.
Full classification of drugs used in anesthesiology (inhalation and intravenous anesthetics, muscle relaxants, benzodiazepines, vasopressors and cardiotonic drugs) here.

Classification of narcotic analgesics

The classification of narcotic analgesics depends on the type of origin, strength of action and type of effect on opiate receptors.

Classification by strength of action

The strength of action of narcotic analgesics is usually compared with the classic representative of opioids – morphine. The strongest narcotic analgesic in the world is sufentanil . Depending on the analgesic strength, narcotic analgesics can be divided as follows:

1. Sufentanil – 500 times stronger than morphine
2. Remifentanil – 200 times stronger than morphine
3. Fentanyl – 100 times stronger than morphine
4. Alfentanil – 30 times stronger than morphine

Classification by type of effect on opioid receptors

According to the type of effect on opioid receptors, narcotic analgesics are divided into the following groups:

• agonists : fentanyl, morphine, sufentanil, alfentanil, remifentanil, omnopon, promedol
• partial agonists : buprenorphine
• mixed agonist-antagonists : tramadol, nalbuphine, butorphanol
• antagonists: naloxone

Classification by origin

By type of origin narcotic analgesics are divided into 3 groups
synthetic n arcotic analgesic i:
fentanyl, sufentanil, alfentanil, remifentanil

P olusynthetic n arkot ical analgesics:
Heroin, dihydromorphone, morphinone, etorphine, buprenorphine

The use of narcotic analgesics

The use of narcotic analgesics in anesthesiology is limited by strict indications, because they are potent substances. Dosing accuracy allows you to avoid side effects, critical incidents, and even more complications. Average doses of narcotic analgesics, infusion rate and doses to maintain general anesthesia are presented in the table.

A more detailed description of narcotic analgesics used in anesthesiology and resuscitation is described below.

Fentanyl: Indications, Doses, Side Effects and Contraindications

Fentanyl used in anesthesiology. By strength 100 times stronger than morphine. Belongs to the group of synthetic opioids, μ-receptor agonist. The onset of action is within 1-2 minutes, and the maximum effect is achieved within 4-5 minutes. The duration of action of fentanyl after a single intravenous injection at a dose of 0.1 mg with a patient weighing 60-80 kg is about 20 minutes.
In induction anesthesia fentanyl dose varies from 2 to 6 mcg/kg in combination with intravenous (propofol) or inhalation anesthetic (sevoran) and muscle relaxants. Maintenance of anesthesia can be achieved with inhalation or intravenous anesthetics, as well as additional administration of fentanyl .0 µg/kg /hour).

Indications and use

( fentanyl 0.1 mg + dormicum 5 mg + atropine 0.5 mg) intramuscularly 30 min before anesthesia

• Sedation

IV infusion: 1–5 mcg/kg/hour

• During anesthesia

IV bolus:

• 1-3 mcg/kg spontaneous breathing
• 2-6 mcg/kg for general anesthesia induction
• 5–10 mcg/kg ventilated
• up to 100 mcg/kg in cardiac surgery

Side effects

Side effects

Respiratory depression and apnea; bradycardia and hypotension; nausea and vomiting; delayed gastric emptying; decreased intestinal motility; constipation; urinary retention; muscular rigidity of the chest.

Contraindications

Contraindications and precautions

Fentanyl causes increased sedation and respiratory depression when interacting with benzodiazepines and antidepressants. Do not use fentanyl in combination with a partial opioid agonist such as buprenorphine.

Alfentanil: indications, doses, side effects and contraindications

Alfentanil (Alfentanil, Alfenta, Rapifen) – narcotic analgesic , 90 073 used in anesthesiology. Approximately has an analgesic effect 30 times stronger than morphine, but 4 times weaker than fentanyl . It belongs to the group of synthetic opioid analgesics, being a μ-receptor agonist . Alfentanil has a short duration of action. The drug was developed by Janssen Pharmaceutica back in 1976 . Alfentanil is not registered in Russia.
Alfentanil causes fewer cardiovascular complications than other similar drugs such as fentanyl and remifentanil, but has more respiratory depression and therefore requires careful monitoring during intravenous anesthesia or sedation. In general anesthesia based on inhalation anesthetics alfentanil reduces the MAC of isoflurane, sevoflurane and desflurane.

Indications and use

Indications and use 0075 use in ambulatory anesthesiology in combination with propofol or benzodiazepines. The duration of action after a single injection is from 5 to 10 minutes.

Induction of anesthesia : 10–20 mcg/kg
Maintenance of anesthesia mcg /kg/min)

Side effects

Side effects

Respiratory depression and apnea; bradycardia and hypotension; nausea and vomiting; delayed gastric emptying; decreased intestinal motility; constipation; urinary retention; muscular rigidity of the chest.

Contraindications

Contraindications and precautions

Patients with hepatic insufficiency may experience an increase in the duration of action of this narcotic analgesic. Alfentanil should not be used in combination with a partial opioid agonist such as buprenorphine.

Remifentanil: indications, doses, side effects and contraindications

Remifentanil ( Remifentanil; Ultiva ) is a narcotic analgesic used in anesthesiology. Belongs to the group of synthetic opioid analgesics with ultra-short action. Due to the very short duration of action of the drug, it is recommended to start the infusion (0.1-1.0 mcg / kg / min) immediately after the bolus dose to ensure a sustained analgesic effect. The infusion rate of remifentanil during general anesthesia ranges from 0.1 to 1.0 mcg/kg/min. Remifentanil reliably suppresses autonomic and hemodynamic responses to noxious stimuli and provides a predictable and rapid awakening period. Quick recovery from anesthesia (about 10 minutes) when used, it is not accompanied by respiratory depression. At a remifentanil infusion rate of 0.5–0.15 µg/kg/min, rapid recovery of spontaneous breathing is provided while maintaining pain relief. Remifentanil is not registered in Russia.

Indications and use

Indications and use

ambulatory anesthesiology in combination with intravenous or inhalation anesthetics. The duration of action after a single injection is from 5 to 15 minutes.

Induction of anesthesia : intravenous infusion 0.5-1 mcg/kg/min 8 min before tracheal intubation.
Maintenance of anesthesia : IV infusion 0.25-0.5 mcg/kg/min or IV bolus 0.5-1 mcg/kg.
Postoperative pain relief : intravenous infusion 0. 025-0.2 mcg/kg/min.

After abdominal and thoracic surgery under conditions of general anesthesia based on propofol (75 mcg/kg/min) and remifentanil (0.5-1.0 mcg/kg/min), a continued infusion of remifentanil (0.05-0.1 mcg / kg / min) to ensure adequate pain relief in the early postoperative period.

Side effects

Side effects

Respiratory depression and apnea; bradycardia and tachycardia; hypertension and hypotension; nausea and vomiting; muscular rigidity of the chest; serotonin syndrome.

Contraindications

Contraindications

• Epidural or intrathecal administration;
• Known history of hypersensitivity to fentanyl analogues.

Sufentanil: indications, doses, side effects and contraindications

Sufentanil (Sufentanil, Sufenta) is a narcotic analgesic used in anesthesiology. Belongs to the group of synthetic opioid analgesics, approximately is 10 times more potent than fentanyl and 500 times more potent than morphine . Structurally, sufentanil differs from fentanyl by the addition of a methoxymethyl group on the piperidine ring (which is believed to reduce the duration of action). The drug was first synthesized by Janssen Pharmaceutica in 1974 year. Due to the high analgesic efficacy of , sufentanil is often used for postoperative pain relief in patients with drug dependence . Currently sufentanil is the most powerful narcotic analgesic in the world. Su fentanyl is not registered in Russia.

Indications and usage

Indications and usage

Sufentanil is used during general anesthesia based on inhalation anesthetics, as well as during total intravenous anesthesia based on propofol.
Induction/intubation: 1–2 µg/kg
General anesthesia: 8–30 µg/kg.

In epidural anesthesia sufentanil is used either as a 40–55 mcg bolus (providing 3 hours of effective analgesia) or in combination with ropivacaine and bupivacaine.

Side effects

Side effects

Considering the pronounced analgesic (opioid) activity of sufentanil , side effects cannot be insured against. These include: nausea, vomiting, pruritus, urticaria, bradycardia, dizziness, visual disturbances, euphoria/dysphoria, agitation, anticholinergic effects (dry mouth, palpitations, tachycardia), respiratory depression, cardiac arrhythmias (ventricular tachycardia, etc.), prolongation of the QT interval, ST segment elevation, myocardial infarction, angina pectoris, cardiac arrest, oliguria.

Intensive therapy with sufentanil can easily lead to addiction!

Contraindications

Contraindications and precautions

Relative contraindication to the introduction of sufentanil is the presence of liver failure in the patient, tk. there may be an increase in the duration of action of this narcotic analgesic.

Use caution for bradycardia, compromised heart, head trauma, hypothyroidism, increased intracranial pressure, impaired renal function, respiratory failure.

Morphine: indications, doses, side effects and contraindications

Morphine (Morphine, morphinum, morfin) is a narcotic analgesic used in anesthesiology and resuscitation. It is the “standard opioid” against which other narcotic analgesics are compared and currently remains a valuable drug for the treatment of acute pain.

The effect of analgesia after intravenous injection occurs after 15 minutes. The duration of action of morphine is 2 to 3 hours.

Indications and uses

Indications and uses

• Pain relief
• Extended Ventilation Synchronization
• Acute left ventricular failure

For pain relief:

• IM: 10 mg every 4-6 hours as needed
• IV: 2. 5 mg every 15 minutes as needed
• IV infusion: 1–5 mg/hour
• epidural: 5–10 mg
• intrathecal: 0.1–0.3 mg

Side effects

Side effects

Frequency of side effects with morphine:

• Itching ≤80%
• Urinary retention (with epidural anesthesia) 15-70%
• Vomiting 7-70%
• Constipation > 10%
• Headache > 10%
• Drowsiness > 10%

Contraindications

Contraindications and precautions the elderly, as well as in patients with hypovolemia and hypothermia. Morphine increases sedative and respiratory depression in combination with benzodiazepines and antidepressants .

Effects of narcotic analgesics

The effects of narcotic analgesics are due to the mechanism of action of these drugs (see below). These include muscle rigidity, postoperative tremors, nausea and vomiting, respiratory and cardiovascular effects, and tolerance.

Mechanism of action

Mechanism of action of narcotic analgesics

Mechanism of action of narcotic analgesics of the brain that modulate analgesia, and the functions of various types of receptors in these networks. Analgesic effects due to the ability of opioids to inhibit the transmission of nociceptive information at the level of the dorsal horns of the spinal cord and activate analgesic pathways descending from the midbrain through the rostral ventromedial areas of the brain into the dorsal horns of the spinal cord.

In the spinal cord opioids act at the level of the synapse either presynaptically or postsynaptically . Opioid receptors are abundantly expressed in the gelatinous substance, where opioids interfere with the release of substance P from the primary sensory neuron. The actions of opioids in the bulbospinal pathways are extremely important for their analgesic efficacy. The action of opioids on the forebrain appears to promote pain relief. However, the role of opioid receptors in all these areas of the brain is not yet fully elucidated .

In humans, morphine-like drugs cause analgesia, drowsiness, mood changes and mental confusion. An important feature of opioid analgesia is that it is not associated with loss of consciousness . Morphine given at the usual dose to a normal person without pain may cause discomfort . Pain relief with morphine-like opioids is relatively selective, while other sensory modalities are not affected. Patients often complain that the pain is still felt, but they feel more comfortable. There is a significant difference between pain caused by stimulation of a nociceptive receptor followed by signaling through an intact neural pathway and pain caused by damage to neural structures, often involving neural hypersensitivity (neuropathic pain). Although nociceptive pain is usually easily treated with opioids, Neuropathic pain typically responds poorly to opioid analgesics , which may require an increase in dose. Under the influence of opioid analgesics, not only the sensation of pain changes , but also the emotional reaction. However, a change in the emotional response to pain stimuli is not the only mechanism of analgesia.

Muscle stiffness

Muscle stiffness after administration of narcotic analgesics

Muscle stiffness during induction of anesthesia is one of the critical incidents in anesthesiology. As is known, narcotic analgesics (opiates) can increase muscle tone and cause muscle rigidity of the chest. It has been noted that this effect varies greatly with different methods of opioid anesthesia due to differences in dosage and rate of administration of opioids. Typically, clinically significant muscle stiffness caused by narcotic analgesics (eg, fentanyl) occurs as soon as the patient loses consciousness. Patients who are conscious may show a mild manifestation of rigidity in the form of hoarseness. Z occlusion of the vocal cords is the main cause of difficulties in bag ventilation through the mask of the respiratory apparatus after the administration of narcotic analgesics. The exact mechanism by which opioids cause muscle rigidity has not been elucidated.

Respiratory effects

Respiratory effects of narcotic analgesics

analgesics. While this rather adverse effect of opioids to cause respiratory depression appears to be preventable, it is still occurs in approximately 0.1-1% of cases in the perioperative period regardless of the route of administration of the opioid. Respiratory depression associated with the effects of opioids may be worsened and/or prolonged when administered with other CNS depressants, including powerful inhalational anesthetics, alcohol, barbiturates, benzodiazepines, and most intravenous sedatives and hypnotics . Older patients are more sensitive to anesthetics and the respiratory depressant effects of opioids. They have a higher plasma concentration of narcotic analgesics when administered per kg of body weight.

Cardiovascular effects

Cardiovascular effects of narcotic analgesics

Administration of large doses of narcotic analgesics as the sole or main anesthetic leads to hemodynamic stability in the postoperative period . The choice of opioid may affect the perioperative hemodynamic profile . For example, and fentanil is less reliable than fentanyl and sufentanil in blocking the increase in blood pressure and heart rate during sternotomy, in patients with coronary heart disease, during coronary artery operations.

Postoperative shivering

Postoperative shivering after administration of narcotic analgesics

Postoperative shivering is common in anesthesia practice . Opioid-based anesthesia lowers the thermoregulatory threshold, probably to the same extent as powerful inhalational anesthetics. alfentanil, morphine, and fentanyl are known to be ineffective in the treatment of postoperative tremors. Studies have shown that tramadol (0.5 mg/kg) is most effective in suppressing tremors after epidural anesthesia.

Postoperative nausea and vomiting

Postoperative nausea and vomiting due to narcotic analgesics

Postoperative nausea and vomiting is not uncommon in anesthesiology . Intraoperative use of narcotic analgesics is a well-known risk factor for postoperative nausea and vomiting . Opioids stimulate the trigger chemoreceptor zone in the rhomboid fossa of the medulla oblongata, possibly via δ receptors, leading to nausea and vomiting. Compared to approximately equivalent doses of fentanyl and sufentanil, Alfentanil administration is associated with a lower incidence of postoperative nausea and vomiting .

Tolerance

Tolerance to narcotic analgesics (narcotics) dependency and dependency were thought to occur only after prolonged use. However, it became known that0072 Tolerance may develop after short-term administration of narcotic analgesics . Intraoperative infusion of remifentanil (0.3 mcg/kg/min) in patients undergoing major abdominal surgery under desflurane anesthesia increased postoperative pain and morphine requirements compared with a low dose of remifentanil (0.1 mcg/kg/min), which indicates the development of acute remifentanil tolerance. In contrast, there is a report that targeted controlled infusion of alfentanil and remifentanil for postoperative pain relief does not result in opioid tolerance . Continuous infusion of remifentanil (0.08 mcg/kg/min) to volunteers for 3 hours did not reduce pain threshold. Thus, the development of acute opioid tolerance in humans remains controversial .