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Opioid strength comparison chart: Opioid Conversion Calculator for Morphine Equivalents


Dose equivalents and changing opioids

  • Switching from one opioid to another should only be recommended or supervised by a healthcare practitioner with adequate competence and sufficient experience. If uncertain, ask for advice from a more experienced practitioner.
  • Opioid rotation or switching may be considered if a patient obtains pain relief with one opioid and is suffering severe adverse effects.
  • When converting from one opioid to another, the initial dose depends on the relative potency of the two drugs and route of administration.
  • An individualised approach is necessary.
  • Conversion factors are an approximate guide only because comprehensive data are lacking and there is significant inter-individual variation.
  • In most cases, when switching between different opioids, the calculated dose-equivalent must be reduced to ensure safety. The starting point for dose reduction from the calculated equi-analgesic dose is around 25-50%.
  • A dose reduction of at least 50% is recommended when switching at high doses (eg, oral morphine or equivalent doses of 500mg/24 hours or more), in elderly or frail patients, or because of intolerable undesirable effects.
  • The half-life and time to onset of action of the two drugs needs to be considered when converting so that the patient does not experience breakthrough pain or receive too much opioid during the conversion period.
  • Once the conversion has occurred, the dose of new opioid should be titrated carefully according to individual response and the patient monitored closely for side effects and efficacy, especially when switching at high doses.
  • Withdrawal symptoms (eg, sweating, yawning and abdominal cramps, restlessness, anxiety) occur if an opioid is stopped/dose reduced abruptly.


Approximate equi-analgesic potencies of opioids for oral administration

(Reviewed August 2020 to reflect current BNF figures)

 Potency Equivalent dose to 10mg oral morphine
Codeine phosphate0.1100mg
Oxycodone1. 56.6mg

* The relative potency of methadone depends on the starting dose and the duration of administration. Conversions to and from methadone should always be undertaken with specialist advice


Transdermal Opioids

(Reviewed August 2020 to reflect current BNF figures)

A. Buprenorphine

Transdermal buprenorphine changed at weekly intervals

 5 microgram/hr10 microgram/hr20 microgram/hr
Codeine phosphate (mg/day)120mg240mg 
Morphine sulphate (mg/day)12mg24mg48mg


Transdermal buprenorphine changed every three or four days (twice weekly)

 35 microgram/hr52 microgram/hr70 microgram/hr
Morphine sulphate (mg/day)84mg126mg168mg


B. Fentanyl

Fentanyl patch strength (microgram/hr)Oral morphine (mg/day)



Further Reading

  • British National Formulary.
  • Fine PG, Portenoy RK; Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation. Establishing “best practices” for opioid rotation: conclusions of an expert panel. Journal of Pain and Symptom Management 2009 ;38: 418-25.
  • Twycross R, Wilcock A, Howard P. PCF 5Palliative Care Formulary. 2014. 
  • UK Medicines Information. Q&A 42.8 What are the equivalent doses of oral morphine to other oral opioids when used as analgesics in adult palliative care? 2016.
  • Webster LR, Fine PG.  Review and critique of opioid rotation practices and associated risks of toxicity. Pain Medicine 2012; 13: 562-70.


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

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

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


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


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.


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


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


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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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 mainly used 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

According to the type of origin narcotic analgesics are divided into 3 groups

  • Synthetic n arcotic analgesic and:
    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.

    Drug name Induction dose Infusion rate Boluses
    Alfentanil 25-100 µg/kg 0.5-2 mcg/kg/min 5-10 µg/kg
    Sufentanil 0.25–2 µg/kg 0.5-1.5 mcg/kg/hour 2.5-10 mcg
    Fentanyl 4-20 µg/kg 2-10 mcg/kg/h 25-100 mcg
    Remifentanil 1-2 µg/kg 0.1-1.0 µg/kg/min 0.1-1.0 µg/kg

    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.
    For 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

    intravenous 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 and precautions

    Fentanyl causes increased sedation and respiratory depression when interacting with benzodiazepines and antidepressants. Fentanyl must not be used in combination with a partial opioid agonist such as buprenorphine.

    Alfentanil: indications, doses, side effects and contraindications

    Alfentanil (Alfentanil, Alfenta, Rapifen) narcotic analgesic , 90 004 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 0006 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 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 0005 ) is a narcotic analgesic used in anesthesiology. Belongs to the group of synthetic opioid analgesics of ultrashort 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 usage

    Indications and usage

    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.



    • 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 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 its high analgesic efficacy, sufentanil is often used for postoperative pain relief in patients with drug dependence. At present 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 mcg/kg
    General Anesthesia: 8–30 mcg/kg.

    In epidural anesthesia sufentanil is used either as a bolus of 40-55 micrograms (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 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 management
    • 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 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 regions 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 has not yet been 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. Opioid analgesics change not only the sensation of pain , but also the emotional response. 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. It is known that 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 during 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

    Respiratory depression 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 given 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 an increase in blood pressure and heart rate during sternotomy, in patients with coronary heart disease, and during operations on the coronary arteries.

    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 to narcotic analgesics (drugs) dependency and dependency were thought to occur only after long-term use. However, it became known that0003 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 .

    1. Aitkenhead A.R., Smith G., Roubatama D.J. Anesthesiology / Per. from English. Vetshevoi M.S. – M.: LLC Reed-Elsiver, 2010. – S. 114–129.
    2. Barash P., Cullen B., Stelting R. Clinical anesthesiology. – M.: Medical literature, 2010. – S. 75–86.
    3. Trescot A., Datta S., Lee M., Hansen H. Opioid pharmacology. – 2008. – Vol. 11. – P. 133–153.
    4. Zöllner C., Schäfer M. Opioids in anesthesia // Anaesthesist. – 2008. – Vol. 57(7). – P. 729-740.
    5. Site: https://www.medscape.com/
    6. Likhvantsev V.V. A practical guide to anesthesiology. M.: OOO “Medical Information Agency”, 2011.
    7. Miller R. Anesthesia by Ronald Miller. Publishing house “Chelovek”, 2015.

    Specialized scientific and practical publications for veterinarians and students of veterinary universities.

    Author: Butova A. A., veterinary anesthetist at the Veterinary Clinic of Dr. Sotnikov,
    Saint Petersburg.

    Approximately five thousand years ago, the opium poppy was grown in Mesopotamia. The prerogative of using its fruits was only among the priests. With the help of opium, they turned to the gods, they already knew about some of its properties and used it for medical purposes 6 . Among the ancient Egyptians for 4-6 millennia BC, only people belonging to the highest caste of clergymen had the right to prepare medicine, and the whole healing business, according to their belief, was under the auspices of the god Thoth, who was called “pharmaki” – a healer. This is where the words with the root “pharma” (“pharmacist”, “pharmacopoeia”, “pharmacology”) came from and have survived to this day 2 . We are told about the use of opium as an anesthetic by many sources that have survived to this day. The most detailed of these is the Ebers Papyrus, estimated to be 5400 years old and now in the University of Leipzig 2 .
    Morphine was the first pure opiate to be isolated. In 1804, the German pharmacist Friedrich Serturner obtained a crystalline powder from the air-dried milky juice of the opium poppy. Mixing opium with food, the scientist experimented on dogs. As a result, the animals fell asleep and did not respond to the painful manipulations that he performed. The first fully synthetic opioid, pethidine, was also synthesized in Germany in 1937, where methadone was received that same year. Fentanyl was first synthesized in Belgium by Paul Janssen in 1960 9 .
    Opioids exert their effect through interaction with specific receptors distributed throughout the central and peripheral nervous system, smooth muscles (gastrointestinal tract, urinary tract, etc.) 2 . which are formed in response to stimulation 8 .
    Opioid analgesics differ in their effectiveness depending on which class they belong to and which receptor they interact with 2 . Five types of opioid receptors have been found: μ (mu), δ (delta), σ (sigma), κ (kappa), and ε (epsilon). Impacts on each of them cause different effects (Table 1)2. To unify the classification of opioid receptors, the International Union of Pharmacology gave them new names: δ (delta) – OP1, κ (kappa) – OP2, μ (mu) – OP3, ε (epsilon) – OP48.

    Classification of drugs acting on opioid receptors:

    • Agonists. They have high affinity and intrinsic activity for receptors (morphine, pethidine, hydromorphone, methadone, fentanyl, sufentanil, alfentanil, remifentanil and codeine).
    • Partial agonists (eg buprenorphine). They do not have full affinity for receptors.
    • Mixed agonist-antagonist (eg butorphanol). They act as agonists of some receptors and antagonists of others. Their affinity and intrinsic activity at the receptors can vary.
    • Antagonists (eg naloxone). Weaken and eliminate the effects of agonists due to their high affinity and low intrinsic activity 8 .

    Table 1. Effects arising from exposure to various opioid receptors

    Opioids are capable of both depressing the central nervous system (i.e., causing its inhibition) and exciting it. Inhibition is manifested in analgesia, a decrease in the level of consciousness, and the characteristic signs of arousal are miosis, nausea and vomiting 10 . Occasionally, agitation and disorientation may occur. This effect is due to the effect of opioids on the hypothalamus, and may also be associated with indirect activation of dopaminergic receptors. In order to stop the excitement, you can combine the use of opioids with phenothiazines (acepromazine), benzodiazepines (diazepam), etc.8. An example of the stimulatory effect of opioids is miosis in dogs. It is the result of μ-coupled stimulation of the visceral nuclei of the oculomotor nuclear complex and the parasympathetic nerve that innervates the pupil 8 .

    Opioids can be used for epidural and spinal analgesia. This route of administration has the advantage of a good level of analgesia at low dosages, which is especially important in emergency and critically ill patients. For example, when epidural morphine is administered, a rather low dosage of 0.1 mg/kg is used, while analgesia begins after 30 minutes and lasts from 12 to 24 hours. Morphine can be mixed with, for example, lidocaine to provide additional analgesia and effect more quickly 5 .
    Opioids should be used with caution in patients with elevated intracranial pressure (eg, TBI, hydrocephalus), as these drugs cause changes in the sensitivity of the respiratory centers to carbon dioxide, resulting in hypercapnia, which causes vasodilation of cerebral vessels and, accordingly, an increase in intracranial pressure due to dilated blood vessels. This does not mean that opioid drugs should not be used, just that the concentration of CO2 in the exhaled air should be monitored, and in case of elevated carbon dioxide levels, artificial ventilation of the lungs should be performed to maintain an adequate amount of carbon dioxide. Intracranial pressure also increases with vomiting, which can be caused by intramuscular administration of morphine. A preventive measure may be the introduction of drugs such as Serenia, Ondansetron.
    Opioids should be used with caution intravenously in pregnant animals because the blood-brain barrier is not yet fully developed in the fetus and severe overdose may occur, although the mother may not show any signs of it. If the use of opioid drugs is unavoidable for any reason, an opioid receptor antagonist, such as naloxone, should be administered to newborn pups in order to stop possible negative consequences. If the use of opioid drugs is unavoidable for any reason, an opioid receptor antagonist, such as naloxone, should be administered to newborn pups to manage possible negative effects.

    Cardiovascular effects of opioids

    Opioids in low doses have little effect on the cardiovascular system. Changes in blood pressure and myocardial contractility are practically absent, however, with the use of morphine, histamine release may occur. The level of the latter begins to rise in the blood plasma from 0.15 mg/kg when administered intravenously for no more than 10 minutes, while there will still be no vascular effects, but with an increase in the dose of morphine to 0.3 mg/kg, the pressure decreases, the frequency increases heart contractions, hypercapnia occurs, adrenaline in the blood plasma rises. To avoid these effects, intravenous morphine should be given slowly over 20 to 30 minutes 7 .
    Opioids can cause vagus-mediated bradycardia (Fig. 1) and atrioventricular block (Fig. 2). These effects are due to stimulation of the nucleus of the vagus nerve in the medulla oblongata. Therefore, in the case of the use of opioid drugs, especially in high doses, it is necessary to monitor and record the heart rate using an ECG. If hemodynamically significant disorders are detected, they can be stopped with atropine.
    Fig. 1. Vagus-mediated bradycardia in a 4-year-old French bulldog during spinal cord decompression at the L5-L7 level associated with the use of analgesia with fentanyl ISI 4 μg/kg/h.

    Fig. 2. Second-degree atrioventricular block in a 7-year-old dachshund during spinal cord decompression at the L7-S1 level, associated with the use of induction of analgesia with fentanyl PSI 24 μg/kg/hour for 10 minutes.

    Effects of opioids on the respiratory system

    The effect of opioids on the respiratory system is the direct inhibition of the central and medullary respiratory centers. These drugs also cause a delayed response (altered threshold) and decreased response (altered sensitivity) to carbon dioxide in the arteries, resulting in carbon dioxide retention. When opioids are used in combination with other sedatives, respiratory depression may be exacerbated. Opioids can affect the thermoregulatory center, which subsequently manifests as tachypnea, and in high doses can cause bronchoconstriction 5 .


    Morphine is a pure μ-agonist that produces dose-dependent analgesic and sedative effects. It is used for severe pain syndrome. Complications are vomiting, diarrhea and bradycardia. The incidence of these side effects can be reduced by slowly administering morphine intravenously rather than subcutaneously or intramuscularly. If it is not possible to do this intravenously, an antiemetic drug, such as Serenia, Ondansetron, should be used before the administration of the opioid. Morphine is the standard of reference for other opioids. Thus, codeine is 10 times weaker, and fentanyl is almost 100 times stronger than this opioid (Table 2) 1 .
    Morphine can be administered as a constant rate infusion (RSI). It has a cumulative effect, so over time, the infusion rate is reduced, focusing on the effect. To enhance the quality of analgesia, intravenous combinations of drugs for PSI can be used, for example, MLA: morphine (0.05–0.1 mg/kg) + lidocaine + ketamine. For intramuscular or subcutaneous administration, dosages of morphine from 0.1 to 1 mg/kg are recommended, the duration of action of the drug is 2–6 hours 5 .
    A more prolonged effect of morphine is observed when used in animals with renal insufficiency, in geriatric patients, as well as in patients with hypovolemia and hypothermia. Morphine increases respiratory depression and depth of sedation when combined with benzodiazepines and antidepressants. This drug should be used with caution in patients with severe depression of the respiratory center and central nervous system, intracranial hypertension, bronchial asthma, as well as in pregnant and lactating animals 8 .
    Table 2. Analgesic potential of opioids relative to morphine

    Fentanyl is a pure μ-agonist. The features of this drug are a rapid onset and a relatively short duration of action, which makes it the drug of choice for PSI during surgical interventions, as well as in the ICU with severe pain. Recommended dosages for dogs are up to 60 mcg/kg/h, for cats up to 24 mcg/kg/h. When using higher dosages during drug withdrawal, a stage of excitation may occur. Can be combined, for example, with LC: fentanyl (2–5 µg/kg/h) + lidocaine + ketamine. In this case, minimal dosages of drugs are used, which reduces the likelihood of side effects while ensuring good quality of analgesia 5 .
    Fentanyl should be used with caution in animals with bronchial asthma, depression of the respiratory center, craniocerebral hypertension, as well as during pregnancy and lactation.

    Remifentanil is a pure μ-agonist. Unlike other opioids, it is metabolized by non-specific plasma esterases, which makes the use of this drug possible (especially) in severe hepatic impairment. Remifentanil has a very short half-life, only 7 minutes, while fentanyl has 10-20 minutes. The effect of the drug wears off quickly, even if the duration of IPS was very long 5 . Of the complications arising from the use of remifentanil, respiratory depression can be distinguished, which quickly resolves after the drug is discontinued. In this regard, respiratory activity should be monitored and, if necessary, adequate ventilation should be provided. Remifentanil is not registered in Russia 1 .

    Sufentanil is a pure μ-agonist. Sufentanil is currently the most powerful narcotic analgesic in the world. Belongs to the group of synthetic opioid analgesics of high efficiency (about 500 times stronger than morphine) and short acting. The drug was first synthesized in 1974 year. Sufentanil is not registered in Russia 1 .

    Tramadol is a μ-opioid receptor agonist, but its analgesic effect is mainly due to inhibition of norepinephrine and serotonin reuptake. Tramadol is currently on the list of potent and toxic substances. Dogs do not form the active metabolite, O-desmethyltramadol, which is responsible for much of its analgesic effect in humans, so its efficacy in these animals remains questionable 8 . Unlike dogs, cats produce this metabolite, so tramadol is considered an effective analgesic in this animal species, despite the fact that it is 10–20 times weaker than morphine 4 . The drug can be administered subcutaneously, intramuscularly, intravenously. Dosage in dogs is 5-10 mg/kg 3 times daily, in cats 1-2 mg/kg 1-2 times daily 5 .
    The indication for use is a pain syndrome of weak and moderate intensity of various etiologies.
    Tramadol should be used with caution in patients with brain injury and intracranial hypertension.

    Butorphanol is an opioid drug with κ-receptor agonist activity and high-affinity μ-receptor antagonist activity. Recommended dosages are 0.2–0.4 mg/kg IV, IM, or subcutaneous bolus or 0.1–0.2 mg/kg/hour ISI. It is believed to be effective for mild to moderate visceral pain and is used as an analgesic for minor elective surgical procedures. For anesthesia, intravenous, intramuscular and subcutaneous routes of administration can be used. The duration of anesthesia in cats and dogs ranges from 30 to 120 minutes. Butorphanol produces a mild sedative effect for approximately 4 hours and is an effective antitussive, so it is useful for premedication in patients undergoing airway examinations and bronchoscopy.
    The respiratory depression associated with butorphanol is less pronounced than with full μ-agonists. The degree of respiratory depression is characterized by a “ceiling effect”, as is its analgesic effect. Thus, an increase in the dose of the drug does not increase the degree of respiratory depression and analgesia, all mixed agonists-antagonists of opioid receptors have this feature. Butorphanol can be used to eliminate the undesirable effects of full μ-agonists 1 and provide κ-receptor mediated analgesia. It is recommended that 0.1–0.4 mg/kg of butorphanol be diluted in a large volume of normal saline (5–10 ml depending on patient size) and administered intravenously in small doses every 2–5 minutes until the expected response of the patient occurs5.
    Butorphanol should be used with caution in pregnant and varnishing patients.

    Naloxone is an opioid antagonist. It binds with high affinity to μ-, κ- and δ-receptors, competitively displacing agonists with lower affinity, thus stopping the action of agonists. Naloxone is a short-acting drug, with a single bolus (2–40 mcg/kg IV) that lasts 15 minutes to 1 hour. If the entire dose of naloxone is administered at once, then by displacing morphine and other opioids from the receptor sites, the antagonist can completely cancel all the effects of opioids. Thus, sedation, respiratory depression, and analgesia can be abruptly withdrawn, resulting in severe, acute pain, agitation, and stress. The diluted drug is recommended to be administered slowly and titrated by intravenous infusion to the desired effect. Since it is difficult to titrate naloxone with only analgesic effect, butorphanol or nalbuphine can be used, which will partially reverse the effect of agonists 5 .


    An integral part of anesthesia, analgesia and intensive care is the use of one of the safest painkillers – opioids. In addition to the analgesic effect, they can provide sedation and suppression of the cough reflex. These drugs play an important role in the treatment of pain in critically ill patients due to their effectiveness and relative safety for the cardiovascular system.


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