How do different opioids compare in strength to morphine. What factors affect opioid potency and conversion. How can healthcare providers safely calculate equivalent doses between opioids. What precautions are needed when switching between opioid medications.

The Importance of Opioid Equivalence in Pain Management

Understanding opioid equivalence is crucial for healthcare providers managing patients with chronic or acute pain. Opioids vary significantly in their potency and effects, making it essential to have a standardized way of comparing their relative strengths. The opioid equivalence chart, also known as the narcotic strength chart, provides a valuable tool for clinicians to safely and effectively transition patients between different opioid medications.

Opioid equivalence is typically expressed in relation to oral morphine, which serves as the standard reference point. By understanding how other opioids compare to morphine in potency, healthcare providers can make informed decisions about dosing and medication switches. This knowledge helps minimize the risks of under- or over-medication when changing opioid regimens.

Interpreting the Opioid Equivalence Chart

The opioid equivalence chart presents approximate potency ratios of various opioids compared to morphine. These ratios allow for the calculation of equivalent doses between different medications. For example, if an opioid has a relative potency of 2 compared to morphine, it means that 1 mg of that opioid is equivalent in analgesic effect to 2 mg of oral morphine.

To use the chart:

1. Identify the current opioid and its dose
2. Find the relative potency of that opioid compared to morphine
3. Multiply the current dose by the relative potency to determine the morphine equivalent dose
4. If switching to a new opioid, divide the morphine equivalent dose by the new opioid’s relative potency

It’s important to note that these conversions are approximate and may require adjustment based on individual patient factors and clinical response.

Key Opioids and Their Relative Potencies

The opioid equivalence chart includes a range of commonly used opioid medications. Here are some key examples:

• Codeine: Relative potency of 0.1-0.15 (meaning it is less potent than morphine)
• Hydrocodone: Relative potency of 1 (similar potency to morphine)
• Oxycodone: Relative potency of 1.5-2 (more potent than morphine)
• Hydromorphone: Relative potency of 5 (significantly more potent than morphine)
• Fentanyl: Relative potency of 100-150 (extremely potent compared to morphine)

These potency ratios highlight the wide range of strengths among different opioids, underscoring the importance of careful dose calculations when switching between medications.

Factors Affecting Opioid Potency and Conversion

While the opioid equivalence chart provides a useful starting point, several factors can influence the actual potency and effectiveness of opioids in individual patients:

1. Route of Administration

The method by which an opioid is administered can significantly affect its bioavailability and potency. For example, oral opioids typically have lower bioavailability compared to parenteral routes due to first-pass metabolism in the liver. Intravenous administration often results in higher peak concentrations and more rapid onset of action.

2. Formulation

Immediate-release and extended-release formulations of the same opioid may have different potency ratios. Extended-release formulations are designed to provide steady drug levels over time, which can affect the overall analgesic effect and duration of action.

3. Individual Patient Factors

Patient-specific characteristics such as age, renal function, hepatic function, and genetic variations in drug metabolism can all impact opioid potency and effectiveness. Elderly patients and those with impaired organ function may require dose adjustments due to altered drug metabolism and clearance.

4. Opioid Tolerance

Patients who have been on long-term opioid therapy may develop tolerance, requiring higher doses to achieve the same analgesic effect. This tolerance can complicate opioid conversions and may necessitate more conservative initial dosing when switching medications.

Special Considerations for Specific Opioids

Certain opioids require special attention when interpreting their relative potencies and performing conversions:

Methadone

Methadone presents unique challenges in opioid conversion due to its complex pharmacokinetics and pharmacodynamics. Its relative potency can vary widely depending on the dosing regimen and individual patient factors. The opioid equivalence chart notes that while a single 5 mg dose of methadone may be equivalent to 7.5 mg of morphine, regular administration can result in much higher relative potency – sometimes exceeding the range provided in the chart.

Due to these complexities, the World Health Organization (WHO) recommends seeking guidance from a specialist when converting to or from regularly administered methadone. This precaution helps ensure safe and effective pain management while minimizing the risks associated with methadone’s unique properties.

Fentanyl

Fentanyl’s high potency requires careful consideration during opioid conversions. Transdermal fentanyl patches, in particular, necessitate specific conversion calculations that take into account the gradual drug release and accumulation over time. Healthcare providers should consult specialized guidelines when converting between fentanyl and other opioids to ensure appropriate dosing and patient safety.

Safe Practices in Opioid Conversion

While the opioid equivalence chart is a valuable tool, it’s essential to approach opioid conversions with caution and adhere to safe practices:

1. Use conservative initial dosing: When switching to a new opioid, consider starting at 50-75% of the calculated equianalgesic dose to account for incomplete cross-tolerance and individual patient variability.
2. Monitor closely: Carefully assess patient response after initiating a new opioid regimen, adjusting the dose as needed based on pain control and side effects.
3. Consider opioid rotation: In some cases, rotating between different opioids may help manage tolerance or side effects while maintaining pain control.
4. Account for concomitant medications: Be aware of potential drug interactions that may affect opioid metabolism or efficacy.
5. Educate patients: Provide clear instructions on the new medication regimen and potential side effects to watch for during the transition.

By following these practices, healthcare providers can optimize pain management while minimizing risks associated with opioid conversions.

Limitations of Opioid Equivalence Charts

While opioid equivalence charts provide valuable guidance, it’s important to recognize their limitations:

• Approximations: The potency ratios provided are approximate and may not account for all individual variations in drug response.
• Incomplete data: Some opioids may have limited data on equianalgesic dosing, particularly newer formulations or less commonly used medications.
• Variability between charts: Different sources may provide slightly different potency ratios, highlighting the need for clinical judgment in interpreting and applying this information.
• Contextual factors: The chart doesn’t account for pain etiology, severity, or other contextual factors that may influence opioid effectiveness.

Healthcare providers should use opioid equivalence charts as a starting point, combining this information with clinical experience, patient-specific factors, and ongoing assessment to optimize pain management strategies.

Future Directions in Opioid Equivalence Research

As our understanding of opioid pharmacology and pain management continues to evolve, several areas of research may impact future iterations of opioid equivalence charts:

1. Pharmacogenomics

Advances in pharmacogenomics may allow for more personalized opioid prescribing based on individual genetic profiles. This could lead to more accurate predictions of opioid response and metabolism, refining equianalgesic dosing calculations.

2. Novel Opioid Formulations

The development of new opioid formulations or delivery systems may necessitate updates to equivalence charts. For example, abuse-deterrent formulations or opioids with unique receptor binding profiles may require specialized conversion considerations.

3. Integration of Non-Opioid Analgesics

As multimodal pain management strategies gain prominence, future equivalence charts may incorporate information on combining opioids with non-opioid analgesics or adjuvant medications. This could provide a more comprehensive approach to pain management and opioid dose optimization.

4. Real-World Data Analysis

Large-scale analysis of real-world patient data may help refine opioid equivalence ratios and identify patterns in patient responses to different opioids. This could lead to more nuanced and evidence-based conversion recommendations.

Ongoing research in these areas will contribute to more accurate and personalized approaches to opioid prescribing and pain management.

Practical Applications of Opioid Equivalence Knowledge

Understanding opioid equivalence has numerous practical applications in clinical practice:

1. Pain Management Optimization

By accurately converting between opioids, healthcare providers can fine-tune pain management regimens to achieve optimal analgesia while minimizing side effects. This is particularly valuable when patients experience inadequate pain relief or intolerable side effects with their current opioid medication.

2. Perioperative Pain Control

In surgical settings, knowledge of opioid equivalence allows for seamless transitions between different pain management strategies. For example, converting from intravenous opioids used during surgery to oral medications for postoperative pain control.

3. Opioid Tapering

When reducing opioid doses or discontinuing opioid therapy, equivalence charts guide the development of appropriate tapering schedules. This helps minimize withdrawal symptoms and ensures adequate pain control during the tapering process.

4. Management of Opioid Shortages

In situations where specific opioid medications become unavailable due to shortages or supply chain issues, equivalence knowledge facilitates rapid and safe substitution with alternative opioids.

5. Improving Patient Safety

Accurate opioid conversions based on equivalence data help prevent overdosing or underdosing when transitioning between medications, reducing the risk of adverse events or inadequate pain control.

These practical applications highlight the critical role of opioid equivalence understanding in delivering safe and effective pain management across various clinical scenarios.

Educating Patients on Opioid Equivalence

While opioid equivalence charts are primarily tools for healthcare providers, patient education on this topic can improve treatment adherence and safety:

• Explain the concept: Help patients understand that different opioids have varying strengths and that switching medications doesn’t necessarily mean their pain is worsening or improving.
• Emphasize safety: Stress the importance of following prescribed dosages and not making independent adjustments based on previous medications.
• Address misconceptions: Clarify that a lower milligram dose of a new opioid doesn’t necessarily mean it’s less effective if it has a higher relative potency.
• Encourage communication: Promote open dialogue about pain control and side effects during medication transitions.
• Provide written information: Offer clear, written instructions on new medication regimens and potential side effects to watch for.

By involving patients in understanding opioid equivalence, healthcare providers can foster a collaborative approach to pain management and improve overall treatment outcomes.

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

^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

© World Health Organization 2018.

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Equianalgesic Chart (Changes in italics)

Guidelines for Patient-Controlled
Intravenous Opioid Administration (PCA) for Adults with Acute Pain

The amount of opioid required to
achieve comfort varies from patient to patient.
Adjust dosing to achieve patient comfort with minimal side effects.

Partially
adapted from the Principles of Analgesic Use in the Treatment of Acute Pain and
Cancer Pain, American Pain Society, 5^th Ed. 2003.

Standard concentrations are listed in parentheses.

Initial Fentanyl Transdermal
Dosage (use only when converting another opioid TO fentanyl patch)*

*Note: Do not use this table to convert from
fentanyl transdermal system to other opioid analgesics because these conversion
dosage recommendations are conservative.
Use of this table for conversion from fentanyl to other opioids can
overestimate the dose of the new agent and may result in an overdosage.

Equianalgesic Chart

Doses listed are equivalent to 10
mg of parenteral morphine. Doses should be titrated according to individual
response. When converting to another opioid, the dose of the new agent should
be reduced by 30-50% due to incomplete cross-tolerance between opioids.

Dosage in this range may lead to
neuroexcitability.

For a single dose, 10 mg IV morphine = 60 mg oral morphine. For chronic dosing, 10 mg IV morphine = 30 mg
oral morphine.

(N)
Non-formulary at UIHC.

Example of opioid conversion:

3. Bolus doses administered by the
   medical/nursing staff

2.     
The
equianalgesic chart indicates that 1.5 mg of parenteral hydromorphone equals
7.5 mg of oral hydromorphone (a 5-fold
increase).

3. The patients current dose of 5 mg per
   day of parenteral hydromorphone is equal to 25 mg per day of oral
   hydromorphone.
4. The next step is to convert 25 mg of
   oral hydromorphone to the daily oral morphine equivalent dose (DOMED).
5. The equianalgesic chart indicates that
   7.5 mg of oral hydromorphone is equal to 30 mg of oral morphine.
6. The patients calculated dose of 25 mg
   of oral hydromorphone is equal to 100 mg of oral morphine.
7. The oral dose of morphine should be
   reduced by 30% to 50% to prevent any risk of overdose after the
   conversion, since opioids do not have complete cross-tolerance. A 33% dose reduction from the
   calculated dose of 100 mg is equal to 67 mg of oral morphine per day.
8. The recommended dosing frequency of
   long-acting morphine (MS Contin
   ^{) is every 12 hours (2 doses per
   day).}
9. MS Contin
   ^{is available in 15 mg, 30 mg, 100 mg and 200 mg controlled-release
   tablets. The tablet strength
   closest to the calculated dose is 30 mg. The proper starting dose should
   therefore be 30 mg of sustained-release morphine every 12 hours.}

Guidelines for
Administering Naloxone for Reversal of Opioid-Induced Respiratory Depression

Opioid
overdose:

0.4 mg 0.8 mg IV/IM/SQ,
titrated in accordance with the patients response; repeat as needed. If given IV, each 0.4 mg should be given over
15 seconds.

Opioid-induced
respiratory depression

0.04 mg/ml (40 mcg/ml)
dilution in syringe (mix 0.4 mg/1 ml of naloxone and 9 ml of normal saline in a
syringe for IV administration).

    
Administer
0.5 ml of diluted solution (0.02 mg or 20 mcg) every 2 minutes until a change
in alertness is observed.

    
Titrate
naloxone until patient is responsive or a total of 0.8 mg (20 ml of diluted
solution) has been given. Continue
looking for other causes of sedation and respiratory depression.

    
Discontinue
naloxone when patient is responsive to physical stimulation, respiratory rate
is > 8 breaths per minute, and
able to take deep breaths when told to do so.

Special
considerations

May need repeated doses or
continuous infusion. Depending on amount
and type of opioid given and time interval since last opioid administration,
the duration of action of some opioids may exceed that of naloxone.

Titrate dose cautiously to
avoid precipitation of profound withdrawal, seizures, and severe pain.

Use of Oral Methadone for Chronic Pain

1. Opioid-nave patients

1. Recommended starting
   dose range is 2.5 mg daily to 2.5 mg TID.
2. For frail and/or
   older patients, the starting dose is 2.5 mg daily.

2. Patients taking
   opioids
1. Determine the daily
   oral morphine equivalent dose of current opioids.
2. Convert daily oral
   morphine equivalent dose (DOMED) to oral methadone.
3. Methadone dose should be adjusted
   every 5 days due to delayed onset of respiratory depression.

Methadone
Conversion Ratios

Example of conversion to oral methadone:

1. Patient is taking 80 mg Oxycontin
   orally 3 times daily.
2. The total daily dose of oxycodone is
   240 mg daily.

3. The next step is to convert 240 mg of
   oral oxycodone to the daily oral morphine equivalent dose (DOMED).
4. The equianalgesic chart indicates that
   20 mg of oral oxycodone is equal to 30 mg of oral morphine.

5. The patients current dose of 240 mg per day
of oral oxycodone is equal to 360 mg per day of oral morphine.

6. The methadone conversion table
   indicates that a conversion factor for a DOMED of 360mg equals 8.3% or a
   12 to 1 ratio of morphine to methadone.
7. The patients DOMED of 360 mg is equal
   to 30 mg of methadone daily.
8. The recommended dosing frequency of
   methadone for chronic pain is 1 to 3 times daily, so the proper daily
   methadone dose would be 10 mg three times daily.
9. May need to use breakthrough medication
   as needed for the first week, while methadone achieves steady-state blood
   levels.

Pain Medicine Service

For difficulties
with pain management, contact the Pain Medicine Service at 6-2320 (clinic) or 3832 (on call pager).

References:

American Hospital Formulary Service Drug
Information 2005. American Society of
Health-System Pharmacists.

American Pain Society (2003). Principles of analgesic use in the treatment
of acute pain and cancer pain (5^th ed.) Glenview, IL: Author.

U.S. Department of Health and Human Services. (1992).

Acute pain management: Operative or medical
procedures and trauma
(AHCPR Publication No. 92-0032).
Rockville, MD: Author.

VA/DoD Clinical Practice Guideline for the
Management of Opioid Therapy for Chronic Pain.
Department of Veterans Affairs
and Department of Defense. Version
1.0 March 2003.

Written
1990

Revised
7/26/1999

Revised 9/2003

Revised
4/2005

Narcotic drugs \ ConsultantPlus

• Main
• Documents
• Narcotic drugs

Decree of the Government of the Russian Federation of 01. 10.2012 N 1002
(as amended on 07/10/2023)
“On approval of large, large and extra large amounts of narcotic drugs and psychotropic substances, as well as significant, large and extra large amounts for …

List of narcotic drugs and psychotropic substances, the circulation of which in the Russian Federation is limited and for which control measures are established in accordance with the legislation of the Russian Federation and international treaties of the Russian Federation (List II)
Psychotropic substances

5 most addictive substances and their effect on our brain

Health

March 1, 2021

About what some drugs, alcohol and nicotine do to our bodies.

This ranking was compiled by British psychiatrist and professor of neuropsychopharmacology David Nutt and his research team.

1. Heroin

Heroin is an opioid drug that causes severe mental and physical dependence. This is due to the fact that when injected, the substance quickly penetrates the brain, easily overcoming the blood-brain barrier between the circulatory and central nervous systems. In the brain, it causes an increased production of dopamine. Experiments on experimental animals have shown an increase in the level of this pleasure hormone by 200%.

Heroin mimics natural brain chemicals that nature has created to control pain and increase pleasure.

An additional addictive mechanism is increased production of the excitatory neurotransmitter glutamate. Combined with the severe withdrawal symptoms—pain, anxiety, cramps, insomnia—it leads to a severe addiction. Withdrawal begins 4-24 hours after taking the last dose, and the addict is in dire need of another portion of the drug. In addition, the body quickly develops tolerance to heroin – a person needs more and more dose each time.

Heroin addicts often die from heart attacks, strokes, as the drug affects the state of the cardiovascular system. Another cause of death is exhaustion, which leads to constant stimulation of the central nervous system. Experts assigned this drug three points out of three possible according to the degree of dependence formation.

2. Cocaine

Cocaine is an alkaloid found in plants of the genus Erythroxylum. In nature, it acts as an insecticide and protects the leaves of shrubs from being eaten by insects. Cocaine has a powerful stimulating effect on the central nervous system, causing a feeling of euphoria.

Normally, the reward system in the brain works according to certain rules. A neurotransmitter – in this case, dopamine – enters the space between neurons called the synapse. Specialized receptors transmit a signal to respond to its appearance, then remove the neurotransmitter from the synapse to stop its effect.

Cocaine blocks dopamine reuptake systems, causing it to work again and again, resulting in a whirlwind of pleasure.

However, cocaine euphoria does not last forever, and after the end of the drug, a phase of depression begins. Other side effects include fatigue, anxiety, and insomnia.

Cocaine is dangerous for the cardiovascular system. It causes powerful spasms that can lead to cerebral hemorrhage, disrupt the heart or other organs. Another negative effect is the state of acute psychosis, in which a person has little control over himself. In addition, there is a myth that cocaine is not addictive, but this is not true.

3. Nicotine

Nicotine, like cocaine, is an alkaloid that naturally acts as an insecticide. This is the main component of tobacco, which is addictive. Nicotine is quickly absorbed by the lungs and transported to the brain. It increases the activity of nicotinic acetylcholine receptors, which leads to the release of adrenaline. This temporarily stimulates various systems of the body, and the person feels more alert and active. And the release of dopamine accompanies smoking with a feeling of pleasure.

Nicotine is toxic, prolonged use contributes to the development of cancer, ischemia, angina pectoris, and so on. WHO claims that up to 50% of smokers die from smoking-related causes.

4. Barbiturates

Sedatives and hypnotics based on barbituric acid have a depressant effect on the central nervous system. Depending on the dosage, the drugs may have a mild relaxing effect or lead to coma.

Barbiturates stimulate receptors for the inhibitory neurotransmitter gamma-aminobutyric acid, resulting in slower transmission of impulses to the CNS. This leads to muscle relaxation, calming, eliminates anxiety. The problem of drug dependence was hushed up for a long time, but subsequently recognized and abandoned barbiturates in favor of benzodiazepines.

However, if cocaine and heroin are illegal, these drugs have long been relatively available, which increases their danger.

5. Alcohol

Absolutely legal in most countries, alcoholic beverages are named the most dangerous drug in the world. They also become addictive fairly quickly. Animal studies have shown that alcohol increases dopamine levels by 40-360%.

Alcohol enhances the effect of gamma-aminobutyric acid (GABA), the main inhibitory mediator of the nervous system. Therefore, the movements and speech of drunk people slow down, and a dose of alcohol relaxes. GABA gradually adapts to changes, reducing the activity of the corresponding receptors, which makes the brain dependent on alcohol.

If a person stops drinking alcohol, reduced activity of GABA receptors leads to a weakening of the nervous inhibition function, and the brain becomes more excitable.

At the same time, ethanol reduces the ability of another neurotransmitter, glutamate, to act on NMDA receptors. With long-term use of alcohol, the number of these receptors increases. The brain becomes less receptive to alcohol and more receptive to glutamate. This increases excitability, leading to withdrawal symptoms: seizures, anxiety.

Another reason for the formation of addiction is the ability to quickly get energy to feed the brain. This requires acetate, an intermediate product of ethanol metabolism. The brain sits down on a simple source of energy.