What is the importance of opioid equivalence charts in pain management. How do different opioids compare in potency to morphine. What factors affect opioid potency and dosing. How can healthcare providers use opioid conversion tables safely.

The Significance of Opioid Equivalence Charts in Pain Management

Opioid equivalence charts play a crucial role in pain management, providing healthcare professionals with a standardized reference for comparing the potency and dosing of different opioid medications. These charts are essential tools for ensuring safe and effective pain relief while minimizing the risk of adverse effects.

Why are opioid equivalence charts important? They allow clinicians to:

• Convert between different opioids when switching medications
• Adjust dosages appropriately when changing routes of administration
• Compare the relative strengths of various opioids
• Calculate equivalent doses to maintain adequate pain control
• Reduce the risk of under- or over-dosing when transitioning between opioids

Comparing Opioid Potency: Morphine as the Gold Standard

In opioid equivalence charts, morphine is typically used as the reference standard against which other opioids are compared. This allows for a consistent basis of comparison across different medications. The relative potency of an opioid is expressed as a ratio to morphine, with morphine having a potency of 1.

How do common opioids compare to morphine in terms of potency?

• Codeine: 0.1 (10 times less potent than morphine)
• Hydrocodone: 1 (approximately equal to morphine)
• Oxycodone: 1.5 (1.5 times more potent than morphine)
• Hydromorphone: 5 (5 times more potent than morphine)
• Fentanyl: 100 (100 times more potent than morphine)

Factors Influencing Opioid Potency and Dosing

While opioid equivalence charts provide valuable guidance, it’s important to recognize that several factors can influence the actual potency and appropriate dosing of these medications in clinical practice. Healthcare providers must consider these variables when using opioid conversion tables:

1. Route of administration
2. Individual patient characteristics (age, weight, kidney function)
3. Opioid tolerance
4. Concurrent medications
5. Pain severity and type

Route of Administration

The route by which an opioid is administered can significantly affect its potency and bioavailability. For example, oral morphine is generally less potent than intravenous morphine due to first-pass metabolism in the liver. Healthcare providers must account for these differences when converting between routes.

Individual Patient Factors

Patient-specific characteristics can impact opioid metabolism and effectiveness. Older adults and those with impaired kidney function may require dose adjustments. Body weight can also influence dosing, particularly for certain opioids like fentanyl patches.

Opioid Tolerance

Patients who have been using opioids for an extended period may develop tolerance, requiring higher doses to achieve the same analgesic effect. This tolerance must be considered when switching between opioids or adjusting dosages.

Safe Use of Opioid Conversion Tables in Clinical Practice

While opioid equivalence charts are valuable tools, they should be used with caution and in conjunction with clinical judgment. How can healthcare providers ensure the safe use of these tables?

• Start with conservative dose conversions, particularly when switching to more potent opioids
• Consider using a lower initial dose (e.g., 50-75% of the calculated equianalgesic dose) when transitioning between opioids
• Monitor patients closely for signs of under- or over-dosing after making changes
• Be aware of the limitations of equivalence charts, especially for certain opioids like methadone
• Consult with pain management specialists or pharmacists when dealing with complex cases

Methadone: A Special Case in Opioid Conversion

Methadone presents unique challenges in opioid conversion due to its complex pharmacokinetics and variable half-life. Why is methadone conversion particularly tricky?

• Non-linear relationship between dose and effect
• Accumulation in tissues over time
• Highly variable half-life between individuals
• Potential for drug interactions

Due to these factors, the WHO guidelines recommend seeking specialist guidance for conversions involving regularly administered methadone. The relative potency of methadone can be much higher than expected when given over an extended period.

Understanding the WHO Opioid Equivalence Chart

The World Health Organization (WHO) provides a comprehensive opioid equivalence chart in their guidelines for cancer pain management. This chart offers valuable insights into the relative potencies of various opioids. What key information does the WHO chart provide?

• Approximate potency ratios relative to oral morphine
• Considerations for immediate-release and extended-release formulations
• Notes on specific opioids with unique properties (e.g., methadone)
• Guidance on converting between different opioids

Healthcare providers can use this chart to calculate equivalent doses when switching between opioids. For example, to convert from morphine to another opioid, divide the morphine dose by the relative potency of the target opioid.

Practical Applications of Opioid Equivalence in Pain Management

Understanding opioid equivalence is crucial for effective pain management in various clinical scenarios. How can healthcare providers apply this knowledge in practice?

Opioid Rotation

Opioid rotation involves switching from one opioid to another to improve pain control or reduce side effects. Equivalence charts guide clinicians in selecting appropriate starting doses for the new medication.

Managing Breakthrough Pain

For patients on long-acting opioids, breakthrough pain may require short-acting rescue doses. Equivalence charts help determine suitable rescue dose strengths based on the patient’s regular opioid regimen.

Transitioning Between Care Settings

When patients move between different care settings (e.g., hospital to home), their pain management regimen may need adjustment. Opioid equivalence knowledge ensures continuity of care and appropriate dosing across various routes of administration.

Codeine: A Weak Opioid with Variable Efficacy

Codeine is a commonly prescribed weak opioid, often used as a first-line treatment for mild to moderate pain. However, its effectiveness can vary significantly between individuals. Why does codeine’s efficacy differ among patients?

• Prodrug metabolism: Codeine must be converted to morphine in the liver to exert its analgesic effect
• Genetic variations: Some individuals lack the enzyme (CYP2D6) necessary for this conversion
• Potential for reduced efficacy or increased side effects depending on metabolism

The WHO equivalence chart lists codeine as having a relative potency of 0.1 compared to morphine. However, healthcare providers should be aware that this can vary based on individual patient factors.

Codeine Administration Routes

The equivalence chart provides information on different routes of codeine administration:

• Oral (PO): 30-60 mg every 4 hours
• Intramuscular (IM): 15-30 mg every 4 hours
• Subcutaneous (SQ): 15-30 mg every 4 hours

It’s important to note that intravenous (IV) administration of codeine is not recommended due to the risk of marked blood pressure decrease, even at low doses.

Fentanyl: A Potent Opioid Requiring Special Considerations

Fentanyl is a highly potent synthetic opioid, approximately 100 times more potent than morphine. Its high potency and unique pharmacokinetics require special consideration when using equivalence charts. What factors should healthcare providers consider when prescribing or converting to fentanyl?

• Transdermal formulations have different conversion ratios than other routes
• Fentanyl patches are typically reserved for opioid-tolerant patients with stable pain
• Conversion to fentanyl often requires dose reduction due to incomplete cross-tolerance
• Short-acting fentanyl formulations (e.g., lozenges, sublingual tablets) have specific dosing guidelines

When converting from oral morphine to transdermal fentanyl, clinicians should use specific conversion tables provided by the manufacturer, as the relationship is not linear across all dose ranges.

The Role of Pharmacokinetics in Opioid Equivalence

Understanding the pharmacokinetics of different opioids is crucial for accurate use of equivalence charts and optimal pain management. How do pharmacokinetic properties influence opioid dosing and effectiveness?

Onset of Action

The time to onset of action varies among opioids and administration routes. For example:

• Oral codeine: 30 minutes
• Intramuscular codeine: 15-30 minutes
• Intravenous morphine: 5-10 minutes

Understanding these differences helps in selecting appropriate opioids for different types of pain and clinical situations.

Duration of Action

The duration of analgesic effect influences dosing frequency and the choice between immediate-release and extended-release formulations. For instance, the WHO chart notes that codeine’s duration of action is:

• Oral route: 6 hours
• Intramuscular route: 4-6 hours
• Subcutaneous route: 4-8 hours

Metabolism and Half-life

The way opioids are metabolized and their half-lives affect their overall potency and duration of action. The WHO chart indicates that codeine is metabolized in the liver with a half-life of 2-4 hours. This information is crucial for:

• Determining appropriate dosing intervals
• Assessing the risk of drug accumulation
• Considering potential drug interactions
• Adjusting doses in patients with liver or kidney impairment

Balancing Efficacy and Safety in Opioid Prescribing

While opioids are effective pain relievers, their use must be balanced with safety considerations. How can healthcare providers use opioid equivalence charts to optimize pain management while minimizing risks?

• Start with the lowest effective dose and titrate slowly
• Use equivalence charts to avoid excessive dosing when switching opioids
• Consider non-opioid and multimodal pain management strategies
• Regularly assess pain control, functional improvement, and potential side effects
• Educate patients on safe opioid use, storage, and disposal

By combining knowledge of opioid equivalence with individualized patient assessment, clinicians can provide effective pain relief while minimizing the risks associated with opioid therapy.

The Future of Opioid Equivalence and Pain Management

As our understanding of pain mechanisms and opioid pharmacology continues to evolve, so too will approaches to opioid equivalence and pain management. What developments can we expect in the future?

• More precise equivalence calculations based on pharmacogenomics
• Advanced algorithms and decision support tools for opioid conversions
• Integration of artificial intelligence to predict individual patient responses to opioids
• Development of novel opioid formulations with improved safety profiles
• Increased emphasis on personalized pain management strategies

These advancements promise to enhance the accuracy and safety of opioid prescribing, ultimately leading to better pain control and reduced risk of adverse effects for patients.

Conclusion: The Ongoing Importance of Opioid Equivalence Knowledge

Understanding opioid equivalence remains a cornerstone of effective and safe pain management. While equivalence charts provide valuable guidance, they must be used in conjunction with clinical judgment, patient-specific factors, and ongoing assessment. As the field of pain management continues to evolve, healthcare providers must stay informed about best practices in opioid prescribing and conversion to ensure optimal outcomes for their patients.

By leveraging opioid equivalence knowledge, considering individual patient characteristics, and staying abreast of emerging research and guidelines, clinicians can navigate the complexities of opioid therapy to provide compassionate and effective pain relief while minimizing risks.

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
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• 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.