What is the approximate potency of opioids relative to morphine? How do different administration routes and formulations affect the potency? Learn more about the pharmacological profiles and opioid conversion tables in this comprehensive guide.

Opioid Potency Comparison: Morphine as the Reference

The WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents provide a comprehensive Table A6.2 that outlines the approximate potency of opioids relative to morphine. This table serves as a valuable reference for healthcare professionals when considering opioid conversions and dosing decisions.

Administration Routes and Formulations: Impact on Potency

The table specifically notes that the potency values are for oral (PO) and immediate-release formulations, unless stated otherwise. This is an important consideration, as the route of administration and release profile can significantly impact the relative potency of an opioid.

Understanding the Opioid Conversion Table

To use the table effectively, the guidelines state that the dose of the opioid in the first column should be multiplied by the relative potency in the second column to determine the equivalent dose of morphine sulfate/hydrochloride. Conversely, the morphine dose can be divided by the relative potency to determine the equivalent dose of another opioid.

Factors Affecting Opioid Potency

The guidelines also note that the relative potency of opioids can be dependent in part on the severity of pain and the dose. Additionally, the potency may be longer-lasting in very elderly patients and those with renal impairment.

Methadone: A Special Case

The table includes a specific note regarding methadone, stating that a single 5 mg dose of methadone is equivalent to 7.5 mg of morphine. However, due to methadone’s variable long plasma half-life and broad-spectrum receptor affinity, the relative potency when administered regularly can be much higher than the range given. Therefore, the guidelines recommend seeking guidance from a specialist when converting to regularly administered methadone.

Acknowledgments and Copyright Information

The table and its accompanying information are adapted with permission from the WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. The work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO).

Does the table provide a comprehensive comparison of opioid potencies relative to morphine? Yes, the table includes a wide range of opioids and their approximate potencies, making it a valuable resource for healthcare professionals.

How do the administration route and formulation affect opioid potency? The table specifically notes that the provided potencies are for oral (PO) and immediate-release formulations, indicating that other routes and release profiles may result in different relative potencies.

What is the significance of the note on methadone? The guidelines highlight that methadone has a variable long plasma half-life and broad-spectrum receptor affinity, resulting in a much higher-than-expected relative potency when administered regularly. This underscores the importance of seeking guidance from a specialist when converting to regularly administered methadone.

Where can I find the full WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents? The guidelines are available through the NCBI Bookshelf, a service of the National Library of Medicine, National Institutes of Health.

Conclusion

The WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents provide a comprehensive Table A6.2 that outlines the approximate potency of opioids relative to morphine. This table serves as a valuable reference for healthcare professionals, while also highlighting important considerations such as the impact of administration route and formulation, as well as the unique characteristics of methadone. The guidelines emphasize the importance of seeking guidance from specialists, particularly when dealing with opioid conversions and dosing decisions.

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

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 of 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, leading to 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 performs the function of fighting insects. 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, long-term 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 been relatively available for a long time, 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. In the body of a regular drinking person, alcohol replaces the usual source of energy – glucose.

According to the World Health Organization, 3.3 million people die every year due to alcohol consumption. The statistics include diseases and injuries associated with drunkenness.

Dr. Nutt himself noted that the legal status of a drug is not necessarily associated with dependence or harm from it. Tobacco and alcohol occupy high positions in the ranking, but remain legal.

However, the existence of this list does not mean at all that substances that are not included in it do not cause addiction. Therefore, the rating should not be taken as a tool for dividing drugs into harmful and harmless. The use of any psychoactive substance has consequences.

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