How do different opioids compare in strength. What factors influence opioid potency. Which opioids are considered strongest and weakest. How can understanding opioid equivalence help prevent overdose. What precautions should be taken when converting between opioids.

The Basics of Opioid Potency and Equivalence

Understanding the relative strength of different opioids is crucial for proper pain management and preventing overdose. The opioid equivalence chart provides a framework for comparing the potency of various opioids to morphine, which is used as the standard reference point. However, it’s important to note that opioid potency is not a simple linear scale.

Factors that influence opioid potency include:

• Route of administration (oral, intravenous, etc.)
• Individual patient factors (age, health status, opioid tolerance)
• Pharmacokinetics and pharmacodynamics of each specific opioid
• Dose-dependent effects

Healthcare providers use opioid equivalence charts as a general guide, but must always consider these additional factors when prescribing or converting between opioids.

Comparing Opioid Strengths: The Morphine Milligram Equivalent (MME)

The concept of Morphine Milligram Equivalent (MME) is central to understanding opioid potency. MME represents the amount of morphine that would provide equivalent analgesic effect to a given dose of another opioid. This allows for standardized comparison across different opioids.

How is MME calculated? The dose of a specific opioid is multiplied by a conversion factor to determine its equivalent morphine dose. For example, if oxycodone has a conversion factor of 1.5, 10 mg of oxycodone would be equivalent to 15 mg of morphine (10 x 1.5 = 15 MME).

Sample MME Conversion Factors

• Morphine: 1 (reference standard)
• Oxycodone: 1.5
• Hydromorphone: 4
• Fentanyl: 100 (for transdermal patches)
• Methadone: Variable, ranging from 3 to 12 depending on dose

It’s crucial to note that these conversion factors are approximations and should be used cautiously, especially when dealing with high-potency opioids or patients with complex pain management needs.

Strongest Opioids: High-Potency Narcotics

While potency can vary based on factors mentioned earlier, some opioids are generally considered to be at the higher end of the strength spectrum. These high-potency opioids require careful management and are often reserved for severe pain or patients with high opioid tolerance.

Top High-Potency Opioids

1. Carfentanil (veterinary use only, extremely dangerous)
2. Sufentanil
3. Remifentanil
4. Fentanyl
5. Hydromorphone

Why are these opioids considered so potent? These medications have a very high affinity for opioid receptors and can produce strong analgesic effects at much lower doses compared to morphine. For instance, fentanyl is estimated to be 50-100 times more potent than morphine, while carfentanil can be up to 10,000 times stronger.

Moderate-Strength Opioids: Balancing Efficacy and Safety

In the middle of the opioid potency spectrum are medications that offer significant pain relief while generally having a more manageable safety profile compared to the strongest opioids. These are commonly used in both acute and chronic pain management.

Common Moderate-Strength Opioids

• Morphine (the reference standard)
• Oxycodone
• Hydrocodone
• Methadone (variable potency)

How do these moderate-strength opioids compare to each other? While they’re all in a similar potency range, there can be significant variation. For example, oxycodone is generally considered about 1.5 times as potent as morphine, while hydrocodone is roughly equivalent to morphine in potency.

Weaker Opioids: Lower-Potency Options

At the lower end of the opioid potency scale are medications that still provide pain relief but are generally considered less potent than morphine. These are often used for mild to moderate pain or as part of a step-wise approach to pain management.

Examples of Lower-Potency Opioids

• Codeine
• Tramadol
• Meperidine (Demerol)

Are these weaker opioids always safer? While they may have a lower risk of respiratory depression at equivalent analgesic doses, they can still cause dependence and other side effects. Additionally, some patients may metabolize these drugs differently, potentially increasing their potency and risk.

Special Considerations: Methadone and Buprenorphine

Methadone and buprenorphine deserve special attention in any discussion of opioid potency due to their unique properties and variable effects.

Methadone: The Potency Paradox

Methadone’s potency is highly variable and dose-dependent. At low doses, it may be only 3-4 times as potent as morphine, but at higher doses, it can be up to 12 times as potent. This variability, combined with its long half-life, makes methadone conversion particularly challenging and potentially dangerous if not managed carefully.

Buprenorphine: Partial Agonist with Unique Properties

Buprenorphine is a partial opioid agonist with high receptor affinity but lower intrinsic activity. This gives it a “ceiling effect” on respiratory depression, potentially making it safer in overdose situations. However, its high binding affinity can complicate pain management and opioid rotation strategies.

Why is careful monitoring crucial when using methadone or buprenorphine? The unique pharmacological properties of these drugs can lead to unexpected results when converting from other opioids or in patients with varying levels of opioid tolerance.

Practical Applications of Opioid Equivalence Charts

Understanding opioid equivalence is not just an academic exercise; it has important practical applications in pain management and harm reduction.

Opioid Rotation

Opioid rotation involves switching from one opioid to another to improve pain control or reduce side effects. Equivalence charts help guide appropriate dosing when making these switches.

Preventing Overdose

By understanding the relative potency of different opioids, healthcare providers can avoid inadvertently prescribing excessive doses when changing medications.

Pain Management Strategies

Equivalence information helps in developing stepped approaches to pain management, starting with lower-potency options and escalating as needed.

How can patients benefit from understanding opioid equivalence? While dosing decisions should always be made by healthcare professionals, patient awareness of relative opioid strengths can promote safer use and better communication with providers.

Limitations and Precautions in Using Opioid Equivalence Charts

While opioid equivalence charts are valuable tools, they come with important limitations and caveats that must be considered in clinical practice.

Individual Variability

Patients may respond differently to opioids based on genetics, overall health, and other factors. Equivalence charts provide general guidance but cannot account for individual variations.

Incomplete Cross-Tolerance

When switching between opioids, patients may not have complete cross-tolerance. This often necessitates dose reductions when rotating to a new opioid, even if the calculated equianalgesic dose suggests otherwise.

Route of Administration Differences

Potency can vary significantly based on how the opioid is administered (oral, intravenous, transdermal, etc.). Equivalence charts may not fully capture these differences.

Non-Linear Potency Relationships

The relationship between dose and effect is not always linear, especially at higher doses or with certain opioids like methadone.

What precautions should be taken when using opioid equivalence information? Healthcare providers should always start with conservative dose estimates when converting between opioids, closely monitor patients, and be prepared to adjust dosing based on individual response.

The Role of Opioid Potency in the Opioid Crisis

The varying potencies of different opioids have played a significant role in the ongoing opioid crisis, particularly with the rise of high-potency synthetic opioids.

Fentanyl and Its Analogues

The extreme potency of fentanyl and related compounds has contributed to a sharp increase in overdose deaths. Even small errors in dosing or the presence of these substances in other drugs can be fatal.

Prescription Practices

Misunderstandings about relative opioid potency have sometimes led to overprescribing or inappropriate conversions between medications, contributing to increased risks of addiction and overdose.

Harm Reduction Strategies

Understanding opioid potency is crucial for developing effective harm reduction strategies, such as targeted naloxone distribution and public education campaigns.

How has improved understanding of opioid potency influenced policy and practice? This knowledge has led to more cautious prescribing guidelines, increased emphasis on opioid safety education, and the development of abuse-deterrent formulations for high-potency opioids.

In conclusion, the opioid equivalence chart serves as a valuable tool for comparing the relative strengths of different narcotic medications. However, it’s crucial to remember that opioid potency is influenced by various factors and that these comparisons should be used as general guidelines rather than absolute rules. Healthcare providers must consider individual patient factors, pharmacological properties of specific opioids, and potential risks when making decisions about opioid prescribing and dosing. As our understanding of opioid pharmacology continues to evolve, so too will our approach to using these powerful medications safely and effectively in pain management.

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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Discover the List of Opioids From Strongest to Weakest to Avoid Overdose Updated 2023

September 11, 2017
by Mark Adams

A Guide to Addictive Opiates: List of Opioids Strongest to Weakest

Post updated 3-10-2023

Creating a list of opioids from strongest to weakest is not as straightforward as simply listing them by potency or by an analgesic effect. A report released by the CDC (1) listed various narcotic pain medications by strength as they compared to morphine. Yet the list doesn’t determine whether the medication also has a similar mechanism of action. Some of the strongest types of pain medication in a hospital may have a similar potency to morphine, but they may also be formulated with a dose ceiling, while morphine does not, rendering them less potent overall.  

The actual potency of some narcotic pain medications and prescription opioids, or pain relievers by strength, may also vary, depending on the route of administration.  Essentially, the list of opioids strongest to weakest is determined by factoring in that a smaller dose of certain painkiller medications may be required to achieve the same pain-relief response to treat severe pain as can be reached with morphine.

With those determinations in mind, the list of common opioids from strongest to weakest is also broken down into three classifications: stronger than morphine, morphine-equivalent and weaker than morphine.

Stronger than Morphine

Opioid use disorders (OUD) are on the rise. Let’s take a look at some of the drugs that are stronger than morphine.

Fentanyl (Duragesic)

 Fentanyl is common among drug abusers and is one of the strongest opioids on the market and is the strongest pain medication in hospital settings. This drug can lead to abuse and addiction. The opioid painkiller medication has a rapid onset and short duration of action. It’s occasionally used as a part of the anesthesia process to help prevent pain following surgery but it is also used to treat severe pain. Depending on the method of administration, it’s estimated that fentanyl can be up to 100 times more potent than morphine and is classified as one of the strongest opioids.

Oxymorphone (Opana ER, Numorphan)

Oxymorphone is a semi-synthetic opioid painkiller medication commonly used to treat severe to chronic pain and to maintain anesthesia. The powerful opioid medication is highly addictive and requires an opioid addiction treatment program to overcome, leading the FDA to ask the manufacturer to remove it from the US market in 2017.

Hydromorphone (Dilaudid, Exalgo, Contin)

Hydromorphone is synthesized from morphine and is commonly used in hospital settings to treat moderate to severe pain. The medication is more soluble in water than morphine, which allows the drug to be delivered in a smaller amount of water.

Heroin (diamorphine)

Heroin is created by combining the morphine alkaloid with acetic anhydride to create a more potent opioid analgesic drug. While heroin was once used in medical settings, it was made a Schedule I Substance under the Controlled Substances Act in 1924 and is now an illicit drug used primarily for recreational purposes. It’s estimated that heroin is approximately 2 to 4 times more potent than morphine. Heroin addiction is a contributing factor to the drug epidemic that the U.S. is facing and is leading to mass overdose deaths. 

Levorphanol (Levo-Dromoran)

Levorphanol is a synthetic opioid painkiller medication created from the compound racemorphan and used to treat moderate to severe pain. Levorphanol is produced using one of the two enantiomers of the compound racemorphan. Levorphanol is several times more potent than morphine and is strongly addicting.

Methadone (Dolophine, Methadone)

Methadone is an opioid painkiller medication used to treat moderate to severe pain. It’s also prescribed to treat opioid dependence in methadone maintenance programs.  It is considered more potent than morphine due to its effectiveness against neuropathic pain. There is also a lower risk of the user developing dose tolerance with methadone (2) as compared to other types of opioids.

Oxycodone (OxyContin, Roxicodone)

Oxycodone has a greater analgesic effect than morphine (6). The semi-synthetic opioid is synthesized from thebaine, an alkaloid found in the opium poppy and is approximately 1.5 times stronger than morphine.

Morphine-Equivalent

Tapentadol (Nucynta, Palexia SR): Technically, tapentadol could be classified as stronger than morphine, as clinical trials (3) indicate the medication provides superior analgesic effects than equivalent doses of oxycodone, but with significantly lower gastrointestinal side effects. However, as tapentadol has a dose ceiling, so it’s listed as a morphine-equivalent ahead in order of strength to morphine.

Morphine (Astramorph, Avinza, Kadian)

Morphine is created from the morphine alkaloid found within the opium poppy and is commonly used to treat moderate to severe pain. Approximately 70% of morphine produced is used as a base to create other opioid medications (5), including oxymorphone, hydromorphone, and heroin.

Hydrocodone (Zohydro ER)

Hydrocodone is a semi-synthetic opiate analgesic created from the codeine alkaloid found within the opium poppy.  Hydrocodone is commonly used to treat moderate to severe pain and is predominantly used within the United States, with 99% of the world’s volume of hydrocodone consumed in that country. Hydrocodone is also commonly available in a variety of formulations, including combinations with paracetamol (Vicodin), ibuprofen (Vicoprofen), or aspirin (Lortab).

Weaker Than Morphine

Pethidine (Meperidine, Demerol)

Pethidine is a synthetic opioid painkiller medication and is usually prescribed to treat moderate to severe pain. While it provides almost equivalent levels of pain relief to morphine in treating post-surgical pain, the method of administration may differ and the dosage used may need to be slightly higher than the comparative dose of morphine to achieve similar results (4).

Codeine

Codeine is created from the codeine alkaloid found within the opium poppy that is commonly used to treat mild to moderate pain. Codeine’s efficacy comes from the drug being broken down in the liver into morphine. Codeine is the most commonly taken opiate medication in the world (5).

Tramadol (Ultram)

Tramadol is an opiate painkiller medication used to treat moderate pain. The medication is synthesized as a racemic mixture using both components of R- and S-stereoisomers.

Laudanum (Opium Tincture)

Of the list of opioids strongest to weakest, the least potent opiate is still available from some pharmacies in the US and UK. The formulation is used primarily to control diarrhea or to ease withdrawal symptoms in babies born to opiate-addicted mothers. In the 1800s morphine was known as laudanum and was readily available from grocers and markets, but was soon restricted once its addictive qualities were known. Today, laudanum is sold as a ‘tincture of opium,’ which contains approximately 10% (100mg) powdered opium, or the equivalent of 1% (10mg) morphine per milliliter. The tincture is considered a single formulation, as it contains all of the alkaloids found within the opium poppy.

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