Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Wednesday, March 2, 2011

Breakthrough Pain and Breakthrough Analgesia

Since the introduction of OxyContin in the US, long acting opioid formulations have advanced along with extended release technology. Those who experience chronic pain are fortunate to have a wide variety of options for round the clock pain control; a regular schedule of a long acting opioid provides a consistent and steady baseline level of pain control.

It's important to keep in mind that 'baseline' analgesia is the key word - A patient who is stablized on a long acting opioid will remain in a similar state to a healthy individual who does not experience chronic pain, due to both constant analgesia and opioid tolerance. This suggests that any unusual sensations of pain greater in intensity than the typical everyday pain (which is controlled with a long acting analgesic) will still be experienced as bothersome to the subject. For example, lower back pain may be effectively treated symptom-wise with MS Contin every 12 hours, but the unusual pain of moving the back the wrong way worsening the symptoms or perhaps breaking a leg, will hurt just as badly as it would for anyone.

Additionally, pain levels vary day by day, for many to an incredible degree, making certain occurences of intermittent pain unforseeable for both the physician and the patient. This is where a secondary opioid should be prescribed, if necessary, for 'breakthrough' pain - breakthrough pain is the most commonly used term for intermittent sudden onset pain which the primary opioid is unable to prevent.

An ideal opioid for breakthrough pain should cater to the nature of the pain; sudden onset pain comes on quickly without warning, which requires an opioid with a similar fast onset. An ideal analgesic for breakthrough pain may generally be fast/short acting; often with long acting comes delayed onset of relief. The opioid must also be potent enough, and in large enough dose, that it provides efficient relief for a patient with already a certain degree of narcotic tolerance. Opioids such as oxycodone and morphine are often ideal for sudden onset pain, depending on the individual - Both are moderately strong and typically take no more than 20 to 30 minutes for effect, while both providing significant relief for roughly 3 hours give or take. Below is an overview of available opioids which fill the need for moderate to severe breakthrough pain; and also explain their suitability for different roles in different situations.

Hydrocodone Compounds: Hydrocodone w/ acetaminophen compounds are often prescribed for breakthrough pain along with the moderate strength long acting opioids such as morphine ER or OxyContin. This is generally an effective approach during the earlier months of treatment before a greater tolerance has developed. A more effective option in certain patients may be a hydrocodone/ibuprofen compound; often containing 7.5 to 10mg of narcotic and 200 to 400mg of NSAID. Hydrocodone compounds can be taken in doses as much as 10 to 20mg at a time, usually every 4 to 6 hours as needed, assuming that the lower-acetaminophen content medicines are used; norco, lortab, zydone, vicoprofen and reprexain are all potential canidates.

Oxycodone Compounds: Oxycodone compounds with acetaminophen or ibuprofen may suit the need for breakthrough pain as well, typically earlier on in therapy when tolerance is low - like hydrocodone compounds, oxycodon combinations contain only limited amounts of narcotic and their use is limited due to the presence of acetaminophen. The highest dose of oxycodone available in a combo form is 10mg - percocet, percodan, endocet, and combunox all suit the need for a combination product for breakthrough pain.

Fast Acting Morphine: As tolerance increases, instant release morphine offers an effective option for those who tolerate the side effects. Numerous branded and generic versions are available in both tablet and liquid forms; tablet forms generally contain 15 to 30mg morphine per tablet, and liquid forms may contain anywhere from 5mg per 5ml to the heavy concentration of 20mg per 1ml (100mg/teaspoon) - the highly concentrated product is useful in those with a compromised ability to swallow, compromised level of consciousness or with vomiting issues, because it allows small single drops to be administered easily into the mouth where they either dissolve inside or comfortably slip down into the stomach. These oral concentrates are popular with cancer or other terminal patients whom are often beyond capacity for simple functions such as swallowing. Liquid formulations also allow for a quicker absorption and onset for rapid pain relief when necessary.

Fast Acting Oxycodone: Oxycodone itself is an effective and popular opioid for those who cannot tolerate morphine due to side effects and those who simply prefer it. Oxycodone has plenty of advantages over morphine; rapid onset and excellent absorbtion by the oral route - bioavailability is much higher than morphine's. Fewer side effects in many patients than with morphine, pruritis/itching in particular is much less pronounced with oxycodone, as well as much lesser degree of sedation and lesser degree of nausea and vomiting. Unlike morphine, oxycodone often produces a stimulating state rather than sedated state - this is common in many patients and habitual users. Oxycodone is generally considered to be much more euphoric than morphine, and for some allow a greater degree of functioning each day. Studies have suggested that oxycodone may be slightly preferable to morphine in the treatment of certain types of pain, specifically visceral pain, affecting organ and soft muscle tissue. Oxycodone has been proven an effective alternative to morphine in most varieties of non-malignant pain. Like morphine, both tablet and liquid form oxycodone is available; tablets are available in a wide variety of doses of 5 to 30mg and liquids are available in as little as 5mg/5ml or the highly concentrated 20mg/1ml; which suits it for those with a low capacity for swallowing and/or stomach issues. Roxicodone is the most popular tablet form with many generics available, while liquid forms are available in a variety of branded and generic forms.

Fast Acting Hydromorphone: Hydromorphone is yet another alternative to morphine for breakthrough pain; most commonly known by the name Dilaudid, hydromorphone is a potent opioid which is very effective in relieving pain, and is well suited for patients with moderate to high tolerance. Although like morphine its bioavailability is low, in the right dose, hydromorphone may provide rapid relief from sudden pain with fewer side effects than morphine in equianalgesic doses; with 4 to 8mg of Dilaudid being similar in analgesic efficacy to 15 to 30mg of oral morphine. Tablets are the most commonly used form of hydromorphone/dilaudid, available in 2, 4, and 8 mg strengths. Brand name and generic hydromorphone is also available in liquid form, and offers rapid absorption of the drug - the standard Dilaudid oral solution contains 1mg per 1ml (5mg/teaspoon) of hydromorphone. Currently in the pharmaceutical development/research pipeline, is a rapid acting nasal spray form of hydromorphone; nasally administered hydromorphone offers a faster onset with better absorption than the oral route - Onset of oral hydromorphone may take 20 to 30 minutes, while nasally administered liquid may take effect in 5 to 15 minutes. Hydromorphone may have an additional clinical advantage to physicians, administered orally, hydromorphone is generally believed to possess lesser liability for development of misuse or compulsive use of the drug, essentially giving it a lesser tendency to precipitate a psychological dependence. This is due to the 'cleaner' effect of hydromorphone which produces less of a subjective opioid 'high' - Note, this only pertains to the oral use of the drug, and while it may offer an advantage in the eyes of physicians, many of us like to 'feel' our opioids when taken orally. Additionally, in cases of patients with already present addictive traits, this presents an incentive to take the drug by other routes such as injection or insufflation; therefore this seemingly positive attribute may serve as a downside in some situations.

Fast Acting Oxymorphone: In a similar category as the previous opioids is oxymorphone, a very potent opioid which is roughly 8 times stronger than morphine and slightly stronger than hydromorphone. Regular rapid release oxymorphone is currently available only in tablet form; the brand name Opana patent only recently expired, and subsequently 2 generic oxymorphone tablets have been introduced. Doses available are 5mg and 10mg. Though much stronger than morphine, oxymorphone has a significantly lower bioavailability than morphine, averaging only 10% in most individuals, meaning higher relative doses must be used. Milligram to milligram, oral oxymorphone has an approximate 1/2 ratio with oral morphine - 15mg oxymorphone is equianalgesic to 30mg morphine or 20mg oxycodone. This applies only to oral use, and by other routes the drug is far more potent than morphine, requiring very small doses. Oxymorphone instant release formulations are generally believed to provide a longer lived analgesia than its close relatives, and may provide significant relief for up to 5 or 6 hours. In the right dose, oxymorphone is a highly effective analgesic which provides an alternative to morphine for highly tolerant individuals or those with severe episodes of breakthrough pain. Patients who are given the drug in an adequate dose, often rate its efficacy as being among the best of the opioids. In equianalgesic doses, OM carries much less pronounced side effects than morphine, primarily the itching/pruritis, nausea & vomiting, and sedation. Many report it to be similar in subjective effect to oxycodone, though often much cleaner or smoother in effect - to many this may translate to less pronounced effects by the oral route; though this only applies to the oral route.

Buccal & Nasal Fentanyl Preparations: Fentanyl is extremely potent and is currenly the strongest opioid available in the US for outpatient management of pain; originally it was released as the 72-hour transdermal formulation after having been only used as an injectable solution in the hospital/surgical setting, however a number of rapid acting formulations have become available more recently. For breakthrough pain, the drug is currently availavle in buccal forms, which rapidly dissolve inside the mouth; on the surface of the inner cheek, gums, or tounge. The brand names for fast acting fentanyl are as follows:

Actiq - buccal fentanyl product in the form of a lolly-pop style lozenge at the end of a stick. Lolly-pop fentanyl is now available in generic forms as well; and though this product is indicated primarily for treatment of cancer related pain, it can be used off label for opioid tolerant individuals who are currently taking a potent long acting opioid such as the fentanyl patch, Opana ER, long acting morphine in high doses, or methadone.

Fentora - buccal fentanyl in the form of a fast dissolving round-tablet. Like Actiq, fentora products wre FDA approved for treatment of malignant pain, but can be used off label for non malignant pain in opioid tolerant individuals currently on potent long acting narcotics.

Newly available is a buccal fentanyl film, by the brand name Onsolis; the film rapidly dissolves on the inner surface of the cheek, gums, or tounge.

Fentanyl nasal spray is available in European countries by the brand name Instanyl, however there are currently no intranasal forms of fentanyl available in the US. It is likely in the coming years for fentanyl nasal spray to be introduced to the US market, and is reportedly being pursued currently.

Fentanyl typically recieves shining reviews from pain patients, and is generally agreed to be one of the most effective opioids for relief of severely debilitating pain, often minimally responsive to other opioids. The rapid absorbtion of instant release fentanyl is superior to most other opioids; patients often report relief within 7 or 8 minutes, often before the medication has completely dissolved. Fentanyl is perhaps one of the best suited opioids for rapid and complete pain relief, due to its fast acting properties and high potency. Analgesic effect of fentanyl usually lasts 1 to 2 hours; which makes it an idea medication in situations such as treatment with methadone or the long acting patch, as it can be used to provide fast relief during the delayed onset of the long acting opioid, with much less tendency to linger in the system once other medications have taken full effect.


  1. Very nicely done. I'm impressed by your work.


  2. "Fentanyl typically receives shining reviews from pain patients, and is generally agreed to be one of the most effective opioids for relief of severely debilitating pain, often minimally responsive to other opioids."

    Fentanyl really is the cleanest pain control I've ever used, but I will never again allow a doctor that much control over me. The withdrawals from it are horrific; they hit quicker, they're stronger and last longer than those from, say, morphine. All it took was one opiophobic, fake PM "Specialist" to destroy my regimen and damned near kill me. That was two years ago, and I'm STILL trying to recover.

    Thanks to the DEA's massive propaganda campaign, even doctors are unaware of the Medical Standard of Care, and the DEA illegally makes certain that doctors who follow it get railroaded VERY visibly into prison. Yes, breakthrough pain requires breakthrough medication, but again, even doctors don't understand how opiates work in CPPs. After my last of six back operations, the neurosurgeon told me that I was already taking FAR stronger meds and in larger doses than he prescribed for post-op pain, so he refused to give me anything at all for it. He refused to believe that the meds I take regularly pretty much handled the "regular" levels of my usual chronic pain and NOTHING ELSE. It doesn't make us invulnerable to any new pain. That's why it's called "breakthrough" pain - it breaks through the analgesia that you maintain, and you need added medication to take care of it. I'd say a major surgery counts as "added pain." He disagreed. Guess who won?


  3. Thanks for reading Axe. Very glad you find it of interest.


  4. To the previous poster; that's a real shame. I'm sorry to hear it.. Clinical and public opiophobia is affecting the lives of far too many people in a very negative way.