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Written by

Professor Dr. Josef Donnerer Professor Dr. Josef Donnerer is from the Institute of Experimental & Clinical Pharmacology, Medical University Graz, Austria

Pharmacological profiles and indications of different opioids

Published 10 November 2017

Professor Dr. Josef Donnerer describes the differences between opioid analgesics, and factors that should be taken into account when selecting opioid analgesia

Key learning points

  • Clinically used opioids have different analgesic potencies, although no significant differences in pain relief are usually observed as doses are normally selected to be equianalgesic.
  • Morphine doses are the units on which opioid equianalgesic calculations are based.
  • In the selection of opioid compounds individual factors such as type of pain, circadian rhythm in pain, and comorbidities should be considered.


Introduction

Opioids produce a variety of effects, with analgesia being the primary clinical use. Opioid-induced analgesia is achieved at supraspinal, spinal and peripheral sites of action along the pain pathway, via agonistic or partial agonistic activity at mu-, delta-, and kappa-opioid receptor subtypes. Reduced gastrointestinal motility, euphoria, dysphoria, sedation, nausea, neuroendocrine effects, respiratory depression and pupil constriction can also occur during opioid therapy, consistent with the association of opioid receptors with a variety of brain areas and to peripheral tissues.1

Clinically-used opioid analgesics are generally regarded as mu-opioid receptor agonists, having similar pharmacological profiles. However, looking experimentally at the three pharmacodynamic responses – analgesia, respiratory depression and constipation, and constructing complete dose-response curves, no two opioids have the same profile. This finding may explain the clinical success of ‘opioid rotation’, which can be tried when a patient experiences poor analgesia with intolerable adverse effects.2

Opioids have different analgesic potencies, which is reflected in the various conversion guidelines available. When addressing the issue in controlled clinical trials of whether one strong opioid (eg morphine) is superior to another strong opioid (eg oxycodone, hydromorphone, methadone) with respect to analgesic efficacy, no significant differences in pain relief are observed. This is actually the expected outcome, as doses normally are selected to be equianalgesic. However, when switching one opioid to another, a lower starting dose of the ‘new’ opioid should be prescribed than suggested by equianalgesic tables.3

Despite the fact that no clear differences are observed in analgesic efficacy between strong opioids, the efficacy vs. safety and patient specific needs can provide evidence for a clear separation in terms of utility.


Opioid selection

In the selection of opioid compounds individual factors such as type of pain, circadian rhythm in pain, and comorbidities should be considered.

Tramadol is one of the opioids recommended for moderate to severe pain (numeric pain rating scale – NRS 4–6). From its pharmacological profile, it is a preferential mu-opioid receptor-agonist as well as a modulator of norepinephrine and serotonin action.1,4

Dihydrocodeine (note: constipation) is only a second choice alternative in this group of opioid analgesics.1,4

Morphine is a commonly used opioid for patients with severe pain (NRS 7–10). If the patient must later be switched to another medication, morphine doses are the units on which opioid equianalgesic calculations are based. Oxycodone and hydromorphone are alternatives for patients with morphine intolerance or allergy. Long-acting oral preparations of morphine, oxycodone and hydromorphone are available for patients who need chronic therapy.1,5

Tapentadol may be effective in neuropathic pain due to its dual mechanism of action.6 Patients with stable pain levels can change to transdermal delivery systems of buprenorphine or fentanyl. Fentanyl is a very lipophilic compound with a more rapid onset of action than morphine. Buprenorphine is a partial opioid agonist.1


Specific considerations for opioids in cancer pain

Sustained-release opioids provide basic analgesia; rapid-onset opioids are for breakthrough pain only. In opioid-naïve patients with medium severe moderate pain (WHO-II) start with tramadol or dihydrocodeine, but for WHO-III low doses of oxycodone, hydromorphone and morphine might be considered. Severe pain requires higher doses of morphine, oxycodone or hydromorphone. Patients with stable pain levels can change to transdermal systems with buprenorphine or fentanyl.

Oral therapy offers a high level of independence for the patient. Small-unit pellet preparations can be taken by patients who have problems swallowing. Transdermal patches containing fentanyl or buprenorphine are indicated for patients with continuous stable pain who have problems swallowing, gastrointestinal passage obstruction or therapy-resistant vomiting. Adhesion to the skin must be ensured. Subcutaneous and sometimes intravenous morphine or oxycodone or hydromorphone is an effective option when oral or transdermal therapy is not possible, or in patients with unstable pain.5


Specific considerations for opioids in chronic non-tumour pain

When the pain is opioid-sensitive, there is evidence of efficacy within 4–12 weeks of opioid therapy. Immediate-release preparations should be used for dose finding, then changed to prolonged-release preparations. In non-responders, opioid rotation is an option. An oral daily dose of 120mg morphine-equivalent should not be exceeded in longer-lasting therapies.7,8


  • Professor Dr. Josef Donnerer is from the Institute of Experimental & Clinical Pharmacology, Medical University Graz, Austria

CLICK HERE – CONSIDERATIONS WHEN PRESCRIBING AN OPIOID



References

  1. Pathan H, Williams J. British Journal of Pain 2012;6(1):11-16.
  2. Kuo A, Wyse BD, et al. British Journal of Pharmacology 2015;172(2):532-548.
  3. Drewes AM, Jensen RD, et al. British Journal of Clinical Pharmacology 2013;75(1):60-78.
  4. Leppert W. Current Pain and Headache Reports 2011;15(4): 271–279.
  5. Ripamonti CI, Bandieri E, et al. Annals of Oncology 2011;22 Suppl 6:vi69-77
  6. Vadivelu N,  Kai A, et al. Therapeutics and Clinical Risk Management 2015;11:95-105.
  7. Häuser W, Bock F, et al. Schmerz 2015;29:109-130.
  8. Kraychete DC, Sakata RK.  Brazilian Journal of Anesthesiology 2012; 62(4):554-562

Date of preparation: October 2017; MINT/PAEU-17026