Clinical Notes : Pharmacology
178. Atypical Opioids :
The atypical opioids Tramadol, Tapentadol and Buprenorphine (1)
Atypical opioids differ from conventional opioids as they do not rely exclusively on mu-receptor agonism for their analgesic effect.
The atypical opioids, buprenorphine, tramadol and tapentadol, have different effects and different adverse effects including toxicity and abuse potential compared with conventional opioids.
These differences result in improved outcomes and reduced risks with the use of atypical opioids for individual patients and society as a whole.
Atypical opioids are the preferred strong analgesics for chronic pain that requires pharmacological treatment.
Tramadol is currently the preferred atypical opioid for the treatment of neuropathic pain, osteoarthritis and cancer pain.
50 mg orally (immediate-release) every 4-6 hours when required, maximum 400 mg/day
orally (extended-release) 100-300 mg once daily, maximum 300 mg/day
Tapentadol is currently the preferred atypical opioid for the treatment of chronic pain.
Palexia 50, 75, or 100 mg every 4 to 6 hours depending on the intensity of pain
On the first day, a second dose may be given 1 hour after the initial dose if pain relief is inadequate
subsequent doses should be given every 4 to 6 hours, adjusted according to response
maximum total dose of 700 mg on the first day and of 600 mg daily on subsequent days
Transdermal Buprenorphine is particularly suitable for use in the elderly.
Butrans Patch delivers buprenorphine in a range of 5 to 20 micrograms/hour
initial dosages should not exceed 5 micrograms/hour in all patients
patches should be replaced every 7 days with the new patch being applied to a different site; use of the same area of the skin should be avoided for the next 3 to 4 weeks.
Buprenorphine behaves quite differently from conventional opioids with primarily mu-agonist effects.
Most complex pharmacology of the three atypical opioids.(2)
potent but partial agonist at the mu-opioid receptor with high receptor affinity explaining its long duration of action.(3)
potent kappa-receptor antagonist.(4)
agonist at the nociceptin or opioid-receptor-like 1 (ORL-1) receptor; the latter effects possibly explain some of the many advantageous effects of buprenorphine.(5)
binds to delta-opioid receptors.
The inter-play between these multiple receptor effects is complex and species-specific.
High potency and good lipophilicity of buprenorphine made it an ideal candidate for the development of transdermal delivery systems.(6)
In comparative trials, buprenorphine has provided equivalent analgesia to morphine, hydromorphone, oxycodone, fentanyl and methadone.(7)
Buprenorphine has proven efficacy and low rates of toxicity in elderly patients and its effects are minimally affected by renal failure or haemodialysis.(7)
Advantages of tramadol are :
respiratory depression with fatal consequences has a zero incidence in a data analysis from the US National Poison Data System.(8)
with regard to long-term use, buprenorphine seems to cause less tolerance than conventional mu-receptor agonists such as fentanyl.(9)
seems to be less immunosuppressive than conventional opioids.(3)
with regard to hypo-gonadism and testosterone suppression (opioid-induced androgen deficiency), the effects of buprenorphine seem to be minimal compared with conventional opioids.(9)
causes less cognitive dysfunction than conventional opioids.(5)
not linked to an increased fracture risk due to falls.(10)
less constipating effects (3)
Specific adverse effects of transdermal buprenorphine are local skin reactions, in particular erythema and pruritus, which are more common than with transdermal fentanyl and may be reduced by topical cortico-steroid administration.(11)
Dependence, abuse potential and diversion
Transdermal buprenorphine seems to be unattractive for drug seekers.
This is confirmed by US data showing that prescription-adjusted rates of intentional abuse and suspected suicidal intent with transdermal buprenorphine were significantly lower than for morphine, oxycodone, oxymorphone, methadone and transdermal fentanyl.(7)
Physical dependence and withdrawal symptoms occur with buprenorphine, but are reported as milder than with conventional opioids, however, to reduce these symptoms gradual dose reduction is recommended.(3)
1. Schug SA
The atypical opioids: buprenorphine, tramadol and tapentadol
MedicineToday : Conventional and Atypical Opioids Supplement September 2018
2. Cowan A.
Buprenorphine: the basic pharmacology revisited.
J Addict Med 2007; 1: 68-72.
3. Kress HG.
Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine.
Eur J Pain 2009; 13: 219-230.
4. Khanna IK, Pillarisetti S.
Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain.
J Pain Res 2015; 8: 859-870.
5. Davis MP.
Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain.
J Support Oncol 2012; 10: 209-219
6. Evans HC, Easthope SE.
Drugs 2003; 63: 1999-2010; discussion 1-2.
7. Coplan PM, Sessler NE, Harikrishnan V, Singh R, Perkel C.
Comparison of abuse, suspected suicidal intent, and fatalities related to the 7-day buprenorphine transdermal patch versus other opioid analgesics in the National Poison Data System.
Postgrad Med 2017; 129: 55-61.
8. Sittl R, Nuijten M, Nautrup BP.
Changes in the prescribed daily doses of transdermal fentanyl and transdermal buprenorphine during treatment of patients with cancer and noncancer pain in Germany: results of a retrospective cohort study.
Clinical Therapeutics 2005; 27: 1022-1031.
9. Bliesener N, Albrecht S, Schwager A, Weckbecker K, Lichtermann D, Klingmuller D.
Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence.
J Clin Endocrinol Metab 2005; 90: 203-206.
10. Vestergaard P, Rejnmark L, Mosekilde L.
Fracture risk associated with the use of morphine and opiates.
J Intern Med 2006; 260: 76-87.
11. Likar R, Kayser H, Sittl R.
Long-term management of chronic pain with transdermal buprenorphine: a multicenter, open-label, follow-up study in patients from three short-term clinical trials.
Clin Ther 2006; 28: 943-952.
The following meds are available in Ireland :
Tramadol (Tradol, Tramadol HCL, Tramake, Tramapine, Xymel, Zydol)
Transdermal Buprenorphine (Butrans, Transtec)
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