Opioid analgesic: Difference between revisions

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imported>Howard C. Berkowitz
(Are not the chemical classes more significant than natural/semisynthetic/synthetic?)
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(Undo revision 100626165 by Howard C. Berkowitz (Talk))
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'''Opioid analgesics''', also called '''narcotics''', are [[drug]]s usually used for treating [[pain]]. Opiod analgesics are defined as "all of the natural and semisynthetic alkaloid derivatives from opium, their pharmacologically similar synthetic surrogates, as well as all other compounds whose opioid-like actions are blocked by the nonselective opioid receptor antagonist [[naloxone]].<ref name="isbn0-07-145153-6">{{cite book |author=Katzung, Bertram G. |title=Basic and clinical pharmacology |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2006 |pages=512 |isbn=0-07-145153-6 |oclc= |doi=}}</ref>
==Pharmacology==
There a several [[opioid receptor]]s. All are are G-protein-coupled [[cell surface receptor]]s.
Clinically useful analgesic families vary in their receptor effects; they range from pure agonists of all receptor types, to selective agonists, to agonist-antagonists.
{| class="wikitable" align="right"
|+ [[Opioid receptor]]s<ref name="isbn0-07-160405-7-=Basic Pharmacology of the Opioid Analgesics">{{cite book |author=Masters, Susan B.; Katzung, Bertram G.; Trevor, Anthony J. |authorlink= |editor= |others= |title=Basic and Clinical Pharmacology |edition=11th| |chapter=Basic Pharmacology of the Opioid Analgesics |chapterurl=http://www.accessmedicine.com/content.aspx?aID=4519483 |publisher=McGraw-Hill Medical |location=New York |year=2009 |origyear= |pages= |quote= |isbn=0-07-160405-7 |oclc= |doi= |url=http://www.accessmedicine.com/resourceTOC.aspx?resourceID=16 |accessdate=}}</ref>
! Receptor!! Functions
|-
| Delta|| Analgesia,
|-
| Kappa|| Analgesia, inhibition of gastrointestinal motility, psychotropic effect
|-
| Mu  || Analgesia, inhibition of gastrointestinal motility, inhibition of  respiration, sedation and physical [[dependency]]
|}
==Available opioid analgesics==
==Available opioid analgesics==
Current opioid analgesics are below<ref name="isbn1-55009-213-8">{{Cite book  | last1 = Kufe | first1 = Donald W. | last2 = Holland | first2 = James F. | last3 = Frei | first3 = Emil | title = Cancer medicine 6 |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6|chapter=78. Management of Cancer Pain|chapterurl=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6.section.18822| date = 2003 | publisher = BC Decker | location = Hamilton, Ont.  | isbn = 1-55009-213-8 | pages =  }}</ref> [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6.table.18830 Tables] of morphine equivalent daily dose and IV to PO conversion are available to help dosing.<ref name="isbn1-55009-213-8"/>
Current opioid analgesics are below<ref name="isbn1-55009-213-8">{{Cite book  | last1 = Kufe | first1 = Donald W. | last2 = Holland | first2 = James F. | last3 = Frei | first3 = Emil | title = Cancer medicine 6 |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6|chapter=78. Management of Cancer Pain|chapterurl=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6.section.18822| date = 2003 | publisher = BC Decker | location = Hamilton, Ont.  | isbn = 1-55009-213-8 | pages =  }}</ref> [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6.table.18830 Tables] of morphine equivalent daily dose and IV to PO conversion are available to help dosing.<ref name="isbn1-55009-213-8"/>
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|  
|  
| Faster blood-brain transfer than morphine but both produce the same primary active metabolite
| Faster blood-brain transfer than morphine but both produce the same primary active metabolite
|-
|-
| [[Hydrocodone]] and [[Oxycodone]]
| [[Hydrocodone]] and [[Oxycodone]]
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|-
|-
| [[Buprenorphine]]  
| [[Buprenorphine]]  
|
| mu, antagonist of delta and kappa
| mu, antagonist of delta and kappa
|
|
|-
|-
! colspan="4"|Fully synthetic opioids
! colspan="5"|Fully synthetic opioids
|-
|-
| [[Meperidine]]
| [[Fentanyl]]  
| meperidine
|
|
| accumulates toxic metabolite
|-
| [[Fentanyl]]
| meperidine
| mu  
| mu  
| Transdermal and transmucosal absorption
| Transdermal and transmucosal absorption
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| methadone
| methadone
| mu  
| mu  
| Good oral absorption; additional applications in addiction medicine
| Good oral absorption
|-
| [[LAAM]]
| methadone
| mu
| Not used for analgesia; long-acting blocker of opioid addiction
|-
| D-[[Propoxyphene]]
|propoxyphene
|mu
|D-propoxyphene primarily analgesic
|-
| L-[[Propoxyphene]]/dextromorphan
|propoxyphene
|mu
|D-propoxylphene primarily antitussive
|-
|-
| [[Tramadol]]  
| [[Tramadol]]  
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|also inhibits norepinephrine reuptake
|also inhibits norepinephrine reuptake
|}
|}
==Effectiveness==
Narcotics are commonly prescribed for [[pain]], and their usage may be increasing.<ref name="pmid18167408">{{cite journal |author=Pletcher MJ, Kertesz SG, Kohn MA, Gonzales R |title=Trends in opioid prescribing by race/ethnicity for patients seeking care in US emergency departments |journal=JAMA |volume=299 |issue=1 |pages=70–8 |year=2008 |pmid=18167408 |doi=10.1001/jama.2007.64}}</ref> In emergency rooms, non-Hispanic white patients are more likely to receive narcotics than patients of other ethnicities.<ref name="pmid18167408"/>
Narcotics are effective for both short (1-16 weeks)<ref name="pmid16717269">{{cite journal |author=Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E |title=Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects |journal=CMAJ |volume=174 |issue=11 |pages=1589–94 |year=2006 |pmid=16717269 |doi=10.1503/cmaj.051528 |url=http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=16717269}}</ref> and long-term (6-24 months) use<ref name="pmid15561393">{{cite journal |author=Kalso E, Edwards JE, Moore RA, McQuay HJ |title=Opioids in chronic non-cancer pain: systematic review of efficacy and safety |journal=Pain |volume=112 |issue=3 |pages=372–80 |year=2004 |pmid=15561393 |doi=10.1016/j.pain.2004.09.019 |url=http://linkinghub.elsevier.com/retrieve/pii/S0304-3959(04)00447-6}}</ref>.
Narcotics, with long-term use, 80% of patients may have [[drug toxicity]], most commonly gastrointestinal. In addition, substrance abuse and "aberrant medication-taking behaviors" may occur.<ref name="pmid17227935">{{cite journal |author=Martell BA, O'Connor PG, Kerns RD, ''et al'' |title=Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction |journal=Ann. Intern. Med. |volume=146 |issue=2 |pages=116–27 |year=2007 |pmid=17227935 |doi= |url=http://www.annals.org/cgi/content/full/146/2/116 |issn=}}</ref> Advice for using administering chronic narcotics<ref name="pmid19187889">{{cite journal| author=Chou R, Fanciullo GJ, Fine PG, Adler JA, Ballantyne JC, Davies P et al.| title=Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. | journal=J Pain | year= 2009 | volume= 10 | issue= 2 | pages= 113-30 | pmid=19187889
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19187889 | doi=10.1016/j.jpain.2008.10.008 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> and for treating acute pain among patients on chronic methadone is available<ref name="pmid16418412">{{cite journal |author=Alford DP, Compton P, Samet JH |title=Acute pain management for patients receiving maintenance methadone or buprenorphine therapy |journal=Ann. Intern. Med. |volume=144 |issue=2 |pages=127–34 |year=2006 |pmid=16418412 |doi= |url=http://www.annals.org/cgi/content/full/144/2/127 |issn=}}</ref>.
==Usage==
[[Clinical practice guideline]]s are available.<ref name="pmid19187889">{{cite journal| author=Chou R, Fanciullo GJ, Fine PG, Adler JA, Ballantyne JC, Davies P et al.| title=Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. | journal=J Pain | year= 2009 | volume= 10 | issue= 2 | pages= 113-30 | pmid=19187889
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19187889 | doi=10.1016/j.jpain.2008.10.008 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6.table.18830 Tables] of morphine equivalent daily dose and IV to PO conversion are available to help dosing.<ref name="isbn1-55009-213-8">{{Cite book  | last1 = Kufe | first1 = Donald W. | last2 = Holland | first2 = James F. | last3 = Frei | first3 = Emil | title = Cancer medicine 6 |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6|chapter=78. Management of Cancer Pain|chapterurl=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6.section.18822| date = 2003 | publisher = BC Decker | location = Hamilton, Ont.  | isbn = 1-55009-213-8 | pages =  }}</ref>
==Adverse effects==
===Constipation===
[[Constipation]] may be reduced by [[methylnaltrexone]], a mu-[[opioid receptor]] antagonist. In a [[randomized controlled trial]], 48% of patients receiving [[methylnaltrexone]] had a bowel movement compared to 15% of patients received placebo ([[number needed to treat]] = 3.0. [http://medinformatics.uthscsa.edu/calculator/calc.shtml?calc_rx_rates.shtml?eer=48.0&cer=15.0 Click here] to adjust these results for patients at higher or lower risk.)<ref>Thomas J, Karver S, Cooney GA, Chamberlain BH, Watt CK, Slatkin NE, Stambler N, Kremer AB, Israel RJ. [http://content.nejm.org/cgi/content/full/358/22/2332 Methylnaltrexone for opioid-induced constipation in advanced illness]. N Engl J Med. 2008 May 29;358(22):2332-43. PMID 18509120</ref> Although mu-receptors provide analgesia, [[methylnaltrexone]] is a charged quaternary amine so that it does not well cross the [[blood-brain barrier]].
===Dependency===
{{main|Opiate dependence}}
Opioid agonist therapy includes [[buprenorphine]] and [[methadone]]. Although [[buprenorphine]]–[[naloxone]] may be less effective than [[methadone]]<ref name="pmid15677600">{{cite journal| author=Schottenfeld RS, Chawarski MC, Pakes JR, Pantalon MV, Carroll KM, Kosten TR| title=Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence. | journal=Am J Psychiatry | year= 2005 | volume= 162 | issue= 2 | pages= 340-9 | pmid=15677600
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15677600 | doi=10.1176/appi.ajp.162.2.340 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16246888 Review in: Evid Based Ment Health. 2005 Nov;8(4):112] <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>, it has more predictable dosing<ref name="pmid15720937">{{cite journal| author=Simoens S, Matheson C, Bond C, Inkster K, Ludbrook A| title=The effectiveness of community maintenance with methadone or buprenorphine for treating opiate dependence. | journal=Br J Gen Pract | year= 2005 | volume= 55 | issue= 511 | pages= 139-46 | pmid=15720937
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15720937 | pmc=PMC1463190 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>, and can be prescribed by qualifying office-based physicians.<ref name="pmid18458279">{{cite journal| author=Sullivan LE, Fiellin DA| title=Narrative review: buprenorphine for opioid-dependent patients in office practice. | journal=Ann Intern Med | year= 2008 | volume= 148 | issue= 9 | pages= 662-70 | pmid=18458279
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18458279 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
====Substance abuse====
With chronic use for treatment of [[pain]], [[dependency]] may lead to substance abuse and "aberrant medication-taking behaviors" may occur.<ref name="pmid17227935">{{cite journal |author=Martell BA, O'Connor PG, Kerns RD, ''et al'' |title=Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction |journal=Ann. Intern. Med. |volume=146 |issue=2 |pages=116–27 |year=2007 |pmid=17227935 |doi= |url=http://www.annals.org/cgi/content/full/146/2/116 |issn=}}</ref>
====Withdrawal====
Adding [[narcotic antagonist]]s combined with [[alpha-adrenergic agonist]]s may reduce [[withdrawal symptom]]s.<ref name="pmid19821290">{{cite journal| author=Gowing L, Ali R, White JM| title=Opioid antagonists with minimal sedation for opioid withdrawal. | journal=Cochrane Database Syst Rev | year= 2009 | volume=  | issue= 4 | pages= CD002021 | pmid=19821290
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=19821290 | doi=10.1002/14651858.CD002021.pub3 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
===Tolerance===
[[N-methyl-d-aspartate receptor]] (NMDA) activation may lead to neuropathic pain and tolerance.<ref name="pmid1824728">{{cite journal| author=Trujillo KA, Akil H| title=Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. | journal=Science | year= 1991 | volume= 251 | issue= 4989 | pages= 85-7 | pmid=1824728
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=1824728 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><ref name="pmid16629581">{{cite journal| author=Prommer E| title=Rotating methadone to other opioids: a lesson in the mechanisms of opioid tolerance and opioid-induced pain. | journal=J Palliat Med | year= 2006 | volume= 9 | issue= 2 | pages= 488-93 | pmid=16629581
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16629581 | doi=10.1089/jpm.2006.9.488 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> [[Methadone]], which is a NMDA antagonist, may reduce tolerance.
==References==
<references/>

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Opioid analgesics, also called narcotics, are drugs usually used for treating pain. Opiod analgesics are defined as "all of the natural and semisynthetic alkaloid derivatives from opium, their pharmacologically similar synthetic surrogates, as well as all other compounds whose opioid-like actions are blocked by the nonselective opioid receptor antagonist naloxone.[1]

Pharmacology

There a several opioid receptors. All are are G-protein-coupled cell surface receptors.

Clinically useful analgesic families vary in their receptor effects; they range from pure agonists of all receptor types, to selective agonists, to agonist-antagonists.

Opioid receptors[2]
Receptor Functions
Delta Analgesia,
Kappa Analgesia, inhibition of gastrointestinal motility, psychotropic effect
Mu Analgesia, inhibition of gastrointestinal motility, inhibition of respiration, sedation and physical dependency

Available opioid analgesics

Current opioid analgesics are below[3] Tables of morphine equivalent daily dose and IV to PO conversion are available to help dosing.[3]

Selected opioids[2]
Specific drug Chemical class Receptor action Comments
Naturally occurring opium alkaloids
Morphine morphine mu, kappa (weak)
Codeine morphine mu (partial agonist) Good oral absorption
Semi-synthetic opioids
Diacetylmorphine (heroin) morphine Faster blood-brain transfer than morphine but both produce the same primary active metabolite
Hydrocodone and Oxycodone morphine mu (partial)
Hydromorphone (Dilaudid) morphine mu
Buprenorphine mu, antagonist of delta and kappa
Fully synthetic opioids
Fentanyl mu Transdermal and transmucosal absorption
Methadone methadone mu Good oral absorption
Tramadol mu also inhibits norepinephrine reuptake

Effectiveness

Narcotics are commonly prescribed for pain, and their usage may be increasing.[4] In emergency rooms, non-Hispanic white patients are more likely to receive narcotics than patients of other ethnicities.[4]

Narcotics are effective for both short (1-16 weeks)[5] and long-term (6-24 months) use[6].

Narcotics, with long-term use, 80% of patients may have drug toxicity, most commonly gastrointestinal. In addition, substrance abuse and "aberrant medication-taking behaviors" may occur.[7] Advice for using administering chronic narcotics[8] and for treating acute pain among patients on chronic methadone is available[9].

Usage

Clinical practice guidelines are available.[8]

Tables of morphine equivalent daily dose and IV to PO conversion are available to help dosing.[3]

Adverse effects

Constipation

Constipation may be reduced by methylnaltrexone, a mu-opioid receptor antagonist. In a randomized controlled trial, 48% of patients receiving methylnaltrexone had a bowel movement compared to 15% of patients received placebo (number needed to treat = 3.0. Click here to adjust these results for patients at higher or lower risk.)[10] Although mu-receptors provide analgesia, methylnaltrexone is a charged quaternary amine so that it does not well cross the blood-brain barrier.

Dependency

For more information, see: Opiate dependence.

Opioid agonist therapy includes buprenorphine and methadone. Although buprenorphine–naloxone may be less effective than methadone[11], it has more predictable dosing[12], and can be prescribed by qualifying office-based physicians.[13]

Substance abuse

With chronic use for treatment of pain, dependency may lead to substance abuse and "aberrant medication-taking behaviors" may occur.[7]

Withdrawal

Adding narcotic antagonists combined with alpha-adrenergic agonists may reduce withdrawal symptoms.[14]

Tolerance

N-methyl-d-aspartate receptor (NMDA) activation may lead to neuropathic pain and tolerance.[15][16] Methadone, which is a NMDA antagonist, may reduce tolerance.

References

  1. ↑ Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical Publishing Division, 512. ISBN 0-07-145153-6. 
  2. ↑ 2.0 2.1 Masters, Susan B.; Katzung, Bertram G.; Trevor, Anthony J. (2009). “Basic Pharmacology of the Opioid Analgesics”, Basic and Clinical Pharmacology, 11th. New York: McGraw-Hill Medical. ISBN 0-07-160405-7.  Cite error: Invalid <ref> tag; name "isbn0-07-160405-7-=Basic Pharmacology of the Opioid Analgesics" defined multiple times with different content
  3. ↑ 3.0 3.1 3.2 (2003) “78. Management of Cancer Pain”, Cancer medicine 6. Hamilton, Ont.: BC Decker. ISBN 1-55009-213-8. 
  4. ↑ 4.0 4.1 Pletcher MJ, Kertesz SG, Kohn MA, Gonzales R (2008). "Trends in opioid prescribing by race/ethnicity for patients seeking care in US emergency departments". JAMA 299 (1): 70–8. DOI:10.1001/jama.2007.64. PMID 18167408. Research Blogging.
  5. ↑ Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E (2006). "Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects". CMAJ 174 (11): 1589–94. DOI:10.1503/cmaj.051528. PMID 16717269. Research Blogging.
  6. ↑ Kalso E, Edwards JE, Moore RA, McQuay HJ (2004). "Opioids in chronic non-cancer pain: systematic review of efficacy and safety". Pain 112 (3): 372–80. DOI:10.1016/j.pain.2004.09.019. PMID 15561393. Research Blogging.
  7. ↑ 7.0 7.1 Martell BA, O'Connor PG, Kerns RD, et al (2007). "Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction". Ann. Intern. Med. 146 (2): 116–27. PMID 17227935. [e]
  8. ↑ 8.0 8.1 Chou R, Fanciullo GJ, Fine PG, Adler JA, Ballantyne JC, Davies P et al. (2009). "Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain.". J Pain 10 (2): 113-30. DOI:10.1016/j.jpain.2008.10.008. PMID 19187889. Research Blogging.
  9. ↑ Alford DP, Compton P, Samet JH (2006). "Acute pain management for patients receiving maintenance methadone or buprenorphine therapy". Ann. Intern. Med. 144 (2): 127–34. PMID 16418412. [e]
  10. ↑ Thomas J, Karver S, Cooney GA, Chamberlain BH, Watt CK, Slatkin NE, Stambler N, Kremer AB, Israel RJ. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008 May 29;358(22):2332-43. PMID 18509120
  11. ↑ Schottenfeld RS, Chawarski MC, Pakes JR, Pantalon MV, Carroll KM, Kosten TR (2005). "Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence.". Am J Psychiatry 162 (2): 340-9. DOI:10.1176/appi.ajp.162.2.340. PMID 15677600. Research Blogging. Review in: Evid Based Ment Health. 2005 Nov;8(4):112
  12. ↑ Simoens S, Matheson C, Bond C, Inkster K, Ludbrook A (2005). "The effectiveness of community maintenance with methadone or buprenorphine for treating opiate dependence.". Br J Gen Pract 55 (511): 139-46. PMID 15720937. PMC PMC1463190.
  13. ↑ Sullivan LE, Fiellin DA (2008). "Narrative review: buprenorphine for opioid-dependent patients in office practice.". Ann Intern Med 148 (9): 662-70. PMID 18458279.
  14. ↑ Gowing L, Ali R, White JM (2009). "Opioid antagonists with minimal sedation for opioid withdrawal.". Cochrane Database Syst Rev (4): CD002021. DOI:10.1002/14651858.CD002021.pub3. PMID 19821290. Research Blogging.
  15. ↑ Trujillo KA, Akil H (1991). "Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801.". Science 251 (4989): 85-7. PMID 1824728.
  16. ↑ Prommer E (2006). "Rotating methadone to other opioids: a lesson in the mechanisms of opioid tolerance and opioid-induced pain.". J Palliat Med 9 (2): 488-93. DOI:10.1089/jpm.2006.9.488. PMID 16629581. Research Blogging.
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