Bradley Monk at 02:06, 26 August 2013

2013-08-26T02:06:22Z

← Older revision		Revision as of 19:06, 25 August 2013
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	Opioids bind to specific [[opioid receptor]]s in the [[nervous system]] and other tissues. There are three principal classes of opioid receptors, [[mu opioid receptor\|μ]], [[kappa opioid receptor\|κ]], [[delta opioid receptor\|δ]] (mu, kappa, and delta), although up to seventeen have been reported, and include the ε, ι, λ, and ζ (Epsilon, Iota, Lambda and Zeta) receptors. Conversely, σ ([[sigma receptor\|Sigma]]) receptors are no longer considered to be opioid receptors because: their activation is not reversed by the opioid inverse-agonist [[naloxone]], they do not exhibit high-affinity binding for classical opioids, and they are stereoselective for [[Dextrorotation\|dextro-rotatory]] [[isomers]] while the other opioid receptors are stereo-selective for [[Laevorotation\|laevo-rotatory]] isomers. In addition, there are three subtypes of [[mu opioid receptor\|μ]]-receptor: μ<sub>1</sub> and μ<sub>2</sub>, and the newly discovered μ<sub>3</sub>. Another receptor of clinical importance is the opioid-receptor-like receptor 1 (ORL1), which is involved in pain responses as well as having a major role in the development of tolerance to μ-opioid agonists used as analgesics. These are all [[G-protein coupled receptor]]s acting on [[GABA]]ergic [[neurotransmission]].		Opioids bind to specific [[opioid receptor]]s in the [[nervous system]] and other tissues. There are three principal classes of opioid receptors, [[mu opioid receptor\|μ]], [[kappa opioid receptor\|κ]], [[delta opioid receptor\|δ]] (mu, kappa, and delta), although up to seventeen have been reported, and include the ε, ι, λ, and ζ (Epsilon, Iota, Lambda and Zeta) receptors. Conversely, σ ([[sigma receptor\|Sigma]]) receptors are no longer considered to be opioid receptors because: their activation is not reversed by the opioid inverse-agonist [[naloxone]], they do not exhibit high-affinity binding for classical opioids, and they are stereoselective for [[Dextrorotation\|dextro-rotatory]] [[isomers]] while the other opioid receptors are stereo-selective for [[Laevorotation\|laevo-rotatory]] isomers. In addition, there are three subtypes of [[mu opioid receptor\|μ]]-receptor: μ<sub>1</sub> and μ<sub>2</sub>, and the newly discovered μ<sub>3</sub>. Another receptor of clinical importance is the opioid-receptor-like receptor 1 (ORL1), which is involved in pain responses as well as having a major role in the development of tolerance to μ-opioid agonists used as analgesics. These are all [[G-protein coupled receptor]]s acting on [[GABA]]ergic [[neurotransmission]].

	~~[[Image:Morphine Numbered Position.svg\|right\|thumb\|275 px\|The numbered substitution positions of the morphine molecule]]~~

	The [[pharmacodynamic]] response to an opioid depends upon the receptor to which it binds, its affinity for that receptor, and whether the opioid is an [[agonist]] or an [[receptor antagonist\|antagonist]]. For example, the [[supraspinal (disambiguation)\|supraspinal]] analgesic properties of the opioid agonist [[morphine]] are mediated by activation of the μ<sub>1</sub> receptor; respiratory depression and [[Substance dependence\|physical dependence]] by the μ<sub>2</sub> receptor; and sedation and spinal analgesia by the κ receptor{{Citation needed\|date=March 2013}}. Each group of opioid receptors elicits a distinct set of neurological responses, with the receptor subtypes (such as μ<sub>1</sub> and μ<sub>2</sub> for example) providing even more [measurably] specific responses. Unique to each opioid is its distinct binding affinity to the various classes of opioid receptors (e.g. the μ, κ, and δ opioid receptors are activated at different magnitudes according to the specific receptor binding affinities of the opioid). For example, the opiate alkaloid [[morphine]] exhibits high-affinity binding to the μ-opioid receptor, while [[ketazocine]] exhibits high affinity to ĸ receptors. It is this combinatorial mechanism that allows for such a wide class of opioids and molecular designs to exist, each with its own unique effect profile. Their individual molecular structure is also responsible for their different duration of action, whereby metabolic breakdown (such as N-dealkylation) is responsible for opioid metabolism.		The [[pharmacodynamic]] response to an opioid depends upon the receptor to which it binds, its affinity for that receptor, and whether the opioid is an [[agonist]] or an [[receptor antagonist\|antagonist]]. For example, the [[supraspinal (disambiguation)\|supraspinal]] analgesic properties of the opioid agonist [[morphine]] are mediated by activation of the μ<sub>1</sub> receptor; respiratory depression and [[Substance dependence\|physical dependence]] by the μ<sub>2</sub> receptor; and sedation and spinal analgesia by the κ receptor{{Citation needed\|date=March 2013}}. Each group of opioid receptors elicits a distinct set of neurological responses, with the receptor subtypes (such as μ<sub>1</sub> and μ<sub>2</sub> for example) providing even more [measurably] specific responses. Unique to each opioid is its distinct binding affinity to the various classes of opioid receptors (e.g. the μ, κ, and δ opioid receptors are activated at different magnitudes according to the specific receptor binding affinities of the opioid). For example, the opiate alkaloid [[morphine]] exhibits high-affinity binding to the μ-opioid receptor, while [[ketazocine]] exhibits high affinity to ĸ receptors. It is this combinatorial mechanism that allows for such a wide class of opioids and molecular designs to exist, each with its own unique effect profile. Their individual molecular structure is also responsible for their different duration of action, whereby metabolic breakdown (such as N-dealkylation) is responsible for opioid metabolism.




			<references/>
	[[Category:Pharmacology]]		[[Category:Pharmacology]]

Bradley Monk: Created page with "{| class="wikitable" style = "float: right; margin-left:15px; text-align:center" |+Opioid comparison |- ! Drug ! Relative Potency{{cite book |first=Ronald D. |last=Mi..."

2013-08-26T02:05:17Z

Created page with "{| class="wikitable" style = "float: right; margin-left:15px; text-align:center" |+Opioid comparison |- ! Drug ! Relative Potency<ref>{{cite book |first=Ronald D. |last=Mi..."

New page

{| class="wikitable" style = "float: right; margin-left:15px; text-align:center"
|+[[Opioid comparison]]
|-
! Drug
! Relative Potency<ref>{{cite book |first=Ronald D. |last=Miller |title=Miller's Anesthesia |url=http://books.google.com/books?id=HPpgOjIGYtAC |year=2010 |publisher=Elsevier Health Sciences |isbn=978-0-443-06959-8 |edition=7th}}</ref>
! Nonionized Fraction
! Protein Binding
! Lipid Solubility<ref>{{cite book |first1=G. Edward |last1=Morgan |first2=Maged S. |last2=Mikhail |first3=Michael J. |last3=Murray |title=Clinical Anesthesiology |year=2006 |publisher=McGraw Hill |isbn=978-0-07-110515-6 |edition=4th}}</ref>
|-
| ''[[Morphine]]''
| ''1''
| ++
| ++
| ++
|-
| [[Meperidine]]
| 0.1
| +
| +++
| ++
|-
| [[Hydromorphone]]
| 10
|
|
|
|-
| [[Alfentanil]]
| 10–25
| ++++
| ++++
| +++
|-
| [[Fentanyl]]
| 75–125
| +
| +++
| ++++
|-
| [[Remifentanil]]
| 250
| +++
| +++
| ++
|-
| [[Sufentanil]]
| 500–1000
| ++
| ++++
| ++++
|-
| [[Etorphine]]
| 1000–3000
|
|
|
|}
Opioids bind to specific [[opioid receptor]]s in the [[nervous system]] and other tissues. There are three principal classes of opioid receptors, [[mu opioid receptor|μ]], [[kappa opioid receptor|κ]], [[delta opioid receptor|δ]] (mu, kappa, and delta), although up to seventeen have been reported, and include the ε, ι, λ, and ζ (Epsilon, Iota, Lambda and Zeta) receptors. Conversely, σ ([[sigma receptor|Sigma]]) receptors are no longer considered to be opioid receptors because: their activation is not reversed by the opioid inverse-agonist [[naloxone]], they do not exhibit high-affinity binding for classical opioids, and they are stereoselective for [[Dextrorotation|dextro-rotatory]] [[isomers]] while the other opioid receptors are stereo-selective for [[Laevorotation|laevo-rotatory]] isomers. In addition, there are three subtypes of [[mu opioid receptor|μ]]-receptor: μ1 and μ2, and the newly discovered μ3. Another receptor of clinical importance is the opioid-receptor-like receptor 1 (ORL1), which is involved in pain responses as well as having a major role in the development of tolerance to μ-opioid agonists used as analgesics. These are all [[G-protein coupled receptor]]s acting on [[GABA]]ergic [[neurotransmission]].

[[Image:Morphine Numbered Position.svg|right|thumb|275 px|The numbered substitution positions of the morphine molecule]]

The [[pharmacodynamic]] response to an opioid depends upon the receptor to which it binds, its affinity for that receptor, and whether the opioid is an [[agonist]] or an [[receptor antagonist|antagonist]]. For example, the [[supraspinal (disambiguation)|supraspinal]] analgesic properties of the opioid agonist [[morphine]] are mediated by activation of the μ1 receptor; respiratory depression and [[Substance dependence|physical dependence]] by the μ2 receptor; and sedation and spinal analgesia by the κ receptor{{Citation needed|date=March 2013}}. Each group of opioid receptors elicits a distinct set of neurological responses, with the receptor subtypes (such as μ1 and μ2 for example) providing even more [measurably] specific responses. Unique to each opioid is its distinct binding affinity to the various classes of opioid receptors (e.g. the μ, κ, and δ opioid receptors are activated at different magnitudes according to the specific receptor binding affinities of the opioid). For example, the opiate alkaloid [[morphine]] exhibits high-affinity binding to the μ-opioid receptor, while [[ketazocine]] exhibits high affinity to ĸ receptors. It is this combinatorial mechanism that allows for such a wide class of opioids and molecular designs to exist, each with its own unique effect profile. Their individual molecular structure is also responsible for their different duration of action, whereby metabolic breakdown (such as N-dealkylation) is responsible for opioid metabolism.

[[Category:Pharmacology]]

Opioid - Revision history

Bradley Monk at 02:06, 26 August 2013

Bradley Monk: Created page with "{| class="wikitable" style = "float: right; margin-left:15px; text-align:center" |+Opioid comparison |- ! Drug ! Relative Potency{{cite book |first=Ronald D. |last=Mi..."