Opioid Analgesia Siba21.9.07

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07/22/09



Opioid analgesia

Presented by– Dr. Sibadatta das

Guided by-- Dr. Neena Mishra



Introduction

• Algesia (Pain)– An unpleasant sensory & emotional

experience which is associated with actual or potential tissue

damage.

• According to Sherrington “ it is a psychical adjunct of an

imperative protective reflex”

• Analgesia –reduced or absence of sense of algesia.

• Opioid – Derived from the word “opus” means “Juice”

• these are synthetic alkaloids derived from theresinous product of puppy seeds of plant Papaver

Somniferous.



Pain

• Pain – Derived from the word poena meaning penalty/punishment

• After any kind of tissue damage pain sensation occurs in twoways,

• First- A sharp pain for a brief period, sensed with in 0.1 msof damage called

• FAST/FIRST PAIN

• Second- A prolonged dull pain, sensed 1 or more secondsafter the infliction of damage, called

• SLOW/SECOND PAIN



Pathwaay

• Consists of ,

• Receptor

• Afferent fbers• Central intigrating system



Receptors

• Though the pathway of both the pain are completely different but receptors for both are same.

• Receptors –> Nocciceptors as these are stimulated by noxiousstimulus.

• These are nothing but free nerve endings.• Usually found in skin(Papilary dermis) , also in

• periosteum, arterial wall, parietal parenchyma etc.

• Most of the visceral tissue parenchyma lacks these receptors.

• Typical feature is NON ADAPTING

• Functionally 4 types:

• a) unimodal b) polymodal c) silent



Unimodal

• Stimulated by single type of stimulus

• Exp:- CHEMICAL

Bradykinin

histamin

Ach

K+

proteolytic enzymes

Substances that sensitizes the receptors to the pain sensation

ProstaglandinsSubstance P

These receptors mostly carries SLOW type of pain hence found in C fibers



• Mecanical:- action like strucking or stabbing causes

deformation of the nocciceptors & its stimulation.

• Thermal :- inrease in temperature causes painminimum temp. required is 450c



polymodal

• Stimulated by various kind of stimuli

• Exp :- VR1-chemicals like capsaicin

temp. >430c

protons

• VRL1- temp. >500c



Silent receptors

• These are activaed only during inflamation

• 40 % of Aδ & 30 % of C fibers are of this kind of fibers







Afferent fibers

Mechanical &

thermal stimuli

Allmost all

kind of stimuli

Substance P

Glutamate

Neo ST tract

Paleo ST tract





Perception of pain

• Perception of pain has both the component

• Cortical &

• subcortical

• Subcortical – for crude perception of pain• Cortical – for localization, & meaningful interpretation of pain



Analgesia

• The reduced or absence of perception of pain.

• The disruption of the path at any point may cause this.

• It may be at spinal cord level --- SPINALCOMPONENT

• Or, above this level --- SUPRASPINAL COMPONENT• Or , --- BOTH.

• To explain the above phenomenon three theories are proposed,

• 1. Gate theory

• 2. modified gate theory

• 3. Opioid systm



GATE THEORY

• Given by Melzack(1986)

• If two afferent fibers arestimulated at same time thenthe larger fiber get priority

than the smaller fiber.• exp:- if Aδ fiber is

stimulated with Aβ fiber (Touch sensation)

then Aβ gets the priority than Aδ.

This is the basis of theaccupressure therapy



• There are descending fiber

parallay along with the

ascending fibers .

• These provide inter neurons

which blocks the pain

sensation to go above.

Modified gate theory



ENDOGENOUS OPIOID SYSTEM

• The opioids are the alkaloid derivative of puppy plant papaver

somniferous , also secreted inside the body endogenously.

• They act over specific receptor and alters the perception of

pain sensation., causing analgesia.

• They are also secreted endogenously



Endogenous opioids• There are mainly 3 opioids found

endogenously



Receptors

• These receptors are formed in dorsal root ganglion of sensory

nerves and travel in both direction peripherally to the receptor

site or rostrally to the brain side.

• Hence these are found in a wide spreaded area from top to

bottom of the path way.

• Mainly 3 receptors are found,

• μ, κ , δ,

• All are G-protein coupled serpentine receptors.



μ, receptors

• The most important receptor.

• Found mainly in PAG mater, NA, NTS, Area

prostrema.

• Selective agonist— Endomorphin 1 & 2

• Selective antagonist– B Funaltrixamine.

• Again of 2 types,

• μ1 -- mediates mainly supraspinal analgesia

• μ 2 -- mediates mainly spinal analgesia , respiratory

depression, & constipation



K receptor

• Found in same position as μ receptor .

• Selective agonist– Dynorphin A

ketocyclazocine

• Selective antagonist– Norbinaltrophimine

• Mainly 2 types,

• K1—mediates spinal anlgesia• K3– mediates supraspinal analgesia but

insignificant



δ receptor

• Mostly found in limbic system , myenteric plexus.

• Selective agonist – Leu/Met enkephalins

• Selective antagonist – Naltrindol

• Analgesia is mostly supraspinal



e



Clinical significance

• Now achieving analgesia through opioids are most commonly

used method in clinical science

• Opioids are two types

natural

sythetic



Natural opioids

• First derived by SURTENER a pharmacist in 1806

• Mainly of 2 types

• PHENANTHRENE DERIVATIVE--

morphenecodeine

thebaine

BENZOISOQUINOLENE DERIVATIV

Papaverine

Noscapeine



• Undergo high fast pass metabolism hence oral dose is not

reliable

• Undergo enterohepatic circulation

•Can cross placenta & blood brain barrier

• Distribution in body is wide



Synthetic opioids

• Agonist – antagonist:-

• Nalorphene

• Pentazocine, Nalbuphine, Butorphanol

• Partial agonist• Buprenorphene

• Antagonist

• Naloxone, Naltrexone, Nalmefene



Other effects than analgesia

• Depression of RAS sedation

• Calming effect on mood

• Respiratory center depression

• Cough center depression• Bronchoconstriction in lungs

• Urinary retaintion

• Billiary colic by sphincter of odi spasm

• Constipation in GIT

• Stimulates CTZ to cause emesis

• Acts as proconvulsant by inhibiting GABAchannels.



REFERENCES

• Review physiology –Ganong 22nd

• Text book of physiology --- Indu khurana 1st

• Applied physiology –samson wright 13th

• Principles of internal medicine – Harison 17th

• Essentials of pharmacology---K.D Tripathy 5th

• Pharmacological basis of theraputics– Goodman & Gilman 11th

• Basis of clinical pharmacology– Katjung 9th

• Text book of physiology--- Guyton & Hall 11th

• www.wikipedia.com

• www.emedicine.com

http://www.wikipedia.com/

http://www.emedicine.com/

http://www.emedicine.com/

http://www.wikipedia.com/



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Opioid Analgesia Siba21.9.07