Opioid Analgesia Siba21.9.07

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 the resinous 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 two ways, • • •

First- A sharp pain for a brief period, sensed with in 0.1 ms of damage called FAST/FIRST PAIN

Second- A prolonged dull pain, sensed 1 or more seconds after 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 noxious stimulus. • 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 Prostaglandins Substance 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 pain minimum 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 Allmost all kind of stimuli

Mechanical & thermal stimuli

Neo ST tract

Glutamate

Substance P

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 are stimulated at same time then the 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 the accupressure therapy

Modified gate theory • There are descending fiber parallay along with the ascending fibers . • These provide inter neurons which blocks the pain sensation to go above.

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

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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-morphene codeine 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