Pain and opioids

โดย ผศ.พญ.พนารัตน รัตนสุวรรณ ยิ้มแยม

วัตถุประสงค

เขาใจถึงประโยชน และโทษของความปวดเขาใจกระบวนการที่ทําใหเกิดความปวด (pain pathway)สามารถใหการประเมินความปวด (pain assessment) และติดตามผลการรักษาความปวดของผูปวยไดเขาใจเภสัชวิทยาของยาระงับปวด (analgesic drugs)

Pain

An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in term of such damage

IASP : subcommitee & taxonomy 1979

What will happen if we haven’t pain sensation?

Advantage of pain

Defense mechanism.We will die.

What will happen if we left our patient pain?

Disadvantage of pain

Effect to every systemRespiratory system Cardiovascular systemNeuroendocrine system Gastrointestinal systemMusculoskeletal systemPsychological

Respiratory system

Operation or injury to chest or abdomen can exaggerate p/o pulmonary dysfunctionSplint of muscle diaphragm and chest wallDecrease lung volume, atelectasis, decrease cough, sputum retention, infection and hypoxemia

Cardiovascular system

Severe pain increase sympathetic nervous systemTachycardiaHypertensionIncrease peripheral vascular resistanceIncrease myocardial oxygen consumptionMyocardial ischemia

Cardiovascular system

Direct blood away from viscera to heart & brainImpair wound healingReduce patient mobility and promote venous stasis

Neuroendocrine

Pain activate stress responseHyperglycemiaImpair wound healing and immune functionSodium & water retention

Gastrointestinal system

Delay gastric emptyingReduction in gut motility

musculoskeletal

Muscle spasmImmobilityIncrease risk of deep vein thrombosis

psychological

AnxietyFearsleeplessness

Pain pathway

Termination Areas in Spinal Cord

III

IIIIV

V

VI

VII

Spinal cordlaminae

A-δ fibresnociceptormechanoreceptor

C-fibresnociceptorthermoreceptormechanoreceptor

Ascending Pain Pathways

Spinalcord

Medullaoblongata

Mesencephalon

Thalamus

Cortex

Pons

Pain assessment

How to assessment pain?

Visual analog scaleVerbal numeric rating scaleCategorical scaleFace scale

Visual analog scale

No pain Worst painfront

1 105432 6 7 8 9

back

Verbal numeric rating scale

0 is no pain10 is worst pain

0 10

Categorical scale

ไมปวด no painปวดนอย mildปวดปานกลาง moderateปวดมาก severe

Face scale

Pain score in practical use

At restActivityAssess as an interval

Pain score > 3

Patients should be treated and follow the effect of medicine.

Analgesic drugs

Analgesic drugs

OpioidNSAIDsAcetaminophenLocal anesthetic drug

opioid

Opium is obtained from the unripe seed capsule of poppy.It has been use for Tx pain for 2000 years ago.Opium contains 25 different alkaloids. Only 2 have analgesic action (morphine,codeine)Morpheus: Greek god of dream and son of hypnos,god of sleep

Classification of opioidBinding to opioid receptors located in the brain & spinal cord.

Opioid receptors

Receptor Action Mu µ Analgesia,euphoria, RS depression,

bradycardia,pruritus, miosis, N/V, inhibit gut motility

Kappa κ Analgesia ,sedation, miosis

Delta δ analgesia

Sigma σ Psychomimetic dysphoria, hallucination,

Opioid drug are classified as:

AgonistPartial agonistAgonist-antagonistAntagonist

Agonist

Drug that bind to and stimulate opioidreceptors and are capable of producing a maximal response from the receptor

, pethidine, codeine, fentanyl, methadone, oxycodone, heroin, hydromorphone

Morphine

Practical point

Useful for patient with severe painNo limit in mg/kgWe can tritrate drug as much as pain is reduce.

painanalgesia

sedation

RS depression

Partial agonist

Drug that stimulate opioid receptors but have a ceiling effectCeiling effect produce a submaximalresponse compare with an agonist

buprenorphine

Partial agonist

Submaximal

Agonist-antagonist

Drug that are agonist at one opioidreceptor type and antagonost at anotherAnalgesic action from κ receptor while acting as antagonist at µ receptorCan precipitate withdrawal sign & symptom in opioid dependent patients.

Pentazocine, nubain (nulbuphine)

Practical point

Partial agonist and agonist-antagonist should be used in mild to moderate pain.Ceiling effect

antagonist

Drug that bind to but do not stimulate opioid receptors and may reverse the effect of opioid agonist

naloxone

morphine

Morphine remains the standard.None is clinically superior in relieving painMetabolize in liver:

1. M-3-G : no analgesic action2. M-6-G: twice as potent as morphineexcreted via kidney ** renal impairment will

built up this metabolite.Histamine release

Meperidine ( pethidine)

First synthesized just prior world war IIAtropine like action: slight tachycardia, dry mouthInteraction with monoamine oxidase inhibitors: hyperpyrexia, convulsion, coma,hypertensionMetabolized in liver and excreted via kidneyNorpethidine: central nervous system excitationTreat shivering associated with volatile anesthetic agents, epidural/spinal anesthesia

Fentanyl

More rapid onset & short duration (30-45 min)Metabolize are inactiveNo histamine release100 times Potent than morphine1-2 ug/kg iv

Codeine

Natural alkaloidMetabolized in liver and 5-10% converted to morphine Treat mild to moderate painMostly combine to paracetamol (TWC)

Naloxone

Dilute to 10 ccTritrate Inj 1ml and repeat every few minute to reverse RS depression and excessive sedation RR < 8 /minLarger dose : withdrawal symptoms: hypertension ,tachycardia , N/V, pain, pulmonary edema, arrhythmia.

Tramadol

Opioid and non-opioid analgesic

Weak mu opioid agonist

Non opioid spinal and CNS effects via

norepinephric and serotoninergic mech.

(inhibit reuptake of NE)

Tramadol

Advantages: minimal sedation, respiratory depression, GI stasis, abuse potentialDisadvantages: cost, dizziness, nausea, dry mouth, sweating, sedationRoutes: parenteral, oralDose: 1-2 mg/kg, every 4-6 hrs

Practical point for opioid use

Acute pain:Right opioidRight doseRight interval Right route

AIMAIM

MEACMEAC

PainPain

AnalgesiaAnalgesia

SedationSedation

Time

Drug concentration

Appropriate blood levelAppropriate blood levelAnalgesic corridorAnalgesic corridor

MEAC = Minimum Effective Analgesic ConcentrationMEAC = Minimum Effective Analgesic Concentration

Side effect of opioid

Side effect to CNS

Nausea / vomitingStimulation of chemoreceptor trigger zone in

medulla and enhance by vestibular stimulationMiosis, sedation, euphoria, RS depressionConfusion (uncommon)Pruritus ( central activation from mu)ConstipationIncrease biliary tract pressure & spasm of the sphincter of OddiUrinary retention (esp; spinal/epidural opioid)

Tolerance, dependence,& addiction

Fear of addiction to opioid given to under treatmentIncidence 0.03% :no prior hx of substance abuse.Addiction must be distinguished from tolerance and physical dependence.

Physical dependence

Show signs & symptoms of withdrawal if drug is antagonized or suddenly stopped or markedly reduce dose.High dose opioid 7-10 days.Tapered dose reductions of 20-25%.Withdrawal: yawning, sweating, lacrimation, rhinorrhea, anxiety, piloerection, chill, ab.cramping, hypertension, N/V

Addiction

Psychological dependenceDrug seeking behavior

Tolerance

Progressive larger dose to obtain the same analgesic effectTolerance to RS depression also develops

Conclusion

เขาใจถึงประโยชน และโทษของความปวด เขาใจกระบวนการที่ทําใหเกิดความปวด (pain pathway)

สามารถใหการประเมินความปวด (pain assessment) และติดตามผลการรักษาความปวดของผูปวยได

เขาใจเภสัชวิทยาของยาระงับปวด (analgesic drugs)

Under-treating pain is no longer acceptable!!!

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