Professional Documents
Culture Documents
Takdir Musba
Department of Anesthesiology,
Intensive Care and Pain Management
Faculty of Medicine , Hasanuddin University
Perception
PAIN PATHWAY
Pain
Modulation
Descending
modulation Dorsal Horn
Ascending
input
Dorsal root
ganglion
Transmission
Transduction
Spinothalamic
Peripheral
tract
nerve
Trauma
Peripheral
nociceptors
Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.
PIB FK UNHAS Makassar, 28 januari 2011
Introduction
Opioid most commonly used analgesic in clinical
practice
Easy availability
Low cost
Effectiveness
Opium ( juice ) papaver somniferum contains 20
distinct alkaloids
Morphine , first isolated in 1803
Opioid : all substances, natural and synthetic that have
morphine – like properties
Doctor’s problem
Opiophobia
Common mis-perception about opioid
PK/Pd of Drugs
Regular assessment
Choice of Analgesic Technique
(Analgesic Ladder of WFSA)
NSAID
and
Paracetamol
Pain Paracetamol
decreases as
time passes
WHO Analgesic
LADDER
OPIOID ORAL
AVAILABLE IN INDONESIA
“ LOGICAL APPROACH TO PAIN CONTROL “
To the bra
C-fibre
Glutamate
Substance P
etc
To the bra
C-fibre
Glutamate
Substance P
etc Opioid
, d, k receptors
Presynaptic
terminal { gCa++
Transmitter release
receptors
Postsynaptic
neuron { gK+
Spinal pain-
transmission
neuron
Basic and Clinical Pharmacology. 8th ed. 2001.
Endogenous opioid
Activation of the Different ORs
Receptor Type Effect
μ ( MOR ) Supraspinal , spinal and peripheral analgesia
Respiratory depression
Gastrointestinal : ileus, constipation, nause, emesis
Pruritus, urinary retention
Cardiovascular depression
Tolerance / dependence
Sedation , euphoria
Miosis
Κ ( KOR ) Spinal analgesia
Dysphoria
Sedation
Diuretion
δ ( DOR ) MOR receptor modulation
Spinal / Supraspinal analgesia
Intrinsic activity
Agonist : drug bind to and stimulate OR, capable produce
max response from receptor ( intrinsic activity 1 )
Antagonist : drug bind to but do not stimulate OR and may
reverse effect of opioid agonist ( intrinsic activity 0 )
Partial agonist : drug bind and stimulate OR but have a
ceiling effect. Produce submaximal response compared
with an agonist ( intrinsic activity > 0 and < 1 )
Agonis-antagonist : drugs that agonist at one OR and
antagonist at another
Intrinsic Activity Opioid Drugs
Agonist Morphine
Fentanyl
Alfentanyl
Sufentanyl
Pethidine
Oxycodone
Diamorphine
Remifentanyl
Agonist-antagonist Butorphanol
Pentazocine
Antagonist Naloxone
Naltrexate
Pharmacokinetics
Absorption, distribution, metabolism and excretion
Older patiens :
lower clearance
Reduced VD
Sex
More effective analgesia in males
Onset and offset analgesic effect later in female
100 Hydromorphone
Methadone
Meperidine
Percent of peak effect
80 Morphine
site concentration
Sufentanil
60
Fentanyl
40
Alfentanil
20
Remifentanil
0
0 5 10 15 20
Minutes since bolus injection
Opioid-induced adverse effect
Respiratory depression
Pruritus
Gastrointestinal effect
Urinary effects
Nausea and Vomiting
Respiratory depression
Less than 0.1 %
Activation of MORs
Decrease MV : RR and TV
Decrease responsiveness of respiratory center in CO2
Decrease RR to late for RD sign
Nociceptive input Vs respiratory depression
R/ naloxone iv 100 – 400 µg titration and maybe
continuous 2 – 5 µg/kg/hr
Pruritus
Histamine release due to iv administration Morphine
and Fentanyl
Neuraxial opioid – induced pruritus
R/ antihistamine, 5-HT receptor antagonist, opioid
antagonist, propofol, NSAIDs, droperidol
R/ ondansentron iv 2 – 4 mg
Gastrointestinal
Delay gastric emptying, increase small and large bowel
transit times, inhibit fluid secretion and permeability
Oral, parenteral, also neuraxial delivery
MORs located in gut and CNS
Side effect – dose related
Partially reversed with naltrexon
• Opioid rotation
Opioid rotation
When changing from one opioid to another :
“ incomplete cross opioid tolerance “
Start with 50 – 75% of the calculated equianalgesic dose
Use more, if pain uncontrolled
Use less, if adverse effect are present
Tolerance
Definition: A change in the dose-response relationship
induced by exposure to the drug and manifest as a need for
a higher dose to maintain an effect.
Develops at different rates to these varying effects:
respiratory depression, somnolence, nausea >> analgesia >
constipation.
Analgesic tolerance is rarely a problem.
Opioid doses remain relatively stable in the absence of worsening
pathology and increased opioid requirements after stable periods is
often a signal of disease progression.
Dependence
Definition: The development of a withdrawal syndrome
following dose reduction or administration of an
antagonist.
• Often develops after only a few days of opioid therapy.
• Not a clinical problem if drug is tapered before
discontinuation.
• Taper by no more than 50% of the dose/day
THANKS FOR YOUR ATTENTION
ALWAYS TRY ……
TO BE A GOOD DOCTOR