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OPIOID

O BJECTIVES
THE ROLE OF OPIOID IN PAIN

MANAGEMENT
PHARMACODYNAMIC OF OPIOIDS
PHARMACOKINETIC OF OPIOIDS
CLINICAL APLICATION OF OPIOIDS

Introduction
Opioid most commonly used analgesic in

clinical practice
Effectiveness
Easy availability
Low cost

Opium ( juice ) papaver somniferum

contains 20 distinct alkaloids


Morphine , first isolated in 1803
Opioid : all substances, natural and
synthetic that have morphine like
properties

W H O AN ALG ESIC LAD D E

1.
2.
3.
4.
5.

By the mouth
By the clock
By the ladder
Individualized for the patient
Attention to detail

Analgesic Ladder ofW FSA


Pain
Intensity

Opiate
And
NSAID
and
Paracetamol

Oral route available


give orally
Oral route unavailable
Rectal paracetamol & NSAID,
Opiate: IV, PCA, IM algorithm,
Epidural infusion analgesia

NSAID
and
Paracetamol

Pain
decreases
as time
passes

Paracetamol

D octors problem

OPIOPHOBIA
Limited information about OPIOID

drug available
Drugs doses and interval
Regular assessment
Common mis-interpretations about
opioid

M YTH S O F U SE O P IO ID !!!!!!!
HEAVY
SEDATION

ADDICTION &
DEPENDENCE

PARENTERAL
MORE EFFECTIVE

AS NEEDED
BASIS

ADEQUATE
PAIN CONTROL

TOLERANCE

DOSE INCREMENT IS
CONSERVATIVE

MYTH
S

NARCOTIC
NARCOTIC IN
IN OLDER
OLDER
BE
BE AVOIDED
AVOIDED

OPIOID EFFECTIVE
FOR ALL

PAIN CANNOT
BE RELIEVED

W e are a D O CTO R
LO G IC A L A PP R O A CH TO PA IN
C O N TR O L

Perception

A n alg esia M ech an ism

Pain

Descending
modulation
Ascending
input

Spinothalami
c
tract

Modulation
Dorsal
Horn

Dorsal root
ganglion

Transmission

Transduction
Peripheral
nerve

Peripheral
nociceptors
Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.

O pioid Receptors in m odulation

(Casy AF, Parfitt RT. Opioid Analgesic Chemistry and receptors. New York; Plenum Press;1996)

O pioid Receptor
MOR or OP3 ( opioid receptor )
Cortex, amygdala,hippocampus,thalamus,

mesenchepalon, pons, medulla and spinal cord

KOR or OP2 ( opioid receptor )


Similar distributed but also in hypothalamus

DOR or OP1 ( opioid receptor )


Not widely distributed
Telencephalon and spinal cord

ORs also identified in peripheral administration


OP4/ ORL-1 : Nociceptin / Orphanin-FQ

M echanism Action ofO pioids


Binding to specific membrane receptor ( ORs )

Pharmacology effect as analgesia


Endogenous opioid peptide ( EOPs ) endorphins,

dynorphins, enkhepalins, binding also to ORs


Endogenous Opioid System (EOS) modulate
nociceptive transmission
Central and Peripheral NS, CV, GI and Immune
Cell.

O pioid M echanism s of Action


Primary
afferent

Presynaptic
terminal

Postsynaptic
neuron
Spinal paintransmission
neuron
Basic and Clinical Pharmacology. 8th ed. 2001.

, , receptors
gCa++
Transmitter release

receptors
gK+

O pioid m echanism s
Descending
controls

To the bra
C-fibre

Glutamate

Substance P
etc

Spinal cord neurone

O pioid m echanism s
Descending
controls

To the bra
C-fibre

Substance P
etc

Glutamate

Opioid

Spinal cord neurone

O pioid analgesics
If pain is not adequately controlled with
NSAID or is expected to be moderate to
severe,
an appropriate opioid should be
added to the NSAID
Patients with absolute or strong
relative contraindications to NSAIDs
an opioid for mild to moderate pain
should be considered.

H ow to give O PIO ID ?
Routes of administration
Intravenous
Intramuscular
Oral
Transdermal
Subcutaneous
Spinal route : Epidural and Intratechal
Buccal
Intranasal
Rectal

O pioid drugs

O pioid in Indonesia
Morphine considered to be the standard opioid

analgesic, oral sustained release and IV prep. available


Fentanyl fast onset, more potent than morphine,
less side effect, transdermal sustained and IV
prep. available
Meperidine is not considered a first-line opioid
analgesic medication, just IV preparation available
Codein, a weak opioid, is pro-drug of morphine, just
oral
Tramadol, a weak opioid that acts on mu-receptors, is
another reasonable alternative, oral and IV preparations

M orphine
Least lipid soluble
Metabolites M6G and M3G ( longer half

lifes )
M6G more potent than morphine
M3G ( no analgesic effect ) role in
tolerance
Slow release ( controlled release or
sustained release ) use for chronic and
cancer pain
Slow onset, prolonged duration fast
titration its impossible

Fentanyl
Highly lipid soluble synthetic opioid
Rapid onset and short duration
Metabolite inactive ( safe for renal

impairment )
Available in IV preparation for rapid
onset and Transdermal preparation as
sustained release
( slow onset
and long duration )

Pethidine
Synthetized as a potential substitute for atropine

( atropine like effect )


Weak affinity for NMDA receptor
Pethidine superior in renal and biliary colic but
evidenced show that all opioids are equally
effective
Metabolite is norphetidine ( normeperidine ) with
long half-life ( 15-20 hrs ) analgesia (
receptors ) but neurotoxicity ( CNS excitation :
anxiety, mood changes, tremors, twitching,
myoclonic , convulsion )
Available in IV preparation

Codeine
Naturally alkaloid like morphine
Metabolized in liver by CYP 2D6

converted to morphine (2-10%)


analgesic effect of Codeine
( ineffective prodrug of morphine )
Usually for mild to moderate pain
Adverse effect more pronounced

Tram adol
Centrally acting synthetic analgesia
Mechanism :
receptors activity
Inhibit reuptake NE and serotonine (5HT )
Act as NMDA antagonist

Considered to have a lower risk of addiction and safety

profile when compared to other opioids


Available in IV preparation and Oral ( single and combined )
Advantages of equianalgesic dose opioid
Less sedation
Less repiratory depression
Less constipation
Nausea and vomiting similar
Not a controlled drug

SEROTONIN
NEOREPINEPHRINE

Thinks w hen prescribing O pioids


Think about the issue of efficacy
Neuropathic / nociceptive / unknown (use
cautiously)
Think about how to initiating therapy
Think about side effects
Think about the issue of tolerance and
addiction
Think about increase in function ( for
chronic pain )

O pioid principles ofusing


Opioid titration
Opioid rescue dose
Opioid rotation
Opioid side-effect management
Opioid sparing strategies

O pioid Titration G uidelines


Titrate with shortacting hydrophilic

opioid;
can be given at interval
based on the time to peak serum
level as needed;
oral ~ 1 hour , sc ~ 30 min, iv ~ 10
min.
Calculate 24 hrs requirements and
convert to long-acting opioid

O pioid D ose Escalation


Always increase by a percentage of the
present dose based upon patients pain rating
and current assessment
50-100% increase
25-50% increase
Moderate pain
4-6/10
Mild pain
1-3/10

Severe pain
7-10/10

O pioid Rescue D ose


Used for breakthrough pain.
Dose:
Approximately 10% of daily dose

equivalent.

Frequency :
Oral
every 1 - 2 hours
Parenteral every 15 - 30 minutes

O pioid Rotation
Equianalgesic doses Opioids
Oral dose
( mg )

Opioid

Parenteral
iv/sc/im
( mg )
150
Meperidine
50
150
Tramadol
100
150
Codeine
50
15
Morphine
5
Fentanyl
0.050
Morphine 50 mg PO in 24 hrs = Fentanyl
patch 25 mcg/hr

O pioid-induced adverse eff


ect
Respiratory depression
Pruritus
Gastrointestinal effect
Urinary effects
Nausea and Vomiting

Develop
tolerance
Prophylaxis

O pioid-sparing strategies
Analgesic adjuvants
e.g. Antiemetics, Laxatives, Antidepressant,
Anticonvulsant, Corticosteroid, Anxiolytics,
NMDA antagonist
Alternate route (e.g. intraspinal)
Anaesthetic/Neurolytic procedures
PM&R approaches
Cognitive therapy
Complementary therapies

e.g., acupuncture, massage, music therapy

Tolerance
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

Dependence
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

Addiction
Addiction is a psychological / behavioural
syndrome characterized by loss of control
and the compulsive use of a substance
despite harm.

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CO N CLU SSIO N
Opioid still a main analgesic to manage pain
The prescriber of an opioid agent should

have current opioid pharmacotherapy


knowledge, judgment, and wisdom to use
opioid
One of strategies to give good analgesia
and low side effect is a Combination of
opioid with non-opioid
We are not an Opiophobia Doctor !!!

Thank
you