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. By the mouth
2. By the clock
3. By the ladder
4. Individualized for the patient
5. Attention to detail
 Analgesic Ladder ofW FSA

Opiate Oral route available

And give orally
Pain Oral route unavailable
NSAID
Intensity and
Rectal paracetamol & NSAID,
Opiate: IV, PCA, IM algorithm,
Paracetamol Epidural infusion analgesia

NSAID
and
Paracetamol

Pain
decreases Paracetamol
as time
passes
 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 !!!!!!!
ADDICTION &
HEAVY DEPENDENCE
TOLERANCE
SEDATION

PARENTERAL DOSE INCREMENT IS

MORE EFFECTIVE CONSERVATIVE

MYTH
AS NEEDED S NARCOTIC
NARCOTIC IN
IN OLDER
OLDER

BASIS BE
BE AVOIDED
AVOIDED

ADEQUATE PAIN CANNOT

PAIN CONTROL BE RELIEVED
OPIOID EFFECTIVE
FOR ALL
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

Modulation
Descending
modulation Dorsal
Horn
Ascending
input
Dorsal root
ganglion
Transmission

Transduction
Spinothalami
Peripheral
c
nerve
tract

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

{
, , receptors
Presynaptic gCa++
terminal Transmitter release

Postsynaptic
neuron { receptors
gK+

Spinal pain-
transmission
neuron
Basic and Clinical Pharmacology. 8th ed. 2001.
 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
Glutamate

Substance P
etc 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 Severe pain

7-10/10
Moderate pain
4-6/10

Mild pain
1-3/10
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 Opioid Parenteral
( mg ) 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.

36
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