Pain is physiological antagonist of CNS depressan effects Opioid need to be titrated : Opioid responsive pain (Pain sensitive opioid) Combined analgesic therapy ie after start with Mo and then adding nerve block,Mo dose should reduced Opioid respiratory depression may occur if used for indication other than analgesia Opioid are mainly effective against steady, dull pain less effective against pain on moving and coughing

1. Choice of Systemic Opioid in Perioperative Analgesia
N.Margarita Rehatta
Faculty of Medicine Airlangga University
Dr Sutomo Hospital

2. • Pain Pharmacotherapy
certain medication – most effective for
certain mechanism of pain
+ consideration factors ie
- efficacy, safety, tolerability
- disease modification
- cost

3. • For the purposes of selecting treatment
useful classification of basic mechanism
- nociceptive,inflammatory,neurophatic.
Pain – produced by one or more mechanism
- skin incisisionn : nociceptive
- amputation of limb : nociceptive+ neurophatic
- acute spine injury : nociceptive + inflammatory
+neurophatic

4. Pain Intensity Nociceptive Inflammatory Neurophatic
Mild NSAID NSAID Lowdose
Neuromodulating
Moderate NSAID-Opioid
combination
NSAID – Opioid
Combination
High dose
neuromodulating
Severe, Opiod, NMDA
inhibitor
Antiinflammatory
agents +dis
modifying
Multidrug
(Anticonvulsan,anti
depressan,opioid)
Tramadol
Analgesic based on Pain Mechanism
Tramadol less effect on gastrointestinal motorfunction,
significant lower resp depression
similar nausea and vomiting

5. Low-tech Intermittent opioid bolus injection
High-tech
Pain
intensity
Oral / IV NSAID
Oral paracetamol +
NSAID
Time
pain decreases or goes away
ACUTE PAIN

6. • Opioid
- Allfull agonist opioid in equianalgesic doses
produces the same analgesic effect
- Equianalgesic doses difficult to determine
interindividual variabilities in kinetics and
dynamics--- need to be titrated
adult patient : better predictor – is age
(Mintyre,Javis 1996,Gammaitni etal,2003)
* genetic,chronopharmacology issues
Acute pain: one opioid not superior over others but better but
better in some patient (level II)

7. Intensity of clinical effect
determined by
1. Access of opioid to the receptor
(distribution)
2. The “fit” of the opioid onto
the receptor (the binding affinity)

8. Intensity of biologic
response
(Analgesia, respirator
depresion etc)
Receptor binding & respons
Exogenus administrered opioids procedure analgesia by mimicking the action
of opioid peptides in specific receptors within CNS

9. Pharmacokinetic- Pharmacodynamic common opioid
Generic
name
Route Equianalgesic
dose(mg)
Peak
(hr)
Duration
(hr)
Half
life(hr)
Comments Precautions
Naturally
Agonists
Morphine im 10-15 0.5-1 3-5 2-3.5 Gold
Standar
ICPBronchial
asthma,increa
sed ICP
Synthetic
Agonist
Pethidine im 75-100 0.5-1 2-3 10%potent
as Mo
Accumulated
metabolites
CI in MOA tx
Fentanyl iv 0.1 0.75-1 1.7min Potent,cont
infusion
Accumulation
,prolonged
effect
Alfentanyl iv 0.5-1 0.5 1.4min id
Remifenanyl : iv, rapid metabolism, by unspecified esterase blood and t issue ,-half life 3-4min

10. Opioid
Morphine : Active Metabolite morphine 6 gluroronic
Pethidine : Metabolite accumulate - convulsion, CNS irritation
Anticholnergic effect
Better than other opioid for colick pain
Fentanyl : Lipid soluble, high hepatic clearance
Transdermal should not used in acute pain
(delayed onset)
Tramadol : Atypical opioid
centrally acting-analgesic efficacy & potency
comparable to pethidine
Not associated with respiratory depression sedation
No physical dependence and tolerance in
long term use
Oral :
- Codein (less effective for post of pain)
- Hydromorphine (6x more potent than Mo)
- Methadone (long onset, steady state)

11. Pain and sensitivity to opiod
- Opiod Insensitivity pain
- Opioid partially sensitive pain
- Opiod sensitive pain (start with test dose in blocks)
- Opioid sensitive but inappropriate

12. Drug Delivery Systems
Direct (to neuraxis)
Epidural
Subarachnoid
Intraventricular
Indirect (via blood-borne carriage)
Via sustemic absorption
Oral
Sublingual
rectal
Inhalational
Via depot formation
Transcutaneous
Intramuscular
Subcutaneous
Direct instillation
Intravenous

13. Clinical Issue
• Intratheca l Mo + GA in Cardiac Surgery (preventive
analgesia)
• Intraoperative Epidural Mo for Spinal Surgery
• (Newer)Ajuvant Analgesic:
ketamin,gabapentin,pregabalin,dexmetomidine
• Fentanyl patch for acute pain ( iontophoretic PC
transdermal)
• PCA regional

14. Pain is physiological antagonist of CNS depressan
effects
Opioid need to be titrated :
Opioid responsive pain (Pain sensitive opioid)
Combined analgesic therapy
ie after start with Mo and then adding
nerve block,Mo dose should reduced
Opioid respiratory depression may occur if used for
indication other than analgesia
Opioid are mainly effective against steady, dull pain
less effective against pain on moving and coughing
*
*
*
Opioid Issues

15. Important consideration in emergency conIditionImportant consideration in emergency conIdition
Physiologic Derangement
Respiratory problem
(Trauma thorax, CNS, Pulmonary concussion
Airway problem, Spine trauma)
Circulation problem
(Blood loss)
Anatomic Derangement
Anatomic location and severity of the injuries
Pain level
(Tissue injury & psychological response)

16. emoga bermanfaat