Adjuvant Analgesic Drugs

Adjuvant analgesic drugs

• Are drugs that have weak or non-
analgesic action when administered
alone but can enhance analgesic
action when coadministered with
analgesic agents.
 Some adjuvant drugs
• 3 drugs are very important and very
related to anesthesiologist.
• Steroids (dexamethasone)
• Clonidine (Alpha 2 agonist)
• Ketamine
• Pregabalin
 Corticosteroids
• Many uses:
– Somatic pain that does not
response to opioids,
hypersensitivity with NSAIDs
– Nerve compression, cord
compression
• Adverse effects
– steroid psychosis; mild euphoria
– proximal myopathy
– other long-term adverse effects
 Dexamethasone
Anti-emetic
Anti-inflammation
Anti-udema
 Analgetic in moderate dose
 Dexamethasone
• long half-life (>36 h), dose once a day
• minimal mineralocorticoid effect
• doses of 2–20 mg/d
 Clonidine ( Alpha 2 agonist)
• It has been using as antihypertensive drug for long time.
• It has analgesic effect when give centrally
such as -Spinal analgesia
- epidural analgesia
• Clonidine can selectively blocking conduction of Adelta and C fiber.
• 1µ/Kg Bw clonidine given perioperatively is well
` tolerated and little effect of – Hypotesion
- bradicardia
- SEDATION
• compare to dexmetomidine, dexmetomidine more selective for
alpha2 receptors and shor duration.
 KETAMIN
Anesthesia Dose > 2 mg/Kg BW
Will implicate in causing Psychomimetic effects, such as;
•Excessive sedation
•Cognitive Dysfunction
•Hallucination
•Nightmares

Subanesthesia Doses (Low Dose) < 1 mg/Kg BW

Have significant analgesic efficacy without those side effects, but
may excerts nausea, vomiting, urinary retention, constipation etc.
•Dose of Ketamin 0.15 mg/Kg BW Should be combined To
•Opioid
•Local Anesthetic
•Other Analgesic Agents
 KETAMIN
More Frequently Use in Postorthopedic Surgical Pain Management

A Single intraoperative injection of ketamin

Arthroscopic Anterior Cruciate
(0,15 mg/kg) improved analgesia and passive
Ligament Surgery
knee mobilization 24 hour after surgery

Outpatient Knee Arthroscopy Improved Postoperative functional Outcome

When combine with epidural or femoral nerve

Total Knee Arthroplasty block, increase postoperative pain relief for
total knee Astroplasty.
• Menigaux C, Guignard B, Fletcher D, Dupont X, Guirimand F, Chauvin M. Anesth Analg. 2000;90:129–135.
• Menigaux C, Guignard B, Fletcher D, Sessler DI, Dupont X, Chauvin M. Anesth Analg. 2001;93:606–612.
• Himmelseher S, Ziegler-Pithamitsis D, Agiriadou H, Martin Jjelen-Esselborn S, Koch E. Anesth Analg. 2001;92: 1290–1295.
• Adam F, Chauvin M, Du Manoir B, Langlois M, Sessler DI, Fletcher D. Anesth Analg. 2005;100:475–480.
 Low dose of Ketamine

Low-dose ketamine is not really an

‘analgesic’, but is better to described as
 ‘anti-hyperalgesic’
 ‘anti-allodynic’
 ‘tolerance-protective’
 GABA
(Gama-amino Butiric Acid is an Amino Acid)

GABA is the major inhibitory

neurotransmitter in the central nervous
system (CNS), with most neuron undergoing
GABA ergic modulation.
WIDE
WIDE DYNAMIC
DYNAMIC RANGE
RANGE SPINAL
SPINAL
NEURON
NEURON
Glutamate
C
(Subs P)

Ad NMDAr
Glutamate
Ab
Glutamate
+ “Wind-up” Brain
Gene induction

Inhibitory
GABA
-
Fibers
Glycine
Opioids
NA, 5HT
 GABAPENTINOID

1. Gabapentin (Neurantin®)
2. Pregabalin (Lyrica®)
 Gabapentin
 Structurally related to the neurotransmiter
GABA but mechanism of action is different.
 Binds to α2δ subunit of voltage-gated calcium
channels in CNS tissues.
 Bioavailability is 27-60% and not dose
proportional.
 Following oral administration, Cmax within 2-3
hour.
 t1/2 is independent of dose and averages 5-7
hour.
 PREGABALIN
– Pregabalin binds to the 2-d subunit of voltage-gated
calcium channels
– Pregabalin reduces calcium influx at presynaptic
terminals in hyperexcited neurons
– Subsequent to 2-d binding, pregabalin reduces
release of excitatory neurotransmitters
• e.g. glutamate, substance P, norepinephrine
– Analgesic, anxiolytic, anticonvulsant activities
– Dose 50 to 75 mg/12 hours

Gee et al. 1996; Fink et al. 2002; Fehrenbacher et al. 2003; Dooley et al. 2002;
Maneuf et al. 2001; Bialer et al. 1999; Welty et al. 1997
 Pregabalin Binding
to Voltage-Dependent
Calcium Channels
Ca 2+

Ion
Ionchannel
channel
Pregabalin
Ca 2+
Ca 2+ Ca 2+ Gabapentin
Pregabalin/
Ca 2+ binding site

Ca 2+
 -
Outside
the cell

  + +  + + d
Cell membrane

Inside
b the cell

Ca 2+
Thank You