Opioids 100613013235-phpapp02

OPIOIDSDR CHANDRA SEKHAR BEHERA
PG 2ND YEAR ANAESTHESIOLOGY
The Magic within The Flower of Joy
Opium poppies are white flowers that thrive in
the dry, warm
climate of southern Asia. This field was grown
for
pharmaceutical purposes.
Saturday, June 15, 2013 1
DEPT OF ANAESTHESIA MKCG MEDICAL
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OPIUM
Source plant(s) Papaver somniferum
Part(s) of plant sap
Geographic origin Indochina Region
Active ingredients Morphine, Codeine
Main producers Afghanistan (primary), Northern India, Thailand, Laos, Myanmar, Mexico, Colombia, Hungary
Main consumers worldwide (#1: U.S.)
Wholesale price $3,000 per kilogram
Retail price $16,000 per kilogram
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HISTORY
first undisputed reference to "poppy juice" is found in the writings of Theophrastus in the
third century B.C.
opium derived from the Greek word for "juice"
obtained from the poppy Papaver sominiferum
Arabian physicians were well versed in its uses and introduced the plant to the Orient
Paracelsus, circa 1500, repopularised the drug in Europe, where it had fallen out of favor
due to toxicity
18th century opium smoking became popular in the Orient and its availability in Europe led
to considerable abuse
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HISTORY
opium contains
more than 20
alkaloids
1806, Sertürner
isolated a pure
substance in
opium, which he
named morphine
•after Morpheus, the
Greek god of dreams
isolation of other
alkaloids soon
followed
•codeine in 1832 and
papaverine in 1848
by the middle of the
19th century, use of
the pure alkaloids
rather than crude
opium was
becoming
widespread
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HISTORY
problems of widespread addiction led
to the search for a morphine antagonist
in 1951 nalorphine was used in the RX of
morphine overdose
at the same time, the analgesic effects
stimulated the development of a
number of new drugs; including
naloxone, pentazocine, butorphanol etc.
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HISTORY
researchers concluded that the interactions and differences between morphine and its
derivatives could only be explained by the existence of more than one receptor type
® receptor dualism(Martin 1967)
1973 : 3 groups of workers described saturable, stereospecific binding sites (following
work by Goldstein)
1975 : the enkephalins were isolated from pig brain
since then researchers have shown that there are three distinct families of endogenous
opioid peptides and multiple categories of opioid receptors
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INTRODUCTION
All natural and semi synthetic opium alkaloid derivatives
synthetic agents and other drug whose upload-like effects are
blocked by naloxone-non selective opioid receptor antagonist
SOURCE-Opium poppy
CONSTITUENTS-Analgesic components-
Morhine,codeine,Thebaine
Nonanalgesic component-papaverine
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CLASSIFICATIONS
Classification
Natural Alkaloids of Opium
phenanthrenes morphine, codeine, thebaine
benzylisoquinolines papaverine, noscapine
Semi-synthetic Derivatives diacetylmorphine (heroin)
hydromorphone, oxymorphone
hydrocodone, oxycodone
Synthetic Derivatives
phenylpiperidines pethidine, fentanyl, alfentanyl, sufentnyl
benzmorphans pentazocine, phenazocine, cyclazocine
propionanilides methadone
morphinans levorphanol
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ENDOGENOUS OPIOIDS
Endogenous Opioids
Endogenous
Peptides
Met-enkephalin
Leu-enkephalin
- Endorphin
Dynorphin A ??
Dynorphin B ??
-Neoendorphin ??
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ENDORPHINS
highest concentrations of b-endorphin occur
in
• pituitary gland
• basal, medial, and arcuate regions of the hypothalamus
• long axoned neurons which synapse in the
septum, periaqueductal grey and thalamic regions of
the midbrain
unclear whether b-endorphin exists
functionally in the spinal cord

ENKEPHALLINS
widely distributed throughout the CNS,
• limbic system (amygdaloid & septal nuclei)
• medial thalamic nuclei
• periaqueductal grey matter & midline reticular formation in the midbrain
• the periventricular grey areas in the medulla
• laminae I, II & IV of the spinal cord (substantia gelatinosa)
• the area postrema (CTZ)
NB: all of which are involved in the reception of afferent
nociceptive information
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STRUCTURE ACTIVITY
complex structures usually with a number of optical
isomers, of which only the l-isomer is most active
structural similarities within this class include,
• structure conforms to a "T-shape"
• a tertiary, positively charged basic nitrogen
• a quaternary carbon, C13 in morphine,
• separated from the basic N by an ethane (-CH2-CH2-) chain
• attached to a phenyl group (phenol, ketone)
• presence of an aromatic ring
• centre is 0.455 nm from the nitrogen atom
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Structure - T
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MORPHINESaturday, June 15, 2013 14
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Schematic of Presynaptic Opiate
actionSaturday, June 15, 2013 15
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RECEPTORS
Type Effects Agonist Antagonist
1
Supraspinal
analgesia
Miosis
Euphoria
Abuse
potential
Morphine
Naloxone
Pentazocine
naltrexone
2
Bradycardia
Respiratory
depression
GIT motility
As above As above
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RECEPTORS
Receptors
Type Effects Agonist Antagonist
Kappa
Spinal
analgesia
Pentazocine Naloxone
Sedation ketacycline Naloxone
Delta
Spinal
analgesia
Pentazocine Naloxone
Dysphoria D-leu-enkephalin ?
Sigma Mydriasis ?ketamine ?
Hallucination
s
N-
allylnormethazocine
?
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OPIOID RECEPTORS
Mu (morphine) MOP OP3
Delta DOP OP1
Kappa KOP OP2
Nociceptin orphaninFQ NOP orphan
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RECEPTOR ACTIVITY
the actions of opioids are generally described with
reference to only 3 types of receptors
• ® µ, k, & d
on the basis of these receptors, drugs can be
divided into 4 groups,
• agonists
• antagonists
• agonist-antagonists
• partial agonists
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TERMINOLOGY
PURE AGONIST-Has
affinity for binding plus
efficacy
PURE ANTAGONIST-Has
affinity for binding but
no efficacy blocks action
of exogenous and
endogenous ligands
MIXED AGONIST-
ANTAGONIST-Produces
agonist effect at one
receptor and antagonist
effect on another
PARTIAL AGONIST-Has
affinity for binding but
low efficacy
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CLASSIFICATION
AGONIST
morphine
PARTIAL
AGONIST
buprenorphine
PURE
ANTAGONIST
naloxone
MIXED AGONIST
ANTAGONIST
nalbuphine
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PARTIAL AGONISTS
drugs that produce a less than
maximal response
and, therefore, have a low
intrinsic activity are called partial
agonists
these display certain
pharmacological features,
•the slope of the dose-response curve is
less than that of a full agonist
•the dose response curve exhibits a ceiling
with the maximal response below that
obtainable by a full agonist
•partial agonists are able to antagonise
the effects of large doses of full agonists
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PARTIAL AGONISTS
NB: this is a
schematic
representation to
illustrate the
differential effects of
various opioid agents;
the actual interactions
responsible for
agonist / partial
agonist activity are
uncertain
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AGONISTS
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ANTAGONISTS
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AGONISTS - ANTAGONISTS
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ANALGESIA
µ-receptors are located on the terminal axons of primary
afferents within laminae I & II (substantia gelatinosa) of the
spinal cord (+ spinal nucleus of the trigeminal nerve)
• decrease the presynaptic release of neurotransmitters, predominantly
substance P
enkephalinergic interneurones in the dorsal horn are
predominantly inhibitory to the soma of cells in the deeper
laminae IV & V
• morphine is inactive at these sites
• met-ENK, a d-receptor agonist inhibits neuronal firing
• both µ & d receptors inhibit spinal transmission of pain
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ANALGESIA
stimulation of pain fibres activates enkephalinergic neurones in
the spinal cord, which play a role in the "gating" of pain and in
mediating the effect of descending medullary analgesic pathways
further modulation of nociception involves the periventricular and
periaqueductal grey matter
• direct microinjections of morphine, or electrical stimulation produce analgesia
which can be blocked by naloxone
• stimulation at this level results in barrages of impulses travelling in descending
pathways to the dorsal horns of the spinal cord
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AGE EFFECTS
radioligand-receptor studies have shown a
marked and widespread reduction in mu and
delta receptor densities with age
this work supports clinical studies which
show a far greater correlation between dose
requirements and age, cf. body weight
this is a specific effect, as similar studies
show an increase in benzodiazepine
receptors
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PHARMACODYNAMICS
“What the drug does to the body”
This means:
• Receptor and cellular level
And..
• Organ system effects
• Such as
• CVS
• CNS
• Resp
• GIT
• Genitourinary
• Placenta/Foetus
• etcSaturday, June 15, 2013 30
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CNS
EEG
SSEP’S
PUPILS
CTZ
CEREBRAL
METABOLIC
RATE
MUSCLE
RIGIDITY
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CNS
EEG
•High voltage,slow delta
waves
SSEP’s
• velocity
and
amplitude
Pupils
•Miosis
CTZ
•N & V with
help from
vestibular
nucleus
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CNS
•10-25% reduction
•Little change to
CBFCMR
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CNS
Pruritis
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OTHER CNS EFFECTS
•nausea & vomiting
•direct stimulation of the CTZ in the area postrema of the
medulla
•also stimulated by apomorphine, a dopaminergic agonist
•may RX with phenothiazines which posses a dominant
dopamine-blocking action
•up to 15-40% of ambulatory patients, may be a vestibular
component
•miosis
•caused by most mu & kappa receptor agonists
•stimulation of the Edinger-Westphal nucleus
•pinpoint pupils being pathognomic of opioid overdose
2
important
excitatory
effects
include,
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MUSCLE RIGIDITY
high doses may produce rigidity, characterised by increasing
muscle tone progressing to severe stiffness, particularly in
the thoracic and abdominal muscles
appears to be a higher incidence with
• large boluses and rapid infusions
• the elderly
• concomitant use of N2O
• with alfentanyl
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CEREBRAL BLOOD FLOW
the opioids generally produce a modest (~ 10-15%)
decrease in CMRO2 and ICP
in contrast to the volatile agents they are cerebral
vasoconstrictors
this occurs even in the presence of nitrous oxide
Guy Ludbrook thinks they uncouple CBF & CMRO2
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CEREBRAL BLOOD FLOW
morphine 1-3 mg/kg + 70% N2O
• insignificant changes in CBF and CMRO2
fentanyl 100 µg/kg + 70% N2O
• dose related decreases in,
• CBF to a maximum of 50%
• CMRO2 to a maximum of 35%
similar changes seen with sufentanyl and alfentanyl
all of these agents decrease CSF formation while not affecting reabsorption
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CVS
HYPOTENSION
BRADYCARDIA
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CVS EFFECTS
morphine & related opioids produce minimal
effects in normal supine subjects
however they do produce,
• peripheral vascular dilation
• reduced peripheral resistance
• depression of the baroreceptor reflexes
® postural hypotension in erect subjects
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CVS EFFECTS
these effects are produced by a number
of mechanisms,
• release of histamine
• a direct centrally mediated reduction in
sympathetic tone - reversed by naloxone
• a vagal induced bradycardia
• direct and indirect (PaCO2) mediated vasodilatation
• splanchnic sequestration of blood
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CVS:BRADYCARDIA
all µ-receptor agonists (except pethidine) HR
risk of bradycardia / asystole on induction,
• Ca++-channel, or b-adrenergic blockers
• concomitant use of benzodiazepines
• muscle relaxants without vagolytic properties (vecuronium)
• muscle relaxants with vagotonic properties (succinylcholine)
• vagal stimuli (laryngoscopy)
• rapid administration of the opioid
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RESPIRATORY
CO2 RESPONSE CURVE
HYPOXIC DRIVE
COUGH
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RESPIRATORY
all µ-receptor agonists
dose dependent depression
of respiration,
• brainstem sensitivity to CO2
• slope of the CO2-ventilation response curve
• apnoeic threshold
• hypoxic drive to respiration
•carotid body chemoreception is virtually
abolished
• pontine & medullary centres involved in
rhythmic respiration
they do not affect hypoxic pulmonary
vasoconstriction
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RESPIRATORY
delayed respiratory depression has been reported with
most of the opioids
• morphine, pethidine, fentanyl, alfentanyl, and sufentanyl
exact cause is unclear, possibly
• secondary plasma drug peaks
• sequestration of ~ 20% of fentanyl in the stomach
• large peripheral storage compartments (skeletal muscle)
• supplemental analgesics and other medications
• lack of nociceptive stimulation
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FACTORS INCREASING RESPIRATORY
DEPRESSION
Factors Increasing Opioid Respiratory Depression
Increasing dose
Intermittent bolus vs. continuous infusion
Increased brain penetration, or drug delivery
decreased distribution, low CO
increased unionised fraction (respiratory alkalosis)
Decreased reuptake from the brain (respiratory alkalosis)
Decreased drug clearance
decreased liver blood flow (abdominal surgery)
intrinsic liver disease
Secondary plasma drug peaks
peripheral storage compartments, lung, fat, muscle
sequestration in the stomach
Increased ionised fraction at the receptor site (respiratory acidosis)
Sleep
Increasing age ( 60 yrs) and neonates
Metabolic alkalosis
Factors Increasing Opioid Respiratory Depression
Increasing dose
Intermittent bolus vs. continuous infusion
Increased brain penetration, or drug delivery
decreased distribution, low CO
increased unionised fraction (respiratory alkalosis)
Decreased reuptake from the brain (respiratory alkalosis)
Decreased drug clearance
decreased liver blood flow (abdominal surgery)
intrinsic liver disease
Secondary plasma drug peaks
peripheral storage compartments, lung, fat, muscle
sequestration in the stomach
Increased ionised fraction at the receptor site (respiratory acidosis)
Sleep
Increasing age ( 60 yrs) and neonates
Metabolic alkalosis
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GIT
STOMACH
SMALL INTESTINE
LARGE INTESTINE
the net effect is to decrease motility
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GUT
INCREASED TONE
URINARY RETENTION
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NEUROENDOCRINE
Generally decreses the responsivness of the hypothalamus
causing Decrese in temp
Decrease relese of GnRH
Increse in GH & Prolactin
May give rise to mild drug induced SIADH
Saturday, June 15, 2013
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49

Tolerance
result from uncoupling of the drug-receptor effect
• decrease in the number of receptors
• reduction of their affinity for a given agonist, and
• subcellular uncoupling of the receptor and second messenger
there is little cross-tolerance between different receptor
groups
high affinity agonists, ie. those with the greatest
receptor reserve, produce least tolerance
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TOLERANCE TO OPIOIDS
Components of different types of tolerance may be present
Some effects of opioids are more susceptible to tolerance than
others:
Rapidly occurring:
• Nausea and vomiting
• Sedation
• Euphoria
• Respiratory depression
Less affected by tolerance:
• Constipation
• MiosisSaturday, June 15, 2013 51
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PHARMACOKINETICS
Remember this means:
• Absorption
• Bioavailability
• Distribution
• Protein Binding
• Metabolism
• t½
• Metabolites
• Excretion
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IMPORTENCE OF KINETICS IN
OPIOIDS
Questions regarding infusions, repeat dosing, context sensitive half-
life, onset times, etc relate to the individual drugs and their kinetics
Lipid solubility allows access across biological membranes (including
BBB). Tends to result in faster effect-site equilibration.
pKa important – opioids are weak bases. A lower pKa means a higher
proportion of drug is unionised (or in its lipid soluble form)
High plasma protein binding restricts volume of distribution
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IDEAL KINETICS FOR OPIOID
INFUSION
Ideal properties:
•Short elimination half life
•Offset by metabolism or excretion, not
redistribution
•No active metabolites
•Tight concentration – effect relationship
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PHARMACOKINETIC PROPERTIES OF
OPIOIDS
Pharmacokinetic Data
Agent Morphine Pethidine Fentanyl Alfentanyl Sufentanyl
pKa' 8.0 8.5 8.4 6.5 8.0
% Unionized 23% < 10% < 10% 90% 20%
Octanol:H2O
1.4 39 813 145 1778
t½
(min) 1.0-2.5 1-2 1-3 1-2
t½
(min) 10-20 5-15 10-30 4-17 15-20
t½
(hrs) 2-4 3-5 2-4 1-2 2-3
VdSS
(l/kg) 3-5 3-5 3-5 0.4-1.0 2.5-3.0
Cl (ml/kg/m) 15-30 8-18 10-20 4-9 10-15
ER 0.8-1.0 0.7-0.9 0.8-1.0 0.3-0.5 0.7-0.9
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MORPHINE
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MORPHINE
• Poor lipid solubility and vd-3-5l/kg
• Conversion of phamacologicaly active
metabolite m6g
• Slow onset and prolong duration
• Pka-8.0 ,
• % unionised at pH-7.4-23
• %plasma protein binding-35
• Clearance-15-30ml/min/kg
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INDICATIONS
• Morphine can be used as an analgesic in hospital settings to relieve:
– pain in myocardial infarction
– pain in sickle cell crisis
– pain associated with surgical conditions, pre- and postoperatively
– pain associated with trauma
– severe chronic pain, e.g., cancer
– pain from kidney stones (renal colic, ureterolithiasis)
– severe back pain
• Morphine can also be used:
– as an adjunct to general anesthesia
– in epidural anesthesia or intrathecal analgesia
– for palliative care (i.e., to alleviate pain without curing the underlying reason for it, usually
because the latter is found impossible)
– as an antitussive for severe cough
– as an antidiarrheal in chronic conditions (e.g., for diarrhea associated with AIDS, although
loperamide (a non-absorbed opioid acting only on the gut) is the most commonly used opioid
for diarrhea).
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CONTRADICTIONS
• The following conditions are relative contraindications for
morphine:
• acute respiratory depression
• renal failure (due to accumulation of the metabolites
morphine-3-glucuronide and morphine-6-glucuronide)
• chemical toxicity (potentially lethal in low tolerance
subjects)
• raised intracranial pressure, including head injury (risk of
worsening respiratory depression)
• Biliary colic.
• Although it has previously been thought that morphine was
contraindicated in acute pancreatitis, a review of the
literature shows no evidence for this.
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59

CODEINE
About
1/10th the
potency of
morphine
lower
efficacy than
morphine
about 10%
converted to
morphine by
CYP450 2D6
10% of
patients do
not possess
this enzyme
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HEROIN
Crosses blood-brain barrier
more rapidly than morphine
2-4 X greater potency than
morphine
Converted to morphine
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HYDROMORPHONE
About 8-10X potency of
morphine
Slightly shorter duration
than morphine
available as suppository
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OXYMORPHONE
Same as
hydromorphone
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OXYCODEINE
About 10X potency of codeine
Also metabolized by CYP450-2D6
Controlled release formulation
(OxyContin)
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HYDROCODONE AND
DIHYDROCODEINE
Same as oxycodone
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PARTIAL AGONIST-BUPRENORPHINE
Partial agonist at
mu receptors
Partial agonist at
kappa3 receptors
Antagonist at
kappa1 receptors
Lower efficacy
analgesic than
morphine
Slow dissociation
from receptor
hence naloxone
resistent
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SYNTHETIC COMPOUND
Meperidine
Fentanyl, Sufentanyl, Alfentanyl
Remifentanyl
Methadone ,tramadol L-α-acetyl-methadol: LAAM
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MEPERIDINE
About 1/8th potency of morphine
shorter duration
fewer smooth muscle spasms than
morphine
No meiosis
biotransformed to a toxic metabolite
that builds up and can cause seizures.
Synergistic with Gila monster venom
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FENTANYL
80 - 100 x
potency of
morphine
fast
onset, short
duration
used i.v. for
anesthesia
available as
patch
available as
oral slow
release
device.
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USES
• Extensivly used for anaesthesia and analgesia in
both operating room and ICUsettings
• Used with benzodiazepines and midazolam in
endoscopic procedure,cardiac
catheterisation, oral surgeries
• Widely used as tansdermal patches to alleviate
pain like in cancer
• Fentanyl given in intrathecaly as spinal
anaesthesia and epiduraly as epidural anaesthsia
and anagesia
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70

SULFENTANIL
Exteremly lipid soluble-rapid effect site equilibration and
rapid redistribution of the drug leading to termination of
effect
High plasma protein binding lead to less Vd than fentanyl
Accumulate in prolong infusion become longer than
alfentnyl at 8 hrs
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ALFENTNIL
Low pKa-very fast equilibaration time with CNS because bulk of
drug in unionised form &cross BBB even though not lipid soluble
as other fentanyl congeners
Low Vd-due to low lipid solubility and high protein
binding.Redistribution is not a significant in offset-requires
metabolism.this explains longer CSHT than sulfentanil until 8 hrs
Metabolised by cyt p450 3A4-Inducible and explains variability
seen
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REMIFENTANIL
Highly unionised-rapid onset of effect
Rapid clearance and small Vd-effect terminated by elimination
Metabolite GR90291 has only 1/4600 th activity –unlikely to produce
effect after infusion
Tight concentration-effect relationship
Very well suited for infusion
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METHADONE
Potency similar to morphine for i.v.
administration, but 4 x more potent
orally
long plasma half-life
used in treatment of narcotic
dependence
Duration of action increases with
repeated use
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LAAM
Extremely long plasma
half-life (>72 hr)
Suppresses opiate
withdrawal for 4-5 days
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TRAMADOL
These actions
are synergistic
for analgesia
α-2
adrenoceptor
agonist
NE and 5-HT
reuptake
blocker
(antidepressant)
Opioid receptor
agonist (mu and
delta)
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ANTAGONISTS
Naloxone Naltrexone Nalmefene
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SIGNS OF OVERDOSE
Stuporous
or in
coma
Respiratory
rate
extremely
low
pinpoint
pupils
low body
temperature
flacid skeletal
muscles, jaw
relaxed
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NALOXONE
no analgesic activity at all
competitive antagonist at mu, kappa, and sigma receptor
displaces morphine and other OPIOID from receptor site
reverses all actions of the OPIOID and does it rather quickly
it will precipitate withdrawal
increased blood pressure
metabolized same as morphine through glucuronic acid and excreted through
kidney

NALTREXONE
Long half-life
effective
orally or
injected
available in
oral form
only
used for
treatment of
dependence
COLLEGE

NALMEFENE
Intermediate
duration (4-6 hr)
orally active
no hepatotoxicity
with long term use
COLLEGE

MIXED AGONIST ANTAGONIST
Nalorphine and
cyclazocine
Pentazocine:
Talwin NX
Butorphanol
Nalbuphine
COLLEGE

NALORPHIN AND CYCLOZOCINE
Kappa3 receptor
agonists
Mu receptor
antagonists
produce
psychotomimetic
effects
produce
dysphoria
COLLEGE

PENTAZOCINE
Kappa and delta agonist
Non addictive and non euphoric
Has ceilling effect
COLLEGE

BUTORPHANOL
Kappa receptor agonist
Mu receptor
antagonist
Available as nasal spray
analgesic eq to
buprenorhine and
nalbuphine
5 X more
potent in
women than
men
COLLEGE

NALBUPHINE
Kappa
receptor
agonist
Mu receptor
antagonist
Little
dysphoria
compared to
nalorphine
Less abuse
potential
than
morphine
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DEPENDENCE AND ADDICTION
Dependence: The propensity
to experience an abstinence
syndrome after
discontinuation of a drug, or
administration of an
antagonist drug. May begin
to develop from 1-2 weeks
with several doses/day.
Addiction: A chronic
condition, characterised by
the compulsive use of a
substance resultant in harm
(physical, psychological or
social) and continued use
despite that harm
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WITHDRAWAL
The time course is a function of the elimination half-life of the opioid
Symptoms will appear within 6 to 12 hours and reach a peak at 24 to
72 hours following cessation of a short half-life drug such as
morphine
36 to 48 hours with methadone, a long half-life drug.
The daily dose required to prevent withdrawal, when ceasing is
approximately one fourth of the previous dose.
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WITHDRAWAL
The onset is characterized by feelings of anxiety, nervousness and irritability
chills and hot flushes.
"wetness" including salivation, lacrimation, rhinorrhea and diaphoresis
piloerection.
At the peak, nausea, vomiting, abdominal cramps, insomnia
and, rarely, multifocal myoclonus.

OPIOID ANAESTHESIA
considerable debate as to whether opioids in their own right
produce anaesthesia
to date there is no study showing that opioids alone, without
muscle relaxants or other supplementation, will reliably
produce anaesthesia in humans
most studies assess the reductions in volatile MAC in animal
models, demonstrating a ceiling effect which is
subanaesthetic
COLLEGE

OPIOID ANAESTHESIA
the problems with these studies include,
• the profile of action of opioids varies considerably with
animal species, thus extrapolation to humans is not readily
achieved
• as inhibition of motor responses occur at deeper levels of
anaesthesia than unconsciousness, amnesia and analgesia,
methods requiring motor responses, eg. tail clamp
studies, underestimate opioid effect
• volatile agents inhibit descending inhibitory pain pathways
activated by the opioids, therefore may decrease the
effectiveness of the opioids
COLLEGE

ANAESTHESIA
presumed specific action of the opioids would not be expected to
produce anaesthesia
postulated that the analgesia produced at subanaesthetic
concentrations and the unconsciousness produced at higher levels
may be mediated by different processes
dual mechanism hypothesis requires that in addition to the
receptor mediated effects, an opioid must be lipid soluble enough
to act as a general anaesthetic
• a biphasic response has been noted for fentanyl and sufentanyl

ANAESTHETIC TECNIQUES USING
OPIOIDS
ANALGESIA
SEDATION
BALANCED ANAESTHESIA
NEUROLEPTANALGESIA-NEUROLEPTANAESTHESIA
TIVA
OPIOID BASED ANAESTHESIA IN CARDIAC SURGERIES
COLLEGE

PCA
Drug Age Lockout Concentration
18-40 yrs 40-70 yrs >70 yrs (mins)
Morphine 1.5-2 mgs 1 mg 0.5mgs 5 1 mg/ml
Pethidine 15-20 mgs 10 mgs 5 mgs 5 10 mg/ml
Fentanyl 15-20
mcgs
10 mcgs 5 mcgs 5 10 mgs/ml
Tramadol 15-20
mcgs
10 mgs 5 mgs 5 10 mgs/ml
COLLEGE

PCA
Nausea 40-90%
Vomiting 8-40%
Pruritis
Sedation
COLLEGE

PCA
Respiratory depression
Urinary retention
Myoclonus (high doses)
Constipation
COLLEGE

OPIOID PATHWAY
opioid pain
inhibition
occurs at
multiple levels
• spinal cord
• brain-stem
• thalamus
COLLEGE

COLLEGE

Opioids 100613013235-phpapp02

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