Opioids

Thursday, April 13, 2023 DEPT OF ANAESTHESIA MKCG MEDICAL COLLEGE

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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.


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OPIUMSource 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

http://en.wikipedia.org/wiki/Papaver_somniferum

http://en.wikipedia.org/wiki/Sap

http://en.wikipedia.org/wiki/Indochina

http://en.wikipedia.org/wiki/Morphine

http://en.wikipedia.org/wiki/Codeine

http://en.wikipedia.org/wiki/Afghanistan

http://en.wikipedia.org/wiki/Northern_India

http://en.wikipedia.org/wiki/Thailand

http://en.wikipedia.org/wiki/Laos

http://en.wikipedia.org/wiki/Myanmar

http://en.wikipedia.org/wiki/Mexico

http://en.wikipedia.org/wiki/Colombia

http://en.wikipedia.org/wiki/Hungary

http://en.wikipedia.org/wiki/United_States


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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

EndogenousPeptides

Met-enkephalin

Leu-enkephalin

- Endorphin

Dynorphin A ??

Dynorphin B ??

-Neoendorphin ??

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


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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

• 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

structural similarities within this class include,


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Structure - T


14MORPHINE


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Schematic of Presynaptic Opiate action


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RECEPTORS

Type Effects Agonist Antagonist

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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 ?

Hallucinations

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

• 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

further modulation of nociception involves the periventricular and periaqueductal grey matter


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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”

• Receptor and cellular level

This means:

• Organ system effects• Such as

• CVS• CNS• Resp• GIT• Genitourinary• Placenta/Foetus• etc

And..


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CNSEEG

SSEP’S

PUPILS

CTZ

CEREBRAL METABOLIC RATE

MUSCLE RIGIDITY


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CNS

EEG• High voltage,slow

delta waves

SSEP’s• velo

city and amplitude

Pupils• Miosis

CTZ• N & V

with help from vestibular nucleus


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CNS

•10-25% reduction•Little change to CBF

CMR


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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

• large boluses and rapid infusions• the elderly• concomitant use of N2O• with alfentanyl

appears to be a higher incidence with


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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

• peripheral vascular dilation• reduced peripheral resistance • depression of the baroreceptor reflexes

® postural hypotension in erect subjects

however they do produce,


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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

• 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

risk of bradycardia / asystole on induction,


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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 DepressionIncreasing 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 DepressionIncreasing 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


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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

• Nausea and vomiting• Sedation• Euphoria• Respiratory depression

Some effects of opioids are more susceptible to tolerance than others:

• Constipation• Miosis

Rapidly occurring:

Less affected by tolerance:


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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).

http://en.wikipedia.org/wiki/Myocardial_infarction

http://en.wikipedia.org/wiki/Sickle_cell_crisis

http://en.wikipedia.org/wiki/Cancer

http://en.wikipedia.org/wiki/Kidney_stones

http://en.wikipedia.org/wiki/Back_pain

http://en.wikipedia.org/wiki/Adjunct

http://en.wikipedia.org/wiki/General_anesthesia

http://en.wikipedia.org/wiki/General_anesthesia

http://en.wikipedia.org/wiki/Epidural_anesthesia

http://en.wikipedia.org/wiki/Epidural_anesthesia

http://en.wikipedia.org/wiki/Palliative_care

http://en.wikipedia.org/wiki/Antitussive

http://en.wikipedia.org/wiki/Antidiarrheal

http://en.wikipedia.org/wiki/AIDS

http://en.wikipedia.org/wiki/Loperamide


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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.

http://en.wikipedia.org/wiki/Contraindications

http://en.wikipedia.org/wiki/Hypoventilation

http://en.wikipedia.org/wiki/Renal_failure

http://en.wikipedia.org/wiki/Morphine-6-glucuronide

http://en.wikipedia.org/wiki/Toxicity

http://en.wikipedia.org/wiki/Biliary_colic

http://en.wikipedia.org/wiki/Acute_pancreatitis


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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

available as suppository


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OXYMORPHONE

Same as hydromorphon

e


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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 durationfewer smooth muscle spasms

than morphine

No meiosisbiotransformed 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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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

NALOXONEno 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


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NALTREXONE

Long half-life

effective orally or injected

available in oral form only

used for treatment of dependence


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NALMEFENE

Intermediate duration (4-6 hr) orally active no hepatotoxicity

with long term use


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MIXED AGONIST ANTAGONIST

Nalorphine and cyclazocine

Pentazocine: Talwin NX

Butorphanol

Nalbuphine


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NALORPHIN AND CYCLOZOCINE

Kappa3 recept

or agonis

ts

Mu recep

tor antagonists

produce

psychotomimetic effects

produce dysphoria


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PENTAZOCINE

Kappa and delta agonist

Non addictive and non euphoric

Has ceilling effect


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BUTORPHANOL

Kappa receptor agonist

Mu recepto

r antago

nist

Available as nasal spray analgesic eq to

buprenorhine and nalbuphine

5 X more

potent in

women than men


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NALBUPHINE

Kappa receptor agonist

Mu receptor antagonist

Little dysphoria

compared to nalorphine

Less abuse potential than

morphine


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DEPENDENCE AND ADDICTIONDependence: 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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WITHDRAWALThe 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.

WITHDRAWALThe 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.


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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


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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

ANAESTHESIA

presumed specific action of the opioids would not be expected to produce anaesthesia

• a biphasic response has been noted for fentanyl and sufentanyl

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


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ANAESTHETIC TECNIQUES USING OPIOIDS

ANALGESIA

SEDATION

BALANCED ANAESTHESIA

NEUROLEPTANALGESIA-NEUROLEPTANAESTHESIA

TIVA

OPIOID BASED ANAESTHESIA IN CARDIAC SURGERIES


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PCADrug 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


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PCA

Nausea 40-90%

Vomiting 8-40%

Pruritis

Sedation


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PCA

Respiratory depression

Urinary retention

Myoclonus (high doses)

Constipation


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OPIOID PATHWAY

opioid pain inhibition occurs at multiple levels

• spinal cord• brain-stem• thalamus


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Opioids

Health & Medicine

Transcript of Opioids