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Opioid Receptors Mechanism of action of Opioids Effects of Opioids Anaesthetic Techniques using opioids Agonist Antagonist opioid compounds Opioid Antagonist
Opioid Receptors
Theory of Receptor Dualism 3 Major types - , , Receptor sub types Other opioid receptors , Opioid receptor like
1(ORL1)
Endogenous peptides
++ +++ ++ + +
IUPHAR
Enkephalins
OP1
DOR
Dynorphins
OP2
KOR
Beta endorphins
OP3
MOR
1
Supra spinal Spinal
2
Spinal
Respiratory
Depression of ventilation
CNS
CVS
Bradycardia
Contd.
1
Urinary retention
2
Constipation (Marked)
Endocrine
Prolactin release
Other Effects
Immune function
Contd.
1
Endorphin Morphine Synthetic Opioids
2
Endorphin Morphine Synthetic Opioids
Antagonist
Distribution
Putamen,Neocortex Thalamus, Hippocampus, Amygdala, Nucleus accumbens, Dorsal Horn of spinal cord
Drugs Morphine Fentanyl Methadone Sufentanil Butorphanol Buprenorphine Naloxone Nalorphine Pentazocine Nalbuphine
Mechanism of Analgesia
Opioid receptors are expressed in various areas of CNS
Amygdala, Mesencephalic reticular formation, Periaqueductal grey matter, rostral ventral medulla Substantia gelatinosa of spinal cord Analgesic effects
1. Direct inhibition of ascending transmission of pain 2. Modulation of descending pain control circuits
Effects of Opioids
Neurophysiologic Effects
1. 2. 3. 4. 5. Analgesic action Anaesthetic action EEG Sensory evoked potential Cerebral Blood Flow(CBF) & Cerebral Metabolic rate (CMR) Intracranial Pressure 7. Neuroprotection
6.
8. Muscle Rigidity 9. Neuroexcitatory Phenomenon 10. Pupil size 11. Thermo regulation and shivering 12. Pruritus
Analgesia
Not assosciated with loss of consciousnes
Nociceptive pain responds better than neuropathic pain
Opioids as anaesthetics
Reduce MAC of volatile Anaesthetcs Potency ratio for MAC reduction Fentanyl : Sufentanil:Alfentanil:remifentanil are 1:12:1/16:1.2 Midazolam is potentiated Propofol action is enhanced
ICP
Isoflurane N2O opioid Anaesthesia donot increse ICP during craniotomy
Opioid sedation donot alter ICP in head injured patients
Neuroprotection
Muscle Rigidity
Factors Affecting Dose and speed of drug administration
Hypercarbia, Hypoxemia
Miscellaneous Increase oxygen consumption, ICP, Fentanyl plasma levels Clinical Manifestations Mechanism for Muscle rigidity Measures to Prevent
Neuroexcitatory Phenomena
Ranges from Delirium to grandmal seizure like activity Meperidine is more potent
Pruritus
Respiratory Effects
1. Therapeutic Effects 2. Non Therapeutic Effects
Therapeutic Effects
Prevents hyper ventilation Attenuates stress response Antitussive action Antimuscarinic, Antihistaminergic, Antiserotoninergic actions
Dose dependent depression of respiration by direct action on brain stem respiratory centers
Receptor mediated Ventilatory response to CO2 is reduced
Treatment - Naloxone
Sleep
Old age & neonates CNS depressants
Renal insufficiency
Hyper ventilation & Hypocapnia Respiratory acidosis Decreased clearance Secondary peaks in plasma opioid levels
Cardiac Mechanism
Contractility Heart rate and rhythm - vagal mediated - asystole especially in premedication with blocker and CCB - Treatment atropine Cardiac conduction - Direct membrane action
Ischemia
Coronary circulation Baro receptor
Cardiogenic reflex
Vascular Mechanism
Paraventricular hypothalamic nucleus which release cortico tropin releasing hormone Locus caerulus nor epinephrine secreting areas of ANS
Mechanism of action
Modulates nociception inhibits HPA axis
Effects
Decrease plasma glucose, ADH, Renin, Aldosterone, cortisol, Growth Hormone
Treatment
Obstetric Effects
Ocular Effects
Decrease IOP during induction of Anaesthesia, succinylcholine administration and tracheal intubation
BALANCED ANAESTHESIA
Anaesthetic phase
Premedication (Mg) Induction
1. With hypnotic (Mg/Kg)
Fentanyl
25-50
Sufentanil
2-5
Alfentanil
250-500
Remifentanil
1.5 2.5
0.1-1
8-23
5-50 0.1-1.0Mg/Kg/min
1.3-2.8
10-30
Infusion
MAC
Intermittent Bolus (Mg) Infusion (Mg/Kg/min) 12.5-5.0 2.5-10 125-250 12.5-25 0.01-0.2
Involves combination of major tranquilizer Butyrophenone Droperidol and a potent opioid analgesic fentanyl
characterised by analgesia
amnesia
Contra indications use of concomitant MAO inhibitors Drug & alcohol abuse Parkinsons disease
Opioid loading doses; Maintenance infusion rates and additional bolus dose for TIVA
Drug
Additional Bolus
OPIOID AGONIST ANTAGONIST Actions of Nalbuphine, Butorphanol and Buprenorphine at opioid receptors
Drugs Receptor Partial agonist Partial agonist Partial agonist Receptor Partial agonist Partial agonist Antagonist agonist
Duration of Analgesia
10 0.3-0.4 2 10 40
Cardiac workload
Blood pressure
=
HR
PAP
= ?
= = =
Drug
OPIOID ANTAGONIST
Naloxone Active at , , receptor Uses Side effects : Hemodynamic alterations Sympathetic activation Increased oxygen consumption and minute ventilation Dose : Initial dose 0.4 to 0.8 mg-IV/intrathecal
OPIOID ANTAGONIST
Naltrexone Active at , , receptor
Uses
Nalmefene
Longer acting
Active at , , receptor
Longer acting
Route of administration Oral 0.5 to 3mg/kg Parenteral- 0.2 to 2 mg/kg Methyl Naltrexone First quaternary ammonium opioid receptor antogonist Doesnot reverse analgesic effects.
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