Lecture 8: Pharmacology Of Pain 1 - Opioids Flashcards
Name some examples of opioids?
- Morphine, Codeine, Oxycodone, Tramadol, Diamorphine (heroin), Buprenorphine, Methadone
Which opioids are naturally occurring, semi synthetic and synthetic?
- Naturally Ocurring: Morphine, Codeine
- Semi synthetic: Diamorphine (heroin), Buprenorphine and Oxycodone
- Synthetic: Fentanyl, Methadone
What are the main things opioids do in pain management?
- Prevent centralization
- Decrease Conduction
Why are the main opioid receptors in the body?
- mu - OP3 - beta endorphin, enkaphalins & endomorphin
- delta - OP1 - enkephalins & beta endorphin
- kappa - OP2 - dynorphin A, B & alpha neoendorphin
- NOP - OP4 - NOFQ (structurally similar to delta and kappa) but doesn’t bind to any other ligands
What are the different levels of the nervous system that morphine acts on?
- Nociceptors
- Spinal Cord
- Supraspinal sites
- Limbic System
What parts of the body have opioid receptors?
- CNS: cortex, thalamus, periaquaductal gray, spinal cord
- Peripheral neurons
- Inflamed Tissue
- Immune cells
- Respiratory and GI tract
What are some pharmacological effects of opioids?
- Sedation and Anxiolysis
- Depression of respiration
- Cough suppression
- Pupillary constriction
- Nausea and Vomiting
- GI symptoms
- Itching, brochoconstriction
What is the mechanism of opioid action?
- Activation of peripheral nociceptive fibres cause release of substance P + other pain signalling neurotransmitters from nerve terminals in dorsal horn of spinal cord.
- Regulated by endogenous endorphins or exogenous opioid agonists. Inhibit substance P and cause analgesia
- Involves changes in transmembrane ion conductance (G protein coupled)
How do opioid agonist work in G protein coupled opioid receptor?
- Causes GDP —> GTP exchange on alpha subunit
- A-GTP subunit dissociates from By subunit
- Both can interact with target proteins
- Causes inhibition of adenylyl cyclase, reduce cAMP
- Cause activation of potassium conductance and inhibition of calcium conductance
- Hyperpolarisation/ reduced neurotransmitter release
What is the main good point on using opioids?
- Analgesia in acute and cancer pain
- Effectiveness questionable in chronic non-cancer pain
What is the main bad point of taking opiods?
- Tolerance - dose of the drug doesnt work so have o increase dose which has side effects
- Drowsiness, dizziness, nausea, constipation, itching
- Long term: sleep apnea, hormonal imbalance, opioid induced hyperalgesia, addiction/overdose
How does opioid induced tolerance occur within process
- Drug of administration elicits opposing reaction within the same system.
- Involves desensitization, internalisation, down regulation and phosphorylation of opioid receptor
How does opioid tolerance occur between process?
- Drug of administration recruits different neuronal circuits that oppose the primary effect: activation of pronociceptive processes after opioid administration
- That counteract opioid analgesia e.g. engaging NMDA receptors
What happens when there is central sensitisation to the mechanism with morphine and how can morphine tolerance happen?
- Enhanced glutamate release which bind to NMDA receptors.
- High dose morphine can also bind to NMDA receptors
- Activation of pain signalling proteins
- MOP receptor activation causes Ca2+ to increase this can remove the Mg2+ block of NMDA receptors. This leads to morphine tolerance
- Blocking NMDA receptor could reduce hypersensitivity in chronic pain and improve analgesic efficacy of morphine
What is the worse side effect of taking opioids?
- Opioid induced hyperalgesia - enhanced pain response to a noxious stimulus
- Can be seen when opioid administration is abruptly terminated or reversed by the administartion of an opioid antagonist (naloxone)
