Pharmacology of Opioids Flashcards
What are the 3 families of Opioid peptides?
Endorphin - β-endorphin
Enkephalin - [Met5]enkephalin & [Leu5]enkephalin
Dynorphin - Dynorphin A & Dynorphin B
What is Naloxone, and how does it work?
Naloxone is an Opioid antagonist
Naloxone stereo-selectively blocks all Opioid receptors
What are the 3 different opioid receptors?
mu-, = Morphine delta-, = [Met5]enkephalin & [Leu5]enkephalin kappa, = Dynorphin
All 3 receptors have the same MOA
What fibres are used to transmit sharp pain?
A-delta fibres
What fibres are used to transmit Dull/Throbbing pain?
C-fibres
They run to the Spinal cord - Dorsal horn
What is the nociceptive pathway?
Noxious stimuli - activates nociceptive afferents
Primary afferents - activates projection neurones in dorsal horn
Projection neurons travel to brain in spinothalamic tract
Opioids inhibit firing of dorsal horn neurones and stop transduction of signal to brain via spinothalamic tract
Where are opioid Receptors present in the body?
High conc in brain
Areas involved with pain control
Brain areas ( Receptors & Peptides)
- Periaqueductal gray (PAG)
- Nucleus Raphe Magnus (NRM)
- Nucleus Reticularis Paragigantocellularis (NRPG)
Dorsal horn of the spinal cord
- Esp. Lamina II (Substantia gelatinosa)
Which areas of the brain does morphine activate?
Morphine activates the PAG & NRM
Causes increase of firing of descending inhibitory pathway to dorsal horn
Involves mainly serotonergic neurons and depletion of 5HT
Effect in PAG & NRM - due to inhibition of GABA release from local interneurons
Thus leads to disinhibition of descending serotonergic pathway which decreasing transmission of nociceptive information through dorsal horn
What are the effects of morphine?
Analgesia Euphoria Respiratory depression Miosis - Pin-point pupils Emesis - Vomiting Constipation Opioid Induced Hyperalgesia Cough suppression Histamine release Hypotension Tolerance Dependence
What are some examples of Strong opioids (mu- agonists)?
Diamorphine (Heroin) - more potent than morphine
Hydromorphone
Buprenorphine - partial agonist
Fentanyl - very short acting
Pethidine -used for labour or minor surgery
Methadone - long acting
Oxycodone
What are some examples of weak opiods?
Codeine
Dihydrocodeine
What are examples of mixed opioid agonist/uptake inhibitors?
Tramadol & Tapentadol
mu- receptor agonist & Noradrenaline & 5HT uptake inhibitor
What are some examples Opioid antagonists?
Naloxone - treat OD
Naltrexone - treat OD
Peripherally active:
- Alvimopan
- Naloxegol
- Methylnaltrexone
Which drugs are used to treat opioid addicts?
Methadone
Suboxone - combination of Buprenorphine & Naloxone
