• Opiates/opioids
    • Routes of administration
      • IV, IM, PO, Epidural, Intrathecal, Transdermal
    • Receptors
      • Gi coupled
        Link:Receptors
      • Mainly pre-synaptic and act by closing voltage gated Ca²⁺ channels, stimulating K⁺ efflux leading to hyperplolarisation & reduced cAMP and so reduced neuronal excitability
      • Receptor locations
        • Nucleus of tracts solitarius
        • Peri-aqueductal grey matter
        • Thalamus
        • Cerebral cortex
        • Spinal cord
        • GI tract
        • Peripheral afferent neurons
      • Receptor classification
        • MOP/OP3/μ
          • Located in supraspinal areas
          • Analgesia, meiosis, euphoria (μ1), respiratory depression, ↓GI motility, bradycardia (μ2)
          • Named after prototype ligand, μorphine
        • KOP/OP2/κ
          • Located at spinal level
          • Sedation, meiosis, respiratory depression, inhibition of ADH
          • Named after prototype ligand κetocyclazazine
        • DOP/OP1/δ
          • Analgesia, respiratory depression
          • Named after location found - vas δeferens
        • NOP/ORL1/Nociceptin receptor
    • Pharmacodynamic effects
      • CNS
        • Analgesia, sedation, euphoria, dysphoria, hallucinations, tolerance, dependence
      • CVS
        • Histamine release, urticaria, hypotension, mild bradycardia (SAN & ANS mediated)
      • Resp
        • Respiratory depression, RR affected > tidal volume, ↓sensitivity to CO₂/O₂, chest wall rigidity, anti-ptussive
      • GI tract
        • Nausea, smooth muscle tone ↑, ↓motility, ↑biliary pressure, constipation
      • Endocrine
        • ↓ACTH, ADH, prolactin, gonadotrophic hormone
      • Eye
        • Stimulation of the Edinger-Westfal nucleus →meiosis
    • Specific opiates
      • Remifentanil
        • Anilopiperidine derivative
        • 1, 2.5 or 5mg vials, lipophilised powder in a glycine buffer
        • 1μg/kg bolus or 0.0125-1μg/kg/min
        • Peak effects 1-3 mins
        • Decreases MAP & heart rate by ~ 20%
        • Can cause chest wall rigidity due to μ receptors on GABA interneurons
        • Clearance 40ml/min; T½ (elimination) 10 mins
        • Metabolised by red cell esterases
      • Nalbuphine
        • Phenanthrene derivative
        • 10mg/ml solution
        • Given SC/IM/IV
        • A μ antagonist and κ agonist so analgesic while antagonising dependency problems. Can be reversed with naloxone
      • Alfentanil
        • T½ (elimination) 100 mins, clearance 6ml/min
        • pKa 6.5
        • Vd 0.5L/kg
      • Fentanyl
        • T½ (elimination) 190 mins, clearance 13 ml/min
        • pKa 8.1
        • Vd 4L/kg
      • Morphine
        • Conjugated to 3- & 6- glucorinide (70%), demethylated (20%), or excreted unchanged in urine.
        • Clearance 16 ml/min