VOLATILE AGENTS



OPIOIDS

| |Agent |Morphine |Pethidine |Tramadol |Naloxone |

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|Drug | | | | | |

| |Class |Phenanthrene |Atropine-like Phenylpiperidine |Phenylpiperidine analogue of |Thebaine derivative |

| | | | |codeine | |

| |Structure | | | | |

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| |Formulation |Iv |Iv |50mg tab |iv |

| | |Syrup |Intranasal |100mg/2ml | |

| | |tablet |Oral |crystalline white powder | |

| | | |epidural | | |

| |Isomers |Levo active |Levo active |R+ mu, ↑5HT | |

| | | | |S- ↑NA | |

| |pKa |7.9 (weak base) |8.5 |9.4 | |

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|P/kin | | | | | |

| |% unionised @ pH 7.4|23% |7% | | |

| |Lipid solubility |Poor |40 x morphine | | |

| | |1 | | | |

| |po absorption |Variable |Good |Good (peak 2hr) |good |

| |Bioavailability |25% (lung uptake 7%) |50% |70% (100% rpt doses) |20% (1st pass) |

| |PPB (%) |35% (albumin) |60% |minimal | |

| |Vdss (L/kg) |3 |4.4 | |2.1 |

| |CL(ml/kg/min) |14 |10 | |22 |

| |Metabolism |HHER (liver, kidney) |Demethylation, hydrolysis |cytP450 (CYP2D6) → desmethyl |HHER |

| | |M3G 75% inactive |Norpethidine – (90%) |tramadol (M1) (6xpotency) |conjugation |

| | |M6G10% active |½ potency, CNS stim | | |

| | | |t1/2 15-40hr | | |

| | | |toxic dose 10-15mg/kg/24hr | | |

| |Excretion |90% renal |Urine pH24hr | | | |

| |Offset | | | |redistribution |

|Other | |Glucuronidation impaired by | | | |

| | |MAOI → prolonged action | | | |

Withdrawal:

Yawning, coryza, lacrimation, insomnia, restlessness→sweaty, abdo pain, hallucination, diarrhoea, vomiting

Spinal reflex hyperexcitability. NA pathway from locus ceruleus important.

Clonidine used to treat.

| |Agent |Morphine |Pethidine |Tramadol |Naloxone |

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|CNS | | | | | |

| |Analgesia |Visceral, m/skel pain |Also LA effects |30% inhibited by naloxone |Binds mu>>delta/kappa |

| | |Not neuropathic |potency=cocaine | |Complete antagonist |

| | |Anti-nociceptive, modulated | | | |

| | |afferent component | | | |

| |Euphoria |Via mu |>morphine | | |

| |Sedation | | |morphine | | |

| |HR |↓ |↑ (atropine) | | |

| |Contractility |0 |↓ (only one) | | |

| |Venodilatation |↓ venous return | | | |

| |Arrhythmias |↓ risk VF | | | |

| |Mechanisms |↓Σ, vagotonic, direct dep SA,| | | |

| | |AV nodes | | | |

|GIT |Motility |↓ |minimal | | |

| |Gastric empty |↓ | | | |

| |Biliary spasm |½ x fent |minimal |minimal | |

| | |3x pethidine | | | |

| |LES tone |↓ | | | |

| |Mechanism |Intramural plexus, central | | | |

| | |effects | | | |

| |Blood flow |↓ (minor due to ↓CO) | | | |

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|Renal | | | | | |

| |Ureteric perist |↑ | | | |

| |Detrusor tone |↑ | | | |

| |Sphincter tone |↑ → retention |5mg/min ivi | | | |

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|Side effects | | | | | |

| | |Nausea |Anti-shiver (kappa) |Anti-shiver ?mech |Reverse analgsia |

| |Other |Pruritis | |Seizures in OD / epilepsy |N&v iv ................
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