- pKa - 8.5 (9% nonionised @ 7.4)
- Octanol water coefficient - 39 (so 40x lipid solubility of morphine)
- phenylpiperidine opioid
- Dose - 25-100 mg (10% morphine potency). Limit 1000 mg 1st day, then 600 mg/day there after.
- Absorption - IV, IM, epidural, po (55% biov)
- Distribution - Vdss 4.5 L/kg. Crosses placenta - foetal 80% of maternal.
- Protein binding - 60%
- Onset 10 min ; Offset 2-3 h
- Metabolism - ß½ 3 h; N-demethylation to norpethidine and then hydrolysis to norpethidinic acid; also direct hydrolysis to pethidinic acid. Renal elimination.
- Norpethidine - ß½ 15 h; 50% analgesic properties, 2x convulsant effects.
- Clearance - 20 mL/kg/min (same as morph & fentanyl)
- Mech - mu and kappa agonist, causing potent spinal and supraspinal analgesia.
- CNS - more euphoria, less N/V than morphine. No miosis, but may cause mydriasis (pupil dilation -atropine-like kappa action). No EEG changes like morphine. ⇡ latency & amplitude of SSEPs.
- NB: has LA action, so can be used as sole agent for neuroaxial block.
- anti-shivering effect (kappa)
- CVS - ⇣ MAP (> than morphine) due to histamine release & alpha adrenergic blockade (vasodilation). Inc HR (atropine like effect). Large doses depress myocardial contractility. May cause hypertensive crisis in those on MAOIs.
- depress myocardial contractility
- Resp - potent resp depressant - greater effect on TV than RR. Histamine release. Chest wall rigidity.
- OWC 1800
- pKa 8.0
- Potency 5-10x fentanyl, 500x morphine.
- Vd 3 L/kg
- Protein binding 93%
- Clearance 12 mL/kg/min
- tß½ 3 hours
- CSHT(8h) 30 min (alfentanil ~60 m)
- mu agonist, also stimulates serotonin release and at high dose has local anaeshetic effect.
- Structurally different from fentanyl, with a methoxymethyl group on the piperidine ring (increases potency and reduces duration of action) and thiophene instead of phenyl ring.
- Natural phenathrene opioid - plant, animal and even human synthesis identified.
- Synthesized by mammalian cells from dopamine, although exact role unclear.
- pKa - 7.9 (20% nonionised @ 7.4)
- Octanol water coefficient - 1.4 (relatively low lipid solubility compared with other opioids)
- 3 rings attached to piperidine ring with a tertiary amine.
- Dose - 50 mcg/kg IV
- analgesia @ [plasma] 0.05 mcg/mL
- epidural: 10-20 mcg/mL
- PCA adult: 50 mg in 50 mL; 1 mL (1 mg) bolus 5 min lockout, commonly used.
- PCA paeds: 1 mg/kg in 50 mL; 1 mL (20 mcg/kg) bolus; background 0.5-1 mL/h (10-20 mcg/kg/h).
- Absorption - IV, IM, s/c, po (3x dose as HER 0.69)
- Distribution - Vdcc 0.3, Vdss 3.5 L/kg
- Protein binding - 30% (albumin)
- Onset: peak onset at 20 min when given parenteral, 60 min orally; Offset 4 h
- Metabolism - t½α 10-20 min, t½ß 2-4 h
- 75% metabolised by conjugation → 90% morphine-3-glucuronide (no activity)
- 10% morphine-6-gluc (13x potency of morphine). MAOIs inhibit glucuronidation.
- Clearance - 15 mL/kg/min
- Mech - mu, kappa, delta agonist. (GI linked). Effective against visceral, skeletal & joint pain.
- CNS - little CNS penetration (cf. heroin, which readily crosses BBB), although alkalisation (⇣pCO2) ⇡ non-ionised fraction, and ⇡pCO2 ⇡CBF. Both ⇡ cerebral morphine concentration.
- 'Ceiling effect' on EEG reaching high voltage, slow frequency (delta 2-4 Hz) waves.
- ⇣ CMRO2 & ⇣ ICP.
- ⇡ cortical stimulation of Edinger-Westphal nucleus → miosis.
- CVS - ⇣ SNS & ⇡ PNS tone. Bradycardia, venodilation, histamine release (causes ⇣ MAP). Orthostatic hypotension due to depression of SNS responses. Direct depressant effect on SA node, slowing conduction (⇡ VF risk).
- Administration with N2O results in CVS depression.
- Resp - Respiratory depression & response to CO2 & hypoxia (shift pCO2/VA curve to right).
- Bronchoconstriction due to histamine release (similar with pethidine). Depresses airway reflexes & ciliary reflexes.
- Renal - diuresis (kappa receptors → ADH release)
- GIT - Nausea & vomiting due to stimulation of CTZ (30-40% of subjets); ileus; constipation; sphincter of Oddi spasm.
Multiple advantages to cuffed ETT in children when compared to dogmatic alternative.
Pethidine (Meperidine) is a phenylpiperidine synthetic opioid first synthesized in 1938. Although widely used in the 20th century, it has fallen out of favour over the past decade due to abuse potential, limited advantages over other opioids and the existence of toxic metabolites.
Sulfentanil is a potent, short-acting synthetic opioid used in anesthesia and critical care. First synthesized by Janssen Pharmaceutica in 1974. It is the most potent opioid licensed for use in humans.
Simple measurement of cortical functional connectivity will not be enough to assess adequacy of general anesthesia.
A single pediatric general anesthetic exposure is associated with increased parental-reported behavioural changes though no difference in general intelligence.
Subcutaneous GTN may assist paediatric radial artery cannulation and improve first pass success.
Videolaryngoscopy may improve first-pass success in the ICU and among less experienced practitioners outside the operating theatre.
Videolaryngoscopy in children and neonates reduced intubation trauma & improved indirect glottic view, although demonstrated no other benefits.
GlideScope-Titanium videolaryngoscopy improved glottic visualisation but prolonged intubation time for placement of double lumen tubes.
Morphine is one of the most commonly used opioids worldwide. First isolated in 1803 and commercially marketed by Merck in 1827.