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.
- 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.
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.
- 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.