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Collections with the topic tag Opioid
Addiction
Analgesia
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Fentanyl
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Obstetric anesthesia
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Perioperative medicine
Remifentanil
Sufentanil
Tapentadol
Tramadol
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A. Physiochemistry
- pKa - 7.3 (58% nonionised @ 7.4)
- Octanol water coeff - 18
- phenylpiperidine opioid
- contain 2 ester bonds so hydrolysed by non-specific tissue esterases.
- Preparation contains 'glycine', so cannot be used epidurally.
- White powder for reconstitution with water - 1, 2, 5 mg packs
B. Pharmacokinetics
- Dose: (100x morphine potency, ~equal to fent)
- TCI: 3-8 ng/mL
- (up to 15 ng/mL for very stimulating procedures)
- Spontaneous ventilation returns @ 1-2 ng/mL
- 0.1-0.3 mcg/kg/min infusion (with propofol 80 mcg/kg/min (= 34 mL/h for 70 kg).
- 0.01-0.05 mcg/kg/min spont vent
- dilute 1 mg to 50 mL = 20 mcg/mL, or 5 mg in 50 mL = 100 mcg/mL.
- paeds: 0.03 mg/kg in 50 mL then 1 mL/h = 0.01 mcg/kg/min.
- Or paediatric whole-ampoule dilutions when advanced pumps are unavailable:
- 1mg in 16.7mLs
- or 2mg in 33.3 mLs
- or 3mg in 50mLs
- → to give a dilution of 60mcg/mL
- then for a patient of XYkg running at X.Y mLs/hr is 0.1mcg/kg/min. eg. for a 42kg patient running at 0.1mcg/kg/min will be 4.2mLs/hr which over 4 hrs uses 16 mL so a 1mg ampoule would be sufficient.
- 1 mcg/kg IV bolus to blunt pressor resp to intubation, better than fentanyl. (equiv. fent 2 mcg/kg, alfent 20 mcg/kg)
- 3-5 mcg/kg for intubation with propofol 2 mg/kg.
- 0.2-0.8 mcg/kg bolus for PCA analgesia (++SEs: sedation, desaturation)
- Absorption - IV
- Distribution - 0.5 L/kg (small)
- Protein binding - 70-90%
- Onset 1-4 min; Offset 4 min (offset due to metab not redist)
- Metabolism - ß½ ~10 min. (CSHT-8h only 4 min!) Metabolised by non-specific plasma esterases to almost-inactive metabolites (GR90291: 1/4600 activity! / t½ 2h).
- Minor pathway - N-dealkylation. NOT metabolised by plasma cholinesterase.
- Clearance - 42 mL/min/kg (30-50% CO)
C. Pharmacodynamics
- Mech - highly selective mu agonist.
- CVS - dec MAP & HR 20-30%. (? low dose glycopyrrolate to attenuate brady).
- No histamine release.
- CNS
- max MAC reduction ~ 85% (0.1-0.2 mcg/kg/min = 60-70% MAC reduction).
- To avoid awareness keep propofol @ at least 80 mcg/kg/min or volatile 0.3 MAC.
- Sedation.
- Beware rapid Opioid Induced Hyperalgesia.
- Resp - ⇣ RR & MV; apnoea. Spontaneous respiration occurs at blood concentrations of 4 to 5 nanogram/mL in the absence of other anaesthetic agents; for example, after discontinuation of a 0.25 microgram/kg/minute infusion of remifentanil, these blood concentrations would be reached in two to four minutes.
- GIT - dec CTZ stimulation as rapidly metabolised; no ion trapping.
- Muscle - muscle rigidity similar to alfentanil, though more than fentanyl.
- May cause chest wall rigidity (inability to ventilate) after single doses of > 1 microgram/kg administered over 30 to 60 seconds or infusion rates > 0.1 microgram/kg/minute.
- Administration of doses < 1 microgram/kg may cause chest wall rigidity when given concurrently with a continuous infusion of remifentanil.
- Foetal - little effect as rapidly metabolised by foetus.
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- Remifentanil infusions above 0.20-0.25 μg/kg/min are associated with hyperalgesia (OIH = Opioid Induced Hyperalgesia) and tolerance (AOT = Acute Opioid Tolerance) respectively.
- Some of these effects can be mitigated by multimodal analgesia (notably ketamine), and possibly by gradual weaning of a remifentanil infusion.
- The findings have been predominately identified in rats and volunteer human studies. The clinical and longterm significance is still uncertain.
- Although OIH and AOT arise from different physiological mechanisms, they are clinically difficult (if not impossible) to differentiate.
- The clinical priority for management is prevention.
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