Pethidine

Chemical

Synthetic opioid of PHENYLPIPERIDINE class

Short onset, immediate acting

Use

  1. Premed
  2. Analgesia
  3. Antispasmodic to tx renal & biliary colic
  4. Post op shivering (kOP in SC)

Presentation

Tablets 50mg

Ampoule: clear, colourless 50mg/mL

Dose / Route

1/10 potency of M

PO: 1 – 2mg/kg Q3h

Parental (IV/IM): 1mg/kg for analgesia; 0.3mg/kg for suppression of post-op shivering

Epidural: 25 – 50mg (more lipid soluble cf M ∴ produces analgesia quicker in 5 – 10mins)

Properties

  • Similar pharmacological activity to M but different structure
  • Phenylpiperidine group ∴resembles F
  • SAR: similar to atropine ∴mild atropine-like activity
  • Mydriasis, antispasmodic, ↑HR

Was discovered by fluke when researching a synthetic atropine

MoA

µOP agonist

kOP agonist (10% activity)

PD

Most clinical actions similar to M

Significant differences

  • Ability to inhibit uptake of 5HT
  • Atropine-like actions

CNS

  • Analgesia
  • Mydriasis

Resp

  • Resp depression
  • Less depression of airway reflexes/antitussive

CVS: No significant CVS effects. ↑HR (atropine like) BUT @ high doses   – VE INOTROPY

GU: less urinary retention 2° atropine activity

GI: less colic & constipation 2° atropine activity

Drug Interactions

Inhibits 5HT uptake

Interacts with MAOI

PK

A

Better absorption cf. M but only 50% as effective PO cf. IM

D

50% PPB

VD 3 – 5L/kg

Crosses placenta

M

Hepatic

HYDROLYSIS to pethidinic acid

DEALKYL(methyl)ATION to norpethidine

Norpethidine hydrolysed → norpethidine acid

Norpethidine = active metabolite

E

Urinary

10% unchanged

Rest as metabolites

Adverse Effects

Toxicity

Interactions

  • Neonates & elderly
    • ↑sensitivity
    • ↓PPB, ↓VD, ↓clearance
  • MAOI
    • Additive inhibition of 5HT uptake
    • Precipitate severe HTN crisis
  • Renal failure
    • Norpethidine accumulation