Core pharmacology

Class Group

Opiate Analgesic

Legacy Cicm Level

-

Introduction

synthetic phenylpiperidine derivative.

Indications Uses

1. for premedication
2. as an analgesic in the management of moderate to severe pain and
3. as an antispasmodic agent in the treatment of renal and biliary colic.

Presentation

Tab: 50mg
Inj: Colourless solution 10/50 mg/l Pethidine HCl

Main Action

µ & κ agonist

Mechanism of action

Binds primarily to inhibitory G-Protein Coupled μ-opioid receptors→ ↑adenylyl cyclase→ ↓cAMP→ hyperpolarization of cell→↓neurotransmitter release

Onset Peak Duration

Onset
PO 15min
IM 10min

Dur 2-3hrs

Physiological effects

inhibitory action,
modulating the pain response to produce analgesia.

Antitussive

Less histamine release than morphine

Adverse Effects Toxicity

CVS
Orthostatic hypotension (histamine release + α blockade).
Tachycardia (mild quinidine-like effect & anticholinergic properties)

RS
Potent resp depressant (TV > RR)
Obtunds response to hypoxia and hypercapnia
Chest wall rigidity,

CNS
More euphoria, less N/V

GIT dec gastric emptying
GU dec uterine tone, inc uterine contractions

Inc ADH secretion, Dec adrenal steroid secretion

Hallucinations
Dependence

Absorption

PO 45-75% (significant first pass)
IM: 100%

Protein binding

49-67%

Volume of distribution

3.5 – 5.3 L/kg

Metabolism

Liver
N-demethylation to norpethidine and hydrolysis to pethidinic acid

Excretion

Renal (1-25% unchanged, rest metabolites)

Norpethidine accumulates in renal and liver failure, 50% potency of pethidine

Half-life

2.4-7 hrs

Special Points

Severe hypertensive episode with MAOIs
Inhibits post-anaesthetic shivering

Route And Dose

PO: 50-150mg Q4hrly
IM: 25-150mg
IV: 25-100mg
Epidural: 25mg

(relative potency 0.1)