OPIOIDS - II

CNS

Agent

Morphine

Pethidine

Tramadol

Naloxone

Analgesia

Visceral, m/skel pain

Not neuropathic

Anti-nociceptive, modulated afferent component

Also LA effects potency=cocaine

30% inhibited by naloxone

Binds mu>>delta/kappa

Complete antagonist

Euphoria

Via mu

>morphine

Sedation

CTZ stim

40% 1^st dose

desensitisation

30-35% first dose

Miosis

Edinger-Westphal nucleus stimulation

EEG

Resembles sleep

Mm rigidity

Inhibit interneurones

CBF

↓ unless ↑CO2

ICP

↓

Resp

Vminute

↓ dose dependent

RR

↓ more than TV

TV

↑

Response CO2

↓ central chemorec → right shift curve

Depression >morphine

Cough reflex

?mech (↑ with subs on phenol OH eg pholcodine)

Nil effect

Ciliary activity

↓

Raw

(?↑ direct+His release)

CVS

CO

(↓)

BP

(↓)

↓ >morphine

SVR

(↓ if His release)

↓

Barorec reflex

↓orthostatic hypot

>morphine

HR

↓

↑ (atropine)

Contractility

0

↓ (only one)

Venodilatation

↓ venous return

Arrhythmias

↓ risk VF

Mechanisms

↓Σ, vagotonic, direct dep SA, AV nodes

GIT

Motility

↓

minimal

Gastric empty

↓

Biliary spasm

½ x fent

3x pethidine

minimal

minimal

LES tone

↓

Mechanism

Intramural plexus, central effects

Renal

Blood flow

↓ (minor due to ↓CO)

Ureteric perist

↑

Detrusor tone

↑

Sphincter tone

↑ → retention

ADH

?↑ or no effect (pain)

Obste-

trics

Uterine tone

Placental T/F

easy

Side effects

His release

>5mg/min ivi

Other

Nausea

Pruritis

Heaviness, warmth

Anti-shiver (kappa)

Anti-shiver ?mech

Seizures in OD / epilepsy

Sweating, xerostomia

Reverse analgsia

N&v iv <2min

↑Σ, withdrawal

Interactions

Combo with N2O or benzo → ↓CO, SVR, BP

MAOI (↓metab)

Inhibit serotonin uptake

MAOI

Drug dependence

Tolerance

12-24hrs

not to constipation/miosis

↓affinity, downregulation, uncoupling from 2^nd mess

Dependence

Onset 48hr, fullblown 25 days

minimal

Withdrawal

Onset 15-20hr

Peak 2-3 days

Offset 10-14 days

Few autonomic effects

More rapid

Shorter duration