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

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

CNS:
Opioid receptors present in cerebral cortex, periaqueductal grey, nucleus accumbens, area postrema, thalamus and NTS
- Analgesia
- Sedation
- Respiratory depression
- Nausea
- Euphoria
- Psychotomimetics
Seizures (due to M6G metabolite)

PNS Excitatory action
Histamine release

inhibitory action,
modulating the pain response to produce analgesia.

shares many of its actions with morphine and
related compounds

PO/IV/IM/SC/SL/IT
Poor bioavailability 30% (good abs but high 1st pass metab)
onset / duration Oral ~30 minutes; I.V.: 5-10 minutes

IV only

onset / duration 1-3 minutes

relative lipid sol 1

but crosses BBB

pKa 8.0 (25% unionised)
slow redistribution

relative lipid sol 50

rapid redistribution
pKa 7.1 (70% union)

prot bind 20-40% (Alb)

Prot bind ~70% (1 acid glycoprotein)

mod Vd 3-4L/kg

Vd 0.3L/kg kids

Metabolised to morphine-3-glucuronide (70%)
and morphine-6-glucuronide (10%) by gut wall and liver.
M6G is 10-20 times potent, may accumulate in renal failure

Rapid metabolism via blood and Plasma esterase
- used in liver/ renal disease, different age, sex, body habitus without sign dose modificn

Excreted mainly in urine as conjugates with 10% in faeces

excretion urine

Half time 2-4hrs (large interpatient Variability)

half life Terminal: 10-20 minutes; effective: 3-10 minutes
No CSHT

CNS: dysphoria, confusion, ↓LoC, ↓cough reflex, miosis(PNS)
CVS: hypotension (↓TPR, blunt baroreceptor reflexes)
Resp: dir ↓resp drive indir via obtundation
GI: ↓gut motility, ↓SB secretions, CTZ→N+V, constipn, CBD spasm.
GU: Urinary retention
skin flushing, pruritis(histamine)
Dependence, addiction,Tolernce. IT – resp dep (rostral migration)

Bradycardia, hypotension, muscle rigidity,
May contribute to hyperalgesia
following prolonged infusion

Opiate Analgesic

Opiate Analgesic

1. for premedication
2. as an analgesic in the management of moderate to severe pain
3. in the treatment of left ventricular failure
4. to provide analgesia during terminal care, and
5. in combination with kaolin in the symptomatic treatment of diarrhoea

1. to provide the analgesic component in general anaesthesia
2. to provide analgesia/sedation in intensive care
3. to provide analgesia during labour when regional anaesthesia is not in
use
4. to provide analgesia/sedation during ‘awake’ fibreoptic intubation.

naturally occuring phenanthrene derivative from papaver somniferum plant

synthetic phenylpiperdine derivative of fentanyl with a unique metabolism

Level 1

Level 2

primarily CNS μ receptor activity, also κ and δ.

Pure mu receptor agonist

either as a clear liquid for injection, orally in immediate (liquid or tablet) and sustained release (MS Contin)

white crystalline powder for reconstitution

Dose 5-10mg titrate eff¬ect, may increase x100 with tolerance

(relative potency 1)

Dose 1mcg/kg bolus, titrate eff¬ect

(relative potency 50-100)

May precipitate encephalopathy in hepatic failure
May precipitate coma in hypopituitarism

Good reversal with naloxone (does not affect epidural analgesia)

Not removed by haemo/peritoneal dialysis

Clearance of metabolite remifentanil acid - prolonged in renal impairment (up to 268 hrs)

Metabolite concentration significantly increased in ICU patients with mod-severe renal impairment – but no evidence of clinically significant mu-opioid effects

Remifentanil not extracted during RRT.
Metabolite extracted 25-35% during hemodialysis.