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 → inhibits adenylyl cyclase → ↓ cAMP → opens K+ channels and inhibits presynaptic voltage-gated Ca2+ channels → hyperpolarisation and ↓ 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.

less likely to ppt histamine release
norad& serotonin axn, excitatory centrally

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/IM/TD. BA PO 30%SL50%skin>90%
onset IM.: 7-8 mins; IV imm; TD 6 hrs
duration IM:1-2 hrs; IV:0.5-1hr; TD 12hrs

IV only

onset / duration 1-3 minutes

relative lipid sol 1

but crosses BBB

pKa 8.0 (25% unionised)
slow redistribution

relative lipid sol 500

Rapid redistribution
pKa 8.4(10% union)

relative lipid sol 50

rapid redistribution
pKa 7.1 (70% union)

prot bind 20-40% (Alb)

prot bind 80-85%

Prot bind ~70% (1 acid glycoprotein)

mod Vd 3-4L/kg

Mod Vd 4-6L/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

Slow Hepatic, primarily via CYP3A4clearance

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 75%

excretion urine

Half time 2-4hrs (large interpatient Variability)

half life I.V.: 2-4 hours, prolonged context sensitive half time

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)

Similar to other opioids. Differences due to lipid sol.
Does not cause delayed respiratory depression because it rapidly diffuses into and out of the CSF. Raised CSHT prolonged infusion may lead to increased duration of action and SE

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

Opiate Analgesic

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. in combination with a major tranquillizer to produce neuroleptanalgesia
3. to provide analgesia during labour when regional anaesthesia is not in
use
4. as an agent used for patient-controlled analgesia
5. in premedication and
6. for palliative care

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

Tertiary amine which is a synthetic phenylpiperidine derivative

synthetic phenylpiperdine derivative of fentanyl with a unique metabolism

Level 1

Level 1

Level 2

primarily CNS μ receptor activity, also κ and δ.

μ receptor agonist

Pure mu receptor agonist

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

colourless solution 50mcg/ml, TDpatch (25mcg-100mcg/hr) and as lozenges

white crystalline powder for reconstitution

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

(relative potency 1)

Bolus: 1-2 mcg/kg
inf: 1-2 mcg/kg/hr

(relative potency 50-100)

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

- Incompatible with thiopental

- Dialysis - unknown

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.