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

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

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)

prot bind 20-40% (Alb)

prot bind 80-85%

mod Vd 3-4L/kg

Mod Vd 4-6L/kg

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

Excreted mainly in urine as conjugates with 10% in faeces

excretion Urine 75%

Half time 2-4hrs (large interpatient Variability)

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

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)

Respiratory depression including postoperative recurrence. Bradycardia. Chest-wall rigidity. Nausea and vomiting. Dependence. Decreased gastrointestinal motility.

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

Similar. 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

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

naturally occuring phenanthrene derivative from papaver somniferum plant

Tertiary amine which is a synthetic phenylpiperidine derivative

Level 1

Level 1

primarily CNS μ receptor activity, also κ and δ.

μ 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

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)

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