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

mod affinity for μ receptors, weak κ, δ
-in spinal desc inh pathways by inh of neuronal reuptake of norad&serotonin
-presynaptic stim of seritonin release

mod affinity for μ receptors, weak κ, δ
-in spinal desc inh pathways by inh of neuronal reuptake of norad&serotonin
-presynaptic stim of seritonin 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

CNS:
- Analgesia
- Hallucinations
- Confusion
- Delirium
- Agitation
- Seizures
- Coma (Serotonin syndrome)

Respiratory depression and
constipation

CNS:
- Analgesia
- Hallucinations
- Confusion
- Delirium
- Agitation
- Seizures
- Coma (Serotonin syndrome)

Respiratory depression and
constipation

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

Bioavailability- 75% PO

relative lipid sol 1

but crosses BBB

pKa 8.0 (25% unionised)
slow redistribution

Crosses placenta
Lipid soluble-crosses BBB

Crosses placenta
Lipid soluble-crosses BBB

prot bind 20-40% (Alb)

Low plasma protein binding, approximately 20%.

Prot bind-20%

20%

mod Vd 3-4L/kg

2.9-4.37 L/kg.

Vd- 2.5-3L/kg

2.5-3L/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

Extensively hepatic via demethylation ,
glucuronidation, and sulfation; active metabolite by CYP2D6 (M1; O-desmethyl tramadol)

Extensively hepatic via demethylation ,
glucuronidation, and sulfation; active metabolite by CYP2D6 (M1; O-desmethyl tramadol)

Excreted mainly in urine as conjugates with 10% in faeces

Urine 90% (30% unchanged), 10% faeces.

Half time 2-4hrs (large interpatient Variability)

T1/2: ~6-8 hrs;
Act metab:7-9hrs;
old, hepatic/renal imp.

T1/2: ~6-8 hrs;
Act metab:7-9hrs;
old, hepatic/renal imp.

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)

Dysphoria,Euphoria. Miosis (excitation of Edinger-Westphal nucleus)
N/V -CTZ stim. Serotonin syndrome with SSRI /SNRI/MAO/TCA
Less resp dep than morphine
analgesic effect in CYP2D6 deficiency

Dysphoria,Euphoria. Miosis (excitation of Edinger-Westphal nucleus)
N/V -CTZ stim. Serotonin syndrome with SSRI /SNRI/MAO/TCA
Less resp dep than morphine
analgesic effect in CYP2D6 deficiency

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

Analgesia

naturally occuring phenanthrene derivative from papaver somniferum plant

Is a synthetic opioid – cyclohexanol derivative
Racemic mix.

Is a synthetic opioid – cyclohexanol derivative
Racemic mix.

Level 1

Level 2

primarily CNS μ receptor activity, also κ and δ.

mod affinity for μ receptors, weak κ, δ

onset / duration ~1 hour / 9 hours (immediate release)

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

immediate release, 12 hour release and 24 hour release
tablets, IV

immediate release, 12 hour release and 24 hour release
tablets, IV

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

(relative potency 1)

Route- PO/IV
Dose- 50-100mg QID for all routes
(Relative pot 0.2)

Route- PO/IV
Dose- 50-100mg QID for all routes
(Relative pot 0.2)

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