chlorhydrate morphine

THERAPEUTIC INDICATIONS

• Intense and/or resistant pain to analgesic of low level.

PHARMACEUTICAL FORM

Morphine hydrochloride is available in glass ampoule with an OPC (one point cut) opening system.

PHARMACO-THERAPEUTIC CLASS

Opioid analgesic, code ATC N02AA01 (N: central nervous system)

PHARMACODYNAMICS

Action on central nervous system :

Morphine has a dose-dependent analgesic action. It may act on psychomotor behavior and cause, depending on the dose and background, either sedation or agitation.

On respiratory centers and that of cough, morphine exerts from the onset of therapeutic doses, a depressive action. The depressor respiratory effects of morphine subside in chronic treatment. Action of morphine on the vomiting center, (via the chemoreceptor trigger zone (CTZ), particularly through stimulation by pain and cochleo-vestibular space), and on gastric emptying endows it with variable emetic properties. Finally morphine results in myosis from central nervous system.

Action on the smooth muscle :

Morphine decreases tonicity and peristalsis of longitudinal fibres while increasing tonicity of circular fibres, causing spasm on sphincters (pylorus, ileum-caecal valvula, anal sphincter, Oddi’s sphincter, vesical sphincter).

PHARMACOKINETICS

Resorption :

• Since it is more quickly resorbed in blood by epidural route (via large venous plexus) than by intrathecal (via small medullary capillaries), morphine-induced analgesia has a sustained release action by intrathecal route.
• By epidural and intrathecal route, supraspinal distribution is delayed.

Biodisponibility of oral administration compared to those administered by subcutaneous route is 50 %. Biodisponibility of oral administration compared to that administered by intravenous route accounts for 30 %.

Distribution :
After resorption, the binding of morphine to plasma proteins accounts for 30 %. Morphine crosses the hemato-encephalic barrier and placenta.

Metabolism :
Morphine is highly metabolized in glucuronoconjugated derivatives which go through an enterohepatic cycle. 6 -glucuronide and normorphine are two active metabolites of the substance-mother.

Elimination :

• Plasma half-life of morphine varies (from 2 to 6 hours).
• Elimination of glucuronoconjugated derivatives is primarily through urine, both by glomerular filtration and tubular secretion.
• Elimination in the feces is low (<10 %).