INTRODUCTION:-
This drug was first isolated by the German
pharmacist “Freidrich Wilhelm Adam Serturner” in 1804 and give the name to this
drug is “morphium” (God of sleep). It is a phenanthrene derivative and
prototypical strong mu receptor agonist. It is used to control the severe pain.
Due to development of hypodermic needle, the use of morphine rapidly increased
for relieve of pain. So after the American Civil war, approximately 100000 soldiers
got “soldier’s disease” (morphine addiction).
MODE OF ACTION:-
When morphine binds to the mu opioid receptor which
is mostly found on the CNS, it activates the alpha G subunit of G protein which
is the inhibitory subunit. It goes and inhibit the adenylate cyclase enzyme due
to which ATP will not be converted into CAMP, in normal condition CAMP inhibits
the potassium channel due to which it blocks the potassium efflux so when CAMP
will not formed then there will be no one which inhibit the potassium efflux.
Due to continuous potassium efflux it makes the membrane hyperpolarized and
stops the action potential due to which pain reduces. And decreased CAMP level
also inhibit the Calcium influx due to which it inhibits the release of neurotransmitter
from the vesicles of pre-synaptic neuron, which comes in response of noxious
stimuli, So it inhibits the signal propagation and produces analgesic effects.
PHARMACOKINETICS:-
1) Morphine’s
absorption occurs in the alkaline environment of the upper intestine and the
rectal mucosa. Its bioavailability of morphine is 80 to 100%. Tmax of parental
morphine is 15 minutes and oral morphine Tmax is 90 minutes with a Cmax of
283nmol/L. The area under curve (AUC) of morphine is 225-290nmol*h/L and its half-life
is 2 to 3 hours.
2) Morphine’s
volume of distribution is 5.31L/kg while morhine-6-glucuronide’s volume of
distribution is 3.61L/kg.
3) Morphine’s
protein binding is 35%, morphine-3-glucuronide’s protein binding is 10% and
morphine-6-glucuronide’s protein binding is 15%.
4) Morphine
is 90% metabolized by the glucuronidation by UGT2B7 and sulfation at positions
3 and 6. It can also be metabolized into normorphine, morphine ethereal sulfate
and codeine.
5) Morphine’s
70-80% of administered dose is excreted within 48hrs. It is mainly eliminated
via urine along with 2-10% of administered dose recovered as unchanged parent
drug and 7-10% morphine’s dose is eliminated via feces.
DOSAGE:-
ORAL:-short-acting oral
dose for severe and chronic pain in adults is 10-30 mg Q4H.
I.M or S.C:-5-20 mg
(usually10 mg) Q4H.
I.V:-initial dose is 4 mg-10 mg slowly over 4-5 minutes Q4H. Daily dose range is 12-120 mg.
ADVERSE EFFECTS:-
1) Miosis
2) Respiratory depression
3) Physical dependence
4) Orthostatic hypotension
5) Increased intracranial tension
6) Nausea
7) Sedation
8) Euphoria
No comments:
Post a Comment