‫االسم‪ :‬نرجس راضي لوتي‬
‫الكلية‪ :‬كلية التقنيات الصحية والطبية‪/‬بغداد‬
‫القسم‪ :‬تقنيات التخدير‬
‫المادة‪ :‬الدوائيات‬
CODEINE
Codeine is an opioid analgesic used to treat moderate to
severe pain when the use of an opioid is indicated.
brand names:
Panadeine, Nurofen Plus and Mersyndol, as well as pharmacy generic products
that contain codeine. cough relief products with brand names such as Codral
and Demazin, as well as pharmacy generic cough medicines
that contain codeine.
Chemical Formula: C18H21NO3
Codeine sulfate is a form of this drug that is commonly used. It is available in
tablet form and indicated for the relief of mild to moderately severe pain,
where the use of an opioid analgesic is appropriate.
The solution form is used by itself or combined in a syrup with other drugs and is
used as a cough suppressant in adults aged 18 and above.
Pharmacodynamics:
General effects
Codeine is a weak narcotic pain reliever and cough suppressant that is
similar to morphine and hydrocodone. A small amount of ingested
codeine is converted to morphine in the body. Codeine increases
tolerance to pain, reducing existing discomfort. In addition to decreasing
pain, codeine also causes sedation, drowsiness, and respiratory
depression.
This drug has shown antitussive activity in clinical trials and has
been effective in cough secondary to tuberculosis and insomnia due
to coughing. Codeine suppresses the cough reflex through a direct
effect on the cough center in the medulla.
Effects on intestinal motility
Codeine may reduce intestinal motility through both a local and possibly central
mechanism of action. This may possibly lead to constipation. The chronic use of
opioids, including codeine sulfate, may lead to obstructive bowel disease,
particularly in patients with underlying disorders of intestinal motility Label.
Effects on the central nervous system
Codeine phosphate is an opioid analgesic with uses similar to those of morphine,
but is much less potent as an analgesic. Its primary site of action is at the mu
opioid receptors distributed throughout the central nervous system. The sedative
activities of codeine are less potent than those of morphine. Codeine may cause
respiratory system depression by the activation of μ-opioid receptors at specific
sites in the central nervous system.
This drug poses an increased risk of compromised ability to
maintain blood pressure due to peripheral vasodilation and other
mechanisms Label.
Effects on chronic cancer pain and other types of pain
Codeine is an opioid analgesic with similar indications to those of
morphine, however, is much less potent in its pain alleviating
properties. Its primary action takes place at the mu opioid
receptors, which are distributed throughout the central nervous
system. The average duration of action is about 4 hours.
Regular dosing of opioid analgesics such as codeine in patients
with severe cancer pain has been well documented to improve
symptoms.
Codeine is a selective agonist for the mu opioid
receptor, but with a much weaker affinity to
this receptor than morphine, a more potent
opioid drug. Codeine binds to mu-opioid
receptors, which are involved in the
transmission of pain throughout the body and
central nervous system. The analgesic
properties of codeine are thought to arise from
its conversion to Morphine, although the exact
mechanism of analgesic action is unknown at this
time.
Absorption
Absorption
Codeine is absorbed from the gastrointestinal tract. The maximum •
plasma concentration occurs 60 minutes after administration
When 60 mg codeine sulfate was given 30 minutes post-ingestion of a •
high high-calorie meal, there was no change in the absorption of
codeine
Food Effects
Steady-state
concentration
The administration of 15 mg codeine sulfate every 4 hours for 5 days lead to •
steady-state concentrations of codeine, morphine, morphine-3-glucuronide
(M3G) and morphine-6-glucuronide (M6G) within 48 hours
Metabolism:
Approximately 70 to 80% of the ingested dose of codeine is
metabolized in the liver by conjugation with glucuronic acid to codeine6¬ glucuronide (C6G) and by O-demethylation to morphine (about 510%) and N-demethylation to norcodeine (about 10%) respectively.
UDP-glucuronosyltransferase (UGT) 2B7 and 2B4 are the major
metabolic enzymes mediating the glucurodination of codeine to the
metabolite, codeine 6 glucuronide.
Cytochrome P450 2D6 is the major enzyme responsible for the
transformation of codeine to morphine and P450 3A4 is the main
enzyme mediating the conversion of codeine to norcodeine. Morphine
and norcodeine are then further metabolized by conjugation with
glucuronic acid. The glucuronide metabolites of morphine are morphine3-glucuronide (M3G) and_ morphine-6-glucuronide _(M6G). Morphine
and M6G have been proven to have analgesic activity in humans. The
analgesic activity of C6G in humans is not known at this time.
Norcodeine and M3G are generally not considered to have analgesic
properties.
Route of elimination:
About 90% of the total dose of codeine is excreted by the
kidneys. Approximately 10% of the drug excreted by the kidneys
is unchanged codeine.
The majority of the excretion products can be found in the urine
within 6 hours of ingestion, and 40-60 % of the codeine is
excreted free or conjugated, approximately 5 to 15 percent as
free and conjugated morphine, and approximately 10-20% free
and conjugated norcodeine.
Half-life:
Plasma half-lives of codeine and its metabolites have been
reported to be approximately 3 hours.
Overdose/toxicity:
Symptoms of opioid toxicity may include confusion,
somnolence, shallow breathing, constricted pupils, nausea,
vomiting, constipation and a lack of appetite. In severe
cases, symptoms of circulatory and respiratory depression
may ensue, which may be life-threatening or fatal.
References:
Nagaraj R. Ayyangar, Anil R. Choudhary, Uttam R. Kalkote, Vasant K. Sharma, "Process for the preparation of codeine from morphine." U.S.
Patent US4764615, issued May, 1912. Schroeder K, Fahey T: Over-the-counter medications for acute cough in children and adults in
ambulatory settings. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001831.
Vree TB, van Dongen RT, Koopman-Kimenai PM: Codeine analgesia is due to codeine-6-glucuronide, not morphine. Int J Clin Pract. 2000 JulAug;54(6):395-8. [
Srinivasan V, Wielbo D, Tebbett IR: Analgesic effects of codeine-6-glucuronide after intravenous administration. Eur J Pain. 1997;1(3):185-90.
Bhandari M, Bhandari A, Bhandari A: Recent updates on codeine. Pharm Methods. 2011 Jan;2(1):3-8. doi: 10.4103/2229-4708.81082.
Chen ZR, Somogyi AA, Reynolds G, Bochner F: Disposition and metabolism of codeine after single and chronic doses in one poor and seven
extensive metabolisers. Br J Clin Pharmacol. 1991 Apr;31(4):381-90.
Takahama K, Wakuda I, Fukushima H, Isohama Y, Kai H, Miyata T: Differential effect of codeine on coughs caused by mechanical stimulation of
two different sites in the airway of guinea pigs. Eur J Pharmacol. 1997 Jun 18;329(1):93-7.
Straube C, Derry S, Jackson KC, Wiffen PJ, Bell RF, Strassels S, Straube S: Codeine, alone and with paracetamol (acetaminophen), for cancer
pain. Cochrane Database Syst Rev. 2014 Sep 19;(9):CD006601. doi: 10.1002/14651858.CD006601.pub4.
Boom M, Niesters M, Sarton E, Aarts L, Smith TW, Dahan A: Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr
Pharm Des. 2012;18(37):5994-6004. doi: 10.2174/138161212803582469.
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Codeine phosphate tablets, 30mg
DailyMed: Codeine and promethazine syrup
EPAR, Codeine
Codeine, MedSafe NZ document
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