 Morphine
oral solution 
What does
morphine oral solution do?
MORPHINE (MSIR®, Roxanol®, Rescudose™, MS/L™,
OMS™) relieves moderate to severe pain. Morphine may be used
to control the pain following surgery, child birth, and other procedures.
Morphine may also be used to treat pain associated with cancer, heart attacks,
sickle cell disease and other medical conditions. Do not share this medicine
with anyone else. Federal law prohibits the transfer of morphine to any
person other than the patient for whom it was prescribed. Generic morphine
solution is available.
What should
my health care professional know before I take morphine?
They need to know if you have any of these conditions:
? diarrhea
? drug or alcohol abuse problem 
? head injury
? heart disease
? intestinal disease
? kidney disease
? liver disease
? lung disease or breathing difficulties
? seizures (convulsions)
? an unusual or allergic reaction
to morphine, oxycodone, codeine,
other medicines, foods, dyes, or preservatives
? pregnant or trying to get pregnant
? breast-feeding
How should
I take this medicine?
Take morphine solution by mouth. Follow the directions on the prescription
label. If morphine upsets your stomach, you can take it with food or milk.
Contact your pediatrician or health care professional regarding the
use of this medicine in children. Special care may be needed. Do not share
this medicine with anyone.
What if I
miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time
for your next dose, take only that dose. Do not take double or extra doses.
What other
medicines can interact with morphine?
? medicines for high blood pressure
? medicines for seizures
Because morphine can cause drowsiness, other medicines that also cause
drowsiness may increase this effect of morphine. Some medicines that cause
drowsiness are:
? alcohol-containing medicines
? barbiturates such as phenobarbital
? certain antidepressants or tranquilizers
? muscle relaxants
? certain antihistamines used in cold medicines Ask your pre scriber
or health care professional about other medicines which may increase the
effect of morphine.
Tell your pre scriber
or health care professional about all other medicines that you are taking,
including non-prescription medicines, nutritional supplements, or herbal
products. Also, tell your pre scriber or health care professional if you
are a frequent user of drinks with caffeine or alcohol, if you smoke, or
if you use illegal drugs. These may affect the way your medicine works.
Check with your health care professional before stopping or starting any
of your medicines.
What side
effects may I notice from taking morphine?
Some side effects can be eased if you lie down after taking your medicine.
Side effects that you should report to your pre scriber or health care
professional as soon as possible:
Rare or uncommon:
? breathing difficulties, wheezing
? cold, clammy skin
? seizures
? slow or fast heartbeat
? severe rash
? unusual weakness More common:
? confusion
? lightheadedness or fainting spells
? nervousness or restlessness
Side effects
that usually do not require medical attention (report to your pre scriber
or health care professional if they continue or are bothersome):
? itching
? blurred vision
? clumsiness, unsteadiness
? constipation
? decrease or difficulty passing urine
? dizziness, drowsiness
? dry mouth
? flushing
? headache
? nausea/vomiting
? pinpoint pupils
? sweating
What do I
need to watch for while I take morphine?
Tell your prescriber or health care professional if your pain does not
go away, if it gets worse, or if you have new or different type of pain.
Use exactly as directed by your pre scriber or health care professional.
If you are taking morphine on a regular basis, do not suddenly stop taking
it. Your body becomes used to the morphine and when you suddenly stop taking
it, you may develop a severe reaction. This DOES NOT mean you are “addicted”
to morphine. Addiction is a behavior related to getting and using a drug
for a non-medical reason. If you have pain, you have a medical reason to
take pain medicine such as morphine to control your pain.
You may get drowsy or dizzy when you first start taking morphine or
change doses. Do not drive, use machinery, or do anything that needs mental
alertness until you know how morphine affects you. Stand or sit up slowly,
this reduces the risk of dizzy or fainting spells. These effects may be
worse if you are an older patient. The drowsiness should decrease after
taking morphine for a couple of days. If you have not slept because of
your pain, you may sleep more the first few days your pain is controlled
to catch-up on missed sleep.
Be careful taking other medicines which may also make you tired. This
effect may be worse when taking these medicines with morphine. Alcohol
can increase possible drowsiness, dizziness, confusion and affect your
breathing. Avoid alcohol while taking morphine.
Morphine will cause constipation. Make
sure to take a laxative and/or a stool softener while taking morphine.
Try to have a bowel movement at least every 2—3 days. If you do not have
a bowel movement for 3 days or more call your pre scriber or health care
professional. They may recommend using an enema or suppository to help
you move your bowels.
Your mouth may get dry. Drinking plenty of water, chewing sugarless
gum or sucking on hard candy may help to relieve dry mouth symptoms.
Have regular dental checks.
If you are going to have surgery, tell your pre scriber or health care
professional that you are taking morphine.
Rarely, morphine may cause you to have hallucinations (to see things
that are not really there) or cause your legs or arms to “jerk” or have
spasms. If you experience these effects, call your pre scriber or health
care professional.
Where can
I keep my medicine?
Keep out of the reach of children in a container that small children
cannot open. Do not share or give this medicine to anyone else. Avoid accidental
swallowing of morphine by someone (especially children) other than the
person for whom it was prescribed as this may result in severe effects
and possibly death.
Store at room temperature between 15 and 30°C (59 and 86°F).
Protect from light. Throw away any unused medicine after the expiration
date.
Advanced Clinical
Information:
Description :Morphine is the principal alkaloid obtained from
the unripened seed capsules of the opium poppy, Papaver somniferum. It
was first isolated in 1803 and is the prototype of the opiate agonists.
Today, the poppy is still the source of the drug because synthesis of morphine
is difficult. Morphine is available for administration as the hydrochloride
or sulfate salt in all dosage forms. Morphine sulfate is a strong analgesic
used for the relief of moderate to severe acute and chronic pain, preoperative
sedation and as a supplement to anesthesia. Morphine is also used for analgesia
during labor. The effect on uterine contractions depends on the stage of
labor when it is administered. Morphine is the drug of choice for
pain associated with myocardial infarction and cancer. Morphine, as well
as other opioids, can produce euphoria, feelings of well being, and tranquility,
subjecting them to potential abuse. All opioid drugs cause physical dependence
with chronic use. Morphine is a schedule C-II controlled substance and
was in use for many years prior to its approval by the newly formed FDA
in 1939. An NDA has been filed for a combination product, MorphiDex, in
August 1998. This product contains morphine and dextromethorophan.
Mechanism of Action:Morphine is a potent µ-opiate receptor agonist.
Opiate receptors include µ (mu), kappa (kappa), and delta (delta),
which have been reclassified by an International Union of Pharmacology
subcommittee as OP1 (delta), OP2 (kappa), and OP3 (µ). These receptors
are coupled with G-protein (guanine-nucleotide-binding protein) receptors
and function as modulators, both positive and negative, of synaptic transmission
via G-proteins that activate effector proteins. Opioid-G-protein systems
include adenylyl cyclase-cyclic adenosine monophosphate (cAMP) and phospholipase{3}
C (PLC)-inositol 1,4,5 triphosphate (Ins(1,4,5)P3)-Ca).
Opiates do not alter the pain threshold of afferent nerve endings to
noxious stimuli, nor do they affect the conductance of impulses along peripheral
nerves. Analgesia is mediated through changes in the perception of pain
at the spinal cord (µ{2}-, delta-, kappa-receptors) and higher levels
in the CNS (µ{1}- and kappa{3} receptors). There is no ceiling effect
of analgesia for opiates. The emotional response to pain is also altered.
Opioids close N-type voltage-operated calcium channels (kappa-receptor
agonist) and open calcium-dependent inwardly rectifying potassium channels
(µ and delta receptor agonist) resulting in hyperpolarization and
reduced neuronal excitability. Binding of the opiate stimulates the exchange
of guanosine triphosphate (GTP) for guanosine diphosphate (GDP) on the
G-protein complex. Binding of GTP leads to a release of the G-protein subunit,
which acts on the effector system. In this case of opioid-induced analgesia,
the effector system is adenylate cyclase and cAMP located at the inner
surface of the plasma membrane.Thus, opioids decrease intracellular cAMP
by inhibiting adenylate cyclase that modulates the release of nociceptive
neurotransmitters such as substance P, GABA, dopamine, acetylcholine and
noradrenaline. Opioids also modulate the endocrine and immune systems.
Opioids inhibit the release of vasopressin, somatostatin, insulin and glucagon.
The stimulatory effects of opioids are the result of “disinhibition”
as the release of inhibitory neurotransmitters such as GABA and acetylcholine
is blocked. The exact mechanism how opioid agonists cause both inhibitory
and stimulatory processes is not well understood. Possible mechanisms including
differential susceptibility of the opioid receptor to desensitization or
activation of more than one G-protein system or subunit (one excitatory
and one inhibitory) by an opioid receptor.
Clinically, stimulation of µ-receptors produces analgesia, euphoria,
respiratory depression, miosis, decreased gastrointestinal motility, and
physical dependence. Kappa-receptor stimulation also produces analgesia,
miosis, respiratory depression, as well as, dysphoria and some psychomimetic
effects (i.e., disorientation and/or depersonalization). Miosis is produced
by an excitatory action on the autonomic segment of the nucleus of the
oculomotor nerve. Respiratory depression is caused by direct action of
opiate agonists on respiratory centers in the brain stem. Opiate agonists
increase smooth muscle tone in the antral portion of the stomach, the small
intestine (especially the duodenum), the
large intestine, and the sphincters.
Opiate agonists also decrease secretions from the stomach, pancreas, and
biliary tract. The combination of effects of opiate agonists on the GI
tract results in constipation and delayed digestion. Urinary
smooth muscle tone is also increased by opiate agonists. The tone of the
bladder detrusor muscle, ureters, and vesical sphincter is increased, which
sometimes causes urinary retention.
Several other clinical
effects occur with opiate
agonists including cough suppression,
hypotension, and
nausea/vomiting. The antitussive effects of opiate agonists are mediated
through direct action on receptors in the cough center of the medulla.
Cough suppression can be achieved at lower doses than those required to
produce analgesia. Hypotension is possibly due to an increase in histamine
release and/or depression of the vasomotor center in the medulla. Induction
of nausea and vomiting possibly occurs from direct stimulation of the vestibular
system and/or the chemoreceptor trigger zone.
Pharmacokinetics:Morphine sulfate is administered orally, parenterally,
intrathecally, epidurally and rectally. It is one-third to one-sixth as
potent when administered orally when compared to intravenous administration.
This is due to significant first-pass metabolism of morphine. It is readily
absorbed from the gut and is absorbed even faster with rectal administration.
Oral absorption of the immediate release products can be increased by food.
Peak analgesia is obtained about 60 minutes after oral administration;
20—60 minutes with rectal administration; 50—90 minutes after SC and IM
injections; and within 20 minutes following IV injection. Oral sustained-release
products have a slower onset of action, and at steady state will have a
lower maximum serum concentration and higher minimum serum concentration
when compared to conventional immediate-release oral morphine. Following
every 12 hour dosing of MS Contin® the maximum plasma concentrations
occur about 4 hours after the dose and following every 24 hour dosing of
Kadian®, the maximum plasma concentration occurs in about 8 hours.
Respiratory depression is most significant after IV administration. The
sensitivity of the respiratory center returns to normal within 2—3 hours.
The elimination half-life of morphine is about 1.5—2 hours; analgesia can
be maintained for 3—7 hours following immediate release morphine administration.
In pediatrics, metabolism of morphine is affected by age of the infant.
Preterm neonates are capable of glucuronidation but this capability is
influenced by gestational and postnatal age and birth weight. The half
life of morphine is approximately 9 hours in preterm neonates, 6.5 hours
in term neonates aged 0—57 days and 2 hours in infants and children aged
11 days to 15 years. The volume of distribution of morphine was similar
regardless of age.
Due to morphine’s hydrophilic properties, it produces intraspinal analgesia
at much lower blood levels compared with lipophilic agents, such as fentanyl.
Morphine distributes within the spine in a rotral or “hook-like” manner
with time. Therefore, a low lumbar injection can provide good analgesia
to the thoracic and upper abdomen after a period of time. The slow rate
of elimination after intrathecal administration accounts for the prolonged
duration of action when used by this route. Morphine 0.2—1 mg intrathecally
may provide pain relief for up to 24 hours. Following epidural administration
of morphine, the onset of analgesia is within 15—30 minutes with a duration
of 4—24 hours. Morphine is rapidly absorbed systemically after epidural
administration. The analgesia obtained from epidural morphine is not dependent
upon systemic morphine concentrations and the duration of analgesia continues
beyond the time during which morphine may be detected in the plasma. If
the intrathecal route is used instead of the epidural, lower doses of morphine
(1/10 the dose) are required to produce similar analgesia since morphine
circumvents the meningeal diffusion barriers.
There is no predictable relationship between morphine serum levels and
analgesic response; however, there is a minimum effective analgesia plasma
level in a given patient. The minimum effective analgesia plasma concentration
of morphine varies from patient to patient. Several factors may affect
a patient’s response to a given opiate agonist including age, prior opiate
therapy, medical condition and emotions. Also, there is no relationship
between morphine plasma levels and incidence of adverse events, although
higher levels are associated with more adverse events than lower levels.
Metabolism of morphine occurs in the primarily in the liver but also
may occur in the brain and kidneys. Morphine is conjugated with glucuronic
acid to form 3-glucuronide (50%), 6-glucuronide (5—15%) and 3,6-glucuronide
and other minor metabolites. Morphine 3-glucuronide antagonizes morphine
and may cause hyperalgesia and myoclonus seen with high dose morphine therapy.
In addition, the 3-glucuronide metabolite may be important in the development
of tolerance to morphine. Morphine 6-glucuronide is a more potent analgesic
than morphine and may significantly contribute to morphine’s activity.
With chronic dosing of morphine, the AUCs of the glucuronide metabolites
are greater than that of morphine.Excretion is largely in the urine and
bile as the morphine- 3-glucuronide and 6-glucuronide metabolites, with
smaller amounts as the secondary conjugate and unchanged drug. Within about
24 hours of the last dose given, urinary elimination approximates 90%.
Between 7—10% is excreted in the feces, mainly via the bile. In patients
with renal dysfunction, accumulation of the morphine-3 glucuronide and
6-glucuronide occurs leading to prolonged serum levels and increased toxicity.
©1994-99 Gold Standard Multimedia
Inc. All rights reserved.
This information is for personal
use only and may not be reproduced/distributed in any form or by any means
in whole or in part without the written consent of the publisher.
1
Codeine 2
Phenobarbital 3
Diazepam 4
Morphine Pentobarbital up  |
The
Drugs : 
Pentobarbital
may decrease the potency of the coumarin anticoalgulants so that patients
recieving such concomitant therapy should have more frequent prothrombin
determinations
.
![[graphic]](butfly8.gif){kind=small}
