Technical Fact Sheet
CHEMICAL CLASS/TYPE
Morphine is an opiate alkaloid, which are a group of chemical compounds with analgesic (pain-relieving) and narcotic (sleep-inducing) properties. Similar compounds in its class include buprenorphine, and the synthetic opioid heroine.
It is found naturally in the environment in the sap of the opium poppy plant, Papaver sominferum (National Center for Biotechnology Information, 2012).
These compounds exert their actions on the body through the opioid receptors, which are found on many different tissues. Morphine has widespread effects in the body, of which the most prominent are on the central nervous system and on smooth muscle (National Center for Biotechnology Information, 2012). Its analgesic action is by modulating the body’s perception of pain.
Morphine has addictive potential and is a drug of abuse due to its euphoric effects. Its chronic use leads to tolerance, physical and metal dependence, therefore its sale and use is strictly regulated (Mayoclinic, 2012).
Its brand names include Avinza, Kadian and Roxanol.
MOLECULAR STRUCTURE
With the chemical formula C17H19NO3, morphine has a molecular weight of 285.3 g/mol.
Its molecular synonym is 7,8-didehydro-4,5-epoxy-17-methylmorphina-3,6-diol sulfate salt pentahydrate (Occupational Safety and Health Administration, 2005).
PHYSICO-CHEMICAL PROPERTIES
Morphine exists as a white solid in the salt form as morphine sulphate. Its melting point is 250⁰C, at which it decomposes (Occupational Safety and Health Administration, 2005). It can be stored at room temperature.
It is absorbed from the gastrointestinal tract, with food reducing its absorption.
40% of the orally administered drug reaches the systemic circulation (National Center for Biotechnology Information, 2012).
The peak analgesia effect occurs 60 minutes after oral administration, and 20 minutes after intravenous injection. Analgesia lasts up to 7 hours. It distributes throughout the body, mainly in kidneys, liver, lung, muscle and brain. It also crosses the placenta. It is secreted in breast milk and sweat, metabolized by the liver to glucuronides, and excreted mainly in the urine. A small proportion is excreted by feces.
The half-life is normally between 3 to 4 hours if taken orally. The regular tablet and liquid usually are taken every 4 hours. Its regular oral tablets are for 15 mg – 60 mg.
If taken intravenously or epidurally, the half- life is only 90 minutes. Renal failure prolongs the half-life.
It is also available as extended release tablets come in 100 mg and 200 mg tablets, which are high doses (Enotes.com, n.d.). These tablets provide enough morphine to provide analgesia for up to 12 or 24 hours (Medline Plus, 2011).
There is no limit to the maximum dose of morphine for inhibiting pain, however, the dose is usually within 1600 mg per day in adults (Mayoclinic, 2012).
The minimum analgesic plasma concentration of morphine ranges from 20 to 40 ng/dl.
Morphine can slowly cross the blood-brain barrier.
USES
The only medical use of morphine is to relieve moderate to severe pain, in several clinical scenarios (Mayoclinic, 2012).
The use of morphine is also not to be stopped abruptly due to the risk of precipitating withdrawal effects, it is always tapered before discontinuation (Medline Plus, 2011).
CURRENT REGULATORY STATUS
Under the Controlled Substances Act of 1970, morphine is on the Schedule II list of controlled substances, which implies that it has some medicinal uses, but also contains the potential for abuse and user addiction. Federal law recognizes that ‘opioids may be used for extended periods in treatment of patients with intractable pain’, while also stipulating that ‘providing opioids to addicts is otherwise unlawful’ (Joranson, 2011).
The Drug Enforcement Administration registers doctors for prescribing morphine and maintains a check on the quantity prescribed. The possession and sale of morphine entails severe penalties including heavy fines and jail time (Joranson, 1990).
Different states in the U.S. have different stances on whether the amount of morphine that can be prescribed to one patient should be limited. As many cancer patients with intractable pain need very large, regular doses of morphine, these restrictions sometimes cause patient suffering.
MODE OF ACTION
There are at least four types of opioid receptors in the brain’s limbic system, thalamus, striatum, hypothalamus, midbrain, spinal cord, intestines, and smooth muscle – mu, kappa and sigma receptors. Morphine has good activity at the former two receptor types (National Center for Biotechnology Information, 2012).
Agonist activity of morphine at the mu receptors mediates analgesia, miosis, hypothermia, and respiratory depression. Morphine also suppresses the cough reflex, the chemoreceptor trigger zone and vomiting center of the brain, and produces a temporary feeling of euphoria. It acts on the delta receptors in the limbic system, which is the likely cause of euphoria. Activity on gut smooth muscle slows gut motility and produces constipation.
Opiate agonists modulate the perception of pain at the spinal cord substantia gelatinosa, and at the levels of higher centers in the brain (spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, and hypothalamus). They also alter the patient's emotional response to pain, so that it is perceived as a sensation but is not unpleasant (National Center for Biotechnology Information, 2012).
Morphine also has endocrinologic effects – it stimulates the release of vasopressin, thyrotropin and corticotropin from the pituitary gland (National Center for Biotechnology Information, 2012).
Morphine has addictive potential, so that the user can become physically and/or psychologically dependent on the drug. He or she experiences unpleasant symptoms if the drug is abruptly withdrawn (Enotes.com, n.d).
ACUTE TOXICITY TO HUMANS
The toxic dose of morphine ranges from 300 to 400 mg oral doses in adults. The LD50 (lethal dose for 50%) in rats with the oral route is 335 mg/kg. If an overdose of morphine is taken, the following signs and symptoms can occur:
Respiratory suppression. This may be exacerbated if the patient is simultaneously taking another suppressant of the central nervous system, such as benzodiazepines, barbiturates, antihistamines, antipsychotics, and antidepressants (Mayoclinic, 2012). Maximal respiratory suppression occurs 70 to 90 minutes after administration, and resolves within 2 to 3 hours.
Pulmonary edema
Seizures or hallucinations
Confusion
Somnolence, leading to coma
Skeletal muscle hypotonicity
Miosis, causing blurred vision
Cold, clammy skin
Urinary urgency and difficult urination
Death by respiratory suppression in very high doses
Anaphylaxis if the patient is allergic to morphine – rash, itching, trouble breathing and swallowing.
The lethal dose of morphine is around 120 – 250 mg intravenously. Morphine blood concentrations of 10 – 100 micrograms/dl are toxic, lethal concentrations are higher than 400 micrograms/dl.
The toxicity of morphine is increased in the presence of alcohol if long-acting oral formulations are used, as alcohol causes a rapid release of morphine into the gut. Therefore, patients are asked to avoid alcohol if they are prescribed the long-acting capsules (Medline Plus, 2011).
It is a Category C drug for use in pregnancy, meaning that adverse pregnancy events have been recorded by animal studies, such as growth retardation and birth defects, however no adequate studies have established its safety in pregnant women. It does not appear to pose any risk to an infant if the breastfeeding mother is taking morphine.
Naloxone is an opioid antagonist used to treat acute toxicity with morphine, it is used to reverse opioid-induced coma. Activated charcoal is also given to minimize its absorption from the gut, if the overdose was by the oral route (National Center for Biotechnology Information, 2012).
CHRONIC TOXICITY TO HUMANS
The chronic use of morphine is associated with genotoxocity. Morphine induces damage to DNA causing its fragmentation, especially in lymphocytes, leading to chromosomal abnormalities in chronic users of morphine and their children.
WITHDRAWAL EFFECTS
If morphine is withheld from a person dependent on it, the following withdrawal symptoms can be seen (Enotes.com, n.d.):
Sneezing/coughing
Rhinorrhea
Muscle pain
Restlessness or Anxiety
Auditory and visual hallucinations
Stomach cramps
Tremor
MAJOR ROUTES OF EXPOSURE IN HUMANS
Morphine can be administered by the following routes (Mayoclinic, 2012):
Oral – tablets, capsules, solutions, syrups, powders
Per-rectally
Intravenous
Subcutaneous, although this route is not preferred
Intramuscular
Epidural
Intrathecal (directly into the spinal cord)
REFERENCES
Enotes.com (n.d.) Morphine. Available at: http://www.enotes.com/morphine-reference/morphine#consequences
National Center for Biotechnology Information. (2012) Morphine - Compound Summary. Available at: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5288826#x332
Occupational Safety and Health Administration. (2005) Chemical Sampling Information: Morphine. Available at: http://www.osha.gov/dts/chemicalsampling/data/CH_255590.html
Mayoclinic. (2012) Morphine (Oral Route). Available at: http://www.mayoclinic.com/health/drug-information/DR603253
Joranson, D.E. (1990) Federal and State Regulation of Opioids. Available at: http ://www.medsch.wisc.edu/painpolicy/publicat/90jpsmf.htm
Medline Plus (2011) Morphine Oral. Available at: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682133.html
