Download A5, Page 1 Essay Code: A5 CHEM 151 9 February 2014 Morphine

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Essay Code: A5
CHEM 151
9 February 2014
Morphine: Its history, chemistry, and uses
Morphine was the first alkaloid to ever be isolated from any plant. It is the main
psychoactive chemical in opium. The recreational use of morphine and its semi-synthetic
derivative, heroin, have taken a great toll on society since their discovery. However, it has
important medical use as an analgesic to relieve intense pain especially for terminally ill patients
and during child birth. Common synthetic derivatives of morphine include dextromethorphan
(over the counter cough suppressant), codeine (cough suppressant and antidiarrheal),
hydromorphone (narcotic analgesic), and diacetylmorphine (recreational drug). This paper will
exemplify the value of morphine and its derivatives by discussing its chemical properties,
clinical uses, and abuse potential.
Opium, also known as poppy tears, is the milky exudate of the opium poppy papaver
somniferum. Opium contains approximately 20 alkaloids including codeine, thebaine, and
morphine among other non-analgesic alkaloids. Morphine, the active constituent in the opium
poppy, was first isolated from opium in 1804 by German pharmacist Friedrich Wilhelm
Sertürner. He named the yellowish-white crystalline powder morphium, after Morpheus, the
Greek god of dreams because the substance had a tendency to cause sleep. He reported that the
substance had effects of euphoria and pain relief at low doses and nausea, vomiting, cough
suppression, slowed breathing, constipation, and psychiatric effects at high doses (“Morphine”,
Encyclopedia Britannica).
In 1925, J.M Gulland and R. Robinson proposed the structure for morphine, which was
confirmed by its total synthesis in 1952 by M. Gates and G. Tschudi. The synthesis had 31 steps
with a 0.06% yield. One of the most efficient syntheses was proposed in 1980 by K. Rice; It has
a 30% yield in 14 steps. Morphine’s chemical formula is C₁ ₇ H₁ ₉ NO₃ with a molecular
weight of 285.34 g/mol. Morphine has a melting point of 255℃, a boiling point of 190℃, and
solubility of 0.15g/L at 20℃ (“Morphine”, Pub Chem). The structure is shown below:
Based on its structural backbone, morphine is classified as a benzylisoquinoline alkaloid
(with two additional rings). The rigid pentacyclic structure consists of a benzene ring and two
partially unsaturated cyclohexane rings which are part of a phenanthrene ring system that has
little conformational flexibility. In addition, it had a piperidine ring and a tetrahydrofuran ring.
The functionality of morphine consists of two hydroxyl functional groups (phenolic and allylic),
an ether linkage, a basic tertiary amine, and five centers of chirality. More than 250 morphine
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derivatives have been developed.Its derivatives include opioid agonists, antagonists, agonistantagonists, partial agonists, and inverse agonists which range from 2% to 2,000% the strength
of morphine. Morphine is the precursor for semi-synthethic opioids such as hydromorphone,
oxymorphone, and diacetylmorphine (Weill, “The Structure of Morphine”).
Opioids are exogenous substances that bind to endogenous opioid receptors throughout
the brain. Endogenous opioids are neurotransmitters called endorphins, enkephalins, and
dynorphins that bind to mu, delta, and kappa receptors in the brain, moderating reactions to
painful stimuli. Opioids also disinhibit dopamine neurons by reducing the amount of GABA
(inhibitory neurotransmitter) released. As a result, opioids increase the amount of dopamine
produced, causing a feeling of euphoria. The effects of opioids include: pain relief, cough
suppression, anxiety relief, shallow breathing, slowing of the digestive tract, histamine release.
Some side effects include drowsiness, nausea or vomiting, sweating, dysphoria, constipation, and
respiratory depression. Opioids can be clinically used for diarrhea, pain management, and cough
control. Due to their effects, opioids are highly addictive and have a high overdose potential.
However, they have the least toxic effects at the cellular level compared to other drugs (Dubuc,
“How Drugs Affect Neurotransmitters”)
Diacetylmorphine is one of the most notorious semi-synthetic derivatives of morphine. It
is created by treating morphine with acetic anhydride via an acetylation reaction (Bedford, et al).
The drug was first synthesized from morphine in 1874 by C. R. Alder Wright. It was
introduced as a commercial product by the Bayer Company in 1898. The company marketed the
drug under the trademark name of Heroin due to its perceived “heroic” effects. At this time,
morphine had become a popular recreational drug and Heroin was marketed as a non-addictive
morphine substitute and cough suppressant. In addition, it was marketed as a cure for morphine
addiction before it was discovered that it metabolizes into morphine once it is absorbed by the
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body. However, contrary to advertising, heroin soon had the highest dependence rates among its
users ( “Heroin”, Ecyclopedia Britannica).
Morphine is able to cross the blood brain barrier but it does not cross easily due to its
poor lipid solubility. Heroin, on the other hand, is much less soluble in water than morphine but
more lipid soluble. As a result, it crosses the blood brain barrier more easily, making it more
potent than morphine. Heroin can be injected (intravenous or intramuscular), smoked, snorted, or
ingested. The most common routes of administration are subcutaneously (skin popping) and
intravenously (mainlining). Although all routes of administration are addictive, the pleasurable
effects of the drug are proportional to the rate at which the drug concentration increases in the
blood. Intravenous injections cause blood concentrations to rise most quickly, providing the most
rapid onset of euphoria after 7-8 seconds, followed by an intramuscular injections (5 to 8
minutes) and smoking or snorting (10-15 minutes). Therefore, IV heroin injections produce an
intense rush that is fast and dramatic but with shorter lasting effects than morphine (“Heroin:
Abuse and Addiction”).
Due to its effects, heroin produces a profound degree of tolerance and physical and
psychological dependence which are motivating factors for compulsive use of the drug. Heroin is
the second most addictive drug after nicotine. Withdrawal from opioids is more dramatic than
withdrawals from other illicit drugs. Symptoms include but are not limited to anxiety, insomnia,
cold sweats, severe muscle and bone ache, fever, involuntary limb spasms, nausea, vomiting, and
hypersensitivity to pain and stress. Heroin withdrawal is not fatal to healthy adults, however, the
user feels as if it is. Treatments for heroin withdrawal include methadone as a replacement drug
(methadone maintenance) and buprenorphine (opioid partial agonist). Both of these drugs
prevent withdrawal without causing positive reinforcing effects (“Drug Use”).
Although morphine and its derivatives are highly addictive. They do serve important
clinical purposes. Morphine is medically used in its hydrochloride, sulfate, acetate, and tartrate
salts. One of its most common uses in the medical field is to treat severe pain. It is effectively
treats acute or chronic severe pain, postoperative pain, and labor pain. Outpatient analgesia is
usually administered orally or transdermally (via a patch). Inpatient analgesia is administered
intravenously via a titration or through patient-controlled analgesia. The doses of the selfadministered morphine are smaller than those administered orally, however, they both provide
effective recovery. Oral administration of morphine provides analgesia that lasts about 3-6 hours
while intravenous, intramuscular, and subcutaneous administrations last 3-4 hours (“Morphine”,
Encyclopedia Britannica).
Morphine is commonly used to treat pain in terminally ill patients. The National Cancer
Institute states that symptoms commonly experienced at the end of life for cancer patients
include pain, delirium, fatigue, cough, dyspnea (shortness of breath), and rattle (the accumulation
of saliva and other fluids in the upper airways of the patient who is to weak to clear their throat).
Morphine can be administered to control pain especially during the patient’s final hours. Several
studies refute associations between hastened death and opioid use. However, cancer patients are
not free of the substance’s addictive properties. Patients that develop an addiction are given
adequate amounts without reluctancy to avoid withdrawal. The use of intermittent injections or
infusions are increased as a patient approaches death. High doses may produce myoclonus
(involuntary muscle twitching), acute confusion, restlessness, hallucinations, and hyperalgesia.
These symptoms may be treated with the administration of an opioid antagonist (“Last Days of
Life”).
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The many uses of morphine and its derivatives make morphine a controversial drug. On
one hand it is an effective pain reliever, cough suppressant, and antidiarrheal. It is especially
beneficial for postoperative analgesia. Its use on terminally ill patients provides them with relief
of fear of uncontrollable pain that many patients face as they approach death. However,
morphine’s side effects are often a concern for family members and health care providers. The
use of the semi-synthetic morphine derivative, heroin, is very detrimental to the user and to
society. According to the National Institute on Drug abuse, an estimated 4.2 million Americans
aged 12 or older had used heroin at least once in their lives. (“Heroin: Abuse and Addiction”).
Heroin is one of the most addictive drugs due to its intense withdrawal symptoms and euphoric
effects; This makes it almost impossible for users to quit and for society to eradicate its use.
Heroin is linked to increases in crime, domestic violence, child abuse, and infectious diseases
like HIV and hepatitis. Since its discovery, morphine has changed the life of its users, whether it
is through beneficial medical uses or through addiction.
Works Cited
Bedford, K. R., S. L. Nolan, R. Onrust, and J. D. Siegers. "The Illicit Preparation of
Morphine and Heroin from Pharmaceutical Products Containing Codeine:
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<https://www.erowid.org/archive/rhodium/chemistry/
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"Drug use." Encyclopaedia Britannica. Encyclopaedia Britannica Online. Encyclopædia
Britannica Inc., 2014. Web. 10 Feb. 2014. <http://www.britannica.com/
EBchecked/topic/172024/drug-use>.
Dubuc, Bruno. "How Drugs Affect Neurotransmitters." The Brain From Top to Bottom.
Institute of Neuroscience, Mental Health, and Addiction, Jan. 2002. Web. 01
Feb. 2014.
"Heroin." Encyclopaedia Britannica. Encyclopaedia Britannica Online. Encyclopædia
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< http://www.news-medical.net/health/Morphine-History.aspx>.
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"Last Days of Life." National Cancer Institute. National Institutes of Health, 10 Dec.
2013. Web. 02 Feb. 2014.<http://www.cancer.gov/cancertopics/pdq/
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Weill, Paul B. "The Structure of Morphine." United Nations Office on Drug and Crime.
N.p., 01 Jan. 1950. Web. 01 Feb. 2014. <https://www.unodc.org/unodc/en/dataand-analysis/bulletin/bulletin_1950-01-01_2_page004.html>.