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Morphine

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Abstract

Morphine is the gold standard for painkillers because it has been used safely and

effectively for a long time. Morphine can be given in many ways, including by mouth,

intravenously, under the skin, and through the birth canal. It is now the standard way to treat

pain in the medical system we have now. Opioids have been shown to have almost no effect

on how well people do tasks that use their senses, their bodies, or their minds. If you take a

lot of morphine, it might make it hard to tap your fingers or keep a low stable value of

isometric force. No research has shown that morphine affects how well you move your large

muscles. The main place where morphine binds to glucuronic acid when the liver breaks

down the drug are at the 3-hydroxyl group. Normorphine and 3-ethereal sulfate are two other

minor metabolites that have been reported along with 3,6-diglucuronide (Hobl et al. 2016).

The half-life of morphine after it is given through an epidural is 90 minutes. When people use

drugs too much regularly, they feel guilty because they know it will hurt them in the long run.

Even if the purpose of giving morphine to a sick person is to make them confused so they

don't feel pain, this is not a moral thing to do.

Introduction

Medicines have their kinship networks, much as people do. In the class of drugs

known as opioids, morphine may be found. Because of its sedative effects, the Greek deity of

slumber, Morpheus, inspired the drug's eponymous name. The opium poppy contains the

alkaloid morphine. The extract from the plant has been used to relieve pain for about 200

years. Morphine is the reference standard for analgesics due to its long history of safe and

effective usage (Bahrami et al. 2020). It has become the standard treatment for pain in the

current medical system.

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The effects of the various opioid medications are similar. They are absorbed into the

bloodstream and then processed in the liver, where they are subsequently employed to dull or

eliminate the feeling of pain. Morphine may be administered in a variety of ways, including

orally, intravenously, subcutaneously, and epidurally. For individuals who are unable to

swallow, it may be given rectally, and it can also be breathed using a mask. The several

routes of administration available for morphine contribute to the drug's overall efficacy.

Purpose

How does morphine work to ease the discomfort? There are three legs to the relay that

carry pain from one person to another. When damage occurs in the body's periphery, runners

or chemicals transport a message of pain to the brain. There are both upward and downward

pathways in the neurological system. Acute pain signals are sent along the afferent neural

route by rapid nerve messengers termed tiny A nerve fibers. C fibers, which are larger in size,

have a role in persistent pain by transmitting impulses more slowly. The first phase of the

relay involves the transport of a chemical signal from the area of injury to the spinal cord's

dorsal horn. When they arrive, the chemicals relay the message to the second group of

chemical messengers across a barrier. These neurotransmitters relay the nociceptor’s pain

signal to the midbrain, a major brain region that processes it. Finally, the nociceptive impulse

is sent to the cortical region of the brain by a last group of messengers. The pain sensation

begins only once the pain signal reaches the cerebral cortex.

When the human body feels pain, its built-in defensive mechanism kicks in. By

secreting its chemicals into the efferent system. The brain can stop or suppress the arriving

pain signals. Reducing or masking the incoming nociceptive impulses to the brain is achieved

by a combination of the body's natural internal reactions and external interventions such as

medicine, heat/cold, and immobility.

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Main findings

Opioids have been shown to have a negligible effect on human performance on

sensory, motor, and attention tasks, according to the vast majority of evaluations. Morphine is

a CNS depressive, therefore it's not unexpected that new research has been able to

demonstrate certain limitations. Critical flicker frequency and Maddox wing test performance

have both been negatively affected by morphine. A high dosage of morphine may affect

finger tapping and the capacity to sustain a low stable value of isometric force, however, no

research has revealed an association between morphine and gross motor skills.

Conclusion

Despite its low cost, morphine is seldom available to individuals in developing

nations. The International Narcotics Control Board estimated that 79% of the world's

morphine was used in first-world nations. However, even though they house 80% of the

worldwide population, the developing nations use just 6% of the world's morphine. Even to

alleviate extreme agony during death, morphine is not widely accessible in certain countries.

The lack of morphine availability is blamed on an unfounded worry about addiction and

misuse, according to pain management specialists. Despite morphine's obvious addictive

potential, Western medical practitioners nonetheless advocate for its usage throughout

therapy and eventual withdrawal.

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Chemical and physical properties

Figure 1.1 shows the Morphine bond.

Molecular Weight 285.34

0.8
XLogP3

Hydrogen Bond Donor Count 2

Hydrogen Bond Acceptor Count 4

Exact Mass 285.13649347

Monoisotopic Mass 285.13649347

Topological Polar Surface Area 52.9 Ų

Heavy Atom Count 21

Complexity 494

Defined Atom 5

Covalent Bond 1

Can the Compound Be Canonicalized Yes

Table 1.1 shows the chemical and physical properties of morphine (Giannos et al.

2021)
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Literature findings

Through its binding to opioid receptors, morphine suppresses afferent fibers of

nociceptors to dorsal horn sensory projecting cells and prevents the transmission of

nociceptors signals to the spinal cord (Bahrami et al. 2020). In most cases, morphine's effects

won't kick in until 6-30 minutes after administration. Modifications in neuron density,

postsynaptic locations, and dendritic terminals may occur as a result of excessive use of

morphine as well as other opioids, all of which contribute to altered synaptic neuroplasticity.

The pain-relieving effects of intravenous morphine vary with the patient's gender. The half-

maximal effective concentration (EC50) in males is 76ng/mL, whereas in women it's

22ng/mL. It's been shown that morphine-6-glucuronide is 22 times less effective than

morphine in narrowing a person's pupils.

The 3-hydroxyl group of morphine is the primary site of conjugation with glucuronic

acid throughout the liver's metabolism of the drug. The 6-glucuronide and, to a lesser degree,

the 3,6-diglucuronide, both of which have pharmacological activity, are formed by secondary

conjugation at the 6-hydroxyl group. Inactive 3-glucuronide and active 6-glucuronide both

have much higher plasma concentrations than the original medication, with the latter seeming

to contribute significantly to the drug's pharmacological action. To a greater extent than in

older children and adults, the medication may be retained in newborns before being

eliminated. The primary morphine metabolite in urine is morphine-3-glucuronide. Other

minor metabolites besides 3,6-diglucuronide that have been reported include normorphine

and 3-ethereal sulfate. Increased and sustained opiate activity may arise from the buildup of

morphine-6-glucuronide in individuals with renal impairment.

Similar to the stated half-life of the drug following IV or IM administration, the

ultimate half-life of morphine after epidural administration is 90 minutes (range, 39-349

minutes) (1.5-4.5 hours).

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About 85% of the effect of morphine is attributed to morphine-6-glucuronide. Both

the mu as well as kappa opioid receptors are activated by morphine and its metabolites. All of

the morphine's actions in the ventral tegmental region of the brain depend on the mu-opioid

receptor. The nucleus accumbent delta-opioid receptor is agonized by morphine to activate

the reward pathway, whereas the breathing and addiction problem is modified by the mu-

opioid receptor.

Poppy straws or dried exudate, depending on its origin, might contain as much as 20%

morphine. Typically, water is used to extract the active ingredients from the crude opium, and

then the aqueous extract is concentrated, combined with alcohol, and made extremely basic

with ammonia solution. Crystallization occurs as its sulfate further purifies morphine, which

often precipitates whereas the other bases stay in solution.

Christian world view

When all that is at stake is calming anxious feelings or relieving pain, it is not morally

permissible to outright forbid the use of morphine. However, morphine formulations should

only be used only under the advice of a competent physician due to the serious risks

associated with their overuse and the negative consequences they are likely to cause.

Morphine addiction is a sin since it leads to compulsive and excessive usage. When it causes

major harm to one's physical health or when, due to the enjoyment and comfort it provides, a

total intoxication, momentary deprivation of the ability to utilize reason is formed, its

excessive use becomes very wicked, even a fatal sin (Devereaux et al. 2018). A single

instance of the latter excess is a sin, while the mortal guilt in habitual excessive use is found

in the awareness of the harm that the continuous ingestion of the drug would then work,

allowing for leniency in the case of a decided breaking off of the routine despite the

occasional provisional relapse into the use.

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Although drug abuse is always wrong, it is not a fatal sin until it reaches the levels

described above of addiction. The use of morphine for the aim of confusion, even though

done to reduce pain, cannot be ethically justified with persons who are very ill, when death is

imminent, unless the goal is to induce restful sleep or as an anesthetic in a medical operation.

Otherwise, depriving the patient of awareness thus close to death must be seen as a normal

reduction of life, which I am not obligated to resist if someone undertakes to do so in good

faith to avert larger evils, but in which I cannot be permitted to agree to or help.
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References.

Bahrami, G., Ehzari, H., Mirzabeigy, S., Mohammadi, B., & Arkan, E. (2020). Fabrication of

a sensitive electrochemical sensor based on electrospun magnetic nanofibers for

morphine analysis in biological samples. Materials Science and Engineering: C, 106,

110183.

Devereaux, A. L., Mercer, S. L., & Cunningham, C. W. (2018). DARK classics in chemical

neuroscience: Morphine. ACS chemical neuroscience, 9(10), 2395-2407.

Giannos, T., Lesnik, S., Bren, U., Hodoscek, M., Domratcheva, T., & Bondar, A. N. (2021).

CHARMM force-field parameters for morphine, heroin, and oliceridine, and

conformational dynamics of opioid drugs. Journal of Chemical Information and

Modeling, 61(8), 3964-3977.

Hobl, E. L., Reiter, B., Schoergenhofer, C., Schwameis, M., Derhaschnig, U., Lang, I. M., ...

& Jilma, B. (2016). Morphine interaction with prasugrel: a double-blind, cross-over

trial in healthy volunteers. Clinical Research in Cardiology, 105(4), 349-355.