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Chemistry of Morphine Report

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Updated: Mar 16th, 2022

Introduction

Morphine refers to a narcotic pain killer that is normally used in the treatment of moderate to extreme pains or aches and severe coughs. It also plays an important role in reducing pain in patients during medical operations and the period after. It is classified under a group of drugs called opiates (Klockgether 244). Opiates are derived from opium which is obtained from the poppy plant. The drug can be taken through various ways which include injection or through the mouth in pill form or syrup form.

History of morphine

Morphine was discovered by a German pharmacist, Freidrich Wilhelm Adam Sertürner. Sertürner was always inquisitive and wanted to find out the therapeutic properties of opium which was much used by 18th-century physicians. He performed several experiments as a novice of pharmacist during his spare time and in the end was able to detach the active substance, organic alkaloid, from the gum produced by the opium poppy.

He carried out tests that proved that opium without the alkaloid did not affect animals while the alkaloid proved to be extremely more powerful than processed opium (Klockgether 245). He called the substance morphine, derived from Morpheus, the Greek god of dreams since it caused its consumers to sleep.

Morphine then began being used as a pain reliever and as a treatment for opium dependence. Many health experts of the time found it suitable to substitute morphine with alcohol for alcohol addicts, they considered that the effects of alcohol were more destructive to the body and could lead to unsociable conduct (Koch 199).

During the American Civil War, morphine was used as an anesthetic in the treatment of injured soldiers. At the end of the war, several of those on whom the drug had been used had developed an addiction to it. The same occurred in the European Franco-Prussian.

In the December of 1914, the United States Congress passed the Harrison Narcotics Act which meant that each stage of morphine production, and other related products, had laid out controls (Koch 202). Possession of such substances was illegalized. However, some of the boundaries in the Harrison Narcotics Act were revised in the year 1970 by the Federal Controlled Substances Act.

There has been an increase in the use of morphine and other narcotic pain killers in the US (Koch 203). Long-standing use of these substances leads to addiction. At the same time, users usually build up a tolerance to pain prescriptions and thus have to increase their intake to attain the same effect.

Extraction of morphine from the opium poppy

Morphine is in nature present in opium and is normally nine to seventeen percent by weight. The percentage depends on the opium source. Presently, there is an improved extraction process and purification of morphine as opposed to earlier methods that were accompanied by several limitations such as unnecessarily prolonged production times, low production efficiencies, and usage of harmful chemicals like sulfur dioxide and chloroform (Andreas 20). The process offers a more cost-effective and environmentally friendly way of obtaining morphine. The earlier methods used either water or an acidic solution to extract alkaloids from opium. This resulted in large volumes of aqueous extract due to low solubility levels of alkaloids in aqueous solutions. Extraction of alkaloids from the aqueous extract needed high volumes of organic solvents, making the process time-consuming and labor-intensive.

With the present method, a basic alcoholic solution is used to extract opium. The extraction process is carried out by stirring opium in a basic alcoholic solution at a pH of about 9. Suitable alcohols that can be used include methanol, ethanol, and isopropanol (Kilpatrick 521). However, methanol is the most ideal since almost all alkaloids like morphine are soluble in it, be it in their neutral, cationic, or anionic forms. Alcohol mixtures may also be used. The pH is regulated to about nine by incorporation of an inorganic base, normally an alkali hydroxide or carbonate. This is in a bid to enable more alkaloids and fewer impurities to be extracted into the alcohol. The process takes between one to two hours and results in the extraction of at least ninety percent of morphine present. In a standard measure, five grams of opium sliced in small pieces should be extracted with zero point four grams in twenty-five milliliters of methanol for one to two hours. A further extraction process can recover all the alkaloids present. It is economical when the second extract is used to extract another batch.

The basic alcoholic solution is then sieved and the alcohol separated to leave behind a deposit. The alcohol is removed from the taken-out alkaloids mainly by evaporation under diminished pressure levels (Kilpatrick 523). This process is much easier and faster than the concentration of aqueous extracts like toluene which were used in earlier methods. Small volumes of filter aid are added to the alcohol extract before distillation to keep foaming and bumping of the extract at bay. Alcohol recovered from this process, especially methanol, can be recycled and for another process of extraction minus taking it through any form of purification.

The residue left behind contains alkaloids. A basic aqueous solution with a pH of at least 11 is then used in the extraction process. An alkali hydroxide usually gives the best results. This process changes the non-morphine-containing base into its morphine form which can dissolve in basic solutions having pH values of 11 and above (Kilpatrick 525).

Any resultant precipitates are filtered out of the basic aqueous solution. The remaining alkaloids are then separated from the aqueous solution containing morphine by drawing out, by the use of a solvent that cannot mix with water. Such solvents include benzene, xylene, diethyl ether, chloroform, or toluene. Toluene is preferred in this process since it harbors no health hazards. During extraction while using these solvents, about eight percent of morphine gets extracted into the solvent. Recovery of this is attained by back extraction by using an additional basic solution.

In the end, the morphine-free base is precipitated out of the aqueous solution by adjusting the pH of the filtrate to values in the range of 8.5 to 9.5. The pH values to precipitate the morphine range from 9.0 to 9.3, with the most ideal being at 9.1. These values are normally attained by the addition of either an organic acid or a mineral acid. The amounts of morphine and its wholesomeness attained by this process are cost-effectively acceptable (Kilpatrick 526). Morphine derived by this process can then be sanitized further or utilized directly in a further process to turn it into codeine. This entire process can be completed in a single day.

Uses and side effects of morphine

As the case is with other medications, morphine usage is most of the time accompanied by various side effects. However, not all people who take the medication will end up with complications (Andreas 24). There are quite a several people who have the capability of tolerating it very well.

Morphine offers relief from aches and gives the patient a sense of comfort. However, opiates in common slow down inhalation, heart rate, and mental activity. General respirations end up being slowed down. Consequently, the body’s forbearance to ache is enhanced.

Another effect that morphine poses, especially to those who don’t use it for medical purposes or as proscribed by a physician, and is abused by being taken in excessive dosages is addiction. This comes as a mental reliance and bodily reliance as well as acceptance. A severe narcotic tendency has a high chance of developing in a small matter of weeks when the drug is used illegitimately (Andreas 26). When aches are being experienced or other disorders for which the drug is recommended, a combination of mental and physical aspects tend to keep actual addiction at bay. However, bodily reliance and forbearance will develop with prolonged opioid rehabilitation.

Morphine also causes constipation for its consumers. Just like other opioids, morphine takes action on the myenteric plexus located in the intestinal canal, thereby slowing down gut motility and leading to constipation. The act of restricting gastric emptying and lowering forward peristalsis of the intestines reduces the rate of intestinal passage. Reduced gut discharge and the rise in intestinal fluid absorption add up to the constipation consequence (Kilpatrick 532)

Morphine also acts on the digestive system in some way through gut spasms following hang-ups of nitrous oxide production. This effect was proved on animals when a nitrous oxide forerunner inverted morphine-provoked alterations in the system motility.

If one stops taking the drug abruptly then they will be subjected to removal symptoms, depending on the quantity of drug taken and for what period. Withdrawal symptoms comprise things like diarrhea, vomiting, cold bouts, restlessness, and abdominal cramps (Kilpatrick 533).

Distribution, absorption, metabolism, and excretion of morphine

Morphine can be taken in various ways which include injection or through the mouth in pill or syrup form. For therapeutic purposes, injection is the most preferred way of administration.

Once the drug gets into the body, a large percentage is acted upon in the liver. Thus, if it is ingested orally, then forty to fifty percent of the intake is what ends up at the central nervous system. Following intramuscular injection or subcutaneous injection, morphine plasma amounts hit a high in about twenty minutes (Koch 205). For oral ingestion, the high is hit in about half an hour.

About eighty-seven percent of morphine intakes are excreted in the urine in seventy-two hours of administration. It is for the most part converted into morphine-3-glucuronide and morphine-6-glucuronide through the process of glucuronidation by phase two enzyme UDP-glucuronosyltransferase-2B7 (Koch 206). Metabolism rate varies with age, sex, diet, genetic orientation, sickness status, and use of any other drugs.

The excretion half-life of morphine is about two hours. However, there exist small disparities between males and females. A small amount is stored in fat and can be identified even after death (Koch 206).

Use of Morphine in Cancer Pain management

Proper and accurate identification of an ailment and subsequent treatment is an essential public health concern. This is why the World Health Organization (WHO) has laid down the procedures and steps to be followed by physicians and other caregivers in the treatment of patients and medication administration.

Ninety to ninety-five percent of all cancer pain can be effectively managed if set guiding principles are followed. The guiding principles group pain into various ranks of strength and the power of prescribed painkilling drugs to the strength (Kilpatrick 538). This is simply because strong aches require strong medications and vice versa.

Mild aches should be treated by the use of non-narcotic drugs like aspirin and non-steroidal anti-inflammatory drugs, commonly referred to as NSAIDs.

Moderate aches on the other hand should be treated using a combination of non-steroidal anti-inflammatory drugs and weak narcotics like codeine.

Severe pain needs to be treated by the use of powerful opioids like Demerol or methadone in combination with a non-steroidal anti-inflammatory drug.

The above guiding principles also have a provision for the inclusion of an adjuvant to these medications. Other than the above, morphine should be used exactly as it is prescribed by a qualified physician (Kilpatrick 543).

Medication taken as a pill should not be crushed but should be swallowed whole such that the medicine is released slowly once the tablet is in the body.

Morphine overdose

A morphine overdose comes about as a result of deliberately or accidentally ingesting or injecting too much of it. An excessive overdose can lead to a coma and death through respiratory restriction if the victim does not get attended to immediately (Andreas 29).

Overdose symptoms include severe drowsiness, chills, a weak pulse rate, fainting, and pinpoint pupils.

Conclusion

Morphine should be used only as per a qualified physician’s directions to avoid any risks associated with the drug which range from addiction and other side effects such as hampered respiration and constipation.

Works Cited

Andreas, Luch. Web.

Kilpatrick, Smith. “Morphine -6-glucuronide: actions and mechanisms” 521- 544.

Klockgether, Radke. “F. W. Sertürner and the discovery of morphine. 200 years of pain therapy with opioids” 244-9.

Koch, Höllt. “Role of receptor internalization in opioid tolerance and dependence.” 199-206.

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