Morphine Research Paper
Exploring the Chemical Abilities of Morphine
Morphine, a narcotic analgesic drug mainly used in medicine for pain relief, was first used alone in the early 1800s (author?2006). Prior to this, morphine was merely a component in opium, which was extracted from the seeds of an opium poppy. Opium has been known to ease pain for millennia, and its primary use as an analgesic in surgeries has been weird word here alive for centuries(Norn S, Kruse PR, Kruse E., 2005). One of the first recorded listings of a medical prescription of opium was in a Sumerian clay tablet in 2100 BC. In the first century, Greek philosopher, Celsus, believed in the use of opium in surgeries. Arabic physicians were also known to use it and by 1000 AD, they were able to recommend it for diarrhea and diseases of the eye (Norn S, Kruse PR, Kruse E., 2005) . In 1805, pharmacist Friedrich Sertürner was the first to isolate the most active substance in opium, morphine, from opium. Thus, he founded the alkaloid research performed in later years to extract the active substances in all kinds of other plants. He named his new-found drug morphine, after the Greek god of dreams, Morpheus (Norn S, Kruse PR, Kruse E., 2005). Years later, morphine was used as a painkiller in the American Civil War, but most soldiers became addicted (2006). In …show more content…
the late 1800s, Bayer Pharmaceuticals attempted to create a non-addictive pain killer by acetylating (adding an acetyl group to) both of morphine’s hydroxyl groups, but instead, what came out of this research, was the drug Heroin (2004). Further studies were conducted to lower the chances of getting addicted to morphine, and what research found was that a more safe and standardized effect was to use pure opium, which can be made by first “cooking” the raw substance to remove any soil, twigs or impurities (A. Nordal, 1956). This does not mean the drug is no longer addictive, simply that it’s addictivity has been decreased. Although several morphine-like drugs have been synthesized to prevent addiction and abuse, the complexity of the system and the way it acts with neurotransmitters makes it impossible to create a non-addictive version of the drug (A. Nordal, 1956). Some common names for the drug today are Avinza®, Kadian®, MS Contin®, Oramorph® SR, and Roxanol-T.
Throughout history, many different methods of preparation have come up concerning morphine. These methods include the Merck process, the Thiboumery and Mohr process, and the Robertson-Gregory process, along with a recent process underway (A.Barbier, 1950).
In the Merck process, the opium from the opium poppy is find another wordexhausted with cold water and the resultant solution is concentrated to a thicker molasses consistency. It is then precipitated hot with powdered sodium carbonate and heated until ammonia stops giving off. When tested with phenolphthalein, the system should remain alkaline. The solution is to stand for 24 hours, then the resultant precipitate is filtered and washed with cold water. When the precipitate appears clean (water runs colourless over it), it is dissolved in 85°C alcohol. Once dissolved, the alcoholic solution is evaporated and a dilute acetic acid solution is added slowly as neutralization proceeds to exhaust the residue. The acetic acid solution is then decolourized with charcoal, then filtered and precipitated with ammonia. The precipitate gets filtered, washed, and purified as it is crystallized with alcohol. This process is not extremely economical, considering the great quantities of alcohol needed during the purification stage in order to accommodate for the slight solubility of morphine (A.Barbier, 1950).
The Thiboumery and Mohr process begins with cutting the opium into three slices and mixing it with three times it’s weight in hot water until a paste is obtained. The liquid is filtered off, and that portion of the process repeats itself once more. The solutions obtained from this are evaporated to half of their original volume, then placed into boiling milk of lime. A 1:10:4 ratio of limes to water to opium should be used.The precipitate is filtered out and re-treated with a 3:1 ratio of water to opium. It is then filtered again.The lime solutions should be concentrated to a quantity twice the weight of the opium used. The solution is filtered again, boiled, and the addition of ammonium chloride helps in precipitating the morphine. This solution cools, then filtered, then the precipitate is washed and purified with hydrochloric acid, then it crystallizes as morphine hydrochloride (A.Barbier, 1950). This is a good process, as the morphine is almost completely separated from the other alkaloids, and the morphine solutions stay clean.
The Robertson-Gregory process yet another way to isolate morphine from opium. The opium is exhausted by five to ten times its weight of cold water until the resultant solution is of a soft extract consistency. The process is then repeated with cold distilled water, which causes impurities to precipitate to be later filtered off so the solution can evaporate. Then, 120g of calcium chloride are added for every kilogram of opium, to the boiling solution, which will be diluted with its volume in cold water. A precipitate of meconate and sulfate of calcium is formed and filtered off. The liquid is then concentrated, creating a new deposit almost exclusively for calcium meconate. This deposit is filtered off, leaving the solution. After a few days, it becomes a crystalline substance composed of morphine hydrochloride and codeine hydrochloride, more commonly known as “Gregory’s Salt”. These crystals are drained, put in a cloth, and drained out in a press. They are purified by multiple crystallizations, decolourized each time with animal charcoal.Once pure, the crystals are dissolved in water and the morphine is precipitated with ammonia, leaving the codeine in solution (A.Barbier, 1950). This process can be inefficient, as some morphine may be left in solution and not precipitated.
A new process being studied currently is to extract the opium with water, concentrate the aqueous extract, precipitate the alkaloids, dissolve them in Benzene, purify the morphine with hydrochloric acid, then use tartrate to completely separate it from the solution (A.Barbier, 1950). This is still under study, but it seems to be suitable for the industry.
Morphine can come in the form of a pill or in an oral solution for use outside of emergency rooms and medical centres, but in order to be prescribed these, the patient must be in severe, around the clock pain. The pill form is usually just a small solid circle of any colour, and typically comes in a dosage of 15mg-30mg per pill (2012). The oral solution is a clear and colourless liquid in which the prescribed dosage can be consumed. Pure morphine, before being made into a pill or solution, is a white crystalline substance with no odour. It’s boiling point is 190℃ and the melting point is 255℃. It is very soluble and has a molar mass of 285.34g/mol (2012).
An isomer of morphine is piperine.
By definition, an isomer has the same chemical components as a given substance, but a different chemical structure. Piperine fits the part as it is exactly that. Since it has the same chemical components, it has the same molar mass, 285.34g/mol. Piperine comes from the piperaceae plant family, which grow peppercorns that are used as spices in the every-day kitchen, which is why it is responsible for the pungent taste in black pepper. In medicine, piperine is used to treat diseases and discomforts, like vitiligo. Piperine can also be used as an insecticide by putting piperine extract on plants and in areas where certain bugs live
(2004).
Morphine is used in medicine to relieve moderate or severe pain throughout the process of surgeries, treatment of severe injuries, or the treatment of diseases. It comes in a pill form or in an oral solution for those suffering from severe, around the clock pain that no other medication can cure. Both of these come in regular intensity and extended-release intensity, the main difference being how long the patient waits between doses (2015).
Besides relieving pain, morphine impairs mental and physical performance, relieves fear and anxiety, produces euphoria, decreases hunger, inhibits the cough reflex, and it usually reduces the sex drive. In women, morphine can interfere with the menstrual cycle. Some potential side-effects of morphine are dizziness, drowsiness, nausea, weight loss, weakness, agitation, confusion, and difficulty urinating (2015). Some of the more serious side effects include a blue or purple tint to the skin, abnormal heartbeat, seizures, fainting, chest pain, rash, swelling, and difficulty breathing/swallowing. While on morphine, it is extremely important to take note of how the patient reacts, as it can be a dangerous drug.
Just as morphine suppresses pain by working with the central nervous system, it also suppresses the respiratory system. When overused, morphine can cause respiratory failure, leading to possible unconsciousness, cardiac arrest, suffocation, coma, and even death. If a patient becomes addicted to morphine and suddenly gets taken off the drug, they can experience a withdrawal forcing strong cravings for the drug (2015). These cravings can affect the patient's ability to make rational decisions, and they may have gotten more of the drug before they even know what happened (2015).
One of the biggest issues with morphine is the high chance of addiction and abuse that comes along with it. Worldwide, incidents of misuse of morphine have risen by 140% between 1992 and 2003 (2015). Coinciding with that, deaths due to opioids also rose 63%. This could be a result of the drastic rise in total number of morphine prescriptions per year, or the fact that between 1997 and 2007, the average prescribed dosage jumped from 96mg to over 700mg (2015). The statistics surrounding morphine are truly alarming. In 2010, pharmaceutical companies produced over 416 tons of the drug. More than 60% of morphine abusers have become dependent to the point of stealing it from friends or family who need it, the average age someone starts misusing morphine is around 21, and the typical addict will use the drug for around 14 years before seeking treatment (2015). But drug abuse is common, right? Well yes, but when morphine has one of the highest relapse rates of any drug, is the third most common cause of drug related emergency room admissions in the U.S, and, tied with heroin, is one of the most common causes of overdose related deaths, it should not be treated lightly (2015). If the moral effects of morphine are not terrifying enough, consider that the annual cost of morphine addiction to American citizens is over $8.6 billion. This includes, theft, health care, lost wages, accidents, and legal fees (2015). So this drug can be great for medical purposes, but when used on the side it has an extremely detrimental effect on humanity and the economy. The following charts show both the legal and illegal use of opioids in adults and youth in 2013.
Source: http://www.ccsa.ca/
When in a lot of pain, the neurotransmitters in the brain are firing at rapid speeds in the reflex arc. This is a biological process in which a nerve cell processes the pain from, for example, a broken bone. This activates a sensory neuron, which sends messages to the central nervous system (spinal cord), activating a motor neuron to then cause the effector to react, which would be a clench of an arm or holding the bone. The following diagram simplifies the process.
Source: aandponline.com
When these neurons fire, they create an action potential which releases neurotransmitters through the axon of one neuron, to bind to the receptors on the dendrite of another neuron. Once these neurotransmitters bind to the receptors, the action potential gets passed on through other neurons to then communicate to the brain that there is pain.
Morphine reacts in many different ways on the nervous system, but inhibition of neurotransmitter release is the most significant. When morphine comes into play, the calcium channels in the presynaptic neuron are blocked, preventing calcium from re-entering the presynaptic terminal (A. Prescr, 1996). This fills up the receptor sites on the presynaptic neuron, preventing the neurotransmitters from releasing. Since the calcium ions can not re-enter the presynaptic terminal, they are left in between the two neurons in a space called the synapse, creating a euphoric feeling, which partially causes morphine’s addictive properties (H. Green). This happens because the brain is tricked into getting rid of some receptors on the neurons in order to keep more calcium ions in the synapse, since it creates such a great feeling. The brain then becomes dependent on morphine to keep that euphoric feeling. Because the neurotransmitters don’t pass through all the neurons, the pain does not get transmitted by action potential through the spinal cord to the brain, effectively easing the pain caused by the stimulus (A. Prescr, 1996). Below is a representation of the neurotransmission.
Source: Crash Course
The chemical formula for morphine is C17H19O3N, it is composed of 17 carbon atoms, 19 hydrogen atoms, 3 oxygen atoms, and one nitrogen atom. Within this structure, 8 pairs of carbons form double bonds with each other. Morphine comes in a pentacyclic shape. This is formed out of a benzene ring (C6H6), two cyclohexane rings (C6H12), a piperidine ring (C5H11N), a tetrahydrofuran ring (C4H8O), two hydroxyl groups (OH-), and an ether linkage between two carbon atoms in the piperidine ring (A. Nordal, 1956).
The shape of morphine has a great impact on its ability to bind to the receptor sites on the nerve and stop the pain signals from getting to the brain. The linear benzene group fits into a flat section on a receptor protein, while the bent carbon atom group fits into a groove beside it. The positively charged nitrogen atom then bonds to a negatively charged group on the receptor, locking the molecules together to block the neurotransmitters (2004).
The research done in this assignment concludes that although complex, morphine is a very useful compound in medicine, as it helps relieve excruciating pain throughout surgeries and treatments. However, it must be used with caution due to its highly addictive properties and dangerous side effects, such as inhibiting breathing and causing heart failure. The chemical composition of morphine helps it perform its complicated tasks in the nervous system by enabling it to bind to receptors on neurons throughout the brain and inhibit neurotransmission. Although extremely dangerous if misused, morphine is a necessary drug in all hospitals to ensure a patient’s health and comfort.
Morphine, a narcotic analgesic drug mainly used in medicine for pain relief, was first used alone in the early 1800s (author?2006). Prior to this, morphine was merely a component in opium, which was extracted from the seeds of an opium poppy. Opium has been known to ease pain for millennia, and its primary use as an analgesic in surgeries has been weird word here alive for centuries(Norn S, Kruse PR, Kruse E., 2005). One of the first recorded listings of a medical prescription of opium was in a Sumerian clay tablet in 2100 BC. In the first century, Greek philosopher, Celsus, believed in the use of opium in surgeries. Arabic physicians were also known to use it and by 1000 AD, they were able to recommend it for diarrhea and diseases of the eye (Norn S, Kruse PR, Kruse E., 2005) . In 1805, pharmacist Friedrich Sertürner was the first to isolate the most active substance in opium, morphine, from opium. Thus, he founded the alkaloid research performed in later years to extract the active substances in all kinds of other plants. He named his new-found drug morphine, after the Greek god of dreams, Morpheus (Norn S, Kruse PR, Kruse E., 2005). Years later, morphine was used as a painkiller in the American Civil War, but most soldiers became addicted (2006). In …show more content…
the late 1800s, Bayer Pharmaceuticals attempted to create a non-addictive pain killer by acetylating (adding an acetyl group to) both of morphine’s hydroxyl groups, but instead, what came out of this research, was the drug Heroin (2004). Further studies were conducted to lower the chances of getting addicted to morphine, and what research found was that a more safe and standardized effect was to use pure opium, which can be made by first “cooking” the raw substance to remove any soil, twigs or impurities (A. Nordal, 1956). This does not mean the drug is no longer addictive, simply that it’s addictivity has been decreased. Although several morphine-like drugs have been synthesized to prevent addiction and abuse, the complexity of the system and the way it acts with neurotransmitters makes it impossible to create a non-addictive version of the drug (A. Nordal, 1956). Some common names for the drug today are Avinza®, Kadian®, MS Contin®, Oramorph® SR, and Roxanol-T.
Throughout history, many different methods of preparation have come up concerning morphine. These methods include the Merck process, the Thiboumery and Mohr process, and the Robertson-Gregory process, along with a recent process underway (A.Barbier, 1950).
In the Merck process, the opium from the opium poppy is find another wordexhausted with cold water and the resultant solution is concentrated to a thicker molasses consistency. It is then precipitated hot with powdered sodium carbonate and heated until ammonia stops giving off. When tested with phenolphthalein, the system should remain alkaline. The solution is to stand for 24 hours, then the resultant precipitate is filtered and washed with cold water. When the precipitate appears clean (water runs colourless over it), it is dissolved in 85°C alcohol. Once dissolved, the alcoholic solution is evaporated and a dilute acetic acid solution is added slowly as neutralization proceeds to exhaust the residue. The acetic acid solution is then decolourized with charcoal, then filtered and precipitated with ammonia. The precipitate gets filtered, washed, and purified as it is crystallized with alcohol. This process is not extremely economical, considering the great quantities of alcohol needed during the purification stage in order to accommodate for the slight solubility of morphine (A.Barbier, 1950).
The Thiboumery and Mohr process begins with cutting the opium into three slices and mixing it with three times it’s weight in hot water until a paste is obtained. The liquid is filtered off, and that portion of the process repeats itself once more. The solutions obtained from this are evaporated to half of their original volume, then placed into boiling milk of lime. A 1:10:4 ratio of limes to water to opium should be used.The precipitate is filtered out and re-treated with a 3:1 ratio of water to opium. It is then filtered again.The lime solutions should be concentrated to a quantity twice the weight of the opium used. The solution is filtered again, boiled, and the addition of ammonium chloride helps in precipitating the morphine. This solution cools, then filtered, then the precipitate is washed and purified with hydrochloric acid, then it crystallizes as morphine hydrochloride (A.Barbier, 1950). This is a good process, as the morphine is almost completely separated from the other alkaloids, and the morphine solutions stay clean.
The Robertson-Gregory process yet another way to isolate morphine from opium. The opium is exhausted by five to ten times its weight of cold water until the resultant solution is of a soft extract consistency. The process is then repeated with cold distilled water, which causes impurities to precipitate to be later filtered off so the solution can evaporate. Then, 120g of calcium chloride are added for every kilogram of opium, to the boiling solution, which will be diluted with its volume in cold water. A precipitate of meconate and sulfate of calcium is formed and filtered off. The liquid is then concentrated, creating a new deposit almost exclusively for calcium meconate. This deposit is filtered off, leaving the solution. After a few days, it becomes a crystalline substance composed of morphine hydrochloride and codeine hydrochloride, more commonly known as “Gregory’s Salt”. These crystals are drained, put in a cloth, and drained out in a press. They are purified by multiple crystallizations, decolourized each time with animal charcoal.Once pure, the crystals are dissolved in water and the morphine is precipitated with ammonia, leaving the codeine in solution (A.Barbier, 1950). This process can be inefficient, as some morphine may be left in solution and not precipitated.
A new process being studied currently is to extract the opium with water, concentrate the aqueous extract, precipitate the alkaloids, dissolve them in Benzene, purify the morphine with hydrochloric acid, then use tartrate to completely separate it from the solution (A.Barbier, 1950). This is still under study, but it seems to be suitable for the industry.
Morphine can come in the form of a pill or in an oral solution for use outside of emergency rooms and medical centres, but in order to be prescribed these, the patient must be in severe, around the clock pain. The pill form is usually just a small solid circle of any colour, and typically comes in a dosage of 15mg-30mg per pill (2012). The oral solution is a clear and colourless liquid in which the prescribed dosage can be consumed. Pure morphine, before being made into a pill or solution, is a white crystalline substance with no odour. It’s boiling point is 190℃ and the melting point is 255℃. It is very soluble and has a molar mass of 285.34g/mol (2012).
An isomer of morphine is piperine.
By definition, an isomer has the same chemical components as a given substance, but a different chemical structure. Piperine fits the part as it is exactly that. Since it has the same chemical components, it has the same molar mass, 285.34g/mol. Piperine comes from the piperaceae plant family, which grow peppercorns that are used as spices in the every-day kitchen, which is why it is responsible for the pungent taste in black pepper. In medicine, piperine is used to treat diseases and discomforts, like vitiligo. Piperine can also be used as an insecticide by putting piperine extract on plants and in areas where certain bugs live
(2004).
Morphine is used in medicine to relieve moderate or severe pain throughout the process of surgeries, treatment of severe injuries, or the treatment of diseases. It comes in a pill form or in an oral solution for those suffering from severe, around the clock pain that no other medication can cure. Both of these come in regular intensity and extended-release intensity, the main difference being how long the patient waits between doses (2015).
Besides relieving pain, morphine impairs mental and physical performance, relieves fear and anxiety, produces euphoria, decreases hunger, inhibits the cough reflex, and it usually reduces the sex drive. In women, morphine can interfere with the menstrual cycle. Some potential side-effects of morphine are dizziness, drowsiness, nausea, weight loss, weakness, agitation, confusion, and difficulty urinating (2015). Some of the more serious side effects include a blue or purple tint to the skin, abnormal heartbeat, seizures, fainting, chest pain, rash, swelling, and difficulty breathing/swallowing. While on morphine, it is extremely important to take note of how the patient reacts, as it can be a dangerous drug.
Just as morphine suppresses pain by working with the central nervous system, it also suppresses the respiratory system. When overused, morphine can cause respiratory failure, leading to possible unconsciousness, cardiac arrest, suffocation, coma, and even death. If a patient becomes addicted to morphine and suddenly gets taken off the drug, they can experience a withdrawal forcing strong cravings for the drug (2015). These cravings can affect the patient's ability to make rational decisions, and they may have gotten more of the drug before they even know what happened (2015).
One of the biggest issues with morphine is the high chance of addiction and abuse that comes along with it. Worldwide, incidents of misuse of morphine have risen by 140% between 1992 and 2003 (2015). Coinciding with that, deaths due to opioids also rose 63%. This could be a result of the drastic rise in total number of morphine prescriptions per year, or the fact that between 1997 and 2007, the average prescribed dosage jumped from 96mg to over 700mg (2015). The statistics surrounding morphine are truly alarming. In 2010, pharmaceutical companies produced over 416 tons of the drug. More than 60% of morphine abusers have become dependent to the point of stealing it from friends or family who need it, the average age someone starts misusing morphine is around 21, and the typical addict will use the drug for around 14 years before seeking treatment (2015). But drug abuse is common, right? Well yes, but when morphine has one of the highest relapse rates of any drug, is the third most common cause of drug related emergency room admissions in the U.S, and, tied with heroin, is one of the most common causes of overdose related deaths, it should not be treated lightly (2015). If the moral effects of morphine are not terrifying enough, consider that the annual cost of morphine addiction to American citizens is over $8.6 billion. This includes, theft, health care, lost wages, accidents, and legal fees (2015). So this drug can be great for medical purposes, but when used on the side it has an extremely detrimental effect on humanity and the economy. The following charts show both the legal and illegal use of opioids in adults and youth in 2013.
Source: http://www.ccsa.ca/
When in a lot of pain, the neurotransmitters in the brain are firing at rapid speeds in the reflex arc. This is a biological process in which a nerve cell processes the pain from, for example, a broken bone. This activates a sensory neuron, which sends messages to the central nervous system (spinal cord), activating a motor neuron to then cause the effector to react, which would be a clench of an arm or holding the bone. The following diagram simplifies the process.
Source: aandponline.com
When these neurons fire, they create an action potential which releases neurotransmitters through the axon of one neuron, to bind to the receptors on the dendrite of another neuron. Once these neurotransmitters bind to the receptors, the action potential gets passed on through other neurons to then communicate to the brain that there is pain.
Morphine reacts in many different ways on the nervous system, but inhibition of neurotransmitter release is the most significant. When morphine comes into play, the calcium channels in the presynaptic neuron are blocked, preventing calcium from re-entering the presynaptic terminal (A. Prescr, 1996). This fills up the receptor sites on the presynaptic neuron, preventing the neurotransmitters from releasing. Since the calcium ions can not re-enter the presynaptic terminal, they are left in between the two neurons in a space called the synapse, creating a euphoric feeling, which partially causes morphine’s addictive properties (H. Green). This happens because the brain is tricked into getting rid of some receptors on the neurons in order to keep more calcium ions in the synapse, since it creates such a great feeling. The brain then becomes dependent on morphine to keep that euphoric feeling. Because the neurotransmitters don’t pass through all the neurons, the pain does not get transmitted by action potential through the spinal cord to the brain, effectively easing the pain caused by the stimulus (A. Prescr, 1996). Below is a representation of the neurotransmission.
Source: Crash Course
The chemical formula for morphine is C17H19O3N, it is composed of 17 carbon atoms, 19 hydrogen atoms, 3 oxygen atoms, and one nitrogen atom. Within this structure, 8 pairs of carbons form double bonds with each other. Morphine comes in a pentacyclic shape. This is formed out of a benzene ring (C6H6), two cyclohexane rings (C6H12), a piperidine ring (C5H11N), a tetrahydrofuran ring (C4H8O), two hydroxyl groups (OH-), and an ether linkage between two carbon atoms in the piperidine ring (A. Nordal, 1956).
The shape of morphine has a great impact on its ability to bind to the receptor sites on the nerve and stop the pain signals from getting to the brain. The linear benzene group fits into a flat section on a receptor protein, while the bent carbon atom group fits into a groove beside it. The positively charged nitrogen atom then bonds to a negatively charged group on the receptor, locking the molecules together to block the neurotransmitters (2004).
The research done in this assignment concludes that although complex, morphine is a very useful compound in medicine, as it helps relieve excruciating pain throughout surgeries and treatments. However, it must be used with caution due to its highly addictive properties and dangerous side effects, such as inhibiting breathing and causing heart failure. The chemical composition of morphine helps it perform its complicated tasks in the nervous system by enabling it to bind to receptors on neurons throughout the brain and inhibit neurotransmission. Although extremely dangerous if misused, morphine is a necessary drug in all hospitals to ensure a patient’s health and comfort.