OPOIDS, OPIATES, AND OPIUM: RESEARCH PAPER ON THE PHARMACOKINETICS AND PHARMACODYNAMICS ON THE HUMAN BODY

INTRODUCTION Opiates, also referred to as a narcotic, in medical terminology describes a chemical substance that traverses the partition of flowing blood and the translucent fluid that occupies the space between the membranes that shelters the brain and spinal cord, also included is the fragile deepest layer of the membranes that encloses the brain and spinal cord. This chemical substance impinges on the natural occurrences of the body and mind. Opioid is a natural product found in poppy plants or may be derived from the poppy plant and mixed with chemicals. The most popular concoctions are codeine, morphine, fentanyl, methadone, and heroin. The medical prescription of an opiate is to suppress pain, although codeine is implemented in cough suppressants. Opiates attach specialized opioid cell binding areas, which are called G protein-coupled receptors; these receptors are responsible for conveying indications of pain in the specific locale of the nerve cells. Their natural binding of a molecule consists of a peptide that contains five amino acids (proteins). Met-enkephalin (Tyr-Gly-Gly-Phe-Met-COO-) Leuenkephalin (TyrGly-Gly-Phe-Leu-COO-) Cite http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/Drugs.html#opiates

Discharge of short polymers, which is an ample molecule made up of a uniformly reproduced pattern of organizational building blocks that naturally will unite by means of fastening small particle molecules into molecules. This will manifest because of the allotment of pairs of electron bonds between the small particle molecules and will structure a molecule that has gathered and merged the small particle molecules that consist of more than one component. This occurs because of the precise connection of amino acids (proteins) combined with the normal course of action of rendering genetic messages and processing the harmful incident of the tissue. This act is because the nerves transmit conveyance from the body to the brain or spinal cord and may travel through blood vessels to an organ. This prevents communication of pain. The discovery of two structures of enkephalin was unconcealed in 1975 by John Hughes and Hans Kosterlitz. See http://www.pbs.org/wgbh/aso/databank/entries/dh75en.html With the above said process explained, an opiate will ameliorate the painkilling outcome of enkephalin nerve cells. The ability to remain unaffected by opiate use is due to homeostasis, in such a manner that there is a decrease in sensitivity in order to counterbalance and maintain the prolonged amounts of an opiate substance. Once a person discontinues usage, the body is not perceptive to the enkephalin never cells and symptoms of withdrawal (fighting addiction) will

come about. See http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/Drugs.html" \t "_blank" l #opiates Different cultures and locations throughout the world use opiates for various reasons. The orthodox medicinal purposes date back to the 1600s through the 1800s to minimize feeling of physical discomfort during surgical operations. In China, by the later part of the 1700s, smoking of opium became an epidemic. This narcotic is not discriminatory, it was prominent with persons of artistic abilities and writers during the nineteenth century, they based their rationale of consumption on basis the narcotic heightened their inventiveness because the drug lowered the obstruction of their mental state. There are also variable medical grounds for the use of opiates. A mixture of opium by camphorated distillates was used for the intent to relieve diarrhea. This was available without a prescription, although to date a prescription is required because it is listed as a controlled substance. CODEINE Chemical Compound and Intended Use Codeine is notable in the medication Tylenol 3 and cough suppressants; this is made from opium poppy and is correlative to morphine and heroin but has less of an affect. The components are C18H21NO3 Cite http://bulkpharm.mallinckrodt.com/attachments/msds/CODEN.htmhttp://bulk pharm.mallinckrodt.com/attachments/msds/CODEN.htm

Codeine was discovered by Pierre-Jean Robiquet in 1832. See www.discoveriesinmedicine.com/Bar/htt The intended use is for discomfort and mental states of anxiousness. Secondary Effects The byproduct of consuming codeine may include hypersensitivity, xerostomia, skin irritation, feelings of lethargy, difficulty having a bowel movement, queasiness, emesis, a drop in blood pressure, ischuria, lack of sexual desire, and shallow respirations. If an individual is taking medication for a psychological disorder there is a high potential that there may be a negative reaction. Prolonged or misuse of codeine may, in addition to the above mentioned, can result in physical and psychological dependency, dyspnea, hypoventilation, harm to the liver or kidney's function, and internal bleeding, and of course death. Route of Administration Tolerance to codeine will vary depending on the amount and duration of consuming this narcotic and on each individuals metabolic rate to breakdown the codeine in their system. Abuse of codeine is linked with bringing forth a feeling of well-being; this can be obtained by overindulging in cough syrup, pill form, injections, rectally, or snorted. If ingested by pill form the codeine will travel through a person's system faster if it is crushed up, this procedure will cut down on the wait time of the high. See

http://www.addictionsearch.com/treatmentarticles/article/codeine-addiction-effects-andtreatment 46.html MORPHINE Pharmacology Morphine's components are likewise to that of endorphins, a chemical located mainly in the pituitary gland, which is classified as an endocrine gland, it and is very minuscule in size, and can be found at the bottom of the hypothalamus, which is a section of the brain positioned below the thalamus and above the brain stem, therefore at the bottom of the brain. The hypothalamus comprises quantities of infinitesimal nuclei that behave in various manners, though the hypothalamus is highly recognized to connect the nervous system to the endocrine system by a passageway of the pituitary gland. This allows for transfer of communication between divergent nerve cells and also between nerve cells and muscles to induce or stop an activity in the cell's to take delivery. Chemical Compound and Intended Use Morphine's key ingredient is opium, derived from the immature seed casing of the poppy plant. The components are CC 17HH 19NO3 Cite http://www.medicallook.com/reviews/Morphine.html Morphine was discovered by Friedrich Sertrne in 1804 See http://science.jrank.org/pages/4450/Morphine.html Morphine's intended use is for alleviation of

temperate to intense discomfort and is widely administered to individuals with cancer or have undergone severe physical injury. Secondary Effects Effects of taking morphine may include difficulty having a bowel movement, loose stools, ischuria (which may lead to atypical growth of fluid in cells which will produce swelling), queasiness, upset stomach, emesis, dyspepsia, lack of desire to eat, changes in sensation to skin, shivers, light-headedness, headaches, bizarre dreams (may result in inability to sleep), injury caused from perception changes, clouded or altered vision, reduction in red blood cells, lack of sexual desire, gustatory changes, xerostomia (which may lead to problems with swallowing and thirst), shakiness or stiffness in muscles, perspiration, lack of vigor, nervousness, agitation, and difficulty with memory, lack of clarity. Prolonged or misuse of morphine may, in additions to the above mentioned, can result in physical and psychological dependency change in breathing patterns, rapid mood change, bradycardia (which may result in a heart attack), hypertension/ hypotension (which may result in abnormal heart rhythm, convulsions, etc.), and of course death. See http://pain.emedtv.com/morphine/morphine-sidehttp://pain.emedtv.com/morphine/morphine-side effects.html Route of Administration Morphine is highly addictive and in a short amount of time, this is because the body will

experience profound withdrawal and an individual will begin to feel ill without having it in their system. Morphine can be taken orally, and many abusers will crush up the pill for faster absorption, injected, snorted, patches, rectally, and liquid form. FENTANYL Pharmacology Fentanyl is a synthetic primary u-opioid, which is in the category of opioid receptors and is made up of voluminous amounts of proteins in which a chemical's duty is to adhere to the receptors chiefly throughout the central nervous system and GI tract. The particular gathering of proteins that exchange information between the cells and externally. An additional substance adheres and shapes a configuration that entails a central atom, which is responsible for attaching to other atoms and allows the element to form. There is a superior chemical attraction for enkephalins (a virile outcome resembling opiates and acts as messenger between nerve cells and responses) and beta-endorphin (a chemical that induces a reaction by binding to cell receptors and imitates opiates by lowering the magnitude of discomfort), although an inferior chemical attraction for dynorphins (a natural pain reliever with no external principal). Chemical Compound and Intended Use Fentanyl is very powerful narcotic, said to be up to 100 times more powerful than morphine, it sets in to eliminate pain near instantly. The components are

C22H28N20.HCI. Cite http://bulkpharm.mallinckrodt.com/attachments/msds/FENTY.htm Fentanyl was first synthesized by Dr. Paul Janssen in 1960. See http://www.pauljanssenaward.com/janssen/scientific.htm Fentanyl is by far more powerful than morphine; the intended use is for persons that have developed a tolerance to other opiates and is for severe or prolonged pain. This medication may be used to comfort those at the end of their life from agony. Secondary Effects Effects of taking fentanyl may include lack of clarity, nervousness, difficulty having a bowel movement, loose stools, dyspepsia, upset stomach, queasiness, emesis, lack of desire to eat, weight loss, xerostomia, light-headedness, perspiration, feeling of sleepiness, insomnia, headache, skin or mouth irritation, injury caused from perception changes, euphoria, swelling, discomfort, numbness, or tingling to the application site, lack of strength, anaphylaxis, dyspnea, constriction of the chest, mucocele, delusions, hyperkinesias, seizures, cardiac dysrhythmia, bradypnea, syncope, lethargy, lack of blood blow to organs, angina, lack of clarity, hemoptysis, ischuria (which may lead to atypical growth of fluid in cells which will produce swelling), altered motor coordination, shivers, aches and pains, rapid mood change, difficulty with memory, changes in sensation to skin, pharyngitis, shivers, clouded or altered vision, skin sores,

hemorrhaging, bruising, swelling or loss of sensation of the extremities, jaundice, and of course death. See http://www.drugs.com/sfx/fentanyl-side-effects.html Individuals that use fentanyl will develop an extensive and intensified tolerance that will necessitate an increase in the amount to achieve the same affect. When an individual is no longer in need of this narcotic, in order to discontinue treatment, they must be weaned off because of the effects of withdrawal. Dependency to fentanyl is beyond habit-forming, not only dangerous, but utterly life threatening. Addiction to fentanyl is the compulsive need to continue its use. The variance of intake alters from medicative to illicit purposes, the individual (addict) will continue to use fentanyl despite the destructive aftermath to the body, and this is not only caused from the addiction but from the horrendous side effects of withdrawal. See http://www.softlandingrecovery.com/articles/fentanyl_withdrawal.htm Route of Administration Fentanyl can be taken by lozenge, patch, dissoluble film, and tablet, intravenously for sedation, nasal sprays, and inhalers. Abusers have been noted to let the patch dry up, or to dry it in the microwave in order to snort this narcotic, insert whichever form into their anus, or boot, very dangerous and ignorant. See http://www.drugs.com/sfx/fentanyl-side-effects.html METHADONE Pharmacology

Methadone's components are to simulate endorphins, a chemical located mainly in the pituitary gland, which is classified as an endocrine gland, it and is very minuscule in size, and can be found at the bottom of the hypothalamus, which is a section of the brain positioned below the thalamus and above the brain stem, therefore at the bottom of the brain. The hypothalamus comprises quantities of infinitesimal nuclei that behave in various manners, though the hypothalamus is highly recognized to connect the nervous system to the endocrine system by a passageway of the pituitary gland. This allows for transfer of communication between divergent nerve cells and also between nerve cells and muscles to induce or stop an activity in the cell's to take delivery. Methadone consists of contrived opioid chemicals that operate by attaching to opioid receptors, established mainly in the spinal cord, brain, intestine and stomach. These receptors incorporate substantial units of proteins that are connected to membranes with a purpose to be an exclusive obstruction in the localization of cells and have cognizance of molecules external of the cell, this sets off cellular responses within. The uopioid, which is in the category of opioid receptors and is made up of voluminous amounts of proteins in which a chemical's duty is to adhere to the receptors chiefly throughout the central nervous system and GI tract. Furthermore, there a substance that adheres and shapes an arrangement comprised of an

atom in a molecule which may or may not be electrically charged, now securing to an arrangement of proximate molecules with molecules that are naturally brought forth by the body's system. Methadone acts by binding to the u-opioid receptor, but also has some connection with a protein that imitates an adhering chemical at the excitable nerve endings of a cell and induces activity of the cell. The receptor antagonist does not bring about a natural outcome alone by attaching to the nerve endings, the purpose is to obstruct or muffle the counteracting activity of the dispatched chemical provocation against the main stimulating chemical that conveys messages between nerve cells and muscles in the spinal cord and brain. Methadone is broken down by a large unit of proteins (CYP3A4, CYP2B6, and CYP2D6) in which their service is to change the state in which oxygen is increased in natural matter. See http://www.netdoctor.co.uk/medicines/100003484.html Chemical Compound and Intended Use Methadone's man made ingredients are to mimic the chemical structure of the narcotics that are derived from the poppy plant; therefore, it is categorized as an opioid. The components are C21H27NO HCL Cite http://www.rxlist.com/dolophinedrug.htm Methadone was first synthesized in 1939 at the pharmaceutical laboratories of the I.G. Farbenkonzern, a subsidiary of the Farbwerke Hoechst, Frankfurt am Main, Germany. Cite http://www.indrohttp://www.indro-http://www.indro-

online.de/historymethadone.htm The intended use is for the remedy of opioid addiction, terminal illness chiefly lung cancer as methadone is noted to suppress the reflex of coughing, moderate to severe pain that is not amenable to non narcotic pain medications. The justification to use methadone as treatment to opioid addiction is because methadone will hinder the withdrawal symptoms from the users' opioid drug of choice and will be administered until the dosage becomes lesser and eventually eliminated. See http://www.netdoctor.co.uk/medicines/100003484.html Secondary Effects Effects of taking methadone may include difficulty having a bowel movement, loose stool, lack of desire to eat, queasiness, emesis, xerostomia, light-headedness, syncope, headache, dizziness, lack of strength, lethargy, feeling of sleepiness, lack of clarity, delusions, lack of sexual desire or ability to perform, if injected discomfort or swelling to the site, perspiration, skin irritation, numbness, or tingling in the hands, legs, or feet; ischuria (which may lead to atypical growth of fluid in cells which will produce swelling), loss of sensation of the extremities, spasms, hemorrhaging, bruising, excessive tear production, shivers, aches and pains, delusions, rapid mood change, seizures, anaphylaxis, mucocele, dyspnea, constriction of the chest, cardiac dysrhythmia, seizures, bradypnea, dyspnea, tachycardia, and of course death. See

http://www.drugs.com/sfx/methadone-side-effects.html Route of Administration Methadone is highly addictive even though it is used primarily to treat heroin dependency. It is about 1.5 times as potent as morphine, oxycodone, and heroin by mass. Cite http://everything2.com/title/methadone Methadone can be one of the most challenging narcotics to battle because it stays in the individuals' system for a significant amount of time and is stored in the tissues of the body as it is fat soluble. The reason that methadone can be used to treat this dependency is because methadone is not a natural opiate, it is synthetic. Methadone can be taken orally by means of tablet form, liquid, injections, illicitly booting, rectally, and smoking it. HEROIN Pharmacology Heroin's components consist of a concoction of natural (poppy plant) and inorganic substances (mainly morphine), this narcotic works by attaching to opioid receptors, naturalized mostly in the spinal cord, brain, intestine and stomach. These receptors contain vast units of proteins that are sessile to membranes designed to be a blockage in the placement of cells and are aware of molecules not in the cell, this commences cellular responses within. The u-opioid, which is in the category of opioid receptors, consists of copious quantities of proteins, coupled

with a chemical that is liable to cling to the receptors mostly direct to the central nervous system and GI tract (spinal cord, brain, intestine and stomach). Additionally, there a substance that coheres and conforms a position made up of an atom in a molecule, next the new attached and bound configuration of molecules close by will combine with molecules that are naturally brought forth by the body's system. Heroin binds to the u-opioid receptor, although it is acquainted with other proteins that simulate an adhering chemical at the excitable nerve endings of a cell, this promotes activity of the cell. The receptor antagonist does not bring about a natural result by attaching to the nerve endings on its own, the function is to obturate or tone down the vex activity of the sent chemical's provocation against the main stimulating chemical that imparts communication between nerve cells and muscles in the spinal cord and brain. Heroin that is consumed by mouth will experience a significant process of biochemical change of the narcotic by the individual's enzymatic systems because the absorption of the narcotic is bated by the time it extends to bloodstream. Injecting heroin is all together different as the purpose is to enter the blood stream almost immediately. Heroin is extensively able to dissolve in fat than morphine alone. Once in the brain, the acetyl group (a distinguished molecule in absorption), is abstracted into 6MAM (an active derivative of metabolism) and morphine which attach to the u-opioid receptors as previously

explained, the outcome is the narcotic makes the individual have a feeling of well being, diminished anxiety, and assuaged pain. Heroin alone shows somewhat low chemical attraction for the u-receptor. See http://www.heroinhelper.com/my_books/little_book_of_heroin/brain_chemicals.shtml Chemical Compound and Intended Use Heroin's central component is morphine. The chemical formula is C21H23NO5 Heroin was first processed in 1874 by C.R. Alder Wright Cite http://itech.dickinson.edu/chemistry/?cat=79 The intended use is for heroin in the United States is none, it is illegal. Secondary Effects The effects of using heroin may include lack of regular activity, dry mouth, drowse out, exaggerated sense of well-being, the entire body begins to feel heavy, changes in sensation to skin, lack of cognitive capacity, emotionless, change in pupils and vision, muscle aches, loose stool, difficulty having a bowel movement, inability to sleep, frightening or upsetting dreams, discontentment, no sexual desire and/or performance, false sense of perception, extreme mood changes, insanity, nausea, emesis, uncontrollable leg twitching, inflammation or infection of tissue below the skins surface, a hollow space may fill with pus from inflammation and/or a bacterial infection, inadequate nutrition/undernourishment, inflammation of the lungs from

infection/bacterium/or a virus, collapsed or hardened veins, inflammation and/or numerous diseases of the liver, infective endocarditis, permanent complications to the central nervous system, preventable injury due to intercepting the brains ability to comprehend pain, seizures, bradypnea, cardiac dysrhythmia, contracting HIV/AIDS, and of course, death from overdose or prolonged abuse of the body. The consequences of using heroin may depend on the way in which the drug was used, the pace at which the individuals body breaks down the narcotic, and the frequency and duration of using. See http://www.opiates.com/heroin/heroin-side-effects.html Heroin crosses through the separation of the flowing blood and cerebrospinal fluid located in the central nervous system at a rate one hundred times faster than morphine due to the fact it is highly dissoluble in fats. Heroin is said to be addictive upon the first use, this is because as the rush diminishes, withdrawal will commence as soon as the effects of this narcotic weaken, and initially this will occur within a few hours. The user will have a strong desire for more, this will lead to tolerance, more heroin in a shorter span, and then on to addiction. The side effects of heroin withdrawal are excruciating and can be life threatening. See http://www.heroin-addiction.info/Heroin_Side_Effects.htm Route of Administration Heroin can be snorted, smoked, and the most popular is by injection. The duration of time needed to get a response from heroin is astounding if the narcotic is administered intravenously, it is said to produce effects in 7 to 8 seconds. Individuals who choose to inject into a muscle or

under the skin will begin to get the rush in 5 to minutes. Some individuals will repeat this process up to four times in one day. See http://faculty.washington.edu/chudler/hero.html

CONCLUSION Codeine, morphine, fentanyl, and methadone are classified as Schedule II drugs under the Controlled Substances Act. Heroin is classified as a Schedule I drug under the Controlled Substances Act. These narcotics show effects largely by means of the -opioid receptor in the central nervous system (CNS). The -opioid receptors are a group of opioid receptorsopioid receptors with superior similarity for enkephalinsenkephalins and beta-endorphinbeta-endorphin but minimal similarities for dynorphinsdynorphins . Opioid receptors are gatherings of large interrelated proteins of specific fundamental membrane proteins that participate in the flow of information amid the cell and external of the body with a compound that performs by attaching to the opioid receptors that are located mainly in the brain and spinal cord (central nervous system) and the gastrointestinal tract as a signal generating molecule, that attaches to a location on an aimed protein. The opioids that are devoid of outside sources are dynorphins (a set of short series of proteins that attach to opioid receptors in the brain that come about from the antecedent protein prodynorphin), enkephalins (short, large molecules, composed of duplicating a component of a polymer chain occupied in adjusting the awareness of pain to the body), endorphins (the originating opioid with short, large

molecules, composed of duplicating a component of a polymer chain with a purpose of transmitting messages amid nerves to muscles. They are created by the pituitary gland (an endocrine gland, which is very minuscule in size, located at the bottom section of the brain positioned below the thalamus and above the brain stem) and the hypothalamus (bottom portion of the brain), endomorphinsendomorphins (short, large molecules, composed of duplicating a component of a polymer chain comprised of four amino acids coupled with peptide bonds with the highest known similarity and exactitude for the opioid receptor ), and nociceptin (17 amino acids that are minuscule replicas of protein molecules utilized by nerve cells for the purpose of intra communication and are devoid of outside sources, they are attaching molecules for the nociceptin receptor). Morphine is considered to naturally exist in the body and includes the necessary characteristics to be the prototype for copying other types of opioids because of the mu3 opiate receptor, an organically occurring morphine in the body is associated with the mu3 opiate receptor and only reacts to morphine. This receptor is a host cell and is comprised of a remote set of natural substances established in the chromosomes of cells and have a main function in preserving and duplicating genetic data by means of the development of proteins by cells that apply DNA (passes on the genetic data for each stage in descent), RNA (supplies the commands to provide genetic data in this information to the cell's protein production locations), and an

assortment of proteins. These are compound chains that alter in span and provide genetic information of amino acid chains (chemically linked proteins that come about in the configuration of protein molecules) that possess mu3 opiate receptor action, and significant natural amino acid chains that contain mu3 opiate receptor action in tissue. The gastrointestinal consequences of morphine take place mainly by opioid-opioid receptors in the bowel by hindering the gastric draining and reducing the oomph for muscle contractions in the intestine, morphine reduces the pace of intestinal passage and reduces stomach discharge and increases the take in of liquids in the intestines, furthermore morphine aides in difficulty having a bowel movement. Fentanyl is a synthetic strong narcotic mimicking chemical at the mu (a class of opioid receptors with a strong similarity for enkephalins (a short, large molecules, composed of duplicating a component of a polymer chain occupied in adjusting the awareness of pain to the body), although a weak similarity for dynorphins (a set of short series of proteins that attach to opioid receptors in the brain that come about from the antecedent protein prodynorphin) and kappa opiate receptors (a class of an opioid receptor that attaches to dynorphin: a set of short series of proteins that attach to opioid receptors in the brain that come about from the antecedent protein prodynorphin) as the main devoid of outside source of attached molecules. Fentanyl operates on the receptors in the brain for opioids; therefore it disregards hints of pain and brings forth a sense of well being. Fentanyl is able to quickly cross from the blood into the brain. There are various medical reasons from past to present why opoids or semi-

synthetic opoids are prescribed. Previous purposes included over the counter cough suppressants, and to date opoids are mainly used for various degrees of pain management and to assist in the quality of end of life care. Opioids are a highly addictive narcotic, as this research paper has established the impact on the whole body and how the chemical compounds of various opoids diminish pain and create a sense of well-being, to all the negative secondary effects that an individual may encounter from consumption. REFRENCES 1) http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/Drugs.html#opiates 2) http://www.pbs.org/wgbh/aso/databank/entries/dh75en.html