puneetcheema1

Puneet Cheema CHEM 367 Final Project

=PHARMACOLOGY OF OXYCODONE COMPARED TO OTHER DRUGS=

Abstract
OxyContin's(compound 2) active ingredient is oxycodone(compound 1). OxyContin's(compound 2) structure is oxycodone HCl [OxyContin 2010]. The side effects can vary for those who abuse it and those who use it for medical purposes [Oxycodone 2013]. The demographics of those use OxyContin(compound 2) are single, 18-25 years old, less educated and not medically insured [Martins 2009]. It can be seen that OxyContin(compound 2) can affect the central nervous system, gastrointestinal tract, smooth muscles, cardiovascular system, endocrine system, and the immune system [OxyContin 2013]. In comparison to clonazepam(compound 3), OxyContin(compound 2) has similar plasma concentration. The pharmacokinetics of clonazepam(compound 3) and OxyContin(compound 2) are compared [Burrows 2003]. Pupils were found to constrict and sedation increased [Burrows 2003]. In a study, the epidural oxycodone(compound 1) was found not to have any substantial proof that it was of better use than IV oxycodone(compound 1) during post abdominal surgery [Backlund 1997]. A dose titration of oxycodone(compound 1) was shown to be effective, tolerable, and generally accepted by cancer patients who have experienced this treatment [Koizumi 2004]. Oxycodone(compound 1) and bupivacaine(compound 5) can be applied intrabursally in order to be more effective rather than being applied alone [Muittari 1999; Muittari 1998]. Levobupivacaine(compound 4b) was found to be a better alternative to providing pain management then racemic bupivacaine [Dekel 2010]. Combining controlled-release oxycodone(compound 1) and controlled-release morphine(compound 5) can be used to treat chronic cancer pain better than controlled-release morphine(compound 5) used by itself [Lauretti 2003]. The antinociceptive effects of oxycodone(compound 1) are instigated by κ-opioid receptors found in diabetic mice. It can interact with μ-opioid receptors when the antinociceptive effects are found in non-diabetic mice [Nozaki 2005]. In a study, rats showed that oxycodone(compound 1) had antinocicpetive effects that occur at quicker rates than morphine(compound 5) [Ross 1997]. In general, oxycodone(compound 1) and OxyContin(compound 2) has benefits when applied medically and can even further their ability to be used medically when they are combined with other pharmaceutical drugs.

Background
Oxycodone(compound 1) has been clinically used since 1917. In humans it can be applied intravenously, intramuscularly, intranasally, subcutaneously, rectally, epidurally, and orally. Oxycodone(compound 1) is used in today's world mostly for chronic pains. The half lives can vary for how the oxycodone(compound 1) are specifically applied. For example, the half life is 2-3 hours when immediate release (IR) oxycodone(compound 1) and it is 8 hours for controlled-release (CR) oxycodone(compound 1). Along with the differences in half-lives, oxycodone(compound 1) has also shown to be more readily absorbed by elderly woman while young man absorbed oxycodone(compound 1) the least [Kalso 2005]. Oxycodone(compound 1) has shown to be an epidemic in specific parts of the country especially Florida where 98 of the top 100 doctors in the country who give out oxycodone(compound 1) in major state cities like Tampa, Orlando, and Miami. In 2010 itself, oxycodone(compound 1) has shown to have lead to 1516 deaths in Florida. The use of other drugs have decreased while oxycodone(compound 1) has escalated. The demographics of the group who died was 41.76 years of age (from a 19-77 years old range), 96.1% Caucasian, 58.1% male, 45.2% single, and 52.9% employed. Among the dead, 47.1% of them were prescribed oxycodone(compound 1) [Ogle 2012]. This may show that doctors should be more keen to prescribing oxycodone(compound 1) because it may have been possibly abused by some of the prescribed users who were deceased in this study.

OxyContin's(compound 2) active ingredient is oxycodone(compound 1), a derivative of opium. This pain reliever was FDA approved in 1995. OxyContin(compound 2) is manufactured by Purde Pharma LP [OxyContin 2010]. OxyContin(compound 2) is known as Oxycodone HCl. It is a prescription drug that is given by doctors. It is meant to be a painkiller. It is meant to be taken in liquid, tablet, or pill form. There are two types of form of medicine application of oxycodone(compound 1): short-acting pain medication and long-acting pain medication. A long-acting pain medicine should be given at consistent times to offer pain relief. Short-acting medicine can be given when the pain is still reoccurring despite taking long-acting pain medicine. This can be considered a "rescue medicine." The short-acting oxycodone(compound 1) is used usually after surgery to deal with post-surgery pains. The long-acting oxycodone(compound 1) can be used for long-term chronic pain. Oxycodone(compound 1) can be taken through the mouth. The quick-acting pill form will last approximately 3 to 4 hours. It can also be taken orally by a liquid. Sustained-release pills like OxyContin(compound 2) can be taken every 12 hours. For long-acting pill, it should not be chewed, broken down, crushed, split, or dissolved. If these forms have been consumed, the dosage of oxycodone(compound 1) can lead to overdose. It can be absorbed all throughout the body [Oxycodone 2010].

The use of Oxycodone(compound 1) has many side effects. The main side effects of the substance, Oxycodone(compound 1) are: (1) Hallucinations, confusion, fainting, and dizziness (2) Mouth, tongue, lips, eyes, and face can swell from Oxycodone(compound 1) use (3) The throat can also swell along with having difficulty of swallowing (4) The skin can develop hives and rash (5) The heart will either develop a fast or slow heartbeat. (6) The respiratory system will lead to difficulty breathing and depressed breathing rate (7) For muscles, seizures may occur These side effects rarely occurs in users who are not abusing the substance [Oxycodone 2013]. People who have taken Oxycodone(compound 1) in overdoses can result in "shallow breathing, bradycardia, cold-clammy skin, apnea, hypotension, miosis, circulatory collapse, respiratory arrest, and death" [Oxycodone 2013].

OxyContin(compound 2) has been labeled with the following statements: "(1) make abuse via injection difficult, and (2) reduce abuse via the intranasal route." This is the first product that FDA has implemented "abuse deterrence" [Zoler 2013]. The FDA commissioner, Hamburg's reasoning behind it was "For too long, drug abusers have been able to crush or dissolve opioid drug products in order to defeat their time-release mechanisms for snorting or injecting the drugs" [Zoler 2013]. On March 24, 2004, the FDA approved of two generic products of CR oxycodone(compound 1). The legal system believed that these generic products would "quicken the pace to make sure we have more safeguards in place to (prevent) the illegal diversion of prescription drugs." It was predicted that these new generic products will lower the price of oxycodone(compound 1) for drug abusers. Statistically based on behavioral economics of drug abuse, legal and illegal drug use increase when the price of the drug has decreased. Abusers prefer brand name products to the generic products. Hence, introducing new generic products that are cheaper may not raise the abuse rate [Bailey 2006]. No employment, income, or population differences were found between non-OxyContin opioid analgeic users and OxyContin(compound 2) users. The majority of the OxyContin(compound 2) user populations were likely to be non-Hispanic Caucasians and Hispanic, while having a small population in the non-Hispanic Black community. The majority of the OxyContin(compound 2) documented users were single and were aged between the 18 and 25 years old. They were more likely to be less educated and not medically insured like the users of other opioids. OxyContin(compound 2) users were found to have more mental health problems and violent behavior. This also includes the use of other drugs or instigating their use of these other drugs at a younger age. OxyContin(compound 2) users tend to be more frequent abusers of other specific analgesics such as hydrocodone, oxycodone(compound 1), and codeine [Martins 2009]. This demographic is very similar to that of the one provided by the Florida study on oxycodone-related deaths. OxyContin(compound 2) users are most likely than other non-OxyContin opioid analgesics users to buy opioid analgesics from a family member, friend, a random stranger, or a drug dealer. They tend to attain the other opioid analgesics that are not OxyContin from other sources. The people who use extramedical OxyContin(compound 2) in 2005-2006 were a very small percent of the general population sample. It was found to be only 0.5%. The abuse that is done for this specific drug does not really constitute as an "epidemic" for the United States because 4.2% of other people in this general population sample use other opioid analgesics [Martins 2009]. However, this study has shown that in some specific regions in America, oxycodone(compound 1) has become a deadly epidemic. In Florida, the oxyodone-related deaths increased by 243.3% from 2004-2009. Out of all the prescription drugs during this time, oxycodone(compound 1) accounted for the most emergency room visits [Ogle 2012].

Purdue Pharma was criticized for promoting OxyContin(compound 2) especially to physicians. It was controversial that it did not provide any their promotional videos through the FDA. The FDA asked Purdue Pharma to add a black box warning. This is considered the highest warning possible that can be placed onto an approved legal drug. OxyContin(compound 2) abuse has transformed from a small regional problem to a national issue. OxyContin(compound 2) is a highly abused drug that people are getting addicted to them. The media has made OxyContin(compound 2) a "villain" of the many abused list of narcotics. It can be argued that this media focus on OxyContin(compound 2) increased the drug's popularity and possibly its' abuse [Jayawant 2005].

Compounds used in the paper
Figure 1. Structure of Oxycodone. Refer to as Compound 1. Figure 2. Structure of OxyContin. Refer to as Compound 2. Figure 3. Structure of Clonazepam. Refer to as Compound 3. Figure 4a. Structure of Bupivacaine. Refer to as Compound 4a. Figure 4b. Structure of Levobupivacaine. Refer to as Compound 4b. Figure 5. Structure of Morphine. Refer to as Compound 5.

Introduction
Despite oxycodone(compound 1) and OxyContin(compound 2) being possibly abusive drugs, they have shown to be efficient medications in the medical field. They can be used in pain management for various illnesses or procedures. In the following paper, the mechanism of oxycodone(compound 1) and OxyContin(compound 2) inside animal bodies are talked about. Their uses during these medical procedures will be evaluated. Oxycodone(compound 1) and OxyContin(compound 2) will also be compared to other drugs that aid in medication.

Human impact of OxyContin
//Mechanism of OxyContin inside the body://

OxyContin(commpound 2) can affect the central nervous system. Despite the fact, the mechanism is not known. The opioid receptors in the central nervous system for compounds that have activity related to opioid-like behaviors that are found throughout the spinal cord and the brain. These compounds are important in the analgesic effects of OxyContin(compound 2) [OxyContin 2013].

In order to test for pharmacodynamics, a study was done using a single-dose, double-blind, placebo, and dose-controlled study. The OxyContin(compound 2) doses are used of 10, 20, and 30 mg in a pain module that involves 182 patients with moderate to severe aches. OxyContin(compound 2) doses of 20 and 30 mg have significant pain reduction compared to the placebo that was used [OxyContin 2013].

The effects on the Central Nervous System are that Oxycodone(compound 1) produces a slowed down respiratory response by direct action on the brain stem's respiratory centers. The respiratory depression that is included involves reduction in the ability of brain stem to respond to respiratory centers in order to enlarge the CO2 tension; it can also involve electrical stimulation. Oxycodone(compound 1) decreases the cough reflux by direct effect on the medulla's cough center. Antitussive effects can occur when the lower doses than the ones that are required for analgesia. Oxycodone(compound 1) can cause miosis. Pinpoint pupils can be a sign of opioid overdoses. Mydriasis can correlate to hypoxia when oxycodone(compound 1) overdose happens [OxyContin 2013].

The effects of Oxycodone(compound 1) on the Gastrointestinal Tract and Other Smooth Muscle. Oxycodone(compound 1) can lead to a reduction of motility with an increase of smooth muscle in the antrum of the duodenum and the stomach. The food digestion in small intestine is delayed and contractions are decreased. Peristaltic waves in the colon are found to decrease while the tone increases to the point where it causes constipation. Other opioid induced effects can lead to a decrease in gastric, biliary secretions, and pancreatic secretions [OxyContin 2013].

The effects of the Cardiovascular system, oxycodone(compound 1) can form a histamine release with or without vasodilatation. The effects of these histamines can include flushing, red eyes, sweating, or hypotension [OxyContin 2013].

The effects on the Endocrine System is that opioids decrease the secretion of ACTH, cortisol, testosterone, and luteinizing hormones in human beings. They can increase the production of prolactin, growth hormone secretion, and secretions of insulin and glucagon from the pancreas [OxyContin 2013].

The effects on the immune system can show that opioids live OxyContin(compound 2) have shown to have a large range of effects on parts of the immune system in animal and in vitro clinical setups. The importance of these findings are relatively unknown. The overall effect of opioids in general on immune system is found to be moderately immunosuppressive [OxyContin 2013].

Human impact of OxyContin compared to clonazepam
//Mechanism of action of OxyContin compared to the mechanism of action of clonazepam://

Oxycodone HCl (OxyContin) is a derived opium alkaloid that is used for pain management. OxyContin(compound 2) is released formula of oxycodone HCl for pain management over long periods of time. It binds to the opiate receptor that is located throughout the central nervous system inside the human body [Burrows 2003]. The opiate receptor agonism results in euphoria, relaxation, respiratory depression, miosis, and analgesia. Respiratory depression can be a cause of death from narcotic overdoses. Oxycodone's pharmacokinetic data can be found in the following table:



According to a study done on chromatography, clonazepam(compound 3) does not have a relationship between its' plasma levels and the doses done daily over a constant period of time. When this drug is used, it is necessary for the plasma concentrations of clonzaepam(compound 3) to be checked because of the unreliability of the plasma level approximations based on the doses [Gerna 1976].

Clonazepam(compound 3) is different from a variety of benzodiazepines as in terms of Hill coefficients. Hill coefficient represents the ability of a compound to bind to a single site. Clonazepam(compound 3) is an example of a benzodiazepine that does not have a 1.0 Hill coefficient which indicates that it has neither negative cooperativity or positive cooperativity. It shows a lack of cooperativity with the binding sites. Instead, clonazepam(compound 3) has a 1.5 Hill coefficient. This shows clonazepam has a positive cooperativity towards its' binding sites [Braestrup 1978].

Clonazepam(compound 3) is a short-acting benzodiazepine that is used for panic disorders and for those who suffer from seizures [Burrows 2003]. Unlike Oxycodone HCl, clonazepam(compound 3) is not a mixture containing two compounds in its' formation. The mechanism of action is virtually unknown but it is predicted that it improves the level of activity of gamma aminobutyric acid (GABA). Gamma aminobutyric acids are primary inhibitory neurotransmitters in the central nervous system. The plasma concentrations of clonazepam(compound 3) are seen to make cyclic comas where patients gain and lose consciousness [Burrows 2003]. Clonazepam's pharmacokinetic data can be found in the following table:

Compared to clonazepam(compound 3), the plasma concentrations are similar with OxyContin(compound 2). The toxic plasma concentration is lower than the toxic plasma concentration listed for OxyContin(compound 2). OxyContin(compound 2) has a lethal list of plasma concentrations while clonazepam(compound 3) does not have a lethal plasma concentration for this study. The duration of the action is 12 hours for clonazepam(compound 3) and the duration of the action is also 12 hours for OxyContin(compound 2). The bioavailability of both of the drugs are very similar, 90% for clonazepam(compound 3) and 60-87% for OxyContin(compound 2). Plasma binding is found to be more prominent in clonazepam(compound 3) than OxyContin(compound 2). The volume of distribution is very similar between the two drugs. The half-life is far larger in clonazepam(compound 3) than OxyContin(compound 2), 19-60 hours vs. 4-6 hours. The clearance is larger for OxyContin(compound 2) than clonazepam(compound 3). It is 0.8 L/min for OxyContin(compound 2) while it is 1.55 mL/min for clonazepam(compound 3) [Burrows 2003].

The serum drug screen used in the experiment was found to be negative for ethanol and positive for benzodiapines, trazodone, and opiates such as oxycodone(compound 1). The drug screen showed positive for benzodiazepines, nicotine and metabolites, opiates, and cannabinoids. The urine drug test showed negative for ethanol [Burrows 2003]. The serum drug screen and urine drug test can be seen in the following table:



Oxycodone(compound 1) was found in the blood, urine, and the gastric portion while clonazepam(compound 3) was not. Clonazepam(compound 3) was found to have larger plasma drug quantitation than oxycodone(compound 1) [Burrows 2003].

Human impact of oxycodone
//Mechanism of action of CR oxycodone doses://

In a pharmaceutical study of a controlled-release (CR) oxycodone(compound 1), pharmacokinetics of a controlled-release oxycodone(compound 1) 20 mg tablet along with two control-released oxycodone(compound 1) 10 mg tablets were used on volunteers and were viewed as a clinical study to show the CR oxycodone(compound 1) effects. The correlation of plasma oxycodone(compound 1) concentrations were measured in terms of objective and subjective calculated of the drug effect that were measured by observers and subjects. Twenty-four subjects were used. The treatment was randomized and all of the study subjects received at least one dose of CR oxycodone(compound 1). The rate of oxycodone(compound 1) absorption were compared between the 20 mg CR oxycodone(compound 1) tablets and the two 10 mg dose of CR oxycodone(compound 1) tablets [Benzinger 1997]. The relationship was present in the following figure:



The bioequivalence is shown to have a higher mean plasma of oxycodone(compound 1) for one 20 mg CR oxycodone(compound 1) up until the 24th hour. After 24 hours, the two 10 mg CR oxycodone(compound 1) has a higher mean plasma from 24 hours to 36 hours [Benzinger 1997].

The strongest relationship with oxycodone(compound 1) plasma concentration with changes are pupil diameters. It had the largest numerical value of any correlation. It was specifically the largest negative correlation of all of the observed pharmacodynamic effects of plasma concentrations of CR oxycodone(compound 1). This means the pupils become constricted. This can be seen in the following correlation table that shows what is measured by the subjects and the observers. An example of a positive correlation in pharmacodoynamic effects of oxycodone(compound 1) with plasma concentrations is sedation which has shown to have a positive correlation in the pharmacodynamic of oxycodone(compound 1) [Benzinger 1997]. Sedation increases with oxycodone(compound 1) consumption. The table represents a correlation scale that was seen by the mean of both groups (two 10 mg CR oxycodone and one 20 mg CR oxycodone):



The following table shows the adverse effects that were seen in the 20 mg oxycodone(compound 1) tablet group and the two 10 mg oxycodone(compound 1) tablet. In total, 33% of the subjects reported adverse effects for 20 mg oxycodone(compound 1) tablet group while 29% of the subjects reported adverse effects for the two 10 mg oxycodone(compound 1) tablets [Benzinger 1997].



//Controlled-release oxycodone used for specifically cancer pain treatment://

In a study done in Japan, 22 cancer patients who haven't had experience with opioid for 2 weeks were chosen. A dose titration study was used to evaluate the efficacy and tolerability of controlled-release oxycodone(compound 1). It starts off with 5 mg oxycodone(compound 1) tablets for every 2 hours. Out of 20 patients, 18 patients received stable pain control. Two-thirds of the patients received adequate pain control without any dose titration. The average length of time was 1.2 days. The pain was reduced initially after an hour after dose intake. 15 patients had at least one side effect. The controlled-release oxycodone(compound 1) tablets offer stable and adequate pain control over this small period of time. A 5 mg oxycodone(compound 1) for every 12 hour have shown to be effective for those who haven't taken opioid analgesics. This showed a low strength controlled-release oxycodone(compound 1) formulation, making it possible to initiate and titrate the dose appropriately for patients who have not extensively received treatment through opioid analgesics [Koizumi 2004].



Human impact of oxycodone compared to bupivacaine and morphine
//Comparison of oxyocdone and buipvacaine in infiltration during shoulder surgery://

In a study, doctors observed the analgesic effects of infiltration of the subacromial bursa with bupivacaine(compound 4a) and oxycodone(compound 1) [Muittari 1999]. It is a non-opiate drug used during anesthesia. The effect of the combination showed that oxycodone(compound 1) 5 mg had a superior results compared to 0.5% bupivacaine(compound 4a) [Muittari 1999]. Intrabursally administered oxycodone(compound 1) involved with shoulder surgery have provided alleviated postoperative pain and it reduce consumption of analgesics. In reducing the need for these analgesics, the efficacy of intrabursal oxycodone(compound 1) is equivalent to that of bupivacaine(compound 4a). It provided lower plasma concentration. It was shown that when oxycodone(compound 1) and bupivacaine(compound 4a) were applied together intrabursally, it became more effective than these drugs to be applied alone during shoulder surgeries [Muittari 1999].

Another study was done, it was a randomized study that involved 45 patients and 3 groups. For each group, 15 patients were assigned. All of these patients received elective shoulder surgery during the use generalized anesthesia. The groups: B, OB, and IPB all received different treatments. Group B received 0.5% bupivacaine(compound 4a). Group OB was treated with 5 mg oxycodone(compound 1) along with 10 mL 0.5% bupivacaine(compound 4a). Group IPB was treated with interscalene plexus blocks. This study showed that the intrabursally administered oxycodone(compound 1) when combined with bupivacaine(compound 4a), Group OB, has shown to be as effective as the interscalene plexus blocks in Group IPB. However, Group IPB was shown to have the best quality of analgesia. The efficacy was similar for both Group OB and Group IPB while for Group B, it was shown to be weaker than the two other groups. Bupivacaine(compound 4a) is much better used in analgesia when combined with oxycodone(compound 1) [Muittari 1998].

In this study, it talks about L-bupivacaine(compound 4b) which has research has shown to provide a better alternative to bupivacaine(compound 4a) because of the blocking properties that racemic bupivacaine(compound 4a) presents. L-bupivacaine(compound 4b) provides a long lasting block between sensory and motor blocks. It can be used to improve postoperative recovery. The toxic potential is also reduced in the L-bupivacaine(compound 4b) in comparison to racemic bupivacaine(compound 4a). In this study, Peripheral arterial obstructive disease (PAOD) patients are studied. Oral slow-release oxycodone(compound 1) is often to have better biodisposability along with reduced side effects compared to oral morphine(compound 5). In this paper, it showed that this slow-release oxycodone(compound 1) option is preferred to epidural analgesia. It was compared to the treatment option with L-bupivacaine(compound 4b). The study included L-bupivacaine(compound 4b) 0.25% every 6 hours, this was labeled as LRA. The oral slow-release oxycodone(compound 1) showed doses initially of 10-20 mg twice a day (group OX). The pain intensity was evaluated from a scale of 0-10 using the visual analogue scale, VAS. When both groups laid still, the LRA group and OX group had very similar levels of pain intensity. When both were under dynamic conditions which is when the limbs are moving, the LRA group was found to be of better use in pain management [Dekel 2010].

//Controlled-release oxycodone used for pain treatment in comparison to morphine://

Controlled-release morphine(compound 5) and controlled-release oxycodone(compound 1) are two pharmacological treatment options for chronic pain found in cancer. Both of these drugs are used often. Each of these drugs have shown to be evaluated separately. The patients usually use either controlled-released morphine(compound 5) and controlled-release oxycodone(compound 1) by itself [Lauretti 2003]. Morphine(compound 5) is an opiate drug used to help relieve pain.

Among the options for treatment of cancer pain, evaluating the coadministration of opioids that act on the various receptors may lead to cooperative advice on how to administer controlled-release morphine(compound 5) and controlled-release oxycodone(compound 1). In the following study, 22 patients were evaluated. Eight patients endured vomiting while taking only controlled-release morphine(compound 5). Three of them preferred controlled-release oxycodone(compound 1) because of the common vomiting that occurred possibly through the use of controlled-release morphine(compound 5). The combination of controlled-release morphine(compound 5) and controlled-released oxycodone(compound 1) for chronic cancer pain have shown to be a better option than controlled-release morphine(compound 5) by itself [Lauretti 2003].

In a medical study, the analgesic effects of epidural oxycodone(compound 1), epidural morphine(compound 5), and IV oxycodone(compound 1) were compared for their pain management after abdominal surgery. Nausea and pruitus are side effects that come after the sedation of these groups (epidural oxycodone, epidural morphine and IV oxycodone). This indicates that the epidural oxycodone(compound 1) is not better than the quality of treatment offered by epidural morphine(compound 5). All of the groups shared similar profiles. The epidural oxycodone(compound 1) did not have any substantial proof that it was of better use than IV oxycodone(compound 1) as well. Respiratory depression happened in 7.7% of epidural morphine(compound 5) patients, 12.5% of epidural oxycodone(compound 1), late respiratory depression was found in 27.3% of IV oxycodone(compound 1) patients [Backlund 1997].

Epidural morphine(compound 5) and epidural bupivacaine(compound 4a) can also be compared. In terms of pain management, epidural morphine(compound 5) treatment has also been found to be more effective than epidural bupivacaine(compound 4a). Patients have stated they were less acceptable to the epidural bupivacaine(compound 4a) treatment because of the muscle weakness that ensured after it was applied [Behar 1979].

Rodents impact from oxycodone digestion
//Antinociceptive effect of oxycodone on mice and rats://

The medical uses or effects of oxycodone(compound 1) have shown to also impact other animals, two examples of these animals are mice and rats. The antinociceptive effects of oxycodone(compound 1) are strongly reconciled by κ-opioid receptors found in diabetic mice. It may interact initially with μ-opioid receptors found in non-diabetic mice [Nozaki 2005]. In mice and rats, the gene symbol of the κ opioid receptors is Oprk1 [κ Opioid 2013]. In mice and rats, the gene symbol of the μ opioid receptor is Oprm1 [μ Opioid 2013]. Morphine(compound 5) interacts primarily with μ-opioid receptors while oxyocdone(compound 1) interact primarily to κ-opioid receptors, similarly to oxycodone in non-diabetic mice(compound 1) in non-diabetic mice [Ross 1997; Nozaki 2005]. The κ opioid receptor is an opioid member of the G-protein-coupled receptors. These opioid receptors are located mainly in the celebral cortex, nucleus accumbens, claustrum and the hypothalamus. They help regulate the nociception, diuresis, feeding, and secretions done through a neuroendocrine pathway [κ Opioid 2013]. The μ opioid receptor is an opioid member of the G-protein-coupled receptor. The μ Opioid receptors are sent throughout the neuraxis (neocortex, thalamus, nucleus accumbens, hippocampus, and amygala) and it is also found throughout the peripheral nervous system, myenteric neurons and vas deferens. μ opioid receptors are involved and associated within respiratory, cardiovascular system, feeding, learning, memory, intestinal movement, locomotor movement, thermoregulation, hormone emission, and the functions of the immune system [μ Opioid 2013].

In a study, rats showed that oxycodone(compound 1) had antinocicpetive effects that provided a maximum effect at a quicker rate compared to morphine(compound 5), the rates measured were ~6 minutes vs ~37-38 minutes [Ross 1997]. In another study, greater antinociceptive response in female rats is found compared to male rats when oxycodone(compound 1) is digested by both. Antinociceptive effect of oxycodone(compound 1) in rats showed sexual dimorphism. There were evident differences in the effect oxycodone(compound 1) had in male and female rats. In humans, oxycodone analgetic sensitivity between genders has been found to be unsubstantial so far according to this paper [Holtman 2006].

Conclusion
Oxycodone(compound 1) and OxyContin(compound 2) are known to be used abusively. However, it has been shown to provide helpful medical applications in the medical field. These substances can be used for pain management for various illnesses and procedures in humans. The mechanism of OxyContin(compound 2) and oxycodone(compound 1) are found inside the human showing the effect on the body systems along with its' plasma concentrations. OxyContin(compound 2) has shown to be compared to clonazepam. Oxycodone(compound 1) was shown to be comparable with bupivacaine, levobupivacaine(compound 4a; compound 4b), and morphine(compound 5). Oxycodone(compound 1) have shown to effect the body systems of other animals such as mice and rats. From this research, it can be seen that oxycodone(compound 1) and OxyContin(compound 2) can be used efficiently in the medical field while even though it is abused by non-medical users, it was found that only 0.5% of a general population sample taken in 2005-2006 used OxyContin(compound 2) non-medically [Martins 2009]. While 4.2% of the other set of population used other opioid analgesics non-medically [Martins 2009]. Oxycodone(compound 1) and OxyContin(compound 2), in some public opinion, is not an "epidemic" in terms of non-medical use [Martins 2009]. The idea that it is not an "epidemic" can be debated. However, oxycodone(compound 1) and OxyContin(compound 2) have shown to be beneficial for medical treatment. That has been proven by multiple reputable sources, it is not as debatable as the non-medical use. Hopefully, in the future, we can expand on our knowledge about more beneficial opportunities these substances, oxycodone(compound 1) and OxyContin(compound 2), can offer to the medical community.