Vicodin
Table of Contents
Background………………………………………… Page 1
Hydrocodone……………………………………….. Page 1 and 2
Acetaminophen……………………………………... Page 2 and 3
History and Social Impact…………………………. Page 3 and 4
Drug Abuse…………………………………………. Page 5 and 6
Conclusion…………………………………………... Page 6 and 7
Appendix …………………………………………… Page 8 and 0
Defined Terms……………………………………… Page 10
Work Cited…………………………………………. Page 11

Background:
Vicodin is an orally taken painkiller composed of a combination of acetaminophen and hydrocodone, classifying it as an opioid pain reliever. In this capacity, Vicodin will bind to opioid receptors and reduce the sending of pain messages to the brain 1. Opioid receptors are used to control pain, slow breathing, and have a general calming affect. In a regular Vicodin tablet, there is 5mg of hydrocodone, which reacts with the 300mg of acetaminophen 2. Individually, hydrocodone and acetaminophen are medically used drugs that are used to relieve pain, however when employed together they having a much more hard-hitting effect. The combined drug works similar to other opiates by travelling along neurological pathways and increasing dopamine levels, resulting in euphoria and pain relief 3. Currently, Vicodin is classified as a level three controlled substance due to its tendency to cause psychological dependence, potential abuse, and its acceptance for medical treatment in the United States. As of 2006, more than 6.4 million people reported that they had misused Vicodin 3. The issue of Vicodin abuse is extremely relevant to my age group, due to it being a popular prescription for young adults after having their wisdom teeth removed and other common surgical procedures.
Hydrocodone:
The hydrocodone in Vicodin, similar to other opiates, relieves pain by binding to receptors in the brain and spinal cord, which block the reuptake of dopamine, and therefore enhancing its effects on the body, due to the block on the presynaptic nerve ending from absorbing the secreted dopamine 4. Dopamine is a neurotransmitter that creates pleasure throughout the human body. Increased amounts of dopamine will create a sense of euphoria, beyond what the human brain is naturally able to produce. Hydrocodone binds to the opioid receptors of sensory neurons, thus activating the G-proteins 5. Then, the G-proteins inhibit adenylate cyclase, thus lowering levels of cAMP (an active adenylate cyclase catalyzing the conversion ATP to cAMP and pyrophosphate) 5. Additionally, the G-proteins activate potassium channels and inactivates calcium channels 5. This process causes hyperpolarization, which results in decreased nerve transmission (so the nerves do not receive signals effectively) and reduced neurotransmitter release 5. As a result of the reaction, pain signals are not perceived and the individual experiences feelings of euphoria.
Acetaminophen
Acetaminophen, the non-opioid component of Vicodin, is a milder, safer, and much more common pain killer than hydrocodone. It more commonly used individually than paired with hydrocodone. On its own, acetaminophen is a pain reliever, and fever reducer. It is used to treat many conditions such as headaches, muscle aches, arthritis, backache, toothaches, colds, and fevers. Unfortunately, the exact process of how acetaminophen relieves pain is unknown 6. However the basic process is as follows. Usually acetaminophen after digestion is metabolized in the liver through the processes of glucuronidation and sulfation 7. Glucuronidation is the addition of glucuronic acid to the substrate, in this case the drug, making the new substance more water-soluble and easier to transport throughout the body. Sulfation, is the addition of sulfate to the drug, making it less active. Several enzymes, UGT1A1, UGT1A6, UGT1A9, and UGT2B15, digest between forty-five and fifty-five percent of a dose of acetaminophen through the glucuronidation process 7. Additionally, many other substances, including SULT1A1, SULT1A3, SULT1A4, SULT1E1, and SULT2A1, metabolize between thirty and thirty-five percent of acetaminophen through sulfation 7. N-acetyl-p-benzoquinone imine (NAPQI) is then activated by several enzymes in the CYP450 family, and then detoxified by glutathione combination in the liver by glutathione S-transferase enzymes. NAPQI is a toxic byproduct when metabolizing a drug. CYP460 is a large group of enzymes which main use is in drug metabolism. Here the substances are bioactivated, meaning they form active components. The result of other processes is absorption into most body tissues, involving other influences 6. Antipyretic activity (reducing fever) is mediated throughout tissues through hypothalamic heat regulating centers of the body 6. Acetaminophen does this by inhibiting prostaglandin synthetase 6.
History and Social Impact
The social significance Vicodin has had on modern society is rooted in its long history as the most frequently prescribed opiate drug in the United States. In 1893, acetaminophen was first recorded for medical use, and twenty seven years later, in 1920, the pharmaceutical company, Knoll, synthesized hydrocodone 8. However, later, in 1934, it was determined by the United States Bureau of Social Hygiene (USBSH) that consistent use of hydrocodone causes its users to build up tolerance to the drug, requiring them to take higher doses, eventually causes addiction 8. In 1971, with the passage of the Controlled Substance Act, hydrocodone became listed as a schedule II controlled substance due to its narcotic qualities; however, when combined with other drugs, such as acetaminophen (creating Vicodin) it is listed as a schedule III controlled substance 8. Under the Controlled Substance Act, drugs and other substances are divided into five schedules. Substance are placed in their respective schedules based on whether they are currently medically accepted, their abuse potential, and their likelihood of causing dependence when abused, with schedule I having the highest potential for abuse and unaccepted medically. Fifty-eight years after first synthesizing hydrocodone, Knoll released Vicodin in its current form (5 mg of hydrocodone and 500 mg of acetaminophen), and five years after that, generic forms of Vicodin were released 8. Since 1990, hydrocodone-related hospital visits have increased by 500% in 2002. Having over 130 million prescriptions written for drugs containing hydrocodone in 2006 and the number shows no sign of decline; concerns over the drug’s prescription and possible abuse have formed 8. These concerns led to the 2009 recommendation that the FDA institute a ban on Vicodin 8. As shown earlier, the use of Vicodin, and other hydrocodone drugs, has spiked since the discovery and because of its addictive qualities and the liver damaging possibilities when taken in excess, therefore the use of hydrocodone drugs has become a major social issue in the United States. The main reason why these drugs, such as Vicodin, are abused so easily is due to the fact that they are classified as schedule III controlled substances, and can thus be refilled when needed due to being medically accepted. Many believe, since it is only considered a schedule III, abuse and/or physical/psychological dependence are only a low to moderate risk, however, recent results have proven otherwise. For these above reasons, the FDA has discontinued the make of Vicodin 10.
Drug Abuse
Abuse of Vicodin is commonly due to the euphoria obtained from the opiate like qualities of hydrocodone. The abuse of Vicodin is largely due to its easy accessibility (being a legally prescribed medication), and the subjective feeling of pain that can be perceived by patients when experiencing withdrawal. Thus, Vicodin is extremely accessible since doctors prescribe it regularly, and it is common in Americans’ medicine cabinets, and it can be easily refilled 9. Due to its easy accessibility, it is regularly abused by teenagers, who are either prescribed the drugs themselves, often after wisdom tooth surgeries, or taken from their families’ medicine cabinet, left over from past surgeries 9. Furthermore, because Vicodin is declared a schedule III controlled substance, it has few limitations. The only difference between Vicodin and pure hydrocodone (a schedule II controlled substance that is listed with morphine and other illicit drugs) is that Vicodin is combined with other painkillers for added effectiveness 9. Adding to the accessibility is the fact that doctors often prescribe Vicodin to patients complaining about chronic pain. However, this chronic pain, usually located in the head and neck, places where opioids receptors are, is likely a result of withdrawals from the drug. Although hydrocodone is the primary concern with Vicodin, acetaminophen, even though being much weaker and sold over-the-counter, is also extremely dangerous when abused. Mild doses of acetaminophen are safe and considered insignificant in their damage to the body because they are easily processed and eliminated, mainly by the liver 2. However, toxic doses of acetaminophen can result in excessive liver damage, and the FDA has issued warnings about these potential consequences. Side effects may also include, stomach bleeding, bloody stools, vomiting blood, weakness or fainting, stomach pain, and ringing in the ears 11. According to the US Food and Drug Administration as little as 25% above the maximum daily dose can cause liver damage. Since it is such a commonly used drugs many people see no problem drinking alcohol when on acetaminophen, however this substantially increases the risk of potentially fatal liver damage. Nevertheless, acetaminophen abuse is an insignificant issue relative hydrocodone, and is nearly unstoppable due to its widespread use.
Side Effects:
Common and the less serious physical side effects of Vicodin are dizziness, lightheadedness, nausea, and vomiting, however many of these effect can be cured if the user lies or sits down 6. The user may also experience several side effects associated with the central nervous system, which include drowsiness, mental clouding, lethargy, impairment of physical or mental performance, anxiety, fear, dysphoria, psychological dependence, and mood changes 6. Additionally, Vicodin can cause constipation and may trigger difficulties with urination, often linked to opiates 6. Respiratory depression is an extremely serious side effect, and is seen as a common sign in cases of overdoses 6. Some patients have experienced temporary and permanent hearing impairments, however these are commonly caused multiple overdoses 6. Rashes, which are often a consequence of many other drugs, are also listed as a side effect 6. Additionally, overdoses of hydrocodone are characterized by respiratory depression, coma, skeletal muscle flaccidity (limpness), cold/clammy skin, hypotension, apnea, circulatory collapse, cardiac arrest, and death 6. Overdoses in acetaminophen may result in fatal hepatic necrosis (this is the most serious effect), renal tubular necrosis, hypoglycemic coma, and coagulation defects 6. Despite many advances in medical and scientific research, some consequences of Vicodin abuse are still unknown. Accordingly, there have been no tests conducted on the potential for Vicodin to transmit carcinogens to fetuses, create mutations in fetuses, or impair fertility 6. There have been no conclusive or effective studies on the effects of Vicodin on pregnant women, thus pregnant women are advised not to take Vicodin for fear that the baby’s health could be compromised. However, babies born to mothers who had been taking opioids regularly prior to delivery are often born dependent on narcotics, which result in extra irritability, hyperactive reflexes, increases in stools, sneezing, yawning, vomiting, and fever 6. Vicodin administered to mothers during delivery may result in respiratory depression in the baby 6. Abbot, the makers of Vicodin, have recently discontinued the manufacturing of the current design of the Vicodin pill. They are attempting to limit the strength of the acetaminophen, in an effort to reduce liver damage dealt from acetaminophen overdosing. A new distribution of the reformulated drug will be released shortly, due to the FDA requesting this change be effected January 2014, with safer dosages of acetaminophen
Conclusion:
As you can see, Vicodin is a very popular and powerful painkiller that can result in addiction due to its opioid characteristics. It functions as a pain killer by blocking dopamine reuptake, creating feelings of euphoria. Hydrocodone enter the central nervous system and binds to opioid receptors in the brain and spinal cord, and relieves discomfort by blocking the body’s natural response to pain. When combined with acetaminophen the compound treats pain more effectively than when used individually.

Appendix:

Vicodin pill:

Acetaminophen

Hydrocodone

Hydrocodone Blocking the Reuptake of Dopamine

Defined Terms:
Opioid receptors are used to control pain, slow breathing, and have a general calming effect.
Hydrocodone: similar to other opiates, relieves pain by binding to receptors in the brain and spinal cord, which block the reuptake of dopamine, and therefore enhancing its effects on the body, due to the block on the presynaptic nerve ending from absorbing the secreted dopamine
Dopamine is a neurotransmitter that creates pleasure throughout the human body.
Acetaminophen is the non-opioid component of Vicodin, is a milder, safer, and much more common pain killer than hydrocodone. It more commonly used individually than paired with hydrocodone. On its own, acetaminophen is a pain reliever, and fever reducer. It is used to treat many conditions such as headaches, muscle aches, arthritis, backache, toothaches, colds, and fevers.
Glucuronidation is the addition of glucuronic acid to the substrate, in this case the drug, making the new substance more water-soluble and easier to transport throughout the body.
Sulfation is the addition of sulfate to the drug, making it less active.
NAPQI is a toxic byproduct when metabolizing a drug.
CYP460 is a large group of enzymes which main use is in drug metabolism.

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