Tuesday, January 18, 2022

Ask & Answer: Hydrocodone vs Oxycodone

The treatment of pain is an important and highly profitable endeavor in modern medicine. The pharmaceutical industry represents nearly $500 billion annually, with opioids used for pain management accounting for about $33 billion. The United States is by far the largest market for painkillers, accounting for more than 60 percent of the global market revenue share. Pain can be acute or chronic in nature, with treatment and management approaches primarily adopting a biomedical approach in which medicine is prescribed that reduces the experience of pain by interfering with the brain’s natural pain response. Two of the most common medications prescribed by physicians for the management of pain are hydrocodone and oxycodone. Each of these medicines interfere with the pain response in the brain and not the actual site of the injury or pain itself, making them highly addictive because they do not actually repair damaged tissue or nerves in any way. There is considerable debate about the actual efficacy of either of these two medications for pain relief, despite their abundant supply and frequent prescriptions. This article offers an overview of the composition, purpose, effects, and side effects of hydrocodone and oxycodone. Rates of addiction and chemical dependency with respect to each are then reviewed, followed by consideration of the efficacy of each in the alleviation of pain. This article concludes with a brief summary and outline of key points.

Hydrocodone Overview


Hydrocodone is a synthetic opiate that is manufactured from codeine, which originates from the opium poppy plant. Sometimes referred to as dihydrocodeinone, the drug has oral, rectal and intravenous bioavailabilities of 70 percent, 75 percent and 100 percent, respectively. Hydrocodone has low protein binding and is processed through hepatic metabolism. The onset of action is between 10 to 20 minutes and has a biological half-life of about three to four hours. The duration of action is four to eight hours. Several different variations of hydrocodone are available, including immediate and controlled release versions and in combination with paracetamol, ibuprofen and aspirin. However, it is this quick euphoric effect that follows oral ingestion that makes hydrocodone the preferred pain management alternative for many patients with varying forms of pain and discomfort.


The primary purpose of hydrocodone is to treat pain and to suppress cough. Hydrocodone is also combined with many other drugs as a secondary analgesic. The drug is recommended for those requiring pain management solutions and who perceive alternative treatments to be insufficient. Hydrocodone is not appropriate for individuals with respiratory disease or impairments, bowel obstructions, osteoporosis, and histories of alcoholism and other forms of substance abuse.


Hydrocodone is a narcotic that functions to alleviate pain by binding to opiate receptors and catalyzing the production of opioids, which provide the euphoric effect that occurs upon consumption. Hydrocodone has a higher level of oral bioavailability than morphine, and is about one tenth as potent. Only available in oral forms, opioid activation occurs at about 10 minutes and a peak effect results after about one hour with a duration of effectiveness at about four to eight hours. Hydrocodone is broken down into its basic metabolic form through the cytochrome P450 enzyme, where it is converted into hydromorphone. Hydrocodone is excreted renally.

Side Effects

Hydrocodone has numerous side and adverse effects that must be considered by potential users. Common side effects include constipation, anxiety, drowsiness, urination difficulties, pupil narrowing, itching, and nausea. There have been cases of hearing loss as a reaction to misuse of the drug. This has been attributed to the hydrocodone’s toxic effects on the auditory nerves. Overdose on hydrocodone is common, and symptoms of this occurrence include changes in pupil diameter, respiratory changes, changes in heartbeat, skin temperature changes, seizures and possible death. Additionally, hydrocodone is addictive and both chemical and psychological dependence on the drug is common. Hydrocodone shares many of the same side effects as oxycodone, although the latter is more potent and has been associated with more severe consequences, including death. An overview of oxycodone is provided in the following section.

Oxycodone Overview


Like hydrocodone, oxycodone is a synthetic opioid derived from the opium poppy. Oxycodone is manufactured from the opiate thebaine and has a slightly higher chemical potency than hydrocodone. Oxycodone is also known as dihydrohyroxycodeinone and has a high likelihood of chemical dependence when consumed beyond the prescribed dosage. The drug has a bioavailability of approximately 60 to 85 percent and protein binding of 45 percent. Oxycodone is processed through hepatic metabolism and has an onset of action of about 10 to 30 minutes. The biological half-life is two to three hours and the duration of action is about three to six hours. Where has hydrocodone is excreted renally, oxycodone is excreted predominantly through urine. Like hydrocodone, it is this quick absorption and euphoric effect that makes oxycodone a preferred option for pain management, despite its lack of impact on the actual source of pain.


Like hydrocodone, oxycodone is used to treat pain and cough. Some evidence suggests that oxycodone is about 50% more potent than hydrocodone for the treatment of pain, although research comparing these two drugs simultaneously is lacking. Some evidence also suggests that equal doses of hydrocodone and oxycodone are needed to treat similar injuries.  Oxycodone is about 1.5 times more potent for treating pain than morphine when consumed orally. Oxycodone is available as a standalone medication for pain management, whereas hydrocodone is frequently manufactured in combination with other drugs. Both immediate and controlled release variations are available. Similar efficacy has been shown for immediate and controlled release varieties of the drug. In some countries, intramuscular and intravenous administration is common.


Like hydrocodone, oxycodone alleviates pain by binding to opioid receptors and preventing the inhibition of neurotransmitter release. The drug is metabolized through the CYP2D6 and CYP3A4 enzymes, and can increase the secretion of prolactin and result in testosterone imbalance. Oxycodone is absorbed and takes effect at about 10 to 30 minutes and has a peak effect of 30 to 60 minutes. Reductions in pain can be expected at about 10 to 15 minutes following ingestion. After converted into its metabolite form, it is bonded with glucuronic acid and then removed through the urinary tract. Evidence suggests that 1 mg of oxycodone has a pain relieving equivalency of about 1.5 mg of morphine when ingested orally.

Side Effects

As with hydrocodone, oxycodone is associated with many side effects and contraindications. Side effects that are most common following consumption include nausea, constipation, vomit, dizziness, and itching. Some less common side effects include a reduction in appetite, central nervous system hyperactivity, and abdominal discomfort. There have been some cases of spinal cord infarction following chronic use of oxycodone. There is a high risk of dependence and addiction associated with oxycodone use, particularly if usage is discontinued suddenly. Withdrawal effects associated with oxycodone discontinuation include panic, anxiety, insomnia, and muscular discomfort. Long-term use of oxycodone can lead to hormonal imbalances.

What are the Rates of Addiction, Chemical Dependency, Misuse, and Abuse?

High rates of addiction and chemical dependency have been documented in regards to both hydrocodone and oxycodone. Furthermore, both drugs are subject to misuse and abuse because of their pleasurable effects and the fact that neither actually treats the cause of the pain being experienced. Nearly 5 million patients in the United States use hydrocodone each month for non-medical purposes, according to the Drug Enforcement Agency. A 2014 survey of substance abuse and mental health demonstrated that about 1 million individuals between 18 and 25, or about 3 percent of this age group, used prescription based painkillers like hydrocodone and oxycodone for non-medical purposes during that year. Additionally, nearly 3 million individuals over the age of 26, or about 1.5 percent of this age group in the United States, used prescription painkillers like hydrocodone and oxycodone for non-medical purposes. Though actual rates of addiction to either drug are difficult to determine, there is some evidence to suggest that oxycodone may play an even larger role in painkiller misuse and abuse than hydrocodone. Oxycodone abuse is a substantial contributor to the United States’ current opioid epidemic and has been directly implicated the deaths of many notable celebrities in recent years. This may be due to the steady rise in prescription rates for oxycodone over the past three decades, leading to greater availability and access. There has been a more than 80 percent increase in the number of prescriptions for oxycodone between 2007 and 2010 alone, and many private clinics throughout the nation have been investigated for over-prescribing this drug. Oxycodone was responsible for nearly 200,00 emergency room visits in the United States in 2010.

What is the Efficacy for Alleviation of Pain?

Several studies have investigated the effectiveness of hydrocodone and oxycodone on the management of different forms of acute and chronic pain. Evidence has generally found moderate efficacy for hydrocodone in the provision of short-term pain relief for patients who can tolerate such drugs. However, research also suggests that this effect lacks clinical importance when implemented in safe recommended dosages and the long-term efficacy of hydrocodone for managing pain is still widely debated in the literature. It should also be noted that existing research on the efficacy of hydrocodone is rife with sources of bias, particularly resulting from attrition caused by patients withdrawing from studies as a result of adverse effects of the drugs or a perceived lack of effectiveness. The greatest support for the efficacy of hydrocodone for the management of pain has been shown when provided in small doses and combined with ibuprofen, although the effects are of short duration and many of the adverse effects discussed above occur in these studies and cause many (sometimes more than 50 percent) of participants to withdraw from the research.

A recent Cochrane systematic review of the efficacy of oxycodone in the management of cancer-related pain showed that this drug had similar levels of effectiveness of other opioids. Based on a review of 23 randomized controlled trials involving more than 2,000 patients, it was found that oxycodone had very similar levels of effectiveness as hydrocodone, as well as similar durations of efficacy. However, side effects were also common and the quality of the evidence supporting the effectiveness of this drug was low according to authors of the review. These findings led authors to conclude that oxycodone should be administered with extreme caution and there is limited support to suggest the drug is a safe alternative to the traditional utilization of morphine. Oxycodone is also considerably more expensive than morphine.

Based on the limited support for either hydrocodone or oxycodone in the alleviation of pain in clinical research, as well as the number of severe side effects and presence of bias in this research, it is somewhat surprising that both drugs are prescribed at the high rates that are currently observed in the United States and many other developed countries. There is insufficient evidence to suggest that either is a viable solution for pain as standalone treatments. Furthermore, their adverse effects and high levels of addictiveness make hydrocodone and oxycodone potentially dangerous to many patients seeking suitable solutions for pain related to conditions like chronic back pain, postoperative pain, and cancer-related pain. Interestingly, these two prescription painkillers are the preferred method of pain management for the majority of patients. This may be due to the immediate euphoric effect, despite the lack of impact this effect has on actual pain relief. This euphoric effect and lack of effectiveness on pain relief when the drugs are excreted makes patients inclined to begin to consume larger doses and for prolonged periods of time. For this reason, both drugs are habit forming and can result in both psychological and physical dependence.

What are some additional considerations about Hydrocodone vs Oxycodone?

There are many considerations that must be made when seeing help for acute or chronic pain, and a thorough understanding of medications being taken is needed to prevent lasting adverse effects and physical health consequences. One consideration that must be made is the unknown long-term effects of consumption of these medications. Public safety and preventative measures have only recently been implemented to regulate misuse and abuse, and researchers have just begun to explore the long-term consequences of prolonged consumption of either of these opiate based painkillers. What is known is that both are highly addictive and can result in severe withdrawal symptoms with discontinued abruptly.  Additionally, patients must consider that individual responses to these opioids vary based on genetic and metabolic factors, making them very risk for many with low tolerance. For this reason, severe side effects and death are not uncommon as a result of overdosing. Fortunately, there are now many effective alternatives for pain that are free of the adverse effects demonstrated in regards to hydrocodone and oxycodone. Furthermore, treatment options exist for addictions to these drugs that involve more chronic solutions to pain, such as inpatient and outpatient rehabilitation and the use of alternative pain management therapies like acupuncture, massage, and potentially safer drug therapies like nonsteroidal anti-inflammatory drugs, acetaminophen, corticosteroids, and even antidepressants. Both hydrocodone and oxycodone have several contraindications and interactions that warrant consideration for those seeking pain relief. Hydrocodone is contraindicated for patients who take anti-anxiety and anti-psychotic medications because of their interactive effects within the central nervous system. When combined with alcohol, hydrocodone can result in depression of the central nervous system.

What are treatment options for hydrocodone and oxycodone addiction?

As greater insight is gained as to the long-term adverse impacts of hydrocodone and oxycodone dependence, treatment options have become increasingly available and more informed. In many cases, withdrawal symptoms are so severe that clinical detoxification is required to promote long-term recovery. Following detoxification, inpatient care may be required to promote life long relapse prevention from these high habit forming drugs. Inpatient care may require full residential care, intensive outpatient care, and partial hospitalization. Inpatient care typically lasts from two to six months and then patients are then placed in outpatient care for six weeks to one year in order to facilitate long-term prevention and to foster the coping skills needed to prevent relapse. The ultimate aim of any comprehensive treatment and rehabilitation program for hydrocodone or oxycodone addiction is sober living, which is developed through continued after care and social support.

Summary and Conclusion

The purpose of this article was to provide an overview of two common medications given to manage pain, including hydrocodone and oxycodone. Rates of addiction and chemical dependency for each drug were then considered, followed by a review of the efficacy of each for alleviating pain. Based on the evidence presented within this article, it is clear that hydrocodone and oxycodone are popular drugs for treating pain, although their clinical efficacy has been widely debated in the literature. Existing literature supporting their efficacy has been rife with bias, primarily resulting from attrition caused by adverse effects of the drugs. Additionally, both drugs are highly addictive and associated with severe side effects, including death. Currently, the potential negative consequences of oxycodone and hydrocodone consumption appear to outweigh any small to moderate benefits in pain alleviation and there are many safer alternative pain management therapies that have demonstrated similar clinical efficacy with far fewer and less severe side effects.