What is Opioid Toxicity?
Opioids and opiates are a group of medicines mainly used to manage severe pain. When someone has mild to moderate short-term pain, doctors usually recommend other drugs like acetaminophen or NSAIDs first. However, if these don’t work well enough, doctors can prescribe medication that combines acetaminophen and an opioid. Severe short-term pain is usually treated with stronger opioids.
Traditionally, the term ‘opiates’ means natural compounds that are typically taken from the base of the poppy flower. ‘Opioids’, on the other hand, are produced through chemical processes. Both opiates and opioids are some of the substances most often misused across the globe. Addiction to these drugs has become a major health problem, particularly in developed countries like the United States, since the 2000s.
About 21 to 29 percent of patients who are prescribed opioids for long-term pain misuse them, and between 8 and 12 percent develop a disorder related to opioid use. It’s also estimated that 4 to 6 percent of people who misuse prescription opioids start using heroin. In 2016, more than 42,000 deaths were related to opioid overdoses, which is a record high. Additionally, about 40% of these overdose deaths involved a prescription opioid.
What Causes Opioid Toxicity?
Opioids, or strong pain relievers, can be created synthetically from different compounds. On the other hand, opiates come from the fluid of the opium poppy, either by refining it directly or with slight chemical changes.
Both opioids and opiates work on certain proteins in the body known as opioid receptors. These receptors are divided into three main categories – mu, kappa, and delta – along with some minor ones like nociceptin and zeta receptors.
Simply put, these receptors do different things: the mu receptors are thought to relieve pain, slow breathing, lower heart rate, cause physical dependence, impact digestion, and provide a feeling of deep happiness or euphoria. Symptoms like hallucinations, constricted pupils, and feelings of unease or dissatisfaction may be caused by the kappa receptors. The delta receptors may help control pain and influence our mood but they might need the help of the mu receptors for effective pain relief.
The nociceptin receptor manages dopamine levels in the brain and can cause clinical effects like pain relief and a reduction in anxiety. The zeta receptor, also known as the opioid growth factor receptor, can influence the growth of certain cells like skin growths and it’s not known to significantly affect the management of pain or emotions.
Risk Factors and Frequency for Opioid Toxicity
There’s been a significant increase in deaths due to opioids and opiates overdose in the United States from 2000 to 2014. This kind of rise has never been seen before. In the early part of 2010, many states implemented stricter regulations on consumers and prescribers. By 2014, there was an alarming increase in deaths, especially due to heroin. To avoid misuse of prescribed opioids, some strategies are recommended:
- For patients who have a tendency to overuse medications, it’s wise to give smaller amounts and have patients check in more often.
- Pill counting is another method to ensure patients follow the prescribed medication schedule.
Random urine tests and a written agreement to define the cases when opioids will be discontinued are other preventive measures. Prescription Monitoring Programs can be used by doctors to lessen misuse by identifying if a patient is getting prescriptions from multiple providers.
Signs and Symptoms of Opioid Toxicity
People who overdose on opioids usually exhibit signs like reduced alertness, slow breathing, sluggish speech, and small “pinpoint” pupils. These small pupils can also be found in individuals who regularly use opioids, even if they are not overly sedated or having breathing problems. One common effect of using opioids, especially in those who use them regularly and older people, is constipation. This is because opioids can slow down bowel movement. However, they can sometimes cause painful bowel spasms, known as “codeine cramps.” Naloxone is the preferred treatment for these spasms.
Those using the drug intravenously often have what’s called “track marks.” These are tiny abrasion-like changes in the skin located over veins. They can be seen usually on the arms and legs, but can also appear on the neck and other body parts.
Testing for Opioid Toxicity
If someone is suspected to have overdosed on opioids, the diagnosis is primarily based on their symptoms. Problems with breathing, such as very slow or stopped breathing, can be a tell-tale sign. It’s crucial that the person’s airway is maintained and they are helped to breathe, as this will be the first line of treatment.
Naloxone is a medication that’s incredibly important in these situations, as it can quickly reverse the effects of an opioid overdose. To administer fluids and medication effectively, good vein access is needed. Usually, initial dosages of naloxone range from 0.4 to 0.8 mg and can help relieve the symptoms affecting the brain and heart. However, in some severe cases, significantly higher doses might be required — some as high as 100 mg — to revive a person from a single overdose event.
At the same time, other health professionals might begin using a bag-valve mask or similar device, which helps restore oxygen to the vital organs of the person who has overdosed.
In dealing with an opioid overdose, it’s essential to follow the Basic Life Support and Advanced Cardiac Life Support guidelines. Laboratory tests such as drug screenings can also be done, although these are usually not helpful in quickly diagnosing an opioid overdose in the moment. Drug screenings are more useful when looking for hidden use of opioids, such as in cases of pre-employment testing.
If there’s a disagreement about the drug screen result between the patient and the healthcare provider, a more detailed test – gas chromatography and mass spectroscopy (GCMS) – can be done to clarify what substances are present in the patient’s sample. In the United States, Medical Review Officers are responsible for managing the data from employment drug testing.
Treatment Options for Opioid Toxicity
Traditional methods of treating opioid addiction often involve self-help counseling and guidance from individuals who’ve successfully overcome their opioid addiction. The focus is usually on living completely free of any drugs, even those prescribed by doctors. However, in recent years, the idea of harm reduction has become more accepted. This approach allows for the use of medications, with the main goal being to maximize positive patient outcomes.
Long-term treatment of patients with opioid addiction using certain medications has become increasingly accepted. These medications include methadone, buprenorphine, and naltrexone. As their use has increased, more research has been conducted to compare different recovery strategies and ways to prevent relapse. Naltrexone, for example, can be taken as an injection that lasts for about a month. During this time, the naltrexone prevents opioids from working.
One downside to naltrexone is that it can make it difficult to control acute pain in circumstances like trauma or other medical emergencies. Also, the injection form of naltrexone isn’t recommended for people with chronic pain. Oral naltrexone is taken daily, but it doesn’t tend to work well when the patient controls when they take it. That said, having the medication administered by a trusted individual might be a promising approach, based on recent research conducted on treating alcoholism.
The Mainstreaming Addiction Treatment (MAT) Act is a recent development that aims to expand access to evidence-based treatment for opioid addiction. This act allows all healthcare providers with a regular controlled substance license to prescribe buprenorphine for opioid use disorder, just like they would with other medications. The goal of the MAT Act is to reduce stigma around opioid use disorder treatment and integrate this treatment across healthcare settings.
As of December 2022, the MAT Act has done away with the DATA-Waiver (X-Waiver) program. Now, all providers registered with the DEA who have authority to prescribe Schedule III drugs can prescribe buprenorphine for opioid use disorder if their state laws allow it. Providers who were previously registered as DATA-Waiver prescribers will get a new DEA registration certificate to reflect this change. They don’t need to take any action to receive it.
There’s no longer a limit on the number of patients a provider can treat with buprenorphine. Also, providers are no longer required to track how many patients they treat with buprenorphine or how many prescriptions they write for it. Pharmacy staff can fill buprenorphine prescriptions using the provider’s DEA number, and they don’t need a DATA 2000 waiver from the provider. However, pharmacy software may still require the X-Waiver information in some cases. Providers still need to comply with any state-level restrictions regarding opioid use disorder treatment.
What else can Opioid Toxicity be?
Sometimes, if a person is unconscious and showing signs typical of opioid overdose, like small pupils and slow breathing, it may be assumed that opioids are the sole cause. If after receiving the opioid-reversal drug naloxone, the person seems to recover, this assumption often holds true. But, in emergency situations, unconscious persons may have other underlying issues making their situation more complicated.
In the past, a combination of four medications known as a “coma cocktail” (dextrose, thiamine, naloxone, flumazenil) was used, but now only naloxone is commonly used in emergencies. Giving too much naloxone can sometimes cause agitation, making it hard to discover if there are other serious issues unrelated to opioid toxicity.
As a result, it’s commonly considered better to first use a very small test dose of naloxone, like 0.4 mg given intravenously, if it’s being used for diagnosis. It’s also crucial to keep in mind that there can be several other reasons why a person might be unresponsive, and these possibilities should be explored based on the person’s medical history and physical symptoms.
What to expect with Opioid Toxicity
While it might seem worrisome, taking opioids for a very short time when needed, isn’t likely to cause addiction or substance misuse. Similarly, a single instance of opioid toxicity, or overdose, doesn’t automatically lead to addiction. Once the effect of the opioid fades, patients are likely to return to their normal physical functions, as long as the overdose hasn’t caused harm to their organs due to lack of oxygen.
There have been instances where a single dose of opioids led to misuse, but this is quite uncommon. The likelihood of developing opioid misuse increases if the patient takes more doses of the drug.
It’s important to distinguish between someone who uses opioids responsibly as prescribed by a doctor, and someone who is developing or has developed an opioid use disorder, a form of substance addiction. According to criteria in the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5), which is used to diagnose such conditions, a patient may have an opioid use disorder if they show any of the following signs. They’re using opioids longer than they planned, they struggle to scale down their usage, they spend a lot of time trying to get opioids, they crave the drug, their use is impeding their social obligations or causing relationship issues, their use is hazardous, they continue using despite negative consequences, they need to take more for the same effect (tolerance), and they experience withdrawal symptoms when they stop or reduce use. The more of these signs a person exhibits, the more likely they are to have an opioid use disorder.
As of 2019, there’s growing evidence supporting medications like methadone or buprenorphine to help patients stabilize and reduce the risk of relapse or further overdose. Completely detoxing from all opioids, even medications like methadone or buprenorphine that help with addiction, doesn’t seem to provide the same advantage in preventing relapse.
Possible Complications When Diagnosed with Opioid Toxicity
If an opioid overdose is not treated promptly, it can lead to severe, long-term damage to the body or even death due to a lack of oxygen in the organs. Prolonged use can make a person tolerant to the drug, increasing the risk of developing an opioid addiction. Using opioids illegally can cause a variety of health problems, mainly related to injecting the drug. These include heart infection and its complications, abscess formation, skin infection, blood clots leading to inflammation of veins, stuck foreign bodies, a severe condition causing painful swelling in the muscles, HIV, hepatitis, and scarring.
In extreme cases, people who smuggle potent opioids internally for illegal sale can experience a sudden failure of their breathing mechanism if the drug packets burst inside their body, which can often be deadly.
Common dangers of opioid abuse include:
- Severe damage to the organs due to lack of oxygen
- Addiction
- Heart infection and associated complications
- Abscesses
- Skin infection
- Blood clots leading to inflammation of veins
- Stuck foreign bodies
- Severe pain and swelling in the muscles
- HIV and Hepatitis infection
- Scarring
- Sudden and severe breathing problems
Preventing Opioid Toxicity
The risks associated with the first dose of outpatient oral painkillers known as opioids for treating intense pain has become a significant topic of conversation in recent years, especially with respect to children and teenagers. Such concerns are so serious that some places in the USA require the legal guardian of the patient to sign a consent form before an outpatient opioid prescription can be given.
If the patient has a high risk of misusing the opioids or overdosing, especially in cases of long-term intense pain, some doctors specializing in pain management have seen positive results from scheduling regular appointments to give out prescriptions containing very small quantities of the medicine. In certain circumstances, they may also prescribe strong daily doses of opioids in order to closely monitor the needs of a specific patient for their safe use. This approach is typically used in cases such as patients in their final stages of cancer, who are also using illegal drugs like heroin.
Many doctors who manage pain-related cases believe that an overdose of opioids doesn’t necessarily mean that all outpatient opioids need to be stopped. However, it’s indeed a serious incident that warrants a detailed discussion with the patient and their family about the risks of another overdose in the future.
It’s crucial for patients taking opioids to understand the increased risks when these drugs are taken together with substances that affect the chemicals in our brains that act as filters of the body information related to pain, known as GABA-ergic. Some examples of these substances are other drugs like benzodiazepines, barbiturates, or even alcohol.
