What is Alpha Receptor Agonist Toxicity?
Alpha-adrenergic agonist toxicity happens due to an overdose or misuse of certain medications, known as alpha agonists. These medications can be classified further into two types: central alpha-2 agonists and peripheral alpha-1 agonists. Central alpha-2 agonists include medications like clonidine, guanfacine, tizanidine, guanabenz, and methyldopa, while peripheral alpha-1 agonists include imidazoline, oxymetazoline, tetrahydrozoline, and naphazoline.
Alpha agonists work on two main types of receptors in the body: the central alpha-2 and peripheral alpha-1 adrenergic receptors. When central alpha-2 receptors are stimulated, they reduce the secretion of chemicals called catecholamines, which are important for the transmission of nerve signals. On the other hand, stimulating peripheral alpha-1 receptors mainly raises blood pressure through making blood vessels constrict.
The risk of toxicity predominantly lies with alpha-2 adrenergic agonist drugs, due to the reduced catecholamine levels that they cause. However, misuse of topical alpha-1 agonists can also cause similar toxic effects. The risk of toxicity is particularly high in children and adolescents, due to the increasing use of these medications.
The side effects of alpha-adrenergic toxicity could include slowed mental activity, slower heart rate, and low blood pressure. However, in most cases, these symptoms can be managed effectively with supportive care. This includes administering intravenous fluids, monitoring airways, and restoring the body’s catecholamine levels if necessary by using vasopressor agents, which constrict blood vessels and increase blood pressure. At present, there’s no officially accepted antidote for alpha-adrenergic toxicity, and naloxone has not been proven to be effective.
What Causes Alpha Receptor Agonist Toxicity?
Alpha-agonist toxicity, or poisoning, can happen by accident or on purpose. This typically comes from someone purposely taking too much of the medication or a child accidentally swallowing the medicine. Overdoses can happen after a person swallows pills, uses skin patches, or uses medication pumps incorrectly or if they malfunction.
A chronic and accidental overdose can also occur when dealing with long-term pain. This is especially true when using oral medications that are gradually released into the system over time or patches that deliver medication through the skin. Errors in the dosage given by a pharmacy or errors in how the medicine is made can also lead to overdosing, which is a big worry when it comes to toxicity in children.
Complications can also arise when alpha-agonists interact with other drugs a person might be taking.
Risk Factors and Frequency for Alpha Receptor Agonist Toxicity
Alpha-2 agonists are medications that doctors prescribe to treat a variety of health issues in people of different ages and backgrounds. They are common and can sometimes lead to negative side effects.
- Clonidine is frequently recommended for adults to manage high blood pressure, withdrawal symptoms from opioids, and as a supplementary treatment in children with attention deficit hyperactivity disorder (ADHD).
- This drug can also enhance REM sleep patterns at night, which can benefit those who are taking stimulant medications.
- Guanfacine is used to treat similar conditions and is particularly common in the pediatric population.
- Tizanidine, another Alpha-2 agonist, is often used to help relax muscles in cases of multiple sclerosis, a condition that can cause rigidity.
- Other types of these drugs, including oxymetazoline, tetrahydrozoline, and naphazoline, are usually available as over-the-counter topical treatments. They are primarily for nasal or ophthalmic use due to their ability to constrict blood vessels. But if taken orally, they can also have Alpha-2 agonist effects.
Unfortunately, these medicines can be abused, used incorrectly, or overdosed on—intentionally or accidentally. Kids are at a particular risk, as they could accidentally swallow these drugs or become victims of dosing mistakes. As these drugs become more commonly prescribed—for ADHD and other behavioral disorders—the potential for risk, especially self-harm in teenagers, increases.
Signs and Symptoms of Alpha Receptor Agonist Toxicity
Alpha-2 agonist toxicity is a medical condition that occurs when there is a decrease in the output of a type of neurochemical called catecholamine, leading to a condition called sympathetic depression. This condition is characterized by numerous symptoms, and the severity can range from mild to severe. It’s essential to note that the symptoms generally appear within the first hour of the onset of the condition. However, they can sometimes start as normal vital signs and mental status, but things can quickly worsen over time.
- Common symptoms include depression of the central nervous system, slower heart rate (bradycardia), and low blood pressure (hypotension).
- Other signs can be pupil constriction (miosis) and below normal reflexes (hyporeflexia).
- In severe cases, symptoms may also progress to a coma, lower body temperature (hypothermia), and breathing difficulties.
- Initially, the individual may present with normal vital signs and mental status, but as the condition worsens, symptoms such as somnolence (strong desire for sleep), further decline in heart rate and blood pressure can develop.
- These symptoms can sometimes start as high blood pressure.
- In extreme cases, a decrease in mental status from somnolence to coma, severe bradycardia and hypotension, occasional hypothermia, and respiratory depression might be the initial presentation if there’s a delay in getting medical help after ingestion.
Testing for Alpha Receptor Agonist Toxicity
The diagnosis of alpha agonist toxicity, a condition that can result from an overdose of certain medications, is typically based on a doctor’s observations rather than on specific laboratory tests. This is because these drugs cannot be identified in standard urine drug tests, and it’s uncommon to measure specific drug levels in the body. Even though these measurements can be done in specialized labs, they generally take a long time, from days to weeks, and are often not necessary.
If your doctor suspects that you may have alpha agonist toxicity, they will first and foremost ensure that your airway, breathing, blood circulation and blood sugar levels are all normal. They will also ask you detailed questions about your medical and medication history, and they might discuss your situation with your family members or friends. They might also check any past medical records or episodes that might be relevant, and inquire about your access to medications.
Your doctor will also perform a physical check-up to closely monitor your vital signs such as body temperature, heart rate, and breathing rate and depth. They will specifically check for conditions like bradypnea and hypopnea, which are both irregular patterns of breathing.
They will also conduct a thorough neurological examination. And just like in all cases of potential poisoning, they will order an electrocardiogram (a test that measures the electrical activity of your heart), a basic metabolic panel (a blood test that measures your sugar level, electrolyte and fluid balance), and a test for the presence of acetaminophen (a common drug that can cause liver damage in large doses).
Depending on your specific situation, your doctor may also order tests to measure the concentration of salicylic acid (a substance that can be harmful in excess) in your blood, monitor your liver function (transaminases), and, if you are female, confirm if you are pregnant or not.
If your doctor suspects there might be other medical or trauma-related reasons causing your symptoms, they might order brain imaging tests. Also, if there is a chance that you might have accidentally inhaled a foreign substance into your lungs (aspiration), they may need to do a chest x-ray.
Treatment Options for Alpha Receptor Agonist Toxicity
If an individual is not showing symptoms but is at risk of alpha-agonist toxicity (a type of drug overdose affecting certain parts of the nervous system), the person can be given activated charcoal, which can help reduce the absorption of the drug into their body. This is only advised if the individual is fully conscious and can protect their own airway. If the person doesn’t show any symptoms within four hours of exposure, then there is little chance of them developing symptoms later, and they can be considered safe. However, the exception is the drug methyldopa, which doesn’t act as quickly.
When a person is showing symptoms of alpha-agonist toxicity, they are usually admitted to the intensive care unit. Symptoms can last for several days. Treatment mostly includes supportive care, like ensuring proper breathing and cardiac monitoring. In serious cases, a patient might need to be intubated, which means having a tube inserted into their windpipe to aid in breathing. Attempts to induce vomiting or using dialysis to speed up the removal of the drug from the body have proven ineffective. There is no specific antidote approved for human use. While the drug naloxone has sometimes helped reverse symptoms, it is not a guaranteed cure and can’t be considered standard treatment. It may be used if there is a chance that the toxicity might be due to opioids (another type of drug), instead of alpha-agonists.
High blood pressure can initially occur with alpha-agonist toxicity but it usually resolves before medical help is sought and should not be treated because it’s short-lived. Treating this initial high blood pressure could make the eventual low blood pressure worse. If a person has persistently slow heart rate and low blood pressure, giving them medicines to constrict their blood vessels (vasopressors) can help. These medicines work to replace catecholamines, chemicals the body produces that are lacking with alpha-2 agonist toxicity. Normally, a low dose is sufficient to reverse symptoms, with the drug of choice usually being norepinephrine.
This type of toxicity is rare to be fatal. When a patient’s vital signs return to normal and their mental status is stable, they can be considered cleared of the toxin.
What else can Alpha Receptor Agonist Toxicity be?
If someone is showing signs of alpha-2 agonist toxicity, it’s important to realize that similar symptoms can be caused by other drugs or medical conditions. This can include anything that slows down the centerpiece of the nervous system (CNS), heart rate (bradycardia), and blood pressure (hypotension). Here are some other drugs that should be considered:
- Beta adrenergic blockers (a type of heart medication)
- Calcium channel blockers (usually used for high blood pressure)
- Cardiac glycosides (used to help heart problems)
- GABA-B agonists such as baclofen (used as a muscle relaxant)
Alpha-2 agonist toxicity could involve constricted pupils and slow breathing, which can look much like an opioid overdose. So if a patient seems to have had an opioid overdose but isn’t responding to antidote medicines like naloxone, alpha-2 agonist toxicity could be what’s really happening.
In addition, some medical conditions that can cause similar symptoms should be considered, including a particular type of shock caused by damage to the nervous system (neurogenic shock) and heart attacks (acute myocardial infarctions) that involve the part of the heart that sends out electrical signals to make the heart beat (sinoatrial node or the atrioventricular node).
What to expect with Alpha Receptor Agonist Toxicity
If the patient is given the proper supportive care, they can generally expect to fully recover within a day.
Possible Complications When Diagnosed with Alpha Receptor Agonist Toxicity
It’s really important to keep blood flowing properly throughout the body. If blood circulation isn’t maintained properly, the patient could be at risk for damage to vital organs. This includes heart damage due to lack of oxygen and brain injury caused by a lack of oxygen.
Potential Risks:
- Lack of proper blood circulation
- Risk of damage to vital organs
- Potential heart damage due to lack of oxygen
- Potential brain injury caused by a lack of oxygen
Preventing Alpha Receptor Agonist Toxicity
Parents need to be informed about the potential risks of drugs known as alpha agonists. These drugs can be found both over-the-counter and by prescription. Doctors should also be highly aware when they recommend these medications, especially when it’s for children who may particularly be at risk.