Abstract
This article takes a close look at the effects of benzodiazepine (BZD) drugs, sparked by a recent incident involving preschoolers. BZDs, used to tackle anxiety and mental issues, have short-term perks but come with risks like memory problems and dependency. Mechanistically, they enhance GABA neurotransmission, calming neural activity. The article explores how BZDs are used for different health problems like calming nerves before surgery or dealing with mental struggles. Despite benefits, caution is advised due to side effects and potential misuse repercussions. Long-term use can lead to dependence and withdrawal.We also dive into BZD poisoning and treatment strategies, including detoxification and Flumazenil antidote. In sum, the article underscores the critical need for comprehensive BZD awareness to safeguard physical and mental well-being, aiming to reshape perceptions and encourage informed decisions.
Introduction
At the beginning of June 2023, news in Taiwan shocked the public. Parents of toddlers at a preschool have accused the kindergarten of drugging their children with medications likely to be phenobarbital and benzodiazepines. The parents discover this scandal due to the fact that the children have demonstrated signs of withdrawal symptoms at home during long holidays. And the result of urine tests and blood tests of toddlers have indicated BZD drug residue. The case is still under investigation; at the meantime, the public needs to know precisely how BZD drugs harm your body, not to mention its adverse effects on children.
What are BZD
Drugs BZD, which stands for benzodiazepines (so-called 'benzo'), is a class of drugs usually used for treating anxiety, insomnia, seizures, and some mental-related conditions. Benzodiazepines are effective in the short term, but long-term use can lead to cognitive impairment, physical dependence, and withdrawal syndrome. BZD drugs are also associated with an increased risk of suicide and have potential risks in pregnancy. Benzodiazepines are commonly misused and controlled substances in many countries. Compared with highly regulated opioid medication, BZD drugs are easier to obtain since patients can take the medicines for a month at one time to treat chronic diseases. This results in BZD drugs being common for patients to commit suicide.
The mechanism of BZD Drug
In general, Benzodiazepines reduce the excitability of neurons by improving the efficiency of the endogenous neurotransmitter GABA. As a result, numerous brain functions are calmed since there is less communication between the neurons.
GABA is an inhibitory neurotransmitter that binds to the alpha-beta subunit on the GABA receptor. When two GABA bind to the receptor, the chloride ion channel in the middle opens, and Cl ions flow into the postsynaptic nerve, increasing the negative potential inside, making it more challenging to reach the action potential. Therefore, GABA achieves a calming effect through inhibition.
BZD drugs are also bound to the GABA receptor, but unlike GABA, BZD is connected to the alpha-gamma subunit. When BZD is combined, it will increase the binding effect of GABA, promote the opening of chloride ion channels, and make it more difficult to generate action potentials.
The Mechanism of BZD drugs (Source: The journal of Pharmacology and Experimental Therapeutics)
How does BZD affect your Body
If prescribed correctly, BZD can be applied to a wide range of clinical effects and can be beneficial. As mentioned in the previous paragraph, BZD is an inhibitory drug often treated for conditions related to motor, system, and coordination difficulty. For example, BZD can be applied to sedation during operations and may result in anterograde amnesia, which lets the patient forget during the operation. Also, it is commonly used for treating mental conditions resulting from the hyperactiveness of the neuro system—for instance, anxiety disorder, panic disorder, obsessive-compulsive disorder, bipolar disorder, and schizophrenia. Moreover, BZD can serve as a muscle relaxant antispasmodic, helpful in treating seizures in the emergency department.
Sometimes, the side effect of taking BZD is dizziness and drowsiness, and the side effects can be more significant with a higher dosage.
When taking high doses of benzodiazepines for recreational use or other reasons, the side effects can be more serious. Symptoms of acute overdose include drowsiness, confusion, dizziness, blurred vision, weakness, and slurred speech. If worse comes to worst, the patients may result in respiratory depression and even coma. In addition, people may become hyper-aggressive and even lower their inhibition, which means that people would do things they usually wouldn't do.
Moreover, long-term side effects can lead to both physical and mental dependence and affect relationships and work performance. When abruptly interrupted, addiction can cause withdrawal symptoms and even convulsions. Children who experience rapid mood changes or a decline in their academic performance may also exhibit warning indicators. In sum, the continuous using of benzo demonstrates the stacking-up effect. The body stores the drug so a person can constantly experience the impact of the medications.
BZD Poisoning
The mechanism of BZD drug poisoning is the same as its pharmacological effect; increasing the effect of GABA leads to CNS depression. (Central Nervous System Depression). Mild symptoms of CNS depression may help control anxiety. However, people who show signs of severe CNS depression should seek medical help immediately.
Symptoms of BZD drug poisoning vary depending on the drug and the amount of medication taken. The worst situation is severe CNS depression, such as respiratory depression and coma. Because BZD has fewer binding sites in the brain stem respiratory center, BZD drugs alone rarely cause respiratory depression, but if the patient takes other sedative drugs (Ex. alcohol, opioids, muscle relaxants) at the same time, or Patients with sleep apnea and other underlying chronic lung diseases have a higher probability of respiratory depression.
Usually, health professionals will make differential diagnoses of patients with BZD poisoning. If the patient can inform the medical staff of the type and dosage of the drug taken after being sent to the emergency department, they can have a more precise treatment direction. However, most patients are already in a state of unconsciousness when they arrive at the emergency department, and differential diagnosis is crucial at this time. Generally speaking, except for the symptoms of CNS depression, most of the other physiological values of patients with BZD poisoning are normal. Patients suspected of BZD poisoning should be tested for serum glucose, venous blood gases, ECG, and pulse oximetry.
According to the half-life, BZD drugs can be divided into short-acting, intermediate-acting, and long-acting. Short-acting BZDs such as Midazolam (Dormicum®) have a half-life of about 1.5-3 hours; long-acting BZDs such as Diazepam (Dupin®) have a half-life of up to 20-50 hours. Since BZD drugs are metabolized by liver enzymes, patients with drug poisoning are saturated with metabolic enzymes, which may prolong the drug metabolism time. If the patient takes medium or long-acting BZD drugs, the half-life is longer than its specific antidote, Flumazenil. Health professionals should pay attention to the possibility of re-sedation after detoxification.
Typically, non-specific detoxification and specific antiddotes are the treatment for BZD poisoning. Non-specific detoxification for patients with BZD poisoning is to give supportive care, including airway, breathing, and circulation. The specific antidote for BZD drug poisoning is Flumazenil (Anexate®). Due to its similar structure to BZD drugs, it can achieve the drug effect by competitively binding to the binding site of BZD on the GABA receptor. Generally speaking, the patient's GCS score (Glasgow coma score) will improve within 1-2 minutes after administering Flumazenil.
Conclusion
BZD is a common drug category; therefore, it's essential to understand how it can affect short- and long-term health to avoid any unintentional harm to people's physical and mental health. By understanding more about the drug, I hope people can change their perception of addiction.
Citation:
(Cover image source: HelpGuide.org)
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