Dr. Kolpe Institute Of Pharmacy collage Kolpewadi, Ahilyanagar, Maharashtra, India
Benzodiazepam, also known as 9-chloro-2-methyl-6-phenyl-2,5-diazabicyclo, are structurally and pharmacologically closely related. It works well for many people whose epilepsy has not responded to other antiepileptic medications and has a wide range of action against the different forms of epilepsy. Its main use are in status epilepticus, where intravenous Benzodiazepam may be used as a first-choice medication instead of diazepam, and in childhood small motor seizures, especially petit mal absences, Lennox-Gastaut syndrome, and infantile spasms. In psychomotor and myoclonic epilepsies, Benzodiazepam is also at least as successful as existing treatments. However, it is unlikely to take the place of phenytoin and barbiturates in the treatment of grand mal or focal motor seizures, unless the patient is not responding to normal treatment. Benzodiazepam's early effectiveness may be followed by a loss of effect; however, by temporarily stopping and restarting treatment, the benefit can frequently be recovered, at least initially. There are frequently side effects from Benzodiazepam. In addition to the less common occurrences of ataxia, dystonia, hypotonia, and hyperactivity, the majority of patients suffer weariness and drowsiness, which are common causes of withdrawal. These side effects are minimized by introducing the medication gradually over a period of two to four weeks, and they typically go away with continuing therapy. Children and newborns may experience hypersalivation and excessive bronchial secretion.
A benzodiazepine medication called Benzodiazepam is used to treat epilepsy, panic disorder, and nonconvulsive status epilepticus in an acute manner. Numerous off-label uses for the medication exist as well, such as tardive dyskinesia, severe mania, sleeplessness, and restless legs syndrome. As a long-acting, potent benzodiazepine, Benzodiazepam acts as an agonist on the GABA-A receptor. By increasing the frequency of chloride channel opening, which causes hyperpolarization of the neurons and decreased firing, benzodiazepines facilitate GABA-A activity. This lowers neuron excitability, which calms the brain. By promoting the synthesis of serotonin, Benzodiazepam also exhibits serotonergic action. In order to help interprofessional team members treat patients with panic and seizure disorders, this exercise will emphasize the Benzodiazepam's indications, mechanism of action, administration, adverse event profile, contraindications, monitoring, and toxicity in clinical settings[1]. One benzodiazepine with a lengthy half-life is Benzodiazepam. It functions as an agonist of the GABA-A receptor. By promoting the synthesis of serotonin, it also exhibits serotonergic function. The FDA has approved Benzodiazepam for the treatment of panic and seizure disorders because of its anxiolytic and anticonvulsant properties. Additionally, Benzodiazepam can be used off-label as a monotherapy or supplementary treatment for REM sleep behavior disorder, insomnia, mania, restless legs syndrome, and tardive dyskinesia[2]. Benzodiazepines are a group of prescription-only medicines that have a sedating/hypnotic and calming effects on the nervous system. Examples of benzodiazepines active ingredients are diazepam, lorazepam, oxazepam, temazepam and alprazolam. Most are now generics (no more under patent), but still widely recognizable under brand names such as Valium or Xanax. They come in tablet and capsule forms and some are available for intravenous use in hospital settings. The arrival of benzodiazepines into clinical practice in the 1960s allowed doctors to offer this medication at a time when few effective therapeutic alternatives were available. Benzodiazepines appeared safe in comparison to barbiturates, chloral hydrate and other drugs, which were problematic due to toxicity and overdose.
Due to the apparent low level of side effects and rapid onset of effect, and together with a pressing mental health need, benzodiazepines were commonly used and prescribed short- and long-term for anxiety, depression, insomnia, mental illness, and neuromuscular conditions. By the 1970s, they were among the most prescribed drugs in the world.
Chemical Structure:
Molecular Formula:
[C9H8N2]
Molecular Weight:
144.17 g/mol
Description:
Benzodiazepam is 9-chloro-2-methyl-6-phenyl-2,5-diazabicyclo one in which the hydrogens at positions 5 and 7 are substituted by 2-chlorophenyl and nitro groups, respectively. It is used in the treatment of all types of epilepsy and seizures, as well as myoclonus and associated abnormal movements, and panic disorders. However, its use can be limited by the development of tolerance and by sedation. It has a role as an anticonvulsant, a GABA modulator and an anxiolytic drug. It is a 1,4-benzodiazepinone and a member of monochlorobenzenes.
Structure[3].
Mode Of Action:
To produce its anticonvulsant, skeletal muscle relaxant, and anxiolytic actions, Benzodiazepam increases the central nervous system's activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). One extremely strong long-acting benzodiazepine is Benzodiazepam. By functioning as a positive allosteric modulator of GABA-A receptors, Benzodiazepam produces pharmacological effects. GABA (gamma-aminobutyric acid) is the endogenous ligand of the GABA-A receptor, a ligand-gated chloride ion selective channel. By increasing the frequency of chloride channel opening, which causes hyperpolarization of the neurons and decreased firing, benzodiazepines facilitate GABA-A activity. This lowers neuron excitability, which calms the brain. Benzodiazepines do not affect GABA-A receptor function when GABA is not present. The cortex and limbic system contain large amounts of the inhibitory neurotransmitter GABA. GABA receptors A, B, and C are the three types. BZDs, however, exclusively affect GABA-A receptors. Each receptor complex is made up of five subunits: two alpha, two beta, and one gamma. It has two GABA-binding sites and one BZD-binding site. BZDs bind to different BZD-binding sites located at the interface between the alpha and gamma subunits of the receptor complex rather than the same receptor site as the endogenous neurotransmitter GABA. The binding causes a conformational shift in the chloride channel of the GABA-A receptor, which causes the cell to become hyperpolarized and explains why GABA has an inhibitory effect throughout the central nervous system[8].
Seizure Disorders:
The actions of Benzodiazepam against various seizure disorders are extensive. Acute treatment of epilepsy and non-convulsive status epilepticus (complex partial seizures or absence seizures) are the drug's main indications. It is also highly effective in managing childhood minor motor seizures, especially petit mal absences, Lennox-Gastaut syndrome, and infantile spasms. Grand mal seizures, focal motor seizures, myoclonic epilepsies, and psychomotor seizures can all be treated with Benzodiazepam. It is not utilized as a first-line treatment for these ailments, nevertheless. Patients who are not responding to conventional treatment can utilize the drug[5].
Panic Disorder:
Patients with panic disorders who also have agoraphobia benefit greatly with Benzodiazepam. Because Benzodiazepam carries a risk of abuse and withdrawal symptoms, it is effective in the short term for treating panic disorder. However, due to its longer half-life, this medication is also less prone than other benzodiazepines to trigger rebound anxiety when stopping. It is also used by clinicians to treat acute panic episodes[6].
Acute Mania:
Benzodiazepam's antimanic impact is linked to its anticonvulsant and serotonin agonist properties. As a result, it can occasionally be useful in treating acute mania. According to the study, it was much more successful than lithium at lowering manic symptoms; fewer patients needed PRN haloperidol administration, and Benzodiazepam treatment resulted in fewer days requiring haloperidol. Thus, Benzodiazepam lowers the likelihood of adverse effects in patients with acute mania and lessens the requirement for antipsychotic medications to treat it. In the emergency room, benzodiazepines plus the antipsychotic haloperidol are thought to be the most effective combination for treating acute agitation[7].
Miscellaneous Uses:
Benzodiazepam is also an option for treating akathisia, restless leg syndrome, and bruxism. American Academy of Sleep Medicine (AASM) suggests using Benzodiazepam for REM sleep behavior disorder (RBD). Topical Benzodiazepam is also being investigated for burning mouth syndrome.
Administration:
Benzodiazepam is available as an immediate-release tablet of 0.5 mg, 1 mg, 2 mg, and orally disintegrated tablets (ODT) of 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, and 2 mg strength. The medication may be administered once at bedtime to minimize somnolence. The patient should take the ODT tablet with water by swallowing it immediately after removing it from the package.
Therapy for Petit Mal Variant (Lennox-Gastaut syndrome), Akinetic and Myoclonic Seizures (myoclonia), and Absence Seizures.
Treatment of Panic Disorder:
For three days, the patient should take 0.25 mg tablets orally twice a day as part of the treatment. After that, the dosage should be increased to 0.5 mg tablets twice a day. One to four milligrams should be the maximum daily dosage.
Treatment of REM Sleep Behavior Disorder:
The recommended dose by AASM is 0.25 mg to 2 mg Benzodiazepam 30 minutes before bedtime.
Use in Specific Patient Population:
Pregnancy Considerations:
The FDA once classified Benzodiazepam as a pregnancy class D medication. It has been connected to some fetal cardiac and facial abnormalities. But the data are inconclusive. When Benzodiazepam is used in late pregnancy, the newborn may experience severe withdrawal symptoms, such as hypotonia, cyanosis, apneic episodes, and poor metabolic responses to cold stress, or they may develop floppy infant syndrome. Only when the clinical advantages of Benzodiazepam during pregnancy exceed the hazards to the developing fetus should it be utilized.
Breastfeeding Considerations:
Benzodiazepam is excreted into the breastmilk, although not in a significant amount. But for the premature neonate or those exposed during the pregnancy, it may cause problems because the pathway by which it undergoes metabolism is usually impaired in newborns. Therefore, such neonates should be monitored for the development of symptoms, and ideally, patients should be advised not to use Benzodiazepam if they are breastfeeding[9].
Liver Impairment and/or Renal Impairment:
No dosage adjustment information is given in the manufacturer's labeling; use it with caution. Benzodiazepam is hepatically metabolized and renally excreted; its level requires monitoring in hepatic or renal impairment as it can lead to toxic drug accumulation in the body in either condition. Benzodiazepam is contraindicated in severe liver disease.
Geriatric Population:
According to the American Geriatric Society (AGS Beers Criteria), benzodiazepines(including Benzodiazepam) AGS Beers Criteria are recognized as Potentially Inappropriate Medication (PIM). Benzodiazepines can cause cognitive dysfunction, delirium, falls, and fractures in older adults. However, use may be justified for seizure disorders and severe generalized anxiety disorder[10].
Adeverse Effect:
The use of Benzodiazepam is most commonly associated with lethargy
Less Common Side Effects:
Benzodiazepam can cause blurred vision
Drug-Drug Interactions:
• Benzodiazepines and opioids used together can cause drowsiness, respiratory depression, coma, and even death. Steer clear of combination.
• Using kratom and Benzodiazepam together may aggravate CNS depression and cause death. Steer clear of combination.
• Because of pharmacodynamic synergism, Benzodiazepam increases sedation when used with antidepressants, antipsychotics, hypnotics, antiepileptic medications, and antihistamines. Keep an eye on the treatment.
• The concentration of Benzodiazepam can be decreased by administering it concurrently with CYP3A4 inducers such as carbamazepine, phenobarbital, phenytoin, and primidone.
• The serum concentration of Benzodiazepam may rise if it is used concurrently with CYP3A4 inhibitors such as voriconazole, telithromycin, nirmatrelvir/ritonavir, ketoconazole, itraconazole, and clarithromycin[12].
Before taking this medicine
narrow-angle glucome
a history of allergic reaction to any benzodiazepine (including alprazolam, diazepam, lorazepam, Valium, Xanax, Versed, and others).
kidney or liver disease;
Tell your doctor if you are pregnant or plan to become pregnant. If you use Benzodiazepam during pregnancy, your baby could be born with life-threatening withdrawal symptoms, and may need medical treatment for several weeks. Do not start or stop seizure medication during pregnancy without your doctor's advice. Benzodiazepam may harm an unborn baby, but having a seizure during pregnancy could harm both mother and baby. Preventing seizures may outweigh these risks. Tell your doctor right away if you become pregnant. Ask a doctor if it is safe to breastfeed while using this medicine. Do not give this medicine to a child without medical advice. Benzodiazepam is not approved to treat panic disorder in anyone younger than 18 years old.
CONCLUSION:
Benzodiazepines (Benzos) Benzodiazepines are A class of medicine that slow down activity in your brain and nervous system. They're most often used for treating anxiety and related mental health conditions, as well as brain-related conditions like seizures. A review of benzodiazepine tolerance concluded that it "appears that tolerance develops relatively quickly for the sedative and anticonvulsant actions of benzodiazepines, whereas tolerance to anxiolytic and amnesic effects probably does not develop at all", although the included randomized controlled trial evidence.
REFERENCES
Saurabh Sapnar*, Swapnil Gaikwad, Vishal Gumnar, Aditi Fufane, Pharmacological Values of Benzodiazepam: A Potent Sedative and Anticovulsant, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 1242-1249. https://doi.org/10.5281/zenodo.15365119
10.5281/zenodo.15365119
