Introduction

Lorazepam is a benzodiazepine medication that is frequently used as a sedative and anxiolytic in inpatient settings due to its rapid (1 to 3 minute) onset of action when administered intravenously. Lorazepam is also one of the few sedative-hypnotics with a low risk of negative side effects. This activity covers the mechanism of action of lorazepam, pharmacology, adverse event profiles, eligible patient demographics, and monitoring, as well as the role of the interprofessional team in lorazepam therapy management.

DJ Richards created Lorazepam, a benzodiazepine medicine. In 1977, it was released in the United States. Because of its rapid (1 to 3 minute) onset of action when delivered intravenously, lorazepam is commonly used as the sedative and anxiolytic of choice in the inpatient context 1. Lorazepam is also one of the few sedative-hypnotics with a low risk of negative side effects.

FDA-Approved Indications

• Anxiety symptoms associated to anxiety disorders are relieved for a period of four months.

• Treatment of status epilepticus

• Premedication for anaesthesia in adults to alleviate anxiety or induce sedation/amnesia 2

Off-Label (Non-FDA-approved) Indications

• Rapid sedation of an agitated patient

• Alcohol withdrawal delirium

• Alcohol withdrawal syndrome

• Insomnia

• Anxiety disorders

• Delirium

• Anticipatory nausea and vomiting caused by chemotherapy (adjunct or breakthrough)

• Catatonia caused by psychological factors 3

Mechanism of Action

Lorazepam binds to benzodiazepine receptors on postsynaptic GABA-A ligand-gated chloride channel neuron benzodiazepine receptors throughout the central nervous system (CNS). It enhances chloride ion conductance into the cell by boosting GABA's inhibitory actions. Because of the shift in chloride ions, the cellular plasma membrane is hyperpolarized and stabilized 4. Its amygdale inhibitory action is advantageous in anxiety disorders, whereas its cerebral cortex inhibitory activity is beneficial in seizure disorders.

Administration

Lorazepam is available in tablet form (0.5 mg, 1 mg, 2 mg, oral concentrate solution 2 mg/mL, 1 mg extended-release capsule, 2 mg extended-release capsule, and 3 mg extended-release capsule), extended-release capsule form (0.5 mg, 1 mg, 2 mg, and 3 mg extended-release capsule), and extended-release capsule form (0.5 mg extended-release capsule, 2 mg extended-release capsule, and 3 mg extended-release capsule). It is given as a 2 mg/mL or 4 mg/mL intravenous (IV) or intramuscular (IM) injection. When given IV, it takes 1 to 3 minutes to take effect, whereas when given IM, it takes 15 to 30 minutes. If used orally, the lorazepam immediate-release pill reaches peak plasma in 2 hours. Lorazepam has an oral bioavailability of 85%, is glucuronidated in the liver by CYP450 enzymes, and a 14-hour half-life 5.

Anxiety Disorder

The first beginning dose is 2 to 3 mg orally, with the possibility of repeating the dose 2 to 3 times per day; the maximum daily dosage is 10 mg 6.

Insomnia Due to Anxiety or Stress

In patients under the age of 65, the dose is 0.5 to 2 mg orally at bedtime, while in patients above the age of 65; the dose is 0.5 to 1 mg orally at bedtime.

Lorazepam in Patients with Acute Coronary Syndrome

Acute coronary syndrome is still a major source of morbidity and mortality around the world. The standard goal of treatment is to achieve rapid reperfusion using primary Percutaneous Coronary Intervention (PCI). PCI, when combined with adequate medical treatment, can improve short- and long-term results after a heart attack (MI). ST Elevation in Patients Myocardial infarction (STEMI) can be treated with fibrinolytics if PCI is not an option. PCI has been widely utilised to treat obstructive coronary artery diseases (CADs) such as unstable angina, recurrent angina after CABG, and Acute Myocardial Infarction (AMI), with clinical symptoms and death rates both reduced 7. Anxiety is a common AMI 8, 9, 10 adverse effect 11, 12. Anxiety, higher heart rate, and enhanced contractility with significantly increased myocardial workload and myocardial oxygen consumption are common adverse effects in those who have experienced a myocardial ischemia episode. The patient population, pain alleviation here is critical not just for increasing patient comfort, but also because pain is linked to sympathetic activation, which induces vasoconstriction, increases heart workload, and lowers myocardial oxygen demand. Titrated intravenous (IV) opioids (e.g., morphine) and benzodiazepines are the most commonly used analgesics in this condition (e.g., lorazepam). Morphine usage, on the other hand, has been related to slower absorption, a delayed onset of action, and diminished effects of oral anti-platelet medications, all of which can lead to early treatment failure in persons who are already vulnerable 8.

Morphine can also lead to hypotension and respiratory collapse.

As a result, sedative medicines are the conventional treatment for anxiety. All MI patients are given lorazepam every night until they are discharged. Lorazepam is an efficient anti-anxiety medication that can also help with depressive symptoms and insomnia. Tachycardia, rapid breathing or shortness of breath, restlessness, disorientation, and mood disturbances are all signs of insomnia and/or restlessness. Lorazepam is most typically recommended to ACS patients as a 0.5 mg oral QD before bedtime dose. According to a prior study, AMI patients with higher levels of anxiety had more chest discomfort, arrhythmias, and mortality than those with lower levels of anxiety (19.6% vs. 6%, p=0.001).

We are aware that there hasn't been a well-designed, randomised, prospective clinical trial comparing treatment methods in patients with ACS. Lorazepam's efficacy and safety in ACS patients has been studied in only a few trials. The goal of this randomised controlled trial was to examine the efficacy and safety of lorazepam with placebo in patients with ACS in terms of chest pain, delirium, arrhythmias, and sleep satisfaction.

Enhancing Healthcare Team Outcomes

Lorazepam, like other benzodiazepine drugs, has the potential to be highly addictive. As a result, prescribing and monitoring these drugs will require an interprofessional team approach. Prescribers (MDs, DOs, NPs, and PAs), psychiatrists, nursing staff, and pharmacists are all members of this team, and each must be on the lookout for symptoms of misuse or harmful effects. This method will help to minimise overuse and unwanted side effects, as well as maximise therapy.

More caution is essential when giving lorazepam in big dosages or for lengthy periods of time, especially in patients who have a history of drug misuse or who are taking opioids. A multidisciplinary team of healthcare professionals, including nurses, pharmacists, and numerous specialist physicians, is required to monitor for signs of misuse, diversion, or concurrent use with other prescription or non-prescription sedative medicines. When administering benzodiazepines like lorazepam, prescribers and pharmacists must maintain track of medication, educate patients, and exercise caution. Individuals at high risk should be identified utilising state and federal restricted drug monitoring and diversion databases who have a large number of and frequent prescriptions for benzodiazepines, opioids, muscle relaxants, and other sedative-hypnotics. Interprofessional care under the supervision of both the doctor and the pharmacist is the only way to ensure safe prescription.

METHODOLOGY

Place of the Study

This study was carried out at a local teaching and General Hospital, Vadodara, Gujarat.

Period of the study

The study will be carried out for a period of 6 months.

Study Design

A Prospective Comparative study.

Study Population

235.

Patient Enrollment

Inclusion Criteria

Patients must be over the age of 18 and have good consciousness and hemodynamic stability to be considered.

Exclusion Criteria

• Severe illness, such as sepsis, urinary tract infection, or pneumonia;

• Psychiatric history;

• Sedative drug usage within one month of randomization;

• Lorazepam contraindications, such as liver failure and allergy; and/or

• Alcohol addiction history.

Study Materials

• Patient data collection and questionnaire form

• Informed consent form

Method of Study

• Patients were accepted into the study based on their eligibility.

• All required information was obtained using a questionnaire form

• Follow-ups were performed

• Baseline laboratory information was collected

• Medication efficacy was compared based on lab values for each follow-up

• At each follow-up, diet control counseling will be provided.

• At the final follow-up, the drug efficacy for the drug will be demonstrated, and results will be presented in contrast to placebo.

Statistical Analysis

• The required information was collected and tabulated and wherever needed the frequencies and percentages to be calculated.

• Qualitative data was recorded and compared using the chi-square test or Fisher's exact test as a number or a percentage.

• The Mann-Whitney U test was used to compare quantitative data, and the results are provided as mean standard deviation. The Z-test for non-inferiority was used to determine whether the trial medication and placebo were non-inferior.

• The percentage difference between groups and the 95 percent confidence interval are used to compare primary endpoint data between groups. All statistical analyses were conducted using SPSS Statistics, and the tests were deemed statistically significant if the p-value was less than 0.05.

RESULTS

A total of 235 people took part in the study. There were 235 people in the study, 120 in the lorazepam group and 115 in the placebo group. Table 1 shows that the placebo group had a greater baseline demographic and ejection percentage than the lorazepam group. The case group's baseline LDL level is somewhat greater than the control group's. Other baseline laboratory data, as shown in Table 2, is comparable across the two groups. Table 3 displays the findings of a medication study on chest discomfort, disorientation, and arrhythmias. When using the Z-test with a 10% margin of non-inferiority, the placebo seems to be non-inferior to lorazepam for the events since the P-value for non-inferiority is 0.001. (chest discomfort, delirium, and arrhythmias). Patient demographics and baseline characteristics (n=235) are shown in Table 1.

As seen in Table 4, the main endpoint occurred at a greater incidence in the lorazepam group than in the placebo group. There were no significant differences between the medicines. In the PCI group, the lorazepam group had a lower incident rate than the placebo group, however the lorazepam group had a higher event rate in the no PCI group, as shown in Table 5. In both groups, the effectiveness of lorazepam in STEMI appeared to be equivalent; however the lorazepam group had reduced chest pain (Table 6). Individuals who lived with others and those who did not had significantly different levels of sleep pleasure.

Lorazepam is administered to all patients with acute coronary syndrome once a day until they are discharged. This is an order for therapy that has been in effect for quite some time. While studies have shown that lorazepam is unsuccessful in the treatment of chest pain or arrhythmias, it's more likely that patients are drowsy and ignorant of their symptoms. More information may be gained if patients are prompted for more details. If patients are prompted for more information, extra information may be obtained. Lorazepam, on the other hand, appears to produce delirium more frequently. Lorazepam, on the other hand, only affects sleep satisfaction for the first night of hospitalisation.

CONCLUSION

The placebo was found to be non-inferior to lorazepam for the cardiac events studied—chest discomfort, delirium, and arrhythmias. The lorazepam group had a significantly higher mean score of first-night sleep satisfaction than the placebo group, indicating that lorazepam can alleviate anxiety and enhance sleep quality in ACS patients during their first night in the hospital.

Funding Support

The authors declare that they have no funding support for this study.

Conflict of Interest

The authors declare that there is no conflict of interest.