Major Research Findings

A double-blind crossover study compared the hypnotic effect, daytime carryover, and safety of triazolam 0.5 mg, lorazepam 2 mg, and placebo. The two active drugs were similar in hypnotic effect and superior to placebo. Patients reported more drowsiness upon awakening and more sleepiness in mid-morning and mid-afternoon after nights on lorazepam than nights on triazolam or placebo. The most common side effects - drowsiness, lightheadedness, restlessness, impaired coordination, dizziness, and nausea - were reported three times as often with lorazepam than with triazolam or placebo. 1 .

5-fluorouracil (5FU) and capecitabine are fluoropyrimidine antineoplastic drugs commonly used in the treatment of different types of cancer. Hereditary dihydropyrimidine deaminase (DPD), thymidylate synthase mutations and drug overdose may lead to life-threatening toxicities. Uridine triacetate (UTA) is an emergency treatment for overdoses and early onset, severe or life-threatening toxicities from fluoropyrimidines. It is approved for use in adults and children within 96 h of last fluoropyrimidine administration. 2 . A case report describes a 64-year-old male treated with 5-FU and oxaliplatin as adjuvant systemic therapy for stage IIIA rectal cancer who developed delayed central nervous system toxicity 18 days after initiating chemotherapy. 2 . He had rapidly worsening encephalopathy and ataxia. Laboratory workups, MRI brain and EEG were negative. He was started on UTA with concerns of 5-FU toxicity due to the life-threatening nature of his condition even beyond the recommended 96-h time cut-off. 2 . He had rapid improvement in clinical status and resolution of encephalopathy. 2 . DPD deficiency testing later resulted as heterozygous for IVS14+1G>A allele indicating enzyme deficiency. 2 .

Reasons for side effects

Lorazepam has been reported to cause more side effects, such as drowsiness and lightheadedness, compared to triazolam or placebo, possibly due to its stronger central nervous system depressant effect compared to triazolam. 1 . 5-FU inhibits cell DNA synthesis and thereby inhibits cell proliferation and division, resulting in its anticancer effect. 2 . Toxicity of 5-FU is often caused by DPD enzyme deficiency or 5-FU overdose, and cytotoxicity through DNA synthesis inhibition is considered to cause side effects such as neurological toxicity. 2 .

Common side effects

Drowsiness

Patients reported more drowsiness upon awakening and more sleepiness in mid-morning and mid-afternoon after nights on lorazepam than nights on triazolam or placebo. 1 .

Lightheadedness

The most common side effects - drowsiness, lightheadedness, restlessness, impaired coordination, dizziness, and nausea - were reported three times as often with lorazepam than with triazolam or placebo. 1 .

Restlessness

The most common side effects - drowsiness, lightheadedness, restlessness, impaired coordination, dizziness, and nausea - were reported three times as often with lorazepam than with triazolam or placebo. 1 .

Impaired coordination

The most common side effects - drowsiness, lightheadedness, restlessness, impaired coordination, dizziness, and nausea - were reported three times as often with lorazepam than with triazolam or placebo. 1 .

Dizziness

The most common side effects - drowsiness, lightheadedness, restlessness, impaired coordination, dizziness, and nausea - were reported three times as often with lorazepam than with triazolam or placebo. 1 .

Nausea

The most common side effects - drowsiness, lightheadedness, restlessness, impaired coordination, dizziness, and nausea - were reported three times as often with lorazepam than with triazolam or placebo. 1 .

Encephalopathy

The patient exhibited rapidly worsening encephalopathy. 2 .

Ataxia

The patient exhibited ataxia. 2 .

Side effect management

Drowsiness

Avoid driving or operating dangerous machinery if you feel drowsy. 1 . Ensure adequate sleep time. 1 .

Lightheadedness

If you experience lightheadedness, exercise caution when standing up or walking. 1 . Consult your doctor if needed. 1 .

Restlessness

If you experience restlessness, try relaxation techniques or consult your doctor. 1 .

Impaired coordination

Avoid driving or operating dangerous machinery if you have impaired coordination. 1 .

Dizziness

If you experience dizziness, exercise caution when standing up or walking. 1 .

Nausea

You can be prescribed medication to suppress nausea. 1 .

Encephalopathy

If you suspect encephalopathy, seek immediate medical attention. 2 .

Ataxia

If you have ataxia, be careful to avoid falls. 2 . Consult your doctor if needed. 2 .

Comparison of Research

Commonalities

Both studies investigated different medications and reported side effects. 1 2 .

Differences

The study comparing triazolam and lorazepam reported more side effects like drowsiness from lorazepam. 1 . The study on 5-FU toxicity reported delayed neurological toxicity. 2 .

Considerations for Real-Life Application

Sleeping pills can cause side effects such as drowsiness. 1 . Exercise caution when driving or operating dangerous machinery. 1 . Anticancer drugs like 5-FU can cause serious side effects. 2 . It is crucial to take these medications as directed by your doctor. 2 .

Limitations of Current Research

The study comparing triazolam and lorazepam had a limited sample size, therefore further research with a larger sample is needed. 1 . The study on 5-FU toxicity was a case report, and more studies with a larger number of patients are required. 2 .

Future Research Directions

Research on the side effects of sleeping pills needs to investigate long-term effects. 1 . In research on 5-FU toxicity, identifying risk factors for side effects, such as DPD deficiency, is crucial. 2 .

Conclusion

Triazolam and lorazepam showed no difference in hypnotic effect, but lorazepam reported more side effects such as drowsiness compared to triazolam. 1 . 5-FU can cause serious side effects, including delayed neurological toxicity. 2 . It is important to obtain appropriate information, such as consulting your doctor, about the side effects of medications. 1 2 .