Benzodiazepines: Their Use either as Essential Medicines or as Toxics Substances
Abstract
:1. Introduction
2. Benzodiazepines
3. Synthesis of Benzodiazepines
4. Benzodiazepines Action Mechanism on the Central Nervous System
5. Pharmacological Differences between the Different Types of Benzodiazepines
6. Degradation of Benzodiazepines in the Organism
7. Toxicological Effects of Inappropriate Use of Benzodiazepines
7.1. An Essential Medicine That May Become a Weapon for the Crime
7.2. Benzodiazepines Effects on Aggressors
7.3. Suicides Mediated by Benzodiazepines
7.4. Benzodiazepines and Traffic Accidents
7.5. Adverse Effects of the Benzodiazepines Consumption by the Elderly
7.6. Adverse Effects on Pregnant Women and Newborn Children
8. Chemically Modified Benzodiazepines
9. Inadequate Use of Medicaments (Benzodiazepines) in Numbers
10. Interference with Other Medications
11. The Other Side of the Benzodiazepines
11.1. Medical Use of Benzodiazepines
11.2. Who Prescribes Benzodiazepines
11.3. Benzodiazepines Benefits
11.4. How and Why Did Benzodiazepines Start to Be Used
12. Some Efforts that Aim toward Obtaining Benzodiazepines with Less Adverse Effects in the Long-Term
13. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Benzodiazepine Name | Some Medical Use | Other Medicines Used for the Same Purpose | Advantages and Disadvantages of Benzodiazepines |
---|---|---|---|
Diazepam | Anxiety disorders, epilepsy, alcohol withdrawal symptoms (AWS), muscle spasms [67] | Fluoxetina (Prozac, Sarafem, Fontex), Escitalopram (Lexapro), Paroxetina (Paxil) (selective serotonin reuptake inhibitors) [67] | The clinical efficacy of Diazepam is recognized because it rapidly reaches its potency of action, by its safety, and high bioavailability. Among its disadvantages is that it can cause urinary retention and compartment syndrome [68] |
Lorazepam | Treatment of alcohol withdrawal symptoms (AWS) [69], treatment of catatonia [70] | Benzodiazepines are the standard although other alternative agents as phenobarbital also are used frequently for the treatment of AWS [71,72], whereas for catatonia, electroconvulsive therapy is usually used [73] | Lorazepam is attractive for treatment of AWS because it is likely to accumulate in liver less than other substances [69]. For the treatment of catatonia, Lorazepam is considered safe and effective (recovery rates >80%). Independent of the blood concentration, the lorazepam can cause significant impairment of driving and psychomotor abilities [68] |
Alprazolam | Treatment of panic disorder (PD), agoraphobia [74], and depression [75]. In addition, it is used as an anxiolytic agent | For PD, fluoxetine and escitalopram (selective serotonin reuptake inhibitors) are also used [76]. For agoraphobia, the treatment with paroxetine, sertraline, citalopram, escitalopram, and clomipramine showed good results [77] | Alprazolam is a high potency BDZ and, due to its effectiveness, it is the most widely used in the pharmacological treatment of panic disorders [76]. It has a recognized efficacy for the treatment of agoraphobia [78]. Its disadvantages include sedation, withdrawal symptoms, and abuse [79] |
Clobazam | It is used as anxiolytic, anticonvulsant and antiepileptic agent [80] | In the treatment of seizures valproic acid, lamotrigine, and topiramate, among others, are used [81] | Clobazam has shown great efficacy and high safety in the treatment of refractory epilepsy in both children and adults; in general, it has shown great benefits for epileptic patients [82]. Moreover, Clobazam (1,5-benzodiazepine) exhibits a better pharmacological profile in both short and long-term seizures treatments than 1,4-benzodiazepine [83]. One case of photo-induced toxic epidermal necrolysis caused by clobazam was reported [84] |
Clonazepam | Treatment of schistosomiasis, a disease considered to be a serious public health problem [85] | Praziquantel can also be used to treat schistosomiasis, although its use can cause resistance to parasites [85] | Methyl-clonazepam has a schistosomicidal effect in humans and could be an alternative to Praziquantel [85], but it can cause adverse effects on the central nervous systems derived from differences in Clonazepam metabolism [86]. Among the adverse effects is that it can cause drowsiness [87] |
Bromazepam | Bromazepam is a BDZ used clinically as anxiolytic [88,89,90] | Dexmedetomidine is a pharmacological option as an anxiolytic to bromazepam [91] | Studies on psychiatric patients suggest that it is better as anxiolytic than diazepam and lorazepam [88]. In addition, it does not produce negative effects on cognitive and motor response [92,93]. Its main point again is that it produces dependency [94] |
Midazolam | Midazolam is used for the treatment of the epileptic state [95] and as a sedative [96] | For the treatment of epilepsy, Sodium Valproate, Cannabidiol, Ethosuximide, Lamotrigine, among others, can also be used [97] | The use of Midazolam for the treatment of epilepsy is associated with a shorter seizure duration [95]. Some adverse effects of intranasal medication are nasal burning and bitter taste [98] |
Flunitrazepam | The use of Flunitrazepam is licensed in Europe, Asia, and Latin America for the treatment of insomnia, as pre-anesthetic and as sedative-hypnotic agent. Nevertheless, its use has not been approved in the U.S. [98] | Other drugs used as hypnotic-sedatives are Barbiturates, Diphenhydramine and receptor agonists such as Zopiclone, Zolpidem, Zaleplon, and Eszopiclone [99] | Flunitrazepam has no advantages over other BDZs. However, it is very popular among alcohol and drug abusers and it may produce violent behaviors [100] including being implicated in sexual assault [101] |
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Sanabria, E.; Cuenca, R.E.; Esteso, M.Á.; Maldonado, M. Benzodiazepines: Their Use either as Essential Medicines or as Toxics Substances. Toxics 2021, 9, 25. https://doi.org/10.3390/toxics9020025
Sanabria E, Cuenca RE, Esteso MÁ, Maldonado M. Benzodiazepines: Their Use either as Essential Medicines or as Toxics Substances. Toxics. 2021; 9(2):25. https://doi.org/10.3390/toxics9020025
Chicago/Turabian StyleSanabria, Edilma, Ronald Edgardo Cuenca, Miguel Ángel Esteso, and Mauricio Maldonado. 2021. "Benzodiazepines: Their Use either as Essential Medicines or as Toxics Substances" Toxics 9, no. 2: 25. https://doi.org/10.3390/toxics9020025