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Benzodiazepine Allergy With Anesthesia Administration: A Review of Current Literature
Elliot HaybargerDMD,
Andrew S. YoungDDS, and
Joseph A. Giovannitti JrDMD
Article Category: Research Article
Volume/Issue: Volume 63: Issue 3
Online Publication Date: Jan 01, 2016
DOI: 10.2344/16-00019.1
Page Range: 160 – 167

Serious complications during surgery have been shown to occur rather infrequently (0.4% of 83,844 cases), but anesthesia-related complications contribute to more than one third of these events. 1 Allergic reactions to medications are among the major factors affecting morbidity and mortality peri- and postoperatively. 1 , 2 The relative allergenicity of benzodiazepines, arguably the most commonly used anxiolytic premedication and a cornerstone in moderate to deep sedation, is explored in an attempt to quantify its allergic history

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Independent Predictors of Delay in Emergence From General Anesthesia
Shigeru MaedaDDS, PhD,
Yumiko TomoyasuDDS, PhD,
Hitoshi HiguchiDDS, PhD,
Minako Ishii-MaruhamaDDS, PhD,
Masahiko EgusaDDS, PhD, and
Takuya MiyawakiDDS, PhD
Article Category: Other
Volume/Issue: Volume 62: Issue 1
Online Publication Date: Jan 01, 2015
DOI: 10.2344/0003-3006-62.1.8
Page Range: 8 – 13

Ambulatory general anesthesia is useful for dental treatment of patients with severe intellectual disabilities because it is hard for them to cooperate with dental treatment and to stay in the hospital. 1 – 3 Because controlling the recovery state is important in managing ambulatory general anesthesia, we perform total intravenous anesthesia consisting mainly of propofol and remifentanil, which allows a quick and comfortable recovery. 4 – 7 Midazolam, a short-acting benzodiazepine injection, was shown to be a clear determinant of delayed

Figure 2.; Dose-response curve for benzodiazepines.
Mark Donaldson,
Gino Gizzarelli, and
Brian Chanpong
Figure 2.
Figure 2.

Dose-response curve for benzodiazepines.

A Review of Current Oral Sedation Agents for Pediatric Dentistry
Regina A. E. DowdyDDS, MS,
Sarah ForgyDDS,
Oussama HefnawiDDS, and
Tiffany A. NeimarDDS
Article Category: Other
Volume/Issue: Volume 70: Issue 3
Online Publication Date: Oct 18, 2023
DOI: 10.2344/anpr-268717
Page Range: 142 – 153

alcohol dehydrogenase in the liver and converted to trichloroethanol, which is the active drug form with similar effects to ethanol. Although not explicitly clear, it is presumed that chloral hydrate exerts its effects via positive allosteric modulation involving GABA A receptors much like barbiturates and benzodiazepines. 1 , 2 The onset of action typically occurs within 30 to 60 minutes. The duration of action of chloral hydrate approximates 4 to 8 hours, with trichloroethanol having a beta/elimination half-life of approximately 8 to 11 hours. 3 , 4 Chloral

Figure 3.; Biotransformation of various benzodiazepines. Parent drugs and their active metabolites vary in their elimination half-lives: L, >24 hours; I, 6–24 hours; and S, <6 hours (derived from Mihic and Harris7).
Daniel E. Becker
Figure 3.
Figure 3.

Biotransformation of various benzodiazepines. Parent drugs and their active metabolites vary in their elimination half-lives: L, >24 hours; I, 6–24 hours; and S, <6 hours (derived from Mihic and Harris7).

Figure 1.  ; Schematic of GABAA receptor depicting competitive antagonism between flumazenil and midazolam at the benzodiazepine (BZD) binding site. Flumazenil acts as a negative allosteric modulator of GABA by facilitating closure of the chloride ion (Cl−) channel and preventing the influx of Cl− ions.
Michelle Wong
<bold>Figure 1. </bold>
Figure 1. 

Schematic of GABAA receptor depicting competitive antagonism between flumazenil and midazolam at the benzodiazepine (BZD) binding site. Flumazenil acts as a negative allosteric modulator of GABA by facilitating closure of the chloride ion (Cl−) channel and preventing the influx of Cl− ions.

Figure 2.; The GABAA receptor complex. The GABAA receptor complex consists of several protein subunits, with each comprised further of subunit families. These subunits provide myriad sites or receptors at which drugs may bind. While GABA and its precise receptor is the normal “commander” of the chloride channel, benzodiazepines can potentiate its influence. Additional drugs such as propofol and barbiturates not only potentiate the influence of GABA but are able to open the channel directly.
Daniel E. Becker
Figure 2.
Figure 2.

The GABAA receptor complex. The GABAA receptor complex consists of several protein subunits, with each comprised further of subunit families. These subunits provide myriad sites or receptors at which drugs may bind. While GABA and its precise receptor is the normal “commander” of the chloride channel, benzodiazepines can potentiate its influence. Additional drugs such as propofol and barbiturates not only potentiate the influence of GABA but are able to open the channel directly.

Figure 3.; Mechanism of N2O-induced anxiolysis. N2O is thought to cause activation of the benzodiazepine (BZ) binding site as its effects are blocked by flumazenil. This action facilitates γ-aminobutyric acid (GABA) activation of its binding site, resulting in chloride ion influx. The increased chloride ion concentration in the neuron might cause activation of calmodulin (CaM), which then activates the enzyme nitric oxide synthase (NOS). NOS converts the amino acid L-arginine (L-Arg) to L-citrulline (L-Cit) and NO, which stimulates the enzyme soluble guanylyl cyclase producing the second messenger cyclic guanosine monophosphate (cyclic GMP). The cyclic GMP, in turn, stimulates a cyclic GMP-dependent protein kinase (PKG) that leads to the anxiolytic drug effect.
Dimitris E. Emmanouil and
Raymond M. Quock
Figure 3.
Figure 3.

Mechanism of N2O-induced anxiolysis. N2O is thought to cause activation of the benzodiazepine (BZ) binding site as its effects are blocked by flumazenil. This action facilitates γ-aminobutyric acid (GABA) activation of its binding site, resulting in chloride ion influx. The increased chloride ion concentration in the neuron might cause activation of calmodulin (CaM), which then activates the enzyme nitric oxide synthase (NOS). NOS converts the amino acid L-arginine (L-Arg) to L-citrulline (L-Cit) and NO, which stimulates the enzyme soluble guanylyl cyclase producing the second messenger cyclic guanosine monophosphate (cyclic GMP). The cyclic GMP, in turn, stimulates a cyclic GMP-dependent protein kinase (PKG) that leads to the anxiolytic drug effect.

Effect of Flumazenil on Disturbance of Equilibrium Function Induced by Midazolam
S. MaedaDDS, PhD,
T. MiyawakiDDS, PhD,
H. HiguchiDDS, PhD, and
M. ShimadaDDS, PhD
Article Category: Research Article
Volume/Issue: Volume 55: Issue 3
Online Publication Date: Jan 01, 2008
DOI: 10.2344/0003-3006-55.3.73
Page Range: 73 – 77

Sedation and general anesthesia are often used for oral surgery as well as dental treatments in patients with intellectual disability or dental phobia. 1 – 3 In intravenous sedation, benzodiazepine injection is useful owing to its outstanding amnesic effect. Propofol has become a major anesthetic drug for intravenous sedation as well as general anesthesia in the last decade because of its short half-life. However, the amnesic effect of propofol is considered weaker than that of benzodiazepines, and vessel pain occurs when it is administered

Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications
Joseph A. Giovannitti JrDMD,
Sean M. ThomsDMD, MS, and
James J. CrawfordDMD
Article Category: Other
Volume/Issue: Volume 62: Issue 1
Online Publication Date: Jan 01, 2015
DOI: 10.2344/0003-3006-62.1.31
Page Range: 31 – 38

attention-deficit/hyperactivity disorder. 18 Clonidine is also useful in the treatment of chronic pain disorders and opiate, benzodiazepine, alcohol, cocaine, food, and tobacco withdrawal. TIZANIDINE Tizanidine is another α-2 agonist, similar to clonidine, but with some important differences. Like clonidine, it has sedative, anxiolytic, and analgesic properties, but it has a shorter duration of action and less effect on heart rate and blood pressure. In a study of 70 patients undergoing general anesthesia, Tabori et al 19 evaluated the effect