Page 474 - Clinical Application of Mechanical Ventilation

440 Chapter 13

Sedatives and Antianxiety Agents
(Benzodiazepines)

Benzodiazepines are given to patients to reduce anxiety, provide amnesia, and improve
benzodiazepines: A group of
drugs with strong hypnotic and tolerance of mechanical ventilation. In addition, they facilitate invasive procedures (e.g.,
sedative actions; used mainly bronchoscopy, intravenous access, suctioning), decrease oxygen consumption, and pro-
to reduce anxiety and to induce
sleep. tect the patient from self-injury.
Mechanism of Action. Binding receptors for benzodiazepines have been identified
in the limbic, thalamic, and hypothalamic levels of the central nervous system
(Mohler et al., 1977). These receptor sites appear to be involved in a large molecular
complex that includes gamma-aminobutyric acid (GABA) receptors and GABA-
gamma-aminobutyric acid regulated chloride ion channels (Figure 13-7).
(GABA): A major central nervous
system inhibitory transmitter that GABA Mechanism. GABA is a major central nervous system inhibitory transmit-
regulates the chloride ion channel
and hyperpolarizes the neurons. ter that opens chloride ion channels. Once hyperpolarized by the GABA action,
Once the neurons are hyperpolarized
and become resistant to repeated the neurons become more resistant to repeated depolarization and sedation results
depolarization, sedation results. (Mohler et al., 1988). Benzodiazepines facilitate the action of GABA, thus produc-
ing clinical sedation, anxiolysis, anticonvulsant effects, amnesia, slowing of reac-
anxiolysis: Diminishing anxiety. tion time, visual accommodation difficulties, and ataxia.

Absorption. Benzodiazepines are normally well absorbed in the gastrointestinal (GI)
Benzodiazepines are tract. In unstable patients, GI tract absorption may be unreliable, and parenteral
normally well absorbed in administration is preferred. Lorazepam and midazolam are rapidly and completely
the gastrointestinal (GI) tract.
In unstable patients, GI tract absorbed intramuscularly, whereas the absorption of chlordiazepoxide and diaz-
absorption may be unreliable, epam is slow and erratic (McEvoy, 1995). Because of the slower onset of action and
and parenteral administration
is preferred. pain associated with intramuscular administration, the intravenous route is pre-
ferred in the critically ill. The lipid solubility of the drugs allows rapid distribution
across the blood-brain barrier with midazolam being the most lipophilic, followed
by diazepam and chlordiazepoxide, and then lorazepam (McEvoy, 1995).

Chloride Channel GABA Receptor
(Picrotoxin Receptor)

Benzodiazepine
Receptor

© Cengage Learning 2014

Barbiturate
Receptor
Figure 13-7 Gamma-aminobutyric acid (GABA) receptor complex. GABA is the most com-
mon inhibitory neurotransmitter in the central nervous system (CNS). Activation of the postsynap-
tic GABA receptor increases chloride conductance through the ion channel thus hyperpolarizing
it and inhibiting the postsynaptic neuron. Once the postsynaptic neurons are inhibited, depres-
sion of the CNS and neuromuscular blockade results.

Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s).
Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.