Nurse Martha is teaching her students about anxiety medications; she explains that benzodiazepines affect which brain chemical?
A. Acetylcholine
B. Gamma-aminobutyric acid (GABA)
C. Norepinephrine
D. Serotonin
Correct Answer: B. Gamma-aminobutyric acid (GABA)
Anti Anxiety medications stimulate the neurotransmitter GABA, which is a chemical associated with relaxation. The other options are not affected by benzodiazepines. Benzodiazepines are a class of drugs that act upon benzodiazepine receptors (BZ-R) in the central nervous system (CNS). The receptor is a protein composed of five transmembrane subunits that form a chloride channel in the center, i.e., GABA-A receptor. The five subunits consist of two alpha, two beta, and one gamma subunit. The extracellular portions of the alpha and beta subunit proteins form a receptor site for gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter.
Option A: The extracellular portions of the alpha and gamma subunit proteins form a binding site for benzodiazepines. Activation of the BZ-R causes a conformational change to a central pore, which allows the entrance of chloride ions into the neuron. The influx of the chloride anion hyperpolarizes the neuron, resulting in the decreased firing of action potentials of that neuron.
Option C: Flumazenil is a GABA-A receptor antagonist, acting to reverse the sedative effects of benzodiazepines. Flumazenil functions through competitive inhibition of the alpha-gamma subunit of the GABA-A receptor. Administration of flumazenil should be carried out judiciously, as it may precipitate withdrawal seizures. Of note, one multi-center trial found that patients with excessive benzodiazepine ingestion could become “re-sedated” after flumazenil began to wear off.
Option D: Benzodiazepine administration can be performed by providing small doses of the medication until the desired effect (i.e., sedation, cessation of seizure activity, anxiolysis) has been achieved. It should be noted that with intravenous administration, it may take 3 to 5 minutes to achieve a CNS drug concentration adequate to produce the desired effect. Therefore, the adequate time between doses should be allowed to prevent oversedation of the patient.