From the Guidelines
Benzodiazepines enter the central nervous system (CNS) through a multi-step process that begins with absorption into the bloodstream, and their path of physiology is primarily characterized by their ability to cross the blood-brain barrier and bind to GABA-A receptors, as described in the most recent study 1.
Key Steps in the Path of Physiology
- Absorption into the bloodstream: Benzodiazepines are lipophilic drugs that are absorbed from the gastrointestinal tract and enter the systemic circulation.
- Crossing the blood-brain barrier: The lipid solubility of benzodiazepines allows them to readily cross the blood-brain barrier (BBB), which is the protective membrane separating the brain from circulating blood.
- Binding to GABA-A receptors: Once inside the CNS, benzodiazepines bind to specific receptor sites on the GABA-A receptor complex, enhancing the inhibitory effects of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain.
Factors Influencing the Path of Physiology
- Lipid solubility: More lipophilic benzodiazepines like diazepam cross the BBB more rapidly than less lipophilic ones such as lorazepam, as noted in 1.
- Age and hepatic function: Elderly patients and those with hepatic dysfunction may experience reduced clearance of benzodiazepines, leading to increased sensitivity and potential for adverse effects, as described in 1 and 1.
- Concurrent medication use: The use of benzodiazepines with other CNS depressants, such as opioids, can increase the risk of respiratory depression and other adverse effects, as highlighted in 1 and 1.
Clinical Implications
- The use of benzodiazepines should be carefully considered and monitored, particularly in vulnerable populations such as the elderly and those with hepatic dysfunction, to minimize the risk of adverse effects and optimize therapeutic outcomes, as emphasized in 1.
- The selection of a specific benzodiazepine should take into account its lipid solubility, potency, and potential for adverse effects, as well as the individual patient's medical history and concurrent medication use, as discussed in 1 and 1.
From the FDA Drug Label
CLINICAL PHARMACOLOGY Diazepam is a benzodiazepine that exerts anxiolytic, sedative, muscle-relaxant, anticonvulsant and amnestic effects. Most of these effects are thought to result from a facilitation of the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system
Diazepam and its metabolites cross the blood-brain and placental barriers
CLINICAL PHARMACOLOGY Pharmacodynamics CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system.
The path of physiology of benzodiazepines into the Central Nervous System (CNS) is as follows:
- Benzodiazepines, such as diazepam and alprazolam, cross the blood-brain barrier and bind to specific receptors in the CNS.
- They facilitate the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, to exert their effects.
- The exact mechanism of action is unknown, but it is thought to involve binding to stereo specific receptors at several sites within the CNS.
- The effects of benzodiazepines on the CNS include anxiolytic, sedative, muscle-relaxant, anticonvulsant, and amnestic effects 2, 3.
From the Research
Path of Physiology of Benzodiazepines into the Central Nervous System (CNS)
The path of physiology of benzodiazepines into the CNS involves several key steps:
- Benzodiazepines quickly diffuse through the blood-brain barrier to affect the inhibitory neurotransmitter GABA, as stated in 4
- They act through allosteric modulation of the GABAA receptor to enhance the activity of GABA, resulting in a slowing of neurotransmission and sedative and anxiolytic effects, as mentioned in 5
- The actions of benzodiazepines are due to the potentiation of the neural inhibition that is mediated by gamma-aminobutyric acid (GABA), as noted in 6
- Practically all effects of the benzodiazepines result from their actions on the ionotropic GABA(A) receptors in the central nervous system, as stated in 6
Mechanism of Action
The mechanism of action of benzodiazepines involves:
- Increasing the conductance of chloride through ionic channels, promoting a state of central nervous system depression, as mentioned in 7
- Binding to specific sites on GABA-A receptors, classified as short, intermediate, or long-acting, as noted in 8
- Interacting with multiple receptors, including dopamine, adrenoreceptor, histamine, muscarinic, and serotonin receptors, as discussed in 8
Effects on the CNS
The effects of benzodiazepines on the CNS include:
- Sedation, hypnosis, decreased anxiety, anterograde amnesia, centrally mediated muscle relaxation, and anti-convulsant activity, as listed in 6
- A slowing of neurotransmission and sedative and anxiolytic effects, as mentioned in 5
- A dose-dependent ventilatory depressant effect, as well as a modest reduction in arterial blood pressure and an increase in heart rate, as noted in 6