![]() ![]() ![]() The exact reason for the reduced responsiveness has not been elucidated but down-regulation of the number of receptors has only been observed at some receptor locations including in the pars reticulata of the substantia nigra down-regulation of the number of receptors or internalization does not appear to be the main mechanism at other locations. What is certain is that surface GABA A receptor protein levels are altered in response to benzodiazepine exposure, as is receptor turnover rate. When potentiation is sustained by long-term use, neuroadaptations occur which result in decreased GABAergic response. Benzodiazepines potentiate the action of GABA, by binding a site between the α and γ subunits of the 5-subunit receptor thereby increasing the frequency of the GABA-gated chloride channel opening in the presence of GABA. When chloride enters the nerve cell, the cell membrane potential hyperpolarizes thereby inhibiting depolarization, or reduction in the firing rate of the post-synaptic nerve cell. ![]() GABA mediates the influx of chloride ions through ligand-gated chloride channels called GABA A receptors. Gamma-Aminobutyric acid ( GABA) is the major inhibitory neurotransmitter of the central nervous system roughly one-quarter to one-third of synapses use GABA. The neuroadaptive processes involved in tolerance, dependence, and withdrawal mechanisms implicate both the GABAergic and the glutamatergic systems. See also: Alcohol withdrawal syndrome § Kindling, and Kindling (sedative–hypnotic withdrawal) Rapid discontinuation may result in a more serious syndrome Muscular spasms, cramps, discomfort or fasciculations.Gastrointestinal disturbance (including nausea, diarrhea, vomiting).Depression (can be severe), possible suicidal ideation.Depersonalization and derealisation (feelings of unreality).Agitation and anxiety, possible terror and panic attacks.As withdrawal progresses, patients often find their physical and mental health improves with improved mood and improved cognition.Ī more complete list of possible symptoms stated in publications: Withdrawal symptoms occur during dose reduction and may include insomnia, anxiety, distress, weight loss, dizziness, night sweats, shakes, muscle twitches, aphasia, panic attacks, depression, derealization, paranoia, indigestion, diarrhea and photophobia. Withdrawal can be managed through awareness of the withdrawal reactions, individualized taper strategies according to withdrawal severity, the addition of alternative strategies such as reassurance, and referral to benzodiazepine withdrawal support groups. More serious symptoms may also occur such as mini-seizures, seizures, and suicide. Typically, benzodiazepine withdrawal is characterized by sleep disturbance, irritability, increased tension and anxiety, panic attacks, hand tremor, shaking, sweating, difficulty with concentration, confusion and cognitive difficulty, memory problems, dry retching and nausea, burning sensations and pain in the upper spine, weight loss, palpitations, headache, muscular pain and stiffness, and a host of perceptual changes. Benzodiazepine withdrawal syndrome ( BZD withdrawal) is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines as prescribed develops a physical dependence on them and then reduces the dose or stops taking them without a safe taper schedule. ![]()
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