Benzodiazepine (BZD) withdrawal: clinical findings and complications
Abrupt cessation of chronic ingestion of BZDs
Administration of BZD antagonist (flumazenil) on patients who have developed -* tolerance/dependence to BZD
Withdrawal Seizure
Negative physiological reactions BZD intake inhibition a mygd to f, • of a la Withdrawal symptoms Benzodiazepine Withdrawal GABA receptor activity (less inhibition alleviated by ingesting BZD Tolerance GABA BZD intake Conformational changes in the GABA receptor 1, receptor’s Withdrawal Insomnia Pro-excitatory 4— state of excitatory neurotransmitters) 4— to the agent activity affinity for the agent
A
Activation of ACC and OFC
Feelings of fear
Activation of PAG
Behavioural response of fight or flight
Legend: Pathophysiology Mechanism
Activation of hypothalamus ‘1` Cortisol CAD, T2DM, Stroke
Sign/Symptom/Lab Finding
Activation of PBN
V
t RR, SOB, Asthma, or a sense of being smothered
Activation of LC
t Sympathetic Activity
t BP, t HR variability, tremor, and diaphoresis
Authors: Usama Malik Reviewers: Sina Marzoughi Aaron Mackie* * MD at time of publication
Notes: • The onset of withdrawal can vary according to the half-life of the BZD involved. Symptoms may be delayed up to three weeks in BZDs with long half-lives, but may appear as early as 24 to 48 hours after cessation of BZDs with short half-lives.
Abbreviations: • ACC: Anterior Cingulate Cortex • BP: Blood Pressure • CAD: Coronary Artery Disease • HR: Heart Rate • LC: Locus Coeruleus • MI: Myocardial Infarction • OFC: Orbitofrontal Cortex • PAG: Periaqueductal Gray • PBN: Parabrachial Nucleus • RR: Respiratory Rate • SOB: Shortness of Breath • T2DM: Type 2 Diabetes
I` atherosclerosis, cardiac ischemia, MI, or sudden death