SEARCH RESULTS FOR: Benzodiazepine

Benzodiazepine (BZD) withdrawal: clinical findings and complications

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

benzodiazepine-wirkmechanismus

Benzodiazepine: Wirkmechanismus

Status-Epilepticus

Status Epilepticus: Pathogenesis and clinical findings Authors: Katherine Liu Reviewers: Negar Tehrani Ephrem Zewdie Ran (Marissa) Zhang Carlos Camara-Lemarroy* * MD at time of publication Structural brain injury (stroke, trauma, hypoxia) Drugs that lower seizure threshold Antiseizure drug discontinuation Alcohol, barbiturate, benzodiazepine withdrawal Metabolic disturbance Infection See “Generalized Seizures” Altered excitability and communication between neuronal structures Isolated generalized seizures Ongoing seizure activity and repetitive neuronal firing Changes in receptor trafficking (seconds to minutes) Changes in neuromodulator expression in hippocampus (minutes to hours) Endocytosis of synaptic GABAA inhibitory receptors ↓ Number of inhibitory GABAA receptors Progressive resistance to benzodiazepines (drugs that upregulate GABA receptors) as seizure continues ↑ Expression of excitatory peptides (substance P, neurokinin B) Abbreviations: • GABA- γ-aminobutyric acid • NMDA- N-methyl-D-aspartic acid • AMPA- α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid NMDA and AMPA excitatory receptors mobilize to synaptic membrane ↑ Number of excitatory NMDA and AMPA receptors ↓ Expression of inhibitory peptide (dynorphin, galanin, somatostatin, neuropeptide Y) Seizure-induced failure of inhibitory mechanisms involved in seizure termination and increased neuronal excitability Status Epilepticus (SE) An abnormally prolonged seizure ≥ 5 minutes or 2+ sequential seizures without full recovery in between ↑↑ Glutamate release and activation of NMDA excitatory receptors ↑ Ca2+ entry into neurons Mitochondrial dysfunction ↑ Reactive oxygen species (nitric oxide) production Neuronal injury/death (↑ risk of developing chronic epilepsy) ↑ Autonomic activity Intense, sustained muscle contractions Persistent stimulus OR altered neuronal landscape (i.e., Immune mediated) Refractory SE: SE that does not respond to 1st or 2nd line therapy Prolonged seizures (≥30 mins) lead to failure of compensatory mechanisms Circulatory collapse ↓ Cerebral blood flow • Hypertension • Hyperglycemia • ↑ Cardiac output • ↑ Secretions • Hypotension • Hypoventilation Energy demands > ATP produced through oxidative phosphorylation Myocytes start utilizing anerobic glycolysis ↑ Lactic acid production ↑ Serum lactate Sustained muscle activity produces body heat Hyperpyrexia (axillary temperature ≥ 40° C) Myocyte injury Leakage of muscle contents into the circulation (Rhabdomyolysis) ↑ Serum creatine kinase Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 27, 2022 on www.thecalgaryguide.com

Benzodiazepine Mechanism of Action

Benzodiazepine: Mechanism of action Anesthetic composed of a fused benzene and diazepine ring that is administered orally or intravenously to produce a sedative or hypnotic effect Ex. Lorazepam, Midazolam, Diazepam Binds to Gamma- aminobutyric acid (GABAA) receptor in vascular smooth muscle and the central nervous system (CNS) APs inhibited in vascular smooth muscle Vascular smooth muscle relaxes Vasodilation ↓ Blood pressure Authors: Victoria Silva Travis Novak Reviewers: Billy Sun Mao Ding Melinda Davis* *MD at time of publication ↑ Frequency of chloride channel opening Hyperpolarization of nerve membrane Action potential (AP) inhibited APs inhibited in the medulla oblongata (the respiratory center) ↓ Respiratory drive: the body fails to ↑ depth and rate of respirations when arterial CO2 ↑ General CNS inhibition Anti-convulsion (Seizures are caused by a burst of uncontrollable, electrical activity in the brain) APs inhibited in the thalamus and hypothalamus (play a role in memory) APs inhibited in the limbic system (the behavioral and emotional response centers in the brain) Hypotension ↓ Cerebral blood flow ↓CO2 diffusion from arterial blood to alveoli ↓O2 diffusion from alveoli to arterial blood Pharyngeal muscle relaxation ↑ Arterial CO2 ↓ Arterial O2 Airway obstruction Amnesia ↑ PaCO2 ↓ PaO2 ↓ Anxiety Anxiolysis Hypercapnia Hypoxemia In high doses: Depression of arousal and loss of consciousness Induction of general anesthesia (No analgesic effect) ↓ Intracranial pressure Benzodiazepine reversal: Temporary cessation of breathing Apnea Flumazenil competitively binds to GABAA Flumazenil reverses the binding of benzodiazepine to GABAA ↓ Frequency of chloride channel opening Depolarization of nerve membrane Benzodiazepine reversal Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 09, 2018, updated April 25, 2023 on www.thecalgaryguide.com

Benzodiazepine mechanism of action

Benzodiazepines: Mechanism of action Sedative-hypnotic, anxiolytic & anti-convulsive agents composed of a fused benzene and diazepine ring that is administered orally or intravenously to produce desired effect (ie., lorazepam, midazolam, diazepam) Authors: Tracey Rice Usama Malik Amy Fowler Victoria Silva Reviewers: Sara Cho Keira Britto Luiza Radu Brienne McLane* Aaron Mackie* * MD at time of publication Benzodiazepine binds to gamma-aminobutyric acid (GABAA) receptors in vascular smooth muscle & the central nervous system (CNS) ↑ Opening of chloride channels Influx of chloride ions into the neuron Hyperpolarization of nerve membrane causing it to be more negative The cell membrane falls below the normal resting potential Medulla oblongata inhibition ↓ Respiratory drive; ↓ depth & rate of respirations Temporary cessation of breathing leads to reduced oxygen supply to the brain ↓ Level of consciousness Pharyngeal muscle relaxation leading to obstruction Hypoventilation and/or apnea General CNS inhibition ↓ Neuronal activity ↓ Electrical brain activity ↓ Seizure activity & hypnotic effect Thalamic & hypothalamic inhibition Disruption of short & long- term memory consolidation Limbic system inhibition ↓ Fear emotions (panic & phobia) Anxiolytic effect (↓ Anxiety) Smooth muscle inhibition Smooth muscles become relaxed &/or less spastic Vasodilation ↓ Preload Hypotension ↓ Cerebral blood flow Pre-syncope or syncope Anterograde amnesia ↓ Visuospatial ability, speed of processing & verbal learning Confusion ↓ Deep stage of non-REM sleep & delayed REM sleep Rapid sleep Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 21, 2024 on www.thecalgaryguide.com

Benzodiazepine

Benzodiazépine: Mécanisme d'action