Chlordiazepoxide is a long-acting benzodiazepine with anxiolytic, sedative and hypnotic activity. Chlordiazepoxide exerts its effect by binding to the benzodiazepine site at the gamma-aminobutyric acid (GABA) receptor-chloride ionophore complex in the central nervous system (CNS). This leads to an increase in the opening of chloride channels, membrane hyperpolarization and increases the inhibitory effect of GABA on the CNS.
Chlordiazepoxide is an anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawal.
Chlordiazepoxide is a sedative and hypnotic medication of the benzodiazepine class; it is used to treat anxiety, insomnia and withdrawal symptoms from alcohol and/or drug abuse. Chlordiazepoxide has a medium to long half-life but its active metabolite has a very long half-life. The drug has amnesic, anticonvulsant, anxiolytic, hypnotic, sedative and skeletal muscle relaxant properties.
Mechanism of action of Chlordiazepoxide
Chlordiazepoxide binds to stereospecific benzodiazepine (BZD) binding sites on GABA (A) receptor complexes at several sites within the central nervous system, including the limbic system and reticular formation. This results in an increased binding of the inhibitory neurotransmitter GABA to the GABA(A) receptor.BZDs, therefore, enhance GABA-mediated chloride influx through GABA receptor channels, causing membrane hyperpolarization. The net neuro-inhibitory effects result in the observed sedative, hypnotic, anxiolytic, and muscle relaxant properties.
A large body of electrophysiological and biochemical observations has linked the actions of benzodiazepines to the functions of receptor chloride ionophore systems that are regulated by gamma-aminobutyric acid. The evidence includes the ability of various benzodiazepines to potentiate the effects of exogenous gamma-aminobutyric acid or to enhance gamma-aminobutyric acid-mediated presynaptic and postsynaptic inhibitory pathways. Further, specific sites for benzodiazepines have been characterized in cell membranes from the brain, and their properties can be modified by gamma-aminobutyric acid and by chloride or related ions that are known to carry current through channels that are regulated by gamma-aminobutyric acid. Two different types of receptors for gamma-aminobutyric acid are detected in hippocampal pyramidal cells; diazepam potentiates somatic responses to gamma-aminobutyric acid that involve increases in chloride conductance. potentiation of responses to gamma-aminobutyric acid requires concentrations of benzodiazepines 10 to 100 fold greater than those achieved in the CSF during therapy. These observations suggest that the anticonvulsant effects of the benzodiazepines may not depend entirely upon actions on gamma-aminobutyric acidergic neurotransmission or on channels for chloride ions.
Indications of Chlordiazepoxide
- Alcohol Withdrawal Syndrome
- Anxiety Disorders
- Burning Mouth Syndrome
- Light Sedation
- Opiate Withdrawal
- Panic Disorder
- Tardive Dyskinesia
- Feeling Anxious
- Peptic Ulcer Disease
- Acute Anxiety
- Psychosomatic disease
- Adjuvants, Anesthesia; Anti-Anxiety Agents, Benzodiazepine; GABA Modulators; Sedatives, Nonbarbiturate
- To ease symptoms of irritable bowel syndrome combined with clidinium bromide.
- Its anticonvulsant and muscle relaxant actions are less pronounced than those of diazepam.
- Chlordiazepoxide is used for the management of agitation associated with acute alcohol withdrawal.
For the management of anxiety disorders or for the short-term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety.
Contra-Indications of Chlordiazepoxide
- Myasthenia gravis
- Acute intoxication with alcohol, narcotics, or other psychoactive substances
- Severe hypoventilation
- Acute narrow-angle glaucoma
- Severe liver deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2)
- Mental Disorder with Loss of Normal Personality & Reality
- Having Thoughts of Suicide
- Drug abuse
- Severe Chronic Obstructed Lung Disease
- Temporarily Stops Breathing While Sleeping
- Severe sleep apnea
- Hypersensitivity or allergy to any drug in the benzodiazepine class
Dosage of Chlordiazepoxide
Strengths: 5 mg; 10 mg; 25 mg; 100 mg
- Mild to moderate anxiety: 5 or 10 mg orally 3 to 4 times a day
- Severe anxiety: 20 or 25 mg orally 3 or 4 times a day
- On days preceding surgery: 5 to 10 mg orally 3 to 4 times per day
- If used as preoperative medication: 50 to 100 mg IM once 1 hour before surgery
- 50 to 100 mg orally, followed by repeated doses as needed until agitation is controlled
- Maximum dose: 300 mg orally per day.
- 6 years and older: 5 mg orally 2 to 4 times a day
- This may be increased to 10 mg orally 2 to 3 times a day
Side Effects of Chlordiazepoxide
The most common
- Difficulty with speaking
- loss of balance control
- muscle trembling, jerking, or stiffness
- Aggressive behavior
- changes in vision, including blurred vision
- difficulty concentrating
- difficulty speaking or swallowing
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- Chest pain or tightness
- dry mouth
- trembling or shaking of the hands or feet
- stomach pain or cramping
- a headache
- stomach pain;
- back pain, joint or muscle pain.
- problems with your vision (including color vision);
- sudden chest pain or trouble breathing;
- pain or swelling in one or both legs;
- a migraine headache;
- pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
- feeling like you might pass out.
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- difficulty with moving
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
- change in vision
- chest pain or tightness
- a cough
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- extra heartbeats
- a headache
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
Chlordiazepoxide may interact with the following drug, supplements, & may change the efficacy of the drug
- ACE inhibitors, Adrenergic neuron blockers, Angiotensin II receptor antagonists, Beta blockers, Calcium channel blockers, Clonidine, Diazoxide, Diuretics, Hydralazine, Methyldopa, Minoxidil, Nitrates, Sodium Nitroprusside – enhanced hypotensive effect
- Alcohol, barbiturates, opiates, antihistamines, antipsychotics – increased sedative effect in combination with benzodiazepines.
- Cimetidine – metabolism of benzodiazepines inhibited by cimetidine (increased plasma concentration)
- Disulfiram – metabolism of benzodiazepines inhibited by disulfiram (increased sedative effects)
- Fluvoxamine – plasma concentration of some benzodiazepines increased by fluvoxamine
- Levodopa – benzodiazepines possibly antagonize effects of levodopa
- Moxonidine – sedative effects possibly increased when benzodiazepines given with moxonidine
- Olanzapine – increased risk of hypotension, bradycardia and respiratory depression when parenteral benzodiazepines given with intramuscular olanzapine
- Phenytoin – benzodiazepines possibly increase or decrease the plasma concentration of phenytoin
- Rifampicin – metabolism of benzodiazepines possibly accelerated by rifampicin (reduced plasma concentration)
- Sodium oxybate – benzodiazepines enhance effects of sodium oxybate (avoid concomitant use)
FDA Pregnancy Category D
The category for chlordiazepoxide is D. However, an increased risk of malformations linked with the use of chlordiazepoxide during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided.
It is not known if chlordiazepoxide crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication.