Chlordiazepoxide; Indications/Uses, Dosage, Side Effects, Interactions, Pregnancy

Chlordiazepoxide








User Review


5
(4 votes)


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.

or

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
  • Depression
  • 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

Dosage of Chlordiazepoxide

Strengths: 5 mg; 10 mg; 25 mg; 100 mg

Anxiety

  • 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

Light Sedation

  • 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

Alcohol Withdrawal

  • 50 to 100 mg orally, followed by repeated doses as needed until agitation is controlled
  • Maximum dose: 300 mg orally per day.

Pediatric Anxiety

  • 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

More common

Rare

Drug Interactions

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)

Pregnancy Catagory of Chlordiazepoxide

FDA Pregnancy Category D

Pregnancy

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.

Lactation

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.

References

  1. https://www.drugs.com/cdi/chlordiazepoxide.html
  2. https://www.webmd.com/drugs/2/drug-32651/chlordiazepoxide-oral/details/list-contraindications
  3. https://pubchem.ncbi.nlm.nih.gov

Chlordiazepoxide

 

Print Friendly, PDF & Email

Sharing to Spread to the World

Leave a Reply

Your email address will not be published.