Diazepam: Difference between revisions
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[[File:Diazepam structure.svg|Diazepam structure|thumb]] | |||
[[File:Diazepam-from-xtal-3D-balls.png|Diazepam 3D model|left|thumb]] | |||
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[[File:5mgrocheaus.jpg|5 mg Roche Diazepam|left|thumb]] | |||
[[File:Synthesis of Diazepam.jpg|Synthesis of Diazepam|thumb]] | |||
'''Diazepam''' is a widely used [[benzodiazepine]] medication, primarily prescribed as a [[sedative]], [[anxiolytic]], [[muscle relaxant]], and anticonvulsant for treating acute [[seizures]] or [[status epilepticus]]. It is available in both oral and intravenous forms, with distinct clinical applications. Oral diazepam is commonly used for managing anxiety disorders, while intravenous diazepam is reserved for emergency anticonvulsant therapy. Although generally well-tolerated, diazepam carries potential risks of dependency and withdrawal and must be used under medical supervision. Rare instances of [[cholestatic liver injury]] have been reported with oral use, but intravenous administration is not linked to liver injury. | '''Diazepam''' is a widely used [[benzodiazepine]] medication, primarily prescribed as a [[sedative]], [[anxiolytic]], [[muscle relaxant]], and anticonvulsant for treating acute [[seizures]] or [[status epilepticus]]. It is available in both oral and intravenous forms, with distinct clinical applications. Oral diazepam is commonly used for managing anxiety disorders, while intravenous diazepam is reserved for emergency anticonvulsant therapy. Although generally well-tolerated, diazepam carries potential risks of dependency and withdrawal and must be used under medical supervision. Rare instances of [[cholestatic liver injury]] have been reported with oral use, but intravenous administration is not linked to liver injury. | ||
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[[Category:21-Hydroxylase inhibitors]] | [[Category:21-Hydroxylase inhibitors]] | ||
[[Category:Anxiolytics]] | [[Category:Anxiolytics]] | ||
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[[Category:Lactams]] | [[Category:Lactams]] | ||
[[Category:TSPO ligands]] | [[Category:TSPO ligands]] | ||
Latest revision as of 18:26, 21 March 2025
Medication for anxiety, seizures, and muscle spasms
| Diazepam | |
|---|---|
| File:Diazepam structure.svg | |
| INN | |
| Drug class | Benzodiazepine |
| Routes of administration | oral, intramuscular, intravenous, rectal, nasal, buccal film |
| Pregnancy category | |
| Bioavailability | 76% (64–97%) oral, 81% (62–98%) rectal |
| Metabolism | Liver – CYP2B6 (minor route) to desmethyldiazepam, CYP2C19 (major route) to inactive metabolites, CYP3A4 (major route) to temazepam |
| Elimination half-life | |
| Excretion | Kidney |
| Legal status | Rx-only |
| CAS Number | 439-14-5 |
| PubChem | 3016 |
| DrugBank | DB00829 |
| ChemSpider | 2908 |
| KEGG | D00293 |
Diazepam is a widely used benzodiazepine medication, primarily prescribed as a sedative, anxiolytic, muscle relaxant, and anticonvulsant for treating acute seizures or status epilepticus. It is available in both oral and intravenous forms, with distinct clinical applications. Oral diazepam is commonly used for managing anxiety disorders, while intravenous diazepam is reserved for emergency anticonvulsant therapy. Although generally well-tolerated, diazepam carries potential risks of dependency and withdrawal and must be used under medical supervision. Rare instances of cholestatic liver injury have been reported with oral use, but intravenous administration is not linked to liver injury.
Mechanism of Action and Pharmacology[edit]
Diazepam exerts its effects by enhancing the activity of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS). By binding to GABA_A receptors, diazepam increases GABA-mediated synaptic transmission and induces its sedative, anxiolytic, anticonvulsant, and muscle-relaxing properties.
Anticonvulsant Effects[edit]
Diazepam's antiseizure effects are particularly valuable in managing acute seizure activity, such as status epilepticus. Its rapid action and ability to suppress the spread of seizure activity make it a preferred choice for emergency treatment. However, it is less effective for long-term seizure control compared to other benzodiazepines like clobazam, clonazepam, and clorazepate.
Pharmacokinetics[edit]
- Absorption: Diazepam is well-absorbed orally, reaching peak plasma concentrations within 1-2 hours.
- Distribution: It is highly lipophilic, allowing rapid penetration of the CNS.
- Metabolism: Metabolized in the liver by cytochrome P450 enzymes, primarily CYP3A4 and CYP2C19, into active metabolites such as desmethyldiazepam.
- Excretion: Excreted mainly via the kidneys in the form of conjugated metabolites.
Clinical Applications and Usage[edit]
FDA Approval and Indications[edit]
Diazepam was first approved by the Food and Drug Administration (FDA) in 1963 and remains widely used for various medical conditions, including:
- Anxiety disorders
- Acute muscle spasms
- Seizures, including status epilepticus
- Premedication for surgical or diagnostic procedures
- Management of alcohol withdrawal syndrome
Dosage and Administration[edit]
- For status epilepticus:
- Intravenous (IV) diazepam at 5-10 mg, repeated every 10-15 minutes if needed, up to a maximum of 30 mg.
- Premedication for anesthesia:
- Intramuscular (IM) diazepam at 10-20 mg.
Adjustments in dosage may be necessary for elderly individuals, patients with liver disease, or those taking other CNS depressants.
Safety and Monitoring[edit]
The long-term use of diazepam can lead to tolerance and dependence. Abrupt discontinuation may result in severe withdrawal symptoms, including agitation, tremors, and seizures. Tapering the dose under medical supervision is crucial to minimize withdrawal effects.
Side Effects and Drug Interactions[edit]
Side Effects[edit]
Common adverse effects of diazepam include:
- Somnolence (drowsiness)
- Confusion
- Dysarthria (difficulty speaking)
- Diplopia (double vision)
- Impaired coordination and coma in cases of overdose
In rare instances, diazepam may cause paradoxical reactions such as increased anxiety, agitation, or hallucinations.
Drug Interactions[edit]
Diazepam may interact with other medications, leading to enhanced sedation or altered drug efficacy:
- CNS depressants: Opioids, barbiturates, alcohol, and other benzodiazepines
- Enzyme inducers/inhibitors: Drugs that affect CYP3A4 activity can alter diazepam metabolism.
Patients should inform their healthcare provider of all medications, including over-the-counter and herbal products, to avoid adverse interactions.
Precautions[edit]
Diazepam should be used cautiously in:
- Elderly patients: Increased sensitivity to sedative effects
- Pregnant women: Risk of fetal benzodiazepine syndrome
- Individuals with a history of substance abuse: High risk of dependence
- Severe hepatic impairment: Risk of prolonged sedation and toxicity
Therapeutic Role and Limitations[edit]
Role in Epilepsy[edit]
Diazepam is primarily a short-term solution for acute seizure management. Chronic epilepsy is better managed with other antiepileptic drugs (AEDs) such as valproate, carbamazepine, or lamotrigine.
Psychiatric Applications[edit]
Diazepam's anxiolytic properties make it a choice for short-term management of severe anxiety. However, cognitive-behavioral therapy (CBT) is preferred for long-term anxiety management.
Limitations[edit]
Despite its effectiveness, diazepam has limitations:
- Dependency risk: Long-term use can lead to benzodiazepine dependence.
- Withdrawal challenges: Abrupt cessation can cause seizures or rebound anxiety.
- Tolerance: Over time, increasing doses may be needed to achieve the same therapeutic effect.
Future Directions[edit]
Research into GABAergic pathways and alternative benzodiazepine receptor modulators may pave the way for safer and more effective therapies.
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