Diazepam: Difference between revisions

(4 intermediate revisions by the same user not shown)

Line 1:

{{MedTemplate

| generic = Diazepam

| brand = Valium

| brand = Valium (oral, IV/IM, rectal), Diastat (rectal gel for breakthrough seizures), Valtoco (nasal spray for breakthrough seizures), Libervant (buccal film)

| structure =

| classes = Benzodiazepine, Anxiolytic

| classes = [[:Category:Benzodiazepines|Benzodiazepine (long-acting)]], [[:Category:Anxiolytics|Anxiolytic]], [[:Category:Anticonvulsants|Anticonvulsant]], [[:Category:Skeletal muscle relaxants|Skeletal muscle relaxant]], [[:Category:Schedule IV controlled substances|Schedule IV controlled substance]]

| ~~mechanism = GABAA positive allosteric modulator~~

| uses = <vote slug="anxiety-disorders-broad-use">Anxiety disorders (FDA)</vote>, <vote slug="alcohol-withdrawal-use">Alcohol withdrawal (FDA; the classic indication for long-acting benzodiazepines)</vote>, <vote slug="preoperative-sedation-use">Preoperative sedation (FDA)</vote>, <vote slug="status-epilepticus-use">Status epilepticus (FDA, IV)</vote>, <vote slug="breakthrough-seizures-use">Breakthrough seizures (FDA, Diastat rectal gel; Valtoco intranasal)</vote>, <vote slug="acute-muscle-spasm-use">Acute muscle spasm (FDA, IV/IM)</vote>, <vote slug="cerebral-palsy-spasticity-use">Cerebral palsy spasticity (FDA)</vote>

| uses =

| starting_dose = Anxiety: 2-10 mg PO 2-4 times daily. Alcohol withdrawal: 10-20 mg PO/IV every 4-6 hours, symptom-triggered. Status epilepticus: 5-10 mg IV. Breakthrough seizures: Diastat rectal 0.2-0.5 mg/kg or Valtoco intranasal 5-20 mg

| starting_dose =

| preparations = Tablets 2, 5, 10 mg; oral solution 1, 5 mg/mL; injection 5 mg/mL; Diastat rectal gel 2.5, 5, 10, 20 mg; Valtoco nasal spray 5, 7.5, 10 mg/dose; Libervant buccal film

| preparations =

| fda_max = 40 mg/day (oral, anxiety)

| fda_max =

| pill_id =

| routes =

| routes = Oral, IV, IM, rectal, intranasal, buccal

| onset =

| onset = 15-60 minutes (oral); 1-5 minutes (IV); 4-10 minutes (rectal or intranasal)

| duration =

| duration = 6-24 hours (parent); much longer when accounting for the long-lived active metabolites

| halflife =

| halflife = Diazepam 20-50 hours; '''N-desmethyldiazepam (nordazepam) 30-200 hours''' is the major active metabolite and accumulates substantially with chronic dosing<ref name="valium-label">FDA Prescribing Information, Valium (diazepam), Roche/Bausch, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/013263s094lbl.pdf</ref>

~~| bioavailability =~~

| bioavailability = ~93% (oral); ~90% (rectal)<ref name="valium-label" />

~~| pregnancy~~ =

| pregnancy = Some signal for cleft palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.{{citation needed}}

~~| legal~~ =

| legal = [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids<ref name="valium-label" />

| ~~intro =~~

| mechanism = <vote slug="diazepam-mech-claim">Classic positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and producing the full benzodiazepine effect spectrum: anxiolysis, anticonvulsant activity, skeletal muscle relaxation, and sedation. The very long elimination half-life combined with the even-longer-lived active metabolite nordazepam is the clinical signature, producing stable plasma levels with infrequent dosing.</vote> The pharmacokinetic profile produces '''self-tapering withdrawal''' as plasma levels gradually decline, the basis of diazepam's preference in alcohol withdrawal protocols. CYP3A4 and CYP2C19 substrate; CYP3A4 inhibitors substantially raise exposure<ref name="valium-label" />.

~~| pharmacokinetics~~ =

~~| pharmacodynamics~~ =

| ~~indications~~ =

| ~~dosing~~ =

| ~~effects =~~

~~| interactions~~ = ~~<pharmaInteractions~~/>

| ~~pregnancy_details =~~

~~| monitoring~~ =

~~| counseling~~ =

~~| anecdotes =~~

~~| seealso =~~

~~| references~~ =

}}

== References ==

~~[[Category:Anxiolytics & Sedative-Hypnotics]]~~

[[Category:Benzodiazepines]]

[[Category:Anxiolytics]]

[[Category:~~GABAA Positive Allosteric Modulators (General)~~]]

[[Category:Anticonvulsants]]

[[Category:~~GABAergics]]~~

[[Category:Skeletal muscle relaxants]]

~~[[Category:Anticonvulsants / Antiepileptics~~]]

[[Category:Schedule IV controlled substances]]

[[Category:~~Muscle Relaxants (CNS-acting)~~]]

MDElliottMD (talk | contribs)