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Chapter 183: Benzodiazepines

Dan Quan

INTRODUCTION

Benzodiazepines, to varying degrees, have in common six major pharmacologic effects: sedative, hypnotic, anxiolytic, amnestic, anticonvulsant, and muscle relaxant.1 Benzodiazepines are commonly used for the short-term treatment of anxiety, insomnia, seizures, and withdrawal from alcohol or sedative-hypnotic agents.2-5 The long-term benefits of benzodiazepines for psychiatric disorders are controversial.6,7 Midazolam, a benzodiazepine with a short duration of action, is also used for procedural sedation and general anesthesia (Table 183-1).

TABLE 183-1Benzodiazepines
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TABLE 183-1 Benzodiazepines
Generic Name Time to Peak Effect (hours)† Elimination Half-Life (hours)‡ Duration of Action (hours) Active Metabolite Half-Life (hours) Oral Dose Equivalents in Milligrams to Diazepam 10 Milligrams
Short Acting
Alprazolam* 1–2 6–12 4-7 No 0.5
Midazolam*

IV 1–2 min

IM 10–15 min

PO 0.5–1

 3–6

IV 2

IM 4–6

PO 4–6

 Yes 5
Oxazepam* 0.3–0.5 5–10 3–6 No 20
Tetrazepam 1–3 15 6–8 No 50–100
Triazolam* 0.25–0.5 2–5 6–7 No 0.25–0.50
Intermediate Acting
Bromazepam 1–3 10–20 <12 Yes 5–6
Cinolazepam 0.5–2 9 9 No 40
Estazolam* 1 10–24 <12 No 1–2
Flunitrazepam 0.25–0.3 18–24 4–6 Yes (36–200) 1
Loprazolam 0.5–4 6–12 <12 No 1–2
Lorazepam*

IV 5–20 min

IM 20–30 min

PO 0.5–1

 9–16 6–8 No 1
Lormetazepam 0.5–2 10–12 <12 No 1–2
Nimetazepam 0.25–0.5 14–30 <12 No 5
Nitrazepam 0.5–5 16–48 <12 No 10
Premazepam 2 10–13 <12 No 3.75
Temazepam* 1.5 9–12 5–20 No 20
Long Acting
Chlordiazepoxide* 2 5–30 5–30 Yes (36–200) 25
Clonazepam* 0.3–0.5 20–80 <12 No 0.5
Clorazepate* 1–2 48 8–24 Yes (36–200) 15
Cloxazolam 2–5 65 18–50 No 1–2
Diazepam*

IV 1–5 min

PO 15–45 min

PR 5–45 min

 20–50

IV 0.25–1

PO 12–24

 Yes (36–200) 10
Flurazepam* 0.5–1 2 12 Yes (50–100) 15–30
Flutoprazepam 0.5–2 60–90 24 Yes 2–3
Halazepam 1–3 — 12–24 Yes (30–100) 20–40
Ketazolam 2.5–3 30–100 12–24 Yes (36–200) 15–30
Medazepam — 36–150 10–12 Yes (36–200) 10
Nordazepam 2 40–50 12–14 Yes (50–120) 10
Phenazepam 1.5–4 60 12 Yes 1
Pinazepam 1–2 20–25 12–24 Yes (40–100) 20
Prazepam 2–6 40–80 12–24 Yes (36–200) 10–20
Quazepam* 0.5–2 27–41 12–24 Yes (28–80) 20

*Available in the United States.

†After oral ingestion, unless otherwise specified.

‡Parent compound.

Isolated benzodiazepine overdose has low mortality, and death is rare.8 However, increased rates of morbidity do result from mixed overdose, especially in combination with opioids. Isolated overdose with high-potency short-acting agents, such as alprazolam, temazepam, and triazolam, is associated with higher incidences of intensive care unit admissions, coma, and mechanical ventilation with toxicity compared to other benzodiazepines, such as diazepam.9 A review of suicide by self-poisoning found that temazepam was 10 times more toxic (fatal toxicity index) and 13 times more lethal (case fatality index) than diazepam.10 In the ED, parenteral administration of benzodiazepines may result in significant complications, particularly respiratory depression and hypotension, especially when combined with opioids or other sedatives.

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