Updated: 6/7/2017

Benzodiazepines

Topic
Review Topic
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Questions
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Evidence
6
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Snapshot
  • A 56-year-old man is brought to the emergency department after being found in the park in a lethargic state. The patient has a history of multiple hospital visits for pain management of acute pancreatitis. Medical history is significant for alcohol use disorder. On physical exam, the patient has slurred speech, nystagmus, and unsteady gait. Laboratory testing is significant for an elevated blood alcohol level. Urine and serum toxicology is negative for illicit drugs. He is started on intravenous thiamine and glucose. Approximately 6 hours after admission the patient becomes nauseous, anxious, tremulous, and develops palpitations. He is subsequently started on intravenous lorazepam. (Alcohol withdrawal)
Introduction
  • Medications
    • short-acting benzodiazepines
      • alprazolam
      • triazolam
      • oxazepam
      • midazolam
    • longer-acting benzodiazepines
      • flurazepam
      • chlordiazepoxide
      • lorazepam
      • diazepam
  • Mechanism of action
    • ↑ the frequency of Cl- channel opening and thus facilitating GABAA action
      • via its binding to the α and γ subunit of the GABAA receptor
        • this in turn ↓ neuron firing
  • Metabolism
    • oxazepam, temazepam, and lorazepam
      • is not dependent on liver metabolism
  • Adverse reaction
    • dependence
    • can have an additive CNS depressive effect with other CNS depressants (e.g., alcohol and barbiturates)
    • the antidote to benzodiazepine overdose is
      • flumazenil
        • a competitive benzodiazepine receptor antagonist
  • Clinical use
    • anxiety and panic disorder
    • status epilepticus
    • alcohol withdrawal
    • anesthesia premedication
    • sleep walking and other parasomnias
    • skeletal muscle relaxation
    • insomnia
 
 

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Questions (5)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.NE.4799) A 61-year-old man presents to the emergency department due to severe malaise. He reports that he began developing tremors, irritability, and severe anxiety approximately 18 hours prior to presentation. He also states that he hears his recently deceased brother speaking to him. Within the past few hours he developed severe nausea and vomited twice. His past medical history is notable for multiple prior hospitalization for acute pancreatitis. He has a 35 pack-year smoking history and drinks multiple alcoholic beverages a day. However, the recent death of his brother motivated him to stop drinking. His temperature is 100.2°F (37.9°C), blood pressure is 150/90 mmHg, pulse is 130/min, and respirations are 22/min. On physical examination, he appears diaphoretic, anxious, and has scleral icterus. Clinical hand findings are shown (Figure A). In addition to fluid resuscitation and vitamin repletion, which of the following would be the best next step in management for this patient? Review Topic

QID: 109329
FIGURES:
1

Chlordiazepoxide

19%

(24/128)

2

Lactulose

27%

(35/128)

3

Midazolam

9%

(12/128)

4

Rifamixin

5%

(7/128)

5

Lorazepam

36%

(46/128)

M1

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PREFERRED RESPONSE 5
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(M1.NE.1) A 15-year-old male sustained a laceration to his left lower extremity (Figure A) during a football game and was stitched up by the EMT later that day. Six days later, the teenager began to experience neck rigidity, laryngospasms, dysphagia, and risus sardonicus. He was taken to the hospital where he was given treatment for an infection caused by a gram-positive, anaerobic bacili that consisted of metronidazole, immunoglobulins targeting the toxoin, and a long-acting medication that facilitates the GABA-A receptor by increasing the frequency of the chloride channel opening. Which of the following medications was he given? Review Topic

QID: 106315
FIGURES:
1

Triazolam

0%

(0/32)

2

Diazepam

84%

(27/32)

3

Oxazepam

3%

(1/32)

4

Flumazenil

3%

(1/32)

5

Midazolam

9%

(3/32)

M1

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PREFERRED RESPONSE 2
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