Benzo Comparison Chart
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| Blank | Midazolam | Lorazepam | Diazepam | Flumazenil
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| Trade Name | Versed | Ativan | Valium | Romazicon
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| Class | BZDP: imidazole ring | BZDP | BZDP | BZDP receptor antagonist
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| IV Sedation Dose Adult | 0.05 mg/kg | 0.04 mg/kg | 0.1 mg/kg IV 0.2 mg/kg po; 15 mg max | 0.2 mg IV; repeat 0.1 mg q min up to 1 mg/hr and 3mg max
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| Potency | moderate Valium x5 | MOST Versed x5/Valium x25 | least | (blank)
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| Available Conc. | 1 mg/ml & 5 mg/ml | 2 mg/ml & 4 mg/ml | 5 mg/ml | 0.1 mg/ml
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| Acid or Base | Base | Base | Base | Base
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| pKa (ionization) | 6.15 (@7.4, > non-ionized) | 11 (@7.4 >> ionized) | 3.3 (@7.4, >> non-ionized) | (blank)
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| Solubility | H2O @ pH <4 (open) Lipid @ pH >4 (closed) | Lipid | LIPID (very) | H2O in vial; Lipid @ physiologic pH
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| Protein Binding | 94% | 98% | 90% competes w/ heparin at binding site | 50%
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| Sedative/ Hypnotic? | Sedative/Hyponotic Anxiolytic | Sedative/Hyponotic Anxiolytic | Sedative/Hyponotic Anxiolytic | REVERSES
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| Analgesia? | NO | NO | NO | NO
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| Amnesia? | YES | YES (most potent) | YES | ?Reverses? (unreliable)
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| Effect Site Equilibration (Onset) | 30-90 sec (also 1-6 min some sources) | 60-120 sec | 45-90 sec | 2 min
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| Duration | 10-30 min | 1-2 hrs; amnesia up to 6 hrs | 15-30 min | 30-60 min
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| Action at Receptor | Agonist @ GABA-Cl- influx, hyperpolarize; 2x affinity of valium | Agonist @ GABA-Cl- influx, hyperpolarize; HIGH RECEPTOR AFFINITY | Agonist @ GABA-Cl- influx, hyperpolarize | Specific BZDP Competitive Antagonist Weak Agonist, <1% VERY HIGH RECEPTOR AFFINITY
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| Saturation | Receptors saturable (ceiling effect):20%- anxiolysis, 30-50%-sedation, >60% hypnosis | Receptors saturable (ceiling effect):20%- anxiolysis, 30-50%-sedation, >60% hypnosis | Receptors saturable (ceiling effect):20%- anxiolysis, 30-50%-sedation, >60% hypnosis | (blank)
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| Ligand or 2nd msgr? | Ligand | Ligand | Ligand | Ligand
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| CNS effects | Dec CMRO2, CBF; No inc ICP but no ischemic protection; CO2-vasodilation response intact; elderly more sens. to cereb. depression | Dec CMRO2, CBF; No inc ICP but no ischemic protection; CO2-vasodilation response intact; elderly more sens. to cereb. depression | Dec CMRO2, CBF; No inc ICP but no ischemic protection; CO2-vasodilation response intact; elderly more sens. to cereb. depression | Increase in ICP secondary to less sedation, not from drug itself
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| SC-mediated skeletal muscle relaxation | Yes | Yes | Yes | (blank)
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| Burst Suppressive | NO | NO | NO | NO
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| Sz | ALL ARE ANTICONVULSANTS (slower/less potent [but more specific] than barbs): membrane stabilization (use in inadvertent IV local anesthetic); also Sz preventative | ALL ARE ANTICONVULSANTS (slower/less potent [but more specific] than barbs): membrane stabilization (use in inadvertent IV local anesthetic); also Sz preventative | ALL ARE ANTICONVULSANTS (slower/less potent [but more specific] than barbs): membrane stabilization (use in inadvertent IV local anesthetic); also Sz preventative | No effect d/t weak agonist
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| CV effects | Minimal Cardiac Effects; more effects with opiods; as induction agent, acts like pentothol (BP, HR) | LEAST Cardiac Effects | Minimal Cardiac Effects; more effects with opiods | No adverse effects Perhaps d/t weak agonist
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| Resp. Effects | Dose Depedent Depression; synergistic with opiods ANY DOSE CAN CAUSE APNEA | Dose Depedent Depression; synergistic with opiods ANY DOSE CAN CAUSE APNEA | Dose Depedent Depression; synergistic with opiods ANY DOSE CAN CAUSE APNEA | Depression not completely reversed
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| Clearance | Eliminated in Urine | Eliminated in Urine | Eliminated in Urine | Very Rapid
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| E1/2 | 2 hrs | 15 hrs | 30 hrs (directly r/t age, up to 2x) | 1 hr
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| Metabolism Type | Hydroxylation and Conjugation | Hydroxylation and Conjugation | Hydroxylation and Conjugation | (blank)
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| Metabolism | No change for age/liver dx; CCB, E-mycin, **Fentanyl** interfere | No change for age; Prolonged for liver failure | Prolonged for age (2x)/ liver dx (5X); Cimetidine interferes | No change for age/liver dx
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| Metabolites | 2 Active: clinically irrelevant unless extreme renal failure (1- & 4-hydroxymidazolam) | (inactive) | 2 Active: Desmethyldiazepam (2x t1/2) Oxazepam (Serax) | (inactive)
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| (blank) | Midazolam | Lorazepam | Diazepam | Flumazenil
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| Enzyme Induction (ETOH is enzyme inducer!!) | CYP450: inducer - rapid metabolism competitor - slower metabolism | CYP450: inducer - rapid metabolism competitor - slower metabolism | CYP450: inducer - rapid metabolism competitor - slower metabolism | (blank)
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| IV Induction/ Infusion | 0.1-0.2 mg/kg, then 0.25-1 mcg/kg/min | (blank) | (blank) | (blank)
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| Misc. Trivia | Can be used for induction - not very smooth; takes longer to induce & emerge than STP; Little PONV/ emergence excitement; No delay in d/c times; Decrease dose for opioids, MAC, elderly, other CNS depressant; doesn't accum as much as Fent/ST | Very thick solution; Limits emergence delirium from Ketamine | Thick solution (organic sol); painful injection; less pain, thrombophlebitis w/ soy formulation; AVIOD IM inj; dec albumin may inc onset and effects @ start; 90-100% bioavailable; USE: evening preop sedation; skeletal musc rela | May need more before BZDPs wear off; requires continuous monitoring
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| Dose Adjust | Peds: 0.2 mg/kg IN or 0.5 mg/kg po onset 10-15 min | Decrease in elderly | Decrease in elderly | (blank)
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