Flumazenil DOA? Metabolism?
30-60 min, meaning you may need to redose
Hepatic metabolism, renal excretion
Why is there a ceiling effect with benzos?
Because all it can do is assist GABA to open the Cl- channels. After that, it can't do anything else to achieve any effects.
Midazolam CV effects?
Dec SVR at induction dosage
Dec BP from anxiolysis
Doesn't attenuate laryngoscopy HR/BP changes
- Facilitate action of GABA and GABA-A receptor, enhance affinity of GABA to the receptor (but DOES NOT activate GABA-A receptor)
- This leads to Cl channels open, inc conductance, hyperpolarization of post-synaptic membrane, increased resistance of post-synaptic membrane to excitation
Diazepam is ≈ day (20-50h)
Desmethyldiazepam is 2-4 days!
Flumazenil (romazicon) dose?
(what about infusion?)
0.2 mg IV, wait 2 min,
0.1 mg IV subsequent doses at 60 sec intervals to
max total 3 mg
Infusion: 0.1-0.4 mg/h
Which benzodiazepine is most potent?
Lorazepam (ativan) It is 5-10x more potent than diazepam
Structure of midazolam (versed)?
Water soluble preparation
(same compound that etomidate has)
Extensive hepatic metabolism
ACTIVE METABOLITE: 1-hydroxy-midazolam
Conjugated and excreted in the urine
Renal failure doesn't effect VD, E1/2t, or clearance
Oxidation, n-demethylation to desmethyldiazepam (ACTIVE METABOLITE)
which is oxidized, conjugated, and excreted in the urine
Dosage of midazolam for...
Premedication peds, IV sedation adults, Induction
Premed peds: 0.25-0.5 mg/kg po (not on drug cards)
Peds po dose max 20mg IV
sedation adults (premedication): 0.5-5 mg IV or 0.04-0.08 mg/kg
Induction: 0.05-0.35 mg/kg over 30-60 sec
*Per drug cards, not powerpoint
Benzos are highly _____ (water/lipid) soluble and _____ (high/low) protein binding
Flumazenil antagonizes what effects of benzos?
Antagonizes depression of ventilation and sedation
What does it mean if a drug has a short effect site equilibration time?
It means that the effects on the brain occur promptly after IV administration
Where are GABAa receptors found?
On POST-synaptic neurons in the CNS
There are barely any GABA receptors outside the CNS
What is the reversal for benzodiazepines?
Specific, competitive benzo antagonist with high affinity for benzo receptors
Do benzos potentiate the neuromuscular blockade?
Midazolam CNS effects?
Decreases CBF and CMRO2
Does NOT attenuate ICP response to laryngoscopy
Anticonvulsant and amnestic
What is flumazenil (romazicon) a derivative of?
Benzene ring fused with 7-member diazepine ring
Lorazepam metabolism and e1/2t?
Metabolites are INACTIVE
Metabolism effected by hepatic function and age E1/2t 10-20h
Slow onset, IV takes 20-30 min to peak, not used as often in OR
Do benzos induce hepatic enzymes?
Midazolam respiratory effects?
Decrease in ventilation (dose dependent)
Hypoxemia and hypoventilation enhanced in presence of opioid
Depress swallow reflex
decreased upper airway activity
Benzodiazepines 5 pharmacological effects?
Muscle Relaxation- spinal
Diazepam dosages for... premedication oral and IV; induction; anticonvulsant?
Premedication oral: 10-15mg
Premedication IV: 0.2 mg/kg (reduces MAC)
Induction: 0.5-1 mg/kg IV
Anticonvulsant: 0.1 mg/kg IV
How does potency of midazolam compare to diazepam?
Midazolam is 2-3x more potent than diazepam
What is the order of benzos from least to most potent?
Diazepam, versed, ativan
50 MCG/kg (max 4 mg) PO
1-4 mg IV
Diazepam is prepared in what solvents?
Painful IV/IM injection
GABA binds to ________
the 2 beta sites
benzos bind to the _______