Exam 1 - Benzodiazepines Flashcards
How do anesthetics mimic sleep?
- Inhibits thalmic and mid-brain RAS
- Reversibly inhibit CNS
What is important to remember about reported cases of awareness?
Important to know what anesthetic they were given (twighlight sedation?)
Many include induction and emergence as awareness
How did we come to use EEG to determine anesthetic depth?
- EEG activity is related to CBF and CMRO2
- Anesthetics alter CBF and CMRO2
Therefore we can use EEG to estimate anesthetic depth
What drugs can decrease BIS?
Synergistic anesthetics like hypnotics, volatiles, NMB, opiods
What range of BIS prevents recall?
40-60
What should the EMG be on a paralyzed patient?
0
What is the supression ratio?
What should it be?
- Measures how often the patient’s BIS hit 0
- Should never have a number here or your anestheic is way too deep
How do sympathomimetics and sympatholytics affect the BIS?
- Sympathomimetics: may have a ↑ BIS due to ↑ catecholamines, but are still amnestic (ketamine)
- Sympatholytics: BIS may be lower due to decreased SNS activity, despite having actually being more aware
What are the 5 effects of benzodiazepines?
- Anxiolysis
- Sedation
- Anterograde amnesia (lasts longer than sedation)
- Anticonvulsant
- Spinal cord mediated muscle relaxation
What is the MOA of benzodiazepines?
- Binds to GABA A⍺/Ɣ subunits increasing Cl- entry into the cell causing hyperpolarization
- Potentiates the GABA site
What are benzos different effects at ⍺1 and ⍺2 subunits?
- ⍺1: sedative, amnestic, anticonvulsant (most abundant)
- ⍺2: anxiolytic, skeletal muscle
What other drugs bind at the GABAA site?
- Barbituates
- Etomidate
- Propofol
- Alcohol
What is the distrubution of benzos?
- Highly lipid soluble
- Highly protein bound to albumin
What drug interactions do you need to worry about with benzos?
- Drugs that cause synergestic effects: alcohol, LA, opiods, ⍺2 agonists, volatiles
What effect may benzos have on clotting?
BZD inhibit platelet aggregating factor causing a conformational change in the membrane… unclear if clinically significant
What does the pH of versed change about its solubility?
pH < 3.5 imidazole ring is open = protonated and water soluble (inactive)
pH > 4.0 = imidazole ring is closed = lipid soluble and unprotonated (active)
pH is 3.5 in solution
What is the onset, peak, half life, and duration of midazolam?
Onset: 1-2 mins
Peak: 5 mins
1/2 time: 2 hours
Duration: short due to rapid distrubution to tissues
How is midzolam metabolized?
What are its metabolites?
- CYP3A4
- Active: 1-hydroxymidazolam (1/2 activity of parent)
What drugs (5) inhibit P450 enzymes?
Cimetidine
Erythromycin
Calcium channel blockers
Antifungal
Fentanyl
C-FACE
What are the neurological effects of midazolam?
- ↓CBF/CMRO2
- Has EEG ceiling effect, unable to produce isoelectric EEG
- Preserves CO2 vasomotor response
- No change in ICP
What are the pulmonary effects of midazolam?
- Dose dependent decrease in ventilation
- Depresses swallowing reflex and upper airway activity = aspiration risk
What are the CV effects of midazolam?
↑ HR, ↓BP, ↓SVR
CO unchanged
What is the preop dosing for midazolam for children and adults?
Children: 0.25-0.5mg/kg orally
Adults: 1-5mg IV
What is the efficacy of midazolam in children?
Midazolam is very safe even at higher does.
Does not prolong emergence or recovery time.
What is the induction dose for midazolam?
0.1-0.2 mg/kg over 30 seconds
Why is versed bad for postoperative sedation?
Awakening is markedly delayed d/t accumulation of active metabolites in tissues
Why do valium and lorazepam burn on injection?
The solvent propylene glycol
What is the onset, peak, half time, and duration of diazepam?
Onset: 1-5 mins
Peak: 1 hour
Half time: 20-40 hours
Duration: Longer than versed, shorter than ativan
How is diazepam metabolized?
Active metabolites?
- CYP3A
- Desmethyldiazepam (48-96hrs) and oxazepam
What are the CNS effects of diazepam?
- ↓CBF/CMRO2
- Potent anticonvulsant
- Can produce an isoelectric EEG
What are the pulmonary effects of diazepam?
- Minimal effects on ventilation but can be worsened by opioiods, EtOH, and COPD
- Depressant effects reversed by painful stimuli
What are the CV effects of diazepam?
- Minimal effects on BP, HR, and SVR
- BP can be dropped with addition of opioids
What are the neuromuscular effects of valium?
Decreases skeletal muscle tone
What is the induction dose for valium?
0.5-1.0 mg/kg IV
Of the 3 benzos in lecture, which one is the most potent amnestic and sedative?
Ativan (lorazepam)
Why does lorazepam have a slower onset of action?
Less lipid soluble, takes longer to reach CNS
What is the peak, half-time, and metabolism of lorazepam?
Peak: 20-30 mins
Half-time: 14 hours
Metabolism: Direct conjugation (better for liver dx)
What is the bolus dose for ativan?
1-4 mg
What drugs do flumazenil reverse?
Any drug that agonizes the GABA receptor - including psych and anti-seizure meds
What is the dosing for Romazicon?
0.2 mg IV then 0.1 mg q 1 min, up to 1 mg total
What dose of flumazenil is needed to reverse sedation?
Reverse therapeutic dose?
Continuous infusion dose?
Sedation: 0.3-0.6 mg
Therapeutic dose: 0.5-1.0 mg
Continuous gtt: 0.1-0.4 mg/hr
What is important to know about Romazicon’s duration of action?
Duration = 30-60 mins; may need to be redosed if the sedative duration is longer than that
When is flumazenil contraindicated?
Antiepileptic drugs
