Lecture 3 - Benzodiazepines (Test 1) Flashcards
What is the principal inhibitory neurotransmitter in the CNS?
Gamma-aminobutyric acid (GABA)
Slide 14
Benzodiazepines facilitate action at which receptor?
GABA-A Chloride Ionophore
Slide 14
By enhancing the affinity of the receptors for GABA, we also enhance which type of channels?
Chloride channels
(Slide 14)
Which GABA subunit is the most abundant and induces sedation, amnesia, and is also has anticonvulsant properties?
Alpha-1
Slide 15
Which GABA subunit works as an anxiolytic and has more effects on skeletal muscles?
Alpha-2
Slide 15
True or False
Benzodiazepines sit on their own site within the GABA receptor.
True
Slide 15
Opposed to alpha-1 and alpha-2, which receptor subtype sits outside the CNS?
Alpha-5
Slide 15
Which other GABA-A receptor binding sites are right beside the benzo sites?
Barbiturates
Etomidate
Propofol
Alcohol
*Can cause synergistic effects
Slide 16
Barbiturates, Etomidate, Propofol, and Alcohol have what type of effect when combined with benzos?
Synergistic
Slide 16
Are benzos highly protein-bound and lipid-soluble? What does this mean in regard to Vd?
Yes, 98%
They have a large volume of distribution due to the lipid solubility, but there is not a large amount of free drug to distribute because of the protein binding.
Slide 17
If you give a patient with cirrhosis or renal failure Versed, what would you expect?
A prolonged effect due to the drug not being metabolized/excreted.
Slide 17
Benzodiazepines decrease __________ activity on an EEG?
Alpha wave
Slide 19
Do benzodiazepines cause antegrade or retrograde amnesia? What does this mean?
Antegrade - The pt won’t remember anything after the drug is given
Slide 19
Benzodiazepines have synergistic effects with what type of drugs?
Alcohol, injected anesthetics, opioids, alpha-2 agonists, and inhaled anesthetics
Slide 20
Benzodiazepines can inhibit _____________ without the normal conformational change.
Platelet aggregation
Slide 21
Why is Valium (Diazepam) not used often in anesthesia?
prolonged duration of action compared to midazolam
(slide 35)
Valium’s onset of action is?
Elimination 1/2 time?
onset: in 1-5 mins
Elimination 1/2 time: in 20-40 hours
(slide 37)
Is Valium water soluble or insoluble?
water INSOLUBLE
(slide 36)
What additive is used in valium for IV administration that causes a burning pain on injection?
Propylene glycol
(slide 36)
Which dissociates from GABA receptors faster, Diazepam or Lorazepam?
Which has a longer E 1/2 time?
Diazepam, diazepam.
(slide 37)
What pathway metabolizes Diazepam?
CYP3A pathway
( - Kane)
What risk factors prolong effects of Diazepam?
- Hepatic failure/Cirrhosis
- Age (elderly d/t increased Vd 2/2 increased body fat)
(slide 37)
6-8 hours after admin of Valium, what are we most concerned about? (Hint: especially outpatient surgeries)
Return of drowsiness 2/2 valium’s active metabolites
(Kane mentioned the scenario with grandpa going home after sx and taking a nap to be found dead later from severe resp. depression d/t to the valium’s active metabolites)
(slide 38)
Which benzo can produce isoelectric EEG?
Diazepam
(slide 39)
Out of Versed, Ativan and Valium, which one would cause minimal decrease in BP, CO, and SVR even with induction doses?
(Hint: It used to be used for cardiac surgery induction*)
Valium (Diazepam)
(Slide 41)
If you give Valium (Diazepam) and you see a change in BP, what could be the cause?
Additives such as opioids & propofol!
Valium alone will not cause a change in BP!
(Slide 41)
Which has more effect on respiratory drive - Midazolam or Diazepam?
Midazolam
Diazepam has “minimal effects on ventilation” but can be exaggerated with opioids, ETOH, and COPD
(slide 40)
Depending upon the dose of Versed, what effects does it have in cardiovascular system?
↑ HR and ↓BP
slide 29
(↓BP is thought to be due to ↓ in SVR)
If you have given nitrous to your patient and then given Valium (Diazepam) would you expect to see a change in BP?
NO!
Nitrous is an additive that will not effect BP when given with Valium!
(Slide 41)
Does versed alter cardiac output?
No.
slide 29
(Versed ↓SVR, the compensatory effect is to ↑HR to maintain CO)
What benzo is known to be a potent anticonvulsant?
At what dose and route per the powerpoint?
Which types of seizures is this med known to treat particularly well?
Valium (Diazepam)
Dose: 0.1 mg/kg IV
Known to be effective in treating: Delirium Tremens, Status Epilepticus, and Lidocaine toxicity related seizures
(slide 39)
Besides Valium, what are some other known longer acting anticonvulsants?
Fosphenytoin and Cerebryx
(slide 39)
Which benzodiazepine was used as a muscle relaxant back in the day before flexeril was invented (decreased tonic effect on spinal neuron)?
(Hint: people developed tolerance to its muscle relaxation properties & it has no action at neuromuscular junction!)
Valium (Diazepam)
(Slide 43)
Do you give versed to pt who is in hypovolemic shock, or hemorrhaging?
No
slide 29
(Versed further decreases BP)
What is the induction dose for Valium (Diazepam)?
0.5-1.0 mg/kg IV
(Slide 44)
In what 3 patient population do we decrease the dose of Valium by 25-50%?
*Elderly
*Liver disease
*Presence of opioids
(Slide 44)
So Dr. Kane mentioned that Valium (Diazepam) can cause a “slight decrease in tidal volume” but what stimulation is adequate to temporarily reverse this mild ventilatory depressant?
Surgical stimulation (so resp. drive isn’t much of a concern intra-op but keep in mind the long elimination 1/2 time for post-op)
(slide 40)
What is the most potent sedative and amnestic compared to Midazolam and Diazepam?
Lorazepam (Ativan)
Slide (45)
Lorazepam (Ativan) resembles Oxazepam (Serax) because?
Oxazepam has an extra Cl- atom!
(Oxazepam is an active metabolite of Temazepam)
(Slide 45)
T/F
Ativan is insoluble in water therefor it requires a solvent such as propylene glycol for preparation.
True
(Slide 46)
When would Versed (midazolam) not inhibit the associated HR/BP responses?
During intubation.
slide 29
(This response is good when someone comes with hypotension.
Intubation will help stimulate the sympathetic system to offset the decrease in BP)
True or false: BIS level changes are correlated to the patients movement?
True
(slide 8)
What BIS level range do we want to achieve to represent adequate general anesthesia?
Want: 40-60 range
(ranges from 0-100)
(slide 8)