Lecture 3 Sedatives/ Hypnotics Test 1 Flashcards
A drug that induces calm or sleep is called a _______.
A drug that induces hypnosis is called a _________.
Sedative
Hypnotic
Both general anesthesia and sleep share similarities in that both inhibit _________ and ___________.
General anesthesia and sleep also reversibly inhibit the ________.
Thalmic
Mid-Brain Reticular Activating System (RAS)
CNS
1 in 10,000 patients will experience this in general anesthesia.
Awareness
In 1937, ___________ could be used to measure the effects of anesthesia.
EEG
In 1952, the depth of anesthesia correlates with ___________ of ether used.
Concentration or MAC
Anesthesia alters ____________ and ______________.
Cerebral Blood Flow (CBF)
Cerebral Metabolic Rate of Oxygen (CMRO2)
What was the issue with using EEG machines to measure the depth of general anesthesia?
Not practical to use so many leads and the device was large and bulky.
In 1996 the __________ was created using 1500 subjects and 5000 hours of EEG signals. It uses an algorithm and pattern to determine a patient’s depth under general anesthesia.
Bispectral Analysis
What was the BIS tested with?
Isoflurane/O2
Propofol/ Nitrous
Propofol/ Alfentanil
BIS change correlates to _____________.
What is the exception?
Patient movement.
The lower the number, the less movement
Exception: High dose narcotics have less correlation between BIS and movement
No patient with a BIS score less than _________ was conscious.
BIS scores less than ________ show that less than 5% chance of return to consciousness within 50 seconds.
58
65
What is the BIS range?
What is the ideal BIS range for someone under general anesthesia?
0 to 100
40 to 60
On the BIS monitor, what is the SQI?
EMG?
EEG?
SR?
SQI - Signal Quality Index
EMG- Electromyographic, tells you if the patient is about to move
EEG- brain activity
SR- Suppression Ratio, should be 0, how many seconds in the last minute has the EEG been flat.
Are BIS monitors 100% reliable?
No, different drugs such as ketamine and epinephrine can give the BIS monitor a falsely high reading despite the patient being adequately sedated.
Very important to look at BIS trends
What are the five main actions of BZDs?
- Anxiolytics
- Sedation
- Anterograde Amnesia (this last longer than sedative effects)
- Anticonvulsant
- Spinal Cord mediated skeletal muscle relaxation (not adequate for surgery)
What were the reasons that BZD replaced barbiturates for preop sedation?
Less tolerance was developed with BZD.
BZD had less potential for abuse.
BZD had fewer and less serious S/E.
BZD does not induce hepatic microsomal enzymes.
What are the similarities between BZD and barbituates?
Similar structure
Specific pharmacologic antagonist (flumazenil)
What is the most commonly used BZD in the perioperative period? This is also used as a preop med and for conscious sedation.
Midazolam (Versed)
Which two BZD have a greater half time than midazolam and more attractive for sedation post-op?
Diazepam (Valium)
Lorazepam (Ativan)
What is the MOA of a BZD?
The mechanism of action is GABA- mediated.
BZD binds at GABA-A Chloride Inophore receptors. This will enhance the affinity of receptors for GABA, opening chloride channels and inducing hyperpolarization.
Which receptor subunit on GABA is the most abundant?
What effect does it have?
What part of the brain does it affect?
Alpha-1
Sedative, Amnestic, Anticonvulsant
Cerebral cortex, Cerebellar cortex, thalamus
What receptor subunit on GABA exhibits anxiolytic and skeletal muscle relaxation?
What part of the brain does it affect?
Alpha-2
Hippocampus, amygdala
Name agents or drugs that can have a synergistic effect with BZD.
Barbituates
Injected Anesthetics (Propofol)
Inhaled Anesthetics
Etomidate
Alcohol
Opioids
Alpha-2 agonist (Precedex)
All these bind to the Alpha subunit on the GABA receptor
The BZD that we use in anesthesia is highly ______________ and highly (98%)________________.
What does that mean?
Lipid Soluble
Protein Bound
This means that BZD will work quickly and go away quickly.
B/c they are lipid soluble, BZD will have a large Vd, just not a large amount because they are highly protein bound
Looking at an EEG, BZD will decrease __________ activity.
Some BZD are unable to produce a _______________ state.
BZD will cause ______________ amnesia.
Alpha
Isoelectric state
Anterograde
BZD inhibits _________________. Increasing the risk of bleeding.
Platelet aggregating factors
What type of structure does a BZD have that allows rapid metabolism?
Imidazole ring
How many more times potent is midazolam compared to diazepam?
2-3x, midazolam has a greater affinity for the receptor
What are special considerations to take into account for patients coming off of midazolam-induced sedation?
Amnestic effects last longer than sedation, have written instructions ready to go
At a pH ___________, midazolam is ___________ with an open ring and protonated.
less than 3.5, water-soluble
At a pH ___________, midazolam is ___________ with a closed ring and non-protonated.
greater than 4, lipid-soluble
Is midazolam irritating to the veins?
No, midazolam is non-irritating
What is the onset time over midazolam?
What is peak effect time?
What is the estimated half-time of midazolam?
1-2 minutes
5 minutes
2 hours (doubles for the elderly).
What causes the short duration of action for midazolam?
Lipid solubility and rapid redistribution
What is the volume of distribution for midazolam?
1 to 1.5L/kg
What metabolizes midazolam?
What does midazolam metabolize into?
Cytochrome P-450 enzymes (CYP 3A4)
Active and inactive metabolites
1-hydroxymidazolam (half the activity of the parent)
What are drugs that can inhibit P-450 enzymes and decrease BZD metabolism?
Cimetidine
Erythromycin
CCB
Antifungal
Fentanyl
Clearance of midazolam is _______ faster than lorazepam.
Clearance of midazolam is _________ faster than diazepam.
5 times
10 times
CMRO2 and CBF effect of midazolam?
Isoelectric EEG with midazolam?
Both Decrease
Unable to produce isoelectric effect with midazolam.
Midazolam is a potent _____________ (even in status)
Anticonvulsant
Midazolam preserves __________________ response to CO2.
Vasomotor
Why is midazolam a great drug to give to neuro patients?
Does not increase ICP.
List pulmonary effects of midazolam.
Dose-dependent and will decrease ventilation and hypoxic drive.
Greater depression with COPD and transient apnea if rapid IV infusion with opioids.
Decrease swallowing reflex.
Decrease upper airway activity.
What are the cardiovascular effects of midazolam?
HR:
BP:
SVR:
Dose-dependent
HR: Increases
BP: Decreases
SVR: Decreases
Does not inhibit BP/HR response to intubation
What is midazolam dosing for sedation in children?
What will be the peak effect time?
0.25 to 0.5 mg/kg (syrup)
20-30 minutes
What is midazolam dosing for sedation in adults?
What will be the peak effect time?
1-5 mg IV
5 minutes
What is midazolam dosing for adult induction?
What will be the preceding dose of opioids?
0.1-0.2 mg/Kg IV over 30-60 seconds
Facilitated by a preceding dose of opioid (1-3 minutes), 50 to 100 mcg of fentanyl (synergistic effect)
It is uncommon to use midazolam for ___________. Instead, supplemented with opioids, propofol, and volatiles.
Midazolam is rarely associated with _____________ or ______________.
Maintenance (but decreases the requirement for volatiles)
N/V; emergence excitement (crazy)
What is midazolam dosing for post-op sedation?
What are the considerations to take into account for this?
1-7 mg/hr IV
-2-3 days max because prolong use will cause T-cell suppression.
-Accumulation of Active metabolites and clearance depends on hepatic metabolism, not redistribution.
Diazepam is highly ____________ soluble and has a more prolonged duration of action than midazolam. Rarely used in anesthesia.
Lipid
What substance is in diazepam that causes irritation and burning to the veins?
Propylene glycol
Soybean formulation is less painful
What is the onset time for diazepam?
What is the half-time for diazepam?
1-5 minutes
20-40 hours (10-20 times longer than versed)
What metabolizes diazepam?
What does diazepam metabolize into?
When will patients experience return drowsiness?
Cytochrome P-450 enzymes (CYP 3A4)
Activate metabolites as nearly as potent as the parent
Desmethydiazepam and oxazepam
Return drowsiness in 6-8 hours
What are CNS effects of diazepam?
CBP:
CMRO2:
Isoelectric EEG:
CBP: decrease
CMRO2: decrease
Isoelectric: Can produce an isoelectric effect
What is the diazepam dose for an anticonvulsant?
What else can this be used to treat?
0.1 mg/kg IV
DTs, status epilepticus, lidocaine toxicity related seizures
What are the pulmonary effects of diazepam?
After __________ mg/kg IV, there will be an increase in PaCO2.
What will reverse ventilatory depressant of diazepam?
A slight decrease in tidal volume that can be exaggerated with opioids, alcohol, and COPD
0.2 mg/kg
Surgical Stimulation
What are the cardiovascular effects of diazepam?
BP:
CO:
SVR:
What are the cardiovascular effects of diazepam?
BP: Minimal
CO: Minimal
SVR: Minimal
BP changes with opioids and unchanged with the addition of nitrous
What are the neuromuscular effects of diazepam?
Decrease muscle tone, decrease tonic effect on spinal neuron
What is the dosing of diazepam for induction?
What are the considerations when it comes to dosing for the elderly, patients with liver disease, or the presences of opioids?
0.5 - 1.0 mg/kg IV
Decrease dose by 25% to 50%
Compared to midazolam and diazepam, ____________ is the most potent sedative and amnestic of the three.
Lorazepam
Lorazepam is ______________ soluble.
This drug has a __________ onset of action and __________ metabolic clearance when compared to midazolam.
Lipid soluble (insoluble in water, will have irritation)
Slower onset and slower metabolic clearance.
(slower entrance to CNS too)
What is the IV dose of Ativan?
What is the peak effect time?
What is its half-time?
1-4 mg IV
20-30 minutes
14 hours
What is different about the metabolism of Ativan compared to versed and valium?
Ativan is not entirely dependent on the CYP450 enzyme.
Organ system effects of Lorazepam?
Similar to other BZD and will be dose dependent.
Which drug acts as a competitive antagonist with a high affinity for BZD receptors and reverses all agonist activity of BZDs?
Flumazenil (Romazicon)
How is Flumazenil metabolized?
What does it metabolize into?
The hepatic microsomal enzyme (CPY P450, CYP 3A4)
Inactive metabolites.
What is the inital dosing of Flumazenil?
0.2 mg IV and titrate to consciousness, give 0.1 mg every minute up to 1 mg total, or return to consciousness.
What is the dosing of Flumazenil to reverse sedation?
What is the dosing of Flumazenil for OD BZD?
0.3 to 0.6 mg
0.5 to 1.0 mg
What to do if the patient is still unconscious after using 1.0 mg of flumazenil?
Use other intoxicants like Narcan.
What is the duration of flumazenil?
What is the continuous infusion rate of flumazenil?
30-60 minutes (half-time for BZD are longer, may need to redose)
0.1 to 0.4 mg/hr
What are the side effects of flumazenil?
What are the special considerations to take when using flumazenil?
None
Contraindicated if BZDs are used as an antiepileptic drug, can precipitate acute withdrawal seizures.
