Sedative and hypnotics Flashcards
sedative
drug that induces calm of sleep
hypnotics
a drug that induces hypnosis or sleep
sleep shares what similarities with anesthesia
Inhibits thalmic and mid-brain RAS
Reversibly inhibit CNS
Consciousness/awareness in the OR in how many people (studies)?
What type of cases?
When else might it happen?
1-2/1000 in a european study
1/10,000 in another study
- typically happens during sedation cases NOT GENERAL ANESTHESIA
- During emergence
How many levels are there to unconsciousness according to freud?
3 concious mind, preconcious, unconscious
When did we discover EEG could measure effects CBF and CMRO2?
1937
When was BIS developed?
1996
What is BIS?
Lower BIS number correlates how to movement?
Bispectral analysis
Lower BIS=Less movement
HIgher BIS = More movement
WHAT ARE the 5 pharmacologic effects of Benzodiazepines?
- Anxiolytics
- Sedation
- Anterograde amnesia
- Anticonvulsant amnesia
5.Spinal-Cord mediated skeletal muscle relaxation
What effect of benzos lasts longer than sedation that we must be mindful of?
Anterograde amnesia
In 1952 what did we discover that led us to using EEG to monitor depth of anesthesia?
we realize depth of anesthesia and and the amount of ether gave correlated.
What effect does using a high dose narcotic technique have on BIS monitoring?
What about hypnotic drugs?
There is less correlation between BIS and movement with narcotics.
Hypnotics have a high correlation between BIS and movement
BIS < 58 correlated with?
Loss of conciousness
BIS < 65 had what correlation?
Had less than 5% chance of return to conciousness within 50 seconds
What is SQI?
Signal Quality Index, tells us whether or not we have a good signal or if we have a lot of artifact.
what is EMG?
Electormyography and it tells us information about muscle activity and if the patient can move.
What is EEG?
Electroencephalogram, this tells information about brainwave activity.
What is SR?
What do we want this number to be?
Suppression Ratio, this tells us how many seconds in the last minute that the EEG has been flat.
We want this number to be zero.
What is typical number we want our BIS to be during general anesthesia cases?
40-60
What drugs may decrease your BIS number?
- volatlies
- hypnotics
- NMBD
- opioids
What drugs may increase your BIS number? why?
Ketamine and Epinephrine
* Stimulates your sympathetic system, this would be a falsely high reading
What drug may artificially lower your BIS score due to lower CMRO2 and CBF?
Betablockers, decrease HR = Decrease CO = decrease CBF= decrease CMRO2
What are 4 benefits of benzos over barbs?
What do we use benzos for in anesthesia?
Less tolerance
Less potential for abuse
Fewer and less serious side effects
Do not induce hepatic microsomal enzymes
***Have replaced barbiturates for preop sedation
What is the antagonist for benzodiazpines?
Romazicon (flumazenil)
Which benzo is the most common preop sedative?
Versed (midazolam)
Which has a longer 1/2 time, midazolam (versed) or Lorazepam (ativan)?
Lorazepam (Ativan)
What is the MOA of benzodiazepines?
GABA mediated, So they bind to a receptor site specific to benzos and they increase the affinity of the GABA receptor. Once the GABA receptor is stimulated the the Cl- channel opens and causes hyperpolarization of the postynaptic membrane which makes it more difficult to depolarize again
Describe the different receptor sites of the GABA A receptor.
What kind of effects do the alpha-1 stimulatory drugs have?
Where do they have their action?
- Sedative, amestic, anticonvulsant
- Cerebral cortex, cerebellar cortex and thalamus
What kind of effects do alpha-2 receptors have? where do they have their action?
- anxiolytic and skeletal muscle relaxation
- hippocampus and amygdala
What other drugs bind to GABA A receptors?
Why does this matter if you’re giving benzos?
- Barbituates
- Etomidate
- propofol
- alcohol
They will have synergistic effects and increase the likelyhood of OD or may have a cross-tolerance
What 4 things can cause differences in onset and duration between drugs of the same class?
Potency (receptor binding affinity)
lipid solubility (crossing the BBB)
Redistribution (to peripheral tissues)
Pharmacokinetics (ADME)
What effect do benzos have on platelets?
they can inhibit platelet aggregating factor, inability to have conformational change so they can aggregate
What is an important feature of Versed’s chemical structure?
imidazole ring, this stabilizes the structure and allows for rapid metabolism
What is the main indication of midazolam for anesthesia?
Pre op med and conscious sedation
How much more potent is midazolam (versed) than diazepam (valium)?
2-3x more potent
Is versed lipid or water soluble?
What is the parenteral solutions pH?
water soluble.
3.5
How does the imidazole ring start out at 3.5 pH?
the imidazole ring is open, making versed water soluble (protonated)
What happens to the imidazole ring when you inject versed
It closes at a pH of 4.0, which makes it lipid soluble and unprotonated
What is the benefit of versed being water soluble and not needing propylene gylcol to stabilize it?
it doesnt burn upon injection
Versed
onset?
peak?
Protein binding?
Duration?
1/2 time? (elderly?)
Vd? (elderly / obese)
Metabolism?
active Metabolites?
What drugs we commonly use that inhibit the CYP450 enzyme activity?
Clearance in comparison to ativan? and valium?
- 1-2 mintutes onset
- 5 minutes peak
- highly protein bound (96-98%)
- Short duration d/t lipid solubility
- 2 hours, doubles in elderly
- 1-1.5 L/kg (LARGE)
- Vd increases in the elderly and obese because they both have more fat RELATIVE to the normal person.
- elderly people have less muscle mass and more fat mass.
- CYP3A4
- Active metabolites- 1-hydroxymidazolam, has half the activity of parent molecule
- DRUGS: cimetidine, erythromycin, CCB, antifungals, fentanyl
- Clearance of versed is 5x faster than ativan and 10x faster than valium
VERSED
CNS?
CNS- Dose related decrease of CMRO2 and CBF; Potent Anticonvulsant even in status; perserves vasomotor response; doesn’t change ICP; cannot produce isoelectric EEG
VERSED
Pulm?
DOSE DEPENDENT decrease in hypoxic drive, worse in COPD. Can cause transient apnea (especially if if give with opioid) Supresses swallowing & upper airway activity (coughing) –> risk of ASPIRATION
VERSED
CV?
Increases HR; decreases BP. CO is maintained. Decreases SVR
VERSED
Dosing for sedation?
Peds? Adult? Elderly?
Peds PO: 0.25 - 0.5 mg/kg (syrup so peak effect is 20-30 min)
Adults IV: 1 - 5 mg; Peak 5 minutes; elderly require decreased dose d/t > CNS activity
VERSED
Induction?
What facilitates induction with versed?
IV : 0.1 - 0.2 mg/kg over 30 - 60 secs; give with Fentanyl 50-100 mcg 1 - 3 mins prior
Facilitated by preceding dose of opioid within 1-3 minutes, Fentanyl 50-100 mcg
VERSED
Maitneance?
Supplemental with?
Rarely associated with?
Uncommon ;
Can be used to supplement opioids, propofol, volatiles;
Rarely associated w/ N/V or emergence excitement
VERSED
Post op sedation?
consideration with IV drip length of time and what happens?
IV gtt: 1 - 7 mg/hr
Prolonged gtt > 3 days: T-cell Suppression
