IV Sedatives and Hypnotics Flashcards
What does GABA stand for?
Gamma Aminobutyric Acid
There are three phases that occur after a bolus injection of propofol:
- Rapid distribution (moves into tissues until they equilibrate with plasma)
- Slow distribution phase (return of drug to the plasma)
- Terminal Phase (removed from the body)
What is context sensitive half time?
Time required to acheive a 50% reduction in concentration after stopping a continuous infusion in drugs that are not limited to the blood (i.e. all IV anesthetics)
Where is propofol metabolized?
The liver
Excreted by the kidneys
How does reduced liver function effect propofol metabolism?
Interestingly, it doesn’t
This suggests there must be other forms of metabolism at work, but we’re not sure what they are
Propofol Classification
GABA Agonist
How does propofol effect ICP?
It lowers ICP by lowering CBF
Generally considered neuroprotective
It’s also a free radical scavenger
What are the characteristic hemodynamic effects of a propofol bolus?
Drop in SBP and DBP WITHOUT the expected increase in HR
What is the drug dose of propofol in healthy adults?
1-2.5 mg/kg
How do elderly patients respond to propofol?
Prolonged effects and increased sensitivity
BECAUSE of decreased CO and clearance
How do pediatric patients respond to propofol?
larger than average volume of distribution and quicker clearance, resulting in creased propofol requirement per kg
When calculating the appropriate propofol amount for a morbidly obese patient, what weight should be used?
LBW, not actual weight
Maintenance of general anesthesia can commonly be acheived with prop infusion of:
100-200 mcg/kg/min
What is the recommended maximum propofol dose?
4 mg/kg/hr
Why isn’t etomidate used as an infusion?
It’s associated with adrenal suppression
Etomidate classification
GABA - A receptor agonist
Is etomidate a good choice for neuro patients?
It reduces ICP, but it’s often associated with EEF spikes
Used frequently for ECT
proconvulsant and lowers the seizure threshold
Why does etomidate cause adrenal suppression?
It inhibits the enzyme that converts cholesterol into cortisol
Ketamine Classification
NMDA receptor Antagonist
Why is ketamine analgesic?
Believed to be in the prevention of developing hyperalgesia
preventing wind up at NMDA receptors
Which patients should not receive ketamine?
CAD patients (if they can’t tolerate the increased BP and HR)
R sided HF patients (increases PVR)
How is ketamine useful in post op pain?
It reduced opiate requirements, but it cannot replace opiates altogether
Most useful in patients who will require high does of opiates
Should ketamine be used in patients with increased ICP?
Historically, no. But studies are showing that ICPs remain normal with ketamine even though it has an excitatory CNS effect
It may even be neuroprotective
Dexmedetomidine Classification
Alpha 2 Adrenergic Agonist
What are the main side effects of ketamine?
emergence delirium
hallucinations
nystagmus
increased salivation
What effect does ketamine have on bronchioles?
Bronchodilator
Precedex provides analgesia at the ______ level
spinal cord
What are the cardiovascular effects of precedex?
bradycardia and hypotension
What do alpha 2 receptors do?
Peripherally, they are located on presynaptic nerve terminals and regulate transmitter release
Centrally,
Benzodiazepine classification
GABA-A receptor agonist
PROPOFOL
CHEMICAL NAME & MOA
2,6 - diisopropylphenol
Direct GABA agonist: Increases Cl influx, causing hyperpolarization
PROPOFOL
ONSET & DURATION
Onset: 30-60 seconds
Duration: 5-10 min
PROPOFOL
INDUCTION DOSE & INFUSION DOSE
INDUCTION: 1.5-2.5 mg/kg
INFUSION: 25-200 mcg/kg/min
What does GABA-A receptor stimulation cause?
Increased Cl- influx into the cell, which hyperpolarizes the neuron and prevents firing
What are the CV effects of propofol?
Decreased BP, SVR, venous tone (hence preload), and myocardial contractility
What are the respiratory effects of propofol?
Decreased sensitivity to CO2, causing apnea and hypoventilation
inhibits hypoxic respiratory drive
What effect dose propofol have on ICP and CBF?
Reduces both
What organs are primarily responsible for propofol metabolism?
Liver and Lungs
What causes Propofol Infusion Syndrome?
Increased long chain triglyceride load in the blood impairs oxidative phosphorylation and fatty acid metabolism
Cells literally starve from lack of oxygen, usually cardiac and skeletal are effected first
What are some risk factors for Propofol Infusion Syndrome?
infusions exceeding 4 mg/kg/hr (67 mcg/kg/min)
Infusion greater than 48 hours
Sepsis
Catecholamine infusions
What is the clinical presentation of propofol infusion syndrome?
How long is propofol in a syringe good for?
6 hours
What are the benefits of fospropofol?
Prevents burning
Doesn’t require preservatives
What are the downsides of fospropofol?
Longer onset and duration
Is ketamine better at treating somatic or visceral pain?
Somatic
What are the cardiovascular effects of ketamine?
KETAMINE
MOA
NMDA receptor Antagonist
Dissociates the thalamus from the limbic system
Also targets opioid, MAO, serotonin, NE, muscarinic and Na channel receptors
KETAMINE
ONSET AND DURATION
ONSET 30-60 seconds
DURATION 10-20 minutes
KETAMINE
INDUCTION, MAINTENANCE, AND LOW DOSE
INDUCTION: 1-2 mg/kg
MAINTENANCE: 1-3 mg/min
LOW DOSE: 1-3 mcg/kg/min
What are the respiratory effects of ketamine?
What are the CNS effects of Ketamine?
What drug prevents hyperalgesia after remifentanil infusion?
Ketamine
Which IV anesthetic has the lowest protein binding rate?
ETOMIDATE
MOA
GABA-A agonist
What is the induction dose of Etomidate?
0.2-0.4 mg/kg
ETOMIDATE
Onset and Duration
Onset: 30-60 seconds
Duration: 5-15 min
What are the cardiovascular effects of etomidate?
Pretty minimal
Small reduction in SVR
Does not blunt the SNS response to laryngoscopy and noxious stimuli, so an opioid or esmolol will be needed
What are the respiratory effects of etomidate?
Does cause respiratory depression, but not nearly as much as propofol or barbituates
What are the CNS effects of Etomidate?
Which anesthetic agent increased mortality in patients with Addison’s Disease?
Etomidate
Which patients should never get etomidate?
Patients who are extremely dependent on cortisol (sepsis, acute adrenal failure)
What IV induction agent has the highest incidence of PONV?
Etomidate
Which drugs should be avoided in patients with Acute Intermittent Porphyria?
Anesthetic management of a patient with porphyria should include:
Which drug is the gold standard for ECT therapy?
Why?
Methohexital
It decreases the seizure threshold
DEXMEDETOMIDINE
MOA
Alpha 2 agonist
DEXMEDETOMIDINE
LOADING DOSE & INFUSION
Loading: 1 mcg/kg over 10 min
Maintenance: 0.4-0.7 mcg/kg/hr
DEXMEDETOMIDINE
ONSET AND DURATION
Onset (with bolus): 10-20 min
Duration: 10-30 min after infusion stopped
Who does precedex impact shivering?
It impairs the shivering mechanism
Why does precedex produce analgesia?
Alpha 2 stimulation in the spinal cord results in reduced glutamate and Substance P release
What is the MOA for benzodiazepines?
GABA-A agonist by increasing the frequency of opening (and therefore Cl influx and hyperpolarization)
What is the induction dose of Versed?
0.1-0.4 mg/kg
What is the sedation dose of Versed?
0.01-0.1 mg/kg
What is the onset and duration of versed?
Onset 30-60 seconds
Duration: 20-60 minutes
Which benzodiazepine is most potent? Least potent?
Most: Lorazepam
Least: Diazepam
What is Flumazenil’s MOA?
Competitive antagonist at the GABA-A receptor
What is the duration of Flumazenil?
Only 30-60 minutes, will probably need redosing before benzo is completely out of their system
