Exam 2 - Barbiturates and Propofol Flashcards
A drug that induces a state of calm or sleep.
Sedative
A drug that induces hypnosis or sleep.
Hypnotic
A drug that reduces anxiety and that has sedation as a side effect.
Anxiolytic
A drug that reversibly depresses the activity of the CNS.
Sedative-Hypnotics
State of drug-induced unconsciousness.
General Anesthesia
What is MAC?
Monitored Anesthesia Care- administration of a combination of sedatives and analgesics to induce a depressed level of consciousness, allowing patients to tolerate unpleasant procedures and enabling clinicians to perform procedures effectively.
AKA Procedure Sedation/ Conscious Sedation
What four groups will intravenous medications be distributed to?
What is the CO% of each group?
Vessel rich group (75%)
Muscle group (18%)
Fat (5%)
Vessel poor group (2%)
What makes up the Vessel-rich group?
Brain
Heart
Kidney
Liver
What makes up the Muscle group?
Skeletal muscle
Skin
What makes up the Vessel-poor group?
Bone
Tendon
Cartilage
What are the 5 components of General Anesthesia?
Hypnosis
Analgesia
Muscle Relaxation
Sympatholysis (hemodynamic stability)
Amnesia
What are the 4 stages of General Anesthesia?
Stage 1: Analgesia
Stage 2: Delirium
Stage 3: Surgical Anesthesia
Stage 4: Medullary Paralysis
What stage can cause death?
Stage 4
What stage consist of the lightest level of anesthesia?
Stage 1
(This is the stage of conscious sedation, the patient can still open their eyes on command, breathe normally, and protective reflexes maintained.)
What is the last sense to leave after induction of anesthesia?
Hearing
Stage 1 begins with the initiation of an anesthetic agent and ends with ___________.
The patient will experience ____ and ____ depression.
Loss of consciousness
Sensory and mental
What are the 3 lower airway reflexes?
Coughing
Gagging
Swallowing
What is the upper airway reflex?
Sneezing
Stage 2 starts with the loss of consciousness to the onset of automatic rhythmicity of vital signs. This stage is characterized by excitement in what areas?
Undesired CV instability
Dysconjugate ocular movements
Laryngospasm
Emesis
What is the response to stimulation in Stage 2 like?
Exaggerated and violent
What stage will have an absence of response to surgical incision and depression in all elements of the nervous system?
Stage 3
Will have all 5 components of anesthesia hypnosis, analgesia, muscle relaxation, sympatholysis, and amnesia
What stage is associated with cessation of spontaneous respiration and medullary cardiac reflex? What are the symptoms of this stage?
Stage 4 (over anesthesia)
All reflexes are absent
Flaccid Paralysis
Marked Hypotension with w/ irregular pulse.
May lead to death
Which stage is prolonged during emergence?
Why?
Stage 2
Anesthetics are redistributed back into the blood from the tissues
What is the benefit of using a barbiturate (thiopental) vs. diethyl ether?
Diethyl ether is slow, unpleasant, and more dangerous for induction of general anesthesia via prolongation of stage 2
Why is thiopental no longer used in the U.S.?
Thiopental was being used for lethal injection - the company did not want this, so they stopped making it
Why are we still talking about barbiturates?
This drug is still used in other countries.
Critical to understand properties of barbiturates (gold standard) as comparison with other drugs.
What is the MOA of Barbituates?
Potentiates GABA-A channel activity; directly mimics GABA
Acts on glutamate, adenosine, and neuronal nicotinic acetylcholine receptors
Barbiturates are a cerebral _____________.
What will be the effect on CBF?
What will be the effect on CMRO2?
Cerebral vasoconstrictor
CBF decreases
CMRO2 decreases by 55%
How do barbiturates help with seizures?
The decrease in CBF and CMRO2 will decrease the metabolic activity of the brain
Do barbiturates cause analgesic effects?
No analgesic effects
What is the onset time of barbiturates?
Barbiturates have a rapid redistribution; at 5 minutes __________ of the total dose remains in the blood.
How much of the total dose will be in the blood after 30 minutes?
30 seconds
50%
10%
What will result from a prolonged infusion time of barbiturates?
Lengthy context-sensitive half-time due to redistrubution from the fat
Where is thiopental rapidly distributed to?
The rate of metabolism of thiopental is equal to what?
Thiopental goes to the brain and viscera in about 1 minute.
Metabolism of thiopental is equal to the early removal of the drug by fat.
What is the site of the initial redistribution for barbiturates?
Equilibrium is reached at ____ minutes to plasma.
When will perfusion decrease?
Who has mass decrease?
Skeletal muscles
15 minutes
Perfusion decrease d/t shock
The elderly will have a mass decrease
Why is the context-sensitive half-time for barbituates so long?
The fat is a reservoir site for the drug, redosing/large dosing will yield cumulative effects.
Usually, barbituates are dosed on ____ body weight.
Ideal (lean)
How are Barbituates metabolized?
How are they excreted?
Elimination half-time consideration for pediatrics?
Hepatocytes 99%
Renal
Shorter half-time (higher metabolism)
Protein binding percentage of barbiturates?
How does this affect drug duration?
Binds to albumin 70 to 85%
Increases the duration of action because the drug will eventually unbind from albumin and be able to reach it’s receptor sites, prolonging the effects.
When the barbiturate is non-ionized it will be ____ soluble, favoring ____.
more lipid soluble and acidosis
When the barbiturate is ionized, it will be ____ soluble, favoring ____ .
less lipid soluble and alkalosis
What are previous uses of barbiturates?
- Premedication for induction → caused “hangovers”
- Grand mal seizures (now uses benzos/propofol)
- Rectal induction with uncooperative/young patients
- Increased ICP, cerebral protection
- Induction
____ isomer is much more potent than ____ isomer, but the barbiturates are only marketed as ____ mixtures.
S- isomer
R- isomer
Racemic Mixture
What are examples of oxybarbiturates?
Methohexital
Phenobarbital
Pentobarbital
What are examples of thiobarbiturates?
Thiopental
Thiamylal
What is the dosing for Thiopental (sodium pentothal)?
4-5 mg/kg IV
For Thiopental, in 30 minutes only ____ % remains in the brain.
Because of this, what are the anesthetic considerations for this medication?
10% (rapid redistribution)
Because of the rapid redistribution, be sure to supplement induction with other anesthetic agents so the patient can stay down during induction.
Where else can thiopental be redistributed?
When do you decrease the dose of thiopental?
Skeletal muscles
In the elderly or if the patient is in shock
What is the fat/blood partition coefficient of thiopental?
The dose of thiopental is calculated on ____ .
The elimination half-time of thiopental is longer than ____ .
11
Ideal body weight
Methohexital
Describes the distribution of a given agent at equilibrium between two substances at the same temperature, pressure, and volume?
Partition coefficient
Describes the distribution of an anesthetic between blood and gas at the same partial pressure?
Blood-gas coefficient
What does a higher blood-gas coefficient correlate with?
Higher solubility of anesthetic in the blood and thus slowing the rate of induction. The blood can be considered a pharmacologically inactive reservoir.
Methohexital has a lower lipid solubility than ___________.
Pentothal
At a normal pH, ____ % of methohexital is non-ionized and ____ % of pentothal is non-ionized?
How does this affect metabolism and recovery?
76% (methohexital)
61% (pentothal)
Fast metabolism and rapid recovery
How does an increased ratio of fat to body weight affect ideal body weight dosing?
Why is this?
It decreases the blood volume (mL/kg)
Adipose tissue has decreased blood supply
What are the excitatory phenomenon with methohexital?
Myoclonus and Hiccups
What is the IV dose of methohexital?
What is the rectal dose of methohexital?
1.5 mg/kg IV
20-30 mg/kg (rectal)
With continuous methohexital infusion, there can be post-op ___________ activity in 1 out of 3 patients.
Seizure
Methohexital is used to induce seizures in patients undergoing _____ .
Temporal lobe resection (lower seizure threshold, easier for seizures to occur)
Methohexital will decrease seizure durations by __________% in ECT patients
35 to 45%
CV effects of barbiturates (5mg/kg of thiopental)
SBP:
HR:
CV effects of barbiturates (5mg/kg of thiopental)
SBP: Transient 10-20 mmHg decrease (offset by compensatory increase in BP)
HR: 15 to 20 bpm increase
Barbituates should cautioned in patients with baroreceptor inhibition including:
- Hypovolemia
- CHF
- Beta Blockade
Anything that would worsen tachycardia and hypotension on induction
Barbiturates will cause ____ release, potentially leading to anaphylaxis if previously exposed.
Histamine
What are the side effects of ventilation with barbiturates?
Dose-dependent. The increasing dose will depress ventilatory centers (medullary and pontine).
Barbiturates and sensitivity to CO2.
Decrease sensitivity to CO2. This means we need a higher level of ETCO2 in order to trigger the medullary and pontine center for spontaneous respiration.
Apnea very likely in the prescene of other depressant drugs
How does spontaneous ventilation return with barbiturates?
Low rate and decreased tidal volume.
What is the side effect of barbiturates through intra-arterial injection?
Treatment?
- Immediate intense vasoconstriction and pain.
- Obscures distal arterial pulses → blanching, followed by cyanosis.
- Gangrene and permanent nerve damage.
Treatment: Vasodilators - (lidocaine and papaverine), prevent vasospasm and sustain adequate blood flow
____ is the desired drug to use during SSEP
Thiopental - doesn’t completely blunt responses
Commonly used to detect changes in nerve conduction and prevent impending nerve injury
2 to 7 days of barbiturate infusion will ____ metabolism of anticoagulants, phenytoin, TCAs, digoxin, corticosteroids, bile salts, and vit K. May persist for 30 days.
Renally, barbituates will cause a modest transient decrease in ________ and _________.
accelerate metabolism, via enzyme induction
Renal blood flow and Glomerular filtration rate - from hypotension
Propofol is a ____ agonist.
Gamma Aminobutyric Acid (GABA) agonist
What is the dose of propofol for induction?
What is the dose of propofol for conscious sedation?
What is the dose of propofol for maintenance?
Rapid injection (< 15 secs) will produce unconsciousness within ____ seconds.
Induction: 1.5 to 2.5mg/kg IV
Conscious sedation: 25 to 100 µg/kg/min
Maintenance: 100 to 300 µg/kg/min
30 seconds
Propofol is a constitution of 1% solution, how many mg/mL is that?
What would 2% be?
1% (10mg/mL)
2% (20mg/mL)
Propofol is packaged with a mixture of what 3 ingredients?
Soybean oil
Glycerol
Purified egg phosphatide (lecithin)
Lecithin is part of the EGG YOLK - allergies
Disadvantages of propofol:
Supports ____ growth
Causes increased plasma ____ concentrations (prolonged use)
____ on injection
- Bacteria
- Triglyceride
- Burns
What are the commercial preparations for propofol?
Ampofol (low lipid emulsions with no preservatives, higher incidence of pain on injection)
Aquavan (prodrug that eliminates pain on injection, byproduct will produce perineal buring, larger Vd, slower onset, high potency)
Nonlipid with Cyclodextrins (studies show significantly more pain on injection)
Immobility from propofol is not caused by drug-induced ____ .
Spinal cord depression
Clearance of propofol is through the ________ more than hepatic blood flow.
Tissue uptake of propofol is greater when it is being metabolized by _________.
Lungs
Cytochrome P450
What metabolizes propofol?
What does it metabolize to?
Where is propofol excreted?
Hepatic enzyme cytochrome P450
Water soluble glucuronic acid metabolites
Excreted by the kidneys
What is the context-sensitive half-time of propofol?
40 minutes (8-hour infusion)
Propofol
Elimination Half Time:
Vd:
Clearance:
SBP trend:
HR trend:
Propofol
Elimination Half Time: 0.5-1.5 hrs
Vd: 3.5-4.5 L/kg
Clearance: 30-60 mL/kg/min
SBP trend: Decreased
HR trend: Decreased
Etomidate
Elimination Half Time:
Vd:
Clearance:
SBP trend:
HR trend:
Etomidate
Elimination Half Time: 2-5 hrs
Vd: 2.2-4.5 L/kg
Clearance: 10-20 mL/kg/min
SBP trend: No change to decrease
HR trend: No change
Ketamine
Elimination Half Time:
Vd:
Clearance:
SBP trend:
HR trend:
Ketamine
Elimination Half Time: 2-3 hrs
Vd: 2.5-3.5 L/kg
Clearance: 16-18 mL/kg/min
SBP trend: Increase
HR trend: Increase
Propofol awakening times with cirrhosis of the liver?
No major difference due to rapid extrahepatic clearance
Will renal dysfunction affect propofol clearance?
No influence on propofol clearance.
Concerns about propofol with pregnancy?
Propofol will cross the placenta but is rapidly cleared in the neonatal circulation
What are the clinical uses of propofol?
- Induction
- Continuous IV infusion (by itself or with other anesthetics, TIVA)
In ICU, ____ -% solution is used to reduce the amount of lipid emulsion administered.
2%
(20 mg/mL)
What is the propofol induction dose for children?
Higher dose d/t larger central distribution volume and clearance rate
Propofol dose consideration for the elderly?
Lower induction dose by 25% to 50%
Plasma levels of propofol for:
Unconsciousness on induction:
Awakening:
Plasma levels of propofol
Unconscious on induction: 2 to 6 μg/mL
Awakening: 1.0 to 1.5 μg/mL
With concious sedation doses of propofol:
________ analgesic and amnestic effects.
Prompt recovery without ____________.
Low incidence of postop ____________.
Anti-convulsant and ____ properties.
________ or ________ used as adjuncts.
With intravenous sedation of propofol:
Minimal analgesic and amnestic effects.
Prompt recovery without residual sedation.
Low incidence of postop PONV
Anti-convulsant properties.
Midazolam or Opioid used as adjuncts.
Propofol is the agent of choice in brief _______ procedures.
GI endoscopy
The anti-emetic effects of propofol are more effective than _______.
What is propofol’s MOA for its anti-emetic effect?
Zofran
Propofol depresses the subcortical pathways and has a direct depressant effect on the vomiting center.
What is the sub-hypnotic dose of propofol?
10 to 15 mg IV followed by 10 μg/kg/min
Propofol also has anti-pruritic effects, what is the dose?
How much will you give if you have 1% propofol?
10 mg IV
1% propofol is 10mg/mL so 1 mL.
Propofol can be used as an anticonvulsant agent, what is the dose?
1 mg/kg IV
Other benefits of propofol include:
Propofol as a bronchodilator
________ at low doses
Potent ________
Does not trigger _______
Other benefits of propofol include:
Propofol as a bronchodilator
Analgesia at low doses
Potent antioxidant
Does not trigger MH
Neurologically, propofol will decrease __________, __________, and ____ .
Autoregulation related to CBF and PaCO2 is ________.
Propofol will decrease CMRO2, CBF, and ICP
Autoregulation related to CBF and PaCO2 is maintained
Large doses of propofol may ________ cerebral perfusion pressure. Need to support MAP.
CPP = MAP - ICP
decrease
EEG changes from propofol is similar to ____ .
Thiopental
Propofol effect on SSEPs?
Propofol has no SSEP suppression, unless volatiles or nitrous is added.
Propofol does cause excitatory movements on induction/emergency (myoclonus) but does not produce ____ .
Seizures
Compare SBP of propofol and thiopental.
The decrease in SBP in propofol is higher than in thiopental d/t inhibition of the SNS causing vascular smooth muscle relaxation, and decrease SVR
Decreases in the level of intracellular calcium decreases inotropy
Direct laryngosocpy reverses propofol induced hypotension
What are these waves related to on EEG?
Delta:
Theta:
Alpha:
Beta:
Gamma:
Deep sleep
Light sleep
Awake
Concentration
Testing
What are the CV side effects if propofol is given to someone with hypovolemia, elderly, LV compromised.
Exaggerated (might consider etomidate instead)
What is the effect on HR with propofol?
Bradycardia d/t decreased SNS response, may depress baroreceptor reflexes preventing compensatory tachycardia.
Profound bradycardia and asystole happens even in healthy adults.
Pulmonary side effects of propofol.
Dose-dependent ventilation depression will cause ____.
________ effect with opioids.
________ hypoxic pulmonary vasoconstriction response.
____________ counteracts the ventilatory depressant effects.
Pulmonary side effects of propofol.
Dose-dependent ventilation depression will cause Apnea.
Synergistic effect with opioids.
Intact hypoxic pulmonary vasoconstriction response.
Painful surgical stimulation counteracts the ventilatory depressant effects.
Propofol’s effect on liver transaminase enzymes or creatine concentration:
Normal
Prolong infusion of propofol can cause _________ injury.
Hepatocellular
This syndrome will cause green urine (from phenols), and no alternation in renal function.
What is the cloudy urine caused by?
Propofol Infusion Syndrome
Uric acid crystallization (no alternation to renal function)
What is the cause of PRIS?
What will this cause in children?
Signs/Sx?
Reversible?
High dose infusion, greater than 75 μg/kg/min for 24 hours.
Cause severe, refractory, and fatal bradycardia in children
Symptoms: Lactic acidosis, bradycardia, rhabdomyolysis, green urine
Reversible in the early stages
What is the treatment for someone with PRIS in cardiogenic shock?
Treatment: Extracorporeal membrane oxygenation (ECMO)
Propofol side effects on other organs:
____ Intraocular pressure.
Inhibits ____ .
Allergic Reactions
Prolonged ____
Abuse and Misuse
Propofol side effects on other organs:
Decrease Intraocular pressure.
Inhibits platelet aggregation
Allergic Reactions
Prolonged myoclonus
Abuse and Misuse
