Lecture 5 (Exam 2) - Induction Drugs (Part 1) Flashcards
Does propofol have more clearance via hepatic or lungs?
Does it have more tissue uptake or CYP450?
Lungs!
This is d/t rapid redistribution
Slide 40
Propofol’s main metabolism is in the ______ by ______ enzymes.
What are the two metabolites produced?
How are they excreted?
liver, CYP450
Metabolites: Water-soluble sulfate and glucuronic acid
excreted by kidneys 🫘
Slide 40 & 41
Why do you warn patients to not operate heavy machinery 🚜 after receiving Propofol?
(Hint: What’s the E 1/2 life?)
E 1/2 life: 30-90mins
Castillo explains this as ‘variable’ and to warn patients to be safe!
Slide 40
Does Propofol have a longer or shorter Context-Sensitive half-time compared to Thiopental?
Why?
What is Propofol’s CSHT?
Shorter! (another reason to love prop)
Bc it is not as lipid soluble vs barbs.
CSHT: 40 mins (8hr infusions)
Slide 40
With Propofol: A cardiovascular side-effect is bradycardia or tachycardia?
And why?
- Bradycardia. (profound bradycardia and asystole even in healthy pts)
- Due to: A decrease in SNS response, and depression of baroreceptor reflexes
(slide 52)
Propofol has a Vd of _______L/kg with a clearance of ______mL/kg/min.
Why do patients wake up quicker with propofol vs other induction drugs?
Vd: 3.5 - 4.5 L/kg
Clearance: 30-60 mL/kg/min
They wake up faster bc of the faster clearance!
*Faster Vd = faster clearance (per Castillo - I think he meant larger Vd?!)
Slide 42
Propofol increases BP and HR.
True or False?
False.
It decreases both.
Slide 42
What is a Pulmonary side-effect seen with Propofol?
And what additional med causes a synergistic effect?
- (dose dependent) depression of ventilation - Apnea
- Opioids
(slide 53)
Thiopental is the Gold Standard when comparing induction drugs.
It decreases BP but does is increase or decrease HR???
Increases HR - in reflex of HOTN (hypotension).
Verbal on Slide 42
Your patient is a chronic alcoholic, ESRD and pregnant. 🤰
Are you at all concerned about her waking up after giving Propofol to her?
Nope. Crazy, I know.
-Propofol could be metabolized through psuedocholinesterases, via the lungs, or by the liver…
-Clearance is good, excretion by psuedocholinesterases.
-It will cross the placenta but is RAPIDLY cleared by the neonate circulation thanks to pseudocholinesterase metabolism.
Slide 43
What is the DOC for induction?
Propofol
Slide 44
What Pulmonary response remains intact with Propofol.
And is this response good or bad and why?
- Intact hypoxic pulmonary vasoconstriction.
- GOOD! “Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation/perfusion matching and systemic oxygen delivery.”
(Pg. 299 in book)
(slide 53)
List the two clinical uses of Propofol discussed.
- Induction
- Cont gtt
Slide 44
Can Painful surgical stimulation counteract the ventilatory depressant effect from Propofol?
YES!
(slide 53)
Does Propofol affect the liver?
No not normally. - Liver transaminase enzymes are normal.
(BUT prolonged infusion can cause Hepatocellular injury)
(slide 54)
For a Propofol gtt, what is the % used in ICU and why?
What is TIVA or ‘Balanced’ anesthesia? and what does TIVA stand for?
ICU gtt is 2% to reduce the amount of lipid emulsion administered. 🥛
Total IV Anesthesia - used in conjunction with other anesthetic drugs (fentanyl, versed gtts).
Does Propofol affect the Kidneys?
NO!
Renal creatinine concentrations are normal
(slide 54)
What are 4 side-effects that can develop with prolonged infusion of Propofol?
- Hepatocellular injury
- “Propofol infusion syndrome”
- Green urine
- Cloudy urine
(slide 54)
What is the induction dose of Propofol for:
1) Adults
2) Children (Black Box warning for Propofol Infusion Syndrome)
3) Elderly
1) 1.5 - 2.5 mg/kg IV
2) “~3 - 3.5mg/kg IV” (⬆️ doses); the BB warning exists but apparently we still give it. (I never gave it to kids unless they were teens)
3) ≤ 1mg/kg” (25-50% ⬇️ doses)
Slide 45
What 2 characteristics in the urine are seen with prolonged Propofol infusions?
And what causes these?
- Green urine- from Phenols
- Cloudy urine- from uric acid crystallization
(remember even with these signs, there is no alteration in renal function)
(slide 54)
Onset of Barbiturates is _____ and _____ awakening due to _____ uptake
30 seconds
rapid awakening
rapid uptake
Slide 19
What is “Propofol Infusion Syndrome”?
What causes it?
What are the signs and symptoms?
How is is diagnosed?
Is is treatable?
- Due to: High dose Infusions of >75mcg/kg/min for longer than 24hrs
- S/S: Lactic acidosis, Brady-arrythmias, Rhabdomylosis
- Dx: ABG and Serum lactate concentrations
- IS reversible in early stages by d/c of infusion but can cause Cardiogenic Shock and pt may need accelerated care towards ECMO support.
(Pg. 302 in book)
(slide 55)
Distribution of barbiturates from brain to other tissues is _______
rapid
Slide 19
Does Propofol cause pain on injection?
If so, what are 2 things to help prevent this?
- Yes (seen in <10% of pts)
- Give Lidocaine prior, Or inject in a larger vein
(slide 56)
How many doses of barbiturates are available at 5 minutes and 30 minutes?
At 5 minutes: 1/2 total dose
At 30 minutes: 10% of the total dose
Slide 19
What are 6 other side effects in other organs from Propofol infusion?
- Pain on injection
- Decreased intraocular pressure (IOP)
- Inhibits platelet aggregation (can promote bleeding)
- Allergic reactions (egg yolk/Lecithin)
- Prolonged myoclonus
- Abuse & misuse
(Also found on pg. 301: “Hypertriglyceridemia with prolonged administration, potential for pulmonary embolism) are believed to be due in large part to the lipid emulsion formulation.”)
(slide 56)
Context sensitive half-time with prolonged infusion of barbiturates is _________.
Long
(The longer you infuse, the more it distributes to fats, muscles, and non-vessel-rich groups, and prolongs the recovery from sedation even after you stop the drip –> know the graph in the slide figure 5-19)
Slide 19
Where does the drug distribute first during induction?
Vessel-rich groups like the brain, heart, kidney, and liver
(then, the drug gets distributed to the muscle group and at last the fat group.)
slide 20
During emergence the drug from ____ and _____ group will reinfuse into ______ .
fat and muscle group
brain and viscera
(that’s why pt’s go from stage 3 to stage 2 and finally after metabolism and excretion, we will able to extubate patient)
Slide 20
Reservoir for barbiturates is _____. So, redosing or using larger doses can cause a _____ effect.
Fat
Cumulative effect.
( That is why the context-sensitive half-time is prolonged with barbiturates.)
Slide 21
Barbiturates are dosed according to ?
Lean body weight
Slide 21
Equilibrium of barbiturates to plasma occurs at _____?
15 minutes
( Muscle group is the site of initial redistribution aside from brain and vessel rich group)
Slide 21
If patient is in shock, what happens to the redistribution of barbiturates to muscle group?
Decreases
Slide 21
Muscle mass is decreased in what population?
Elderly and women
Slide 21
How are Barbiturates metabolized and excreted?
Metabolism is 99% via hepatocytes
Excretion via renal
Slide 22
Why do pediatric patients have shorter half-time elimination than adults?
Higher clearance aka higher metabolism (according to DR. Castillo)
Slide 22
What is the percentage protein binding of Barbiturates?
Albumin 70% to 85%
Slide 22
70% to 85% of the albumin-bound barbiturates are active or inactive drug?
Inactive drug
(In order for the drug to be active and reach to effector site, it needs to be unbound or free from plasma albumin/protein)
Slide 22
Lipid soluble form of barbiturates favors ______.
Less lipid soluble form of barbiturates favors ______.
Acidosis and are in Non-ionized form
Alkalosis and are in ionized form.
( so Barbiturates are acidic drug. Barbiturates tend to stay in non-ionized forms and likes to stay in fat and muscle reservoir.)
Slide 23
What are the clinic implications of Barbiturates?
Previously used for hangover
Treat grand mal seizures ( now benzos used)
Rectal administration with uncooperative /young patients ( now we have PO versed or intranasal spray of precedex.)
Increased ICP, cerebral protection, and induction ( barbiturates causes vasoconstriction, ↓CBF,↓CMRO2)
Slide 23
Which isomers of barbiturates are more potent?
S-isomers are more potent than R-isomers of barbiturates
(marketed only as racemic mixture)
Slide 24
Barbiturates are divided into two groups:
Oxybarbiturates
Thiobarbiturates
( we don’t use these drugs anymore in US.)
Slide 24
Name some examples of oxybarbiturates.
Methohexital
phenobarbital
pentobarbital
Slide 24
Name some examples of Thiobarbiturates:
Thiopental
Thiamylal
Slide 24
What is the dose of Thiopental (Sodium Pentothal) and elimination half time?
4mg/kg IV and elimination half-time is longer than methohexital
(longer than propofol and etomidate combined)
Slide 25
In 30 minutes, how much of thiopental stays in the brain?
10% ; causes rapid distribution to skeletal muscles and fat. So need to supplement with inhaled anesthetic quickly so that pt does not wake up after 30 minutes.
Slide 25
Do we increase or decrease thiopental dose in elderly/ shock patients?
Decrease
( Thiopental favors acidic environment)
Slide 25
What is Fat/blood partition coefficient of Thiopental?
11
(which is really high, so the dose is calculated on IBW.)
Slide 25
Do barbiturates cause an induction in enzymes?
Yes
(Slide 33)
With prolonged continuous infusion of barbiturates, how long does it take for there to be an induction of enzymes?
2-7 days
(Slide 33)
With the induction of enzymes by barbiturates, what are some drugs that can be affected?
Would you have to increase their dose or decrease their dose?
Anticoagulants
Phenytoin
Tricyclic Anti-Depressants
Digoxin
Corticosteroids
Bile Salts
Vitamin K
You would have to increase the dose!
(Slide 33)
- What is SSEP?
- When do we use it?
- Why are barbiturates used with SSEP?
- Somato Sensory Evoked Potential!
- SSEP is the sensory level we monitor with scoliosis surgery because we do not want the surgeon to cut the nerves in the spine that can affect the upper and lower extremities!
- They are the desired drugs because they do not affect the neuron transmission component!
(Slide 33)
With barbiturates there is a moderate transient decrease in _____ and _____.
Renal Blood Flow
GFR
(Slide 33)
Is propofol a GABA agonist?
Yes!
(Slide 35)
What is the propofol induction dose for a healthy adult?
1.5 to 2.5 mg/kg IV
(Slide 35)
For the elderly would we increase or decrease the propofol induction dose?
Decrease
(Dr Castillo)
For children, would we increase or decrease the propofol induction dose?
Increase
(Dr Castillo)