non-barb IV induction agents Flashcards
1
Q
What is the generic propofol prepared in?
what does this imply
A
sodium metabisulfite
Caution/avoid in asthmatics because this preparation leads to bronchospasm
2
Q
propofol CV effects
A
- HUGE ↓ in BP (25-40%)
- Greater than with sodium pentothal (STP)
- Dose dependent myocardial depression & vasodilation result in:
- ↓ in SV, ↓ CO & ↓ SVR
- Heart rate unchanged (? baroreceptor inhibition)
- Baroreceptors do not activate nor are inhibited
3
Q
non-barb induction drug that inhibits CYP450
A
Precedex
4
Q
Ketamine amnesia
A
Produces ‘dissociative anesthesia’
- depression of neuronal function in association areas of the cerebral cortex & thalamus
- stimulation of the hippocampus (limbic systems)
produces a marked sensory loss and analgesia, and amnesia
5
Q
Etomidate is what drug class?
A
Carboxylated Imidazole derivative
Imidazole= C3H4N2
6
Q
Etomidate
CNS effects
A
- Rapid loss of consciousness after a single dose
- Cerebral vasoconstriction leads to decreased CBF, ICP, CMRO2, IOP
- Increases EEG activity in epileptogenic foci
- increases myoclonic movements more than propofol and methohexital (disinhibiting extrapyramidal system)
- Anticonvulsant properties, BUT can be associated with Grand Mal Seizures (caution in pt with hx of seizures)
- High N/V
7
Q
induction agent that supresses cortisol synthesis
A
etomidate (Amidate)
8
Q
Precedex metabolism?
A
rapid metabolism
conjugation and CYP45 metabolism
Metabolites cleared in urine and bile
Inhibits CYP-450 (can interfere with opioid clearance)
9
Q
Etomidate causes _1_
via inhibition of the coversion of _2_ to _3_
The enzymes inhibited are _4_ and _5_
This inhibition may provide an advantage of having _6_
A
- dose-dependent adrenocortical supression (adrenal cortex)
- cholesterol to
- cortisol
- 11 beta-hydroxylase
- 17-alpha-hydroxylase
- Stress free anesthesia
10
Q
Ketamine pharmacokinetics
Vd, lipid solubility, onset, DOA, E½t
A
Large Vd (3 L/kg)
High lipid solubility
onset - 30 sec(rapid), short duration
max effect for 1 min, effect terminated by redistribution
DOA 5-10 min
E1/2t 2-3h
11
Q
Which of these non-barb induction agents have analgesia effects?
(Ketamine, etomidate, propofol)
A
KETAMINE
12
Q
Propofol metabolism
A
depends on hepatic blood flow ; clearance exceeds hepatic blood flow
CYP450; mainly by glucuronidation
metabolized to 2 inactive metabolites: glucuronide & sulfate & 1 weak metabolite 1-hydroxypropofol (1/3 potency)
excreted by urine
13
Q
myoclonus side effect comparison
thiopental, etomidate, methohexital, propofol
A
etomidate > methohexital (brevital) > propofol > thiopental (STP)
14
Q
drugs that induce changes in the EEG
A
Thiopental (Pentothal)
Propofol
15
Q
Amnestic dose of propofol
A
30 mcg/kg/min
16
Q
Ketamine class
A
Phencyclidine derivative (PCP)
Non-barb induction agent
17
Q
What solvent is etomidate prepared in?
A
Propylene glycol solvent (anti-freeze)
these were the older drugs, newer drugs don’t cause pain anymore (?)
18
Q
With Etomidate physiologic activity will be ___________ in an acidotic patient
A
Less, but not much.
It is a basic solution with a pH of 8.2, however the pKa is 4.2 and it is 99% ionized at physiologic pH
19
Q
What is the structure of propofol?
A
2,6-di-iso-propylphenol
Oil at room temp, insoluble in aqueous solution
very lipid soluble
20
Q
What type of patients may have and exaggerated respone to hypotension with propofol?
A
- Hypovolemic
- Elderly
- those with poor LV function d/t CAD
Rapid hydration (bolus) prior to administration is recommended
21
Q
How does ampofol formulation differ from diprovan/propofol preparation?
A
Low lipid formula: 5% soy, 0.6% egg lecithin
No preservative needed
More pain with injection
22
Q
propofol other side effects
A
- Pain on injection (premedicate with lidocaine)
- Crosses placenta, rapidly removed from fetal circulation
- Usually use just to induce
23
Q
Which non-barb induction agent potentiates neuromuscular blockade?
A
Etomidate
Enhances NDMR activity
24
Q
Ketamine is a racemic mixture of which enantiomers?
A
Equal parts R and S enantiomers
S enantiomer is
- more potent analgesic
- faster metabolism
- lower incidence of emergence delirium
25
Does propofol depress the spinal cord?
NO
26
Potential **side effects** of propofol due to **lipid emulsion**
1. risk of **infection**
2. pain on injection
3. hyper**triglyceride**mia
4. potental for **pulmonary embolism**
5. bradycardia **(rare** 1.4/100,000**)**
27
Etomidate doses:
induction, maintenance, sedation
Induction 0.2 - 0.3 mg/kg
Maintenance: 10 mcg/kg/min with N2O and opioid (but inc PONV)
Sedation: 5-8 mcg/kg/min
28
propofol
onset, DOA, E½t, redistribution time, contex sensitive time ½t
onset ≈30 sec
DOA 5-10 min (then redistributed)
E½t 0.5-1.5 hrs
redistribution time 2-8 min
contex sensitive time ½t 40 min
29
Propofol induction dose?
Adult vs. toddler
GA maintenance dose?
Sedation infusion dose?
* Induction **1 - 2.5 mg/kg**, up to 3mg/kg
* toddlers/Kids higher dose bc they have a larger central distribution and higher clearance rate
* Elderly need lower dose due to smaller central distribution and lower clearance rate
* GA 100-300 **mcg**/kg/**min**
* Sedation 25-100 **mcg**/kg/**min**
30
Dexmedetomidine MOA
Central and peripheral alpha2 adrenergic receptor agonist
* producing sedation by
* decreasing sympathetic nervous system activity
* decreasing the level of arousal
* regulates the cardiovascular system by
* inhibiting norepinephrine release
* *decreases sympathetic outflow* from the CNS and *augments cardiac vagal activity*
31
propofol class
used in
a phenol derivative
2,6 di-iso-propylphenol
non-barb induction, general anesthesia, TIVA, maintenance
32
How is propofol supplied?
What implications does this have?
1.2% egg
10% soybean oil
2.25% glycerol base solution
* worry about egg **yolk** allergy
* painful on injection
* the prep supports bacterial growth
33
Where does precedex produce hypnosis and anagesia?
Hypnosis in locus ceruleus
Analgesia in spinal cord
34
Does propofol potentiate muscle relaxants?
Nope
35
Ketamine MOA?
* blocks the opening of the NMDA channel and prevents further ion influx → inhibits the excitatory response of glutamate → inhibits memory formation
* When glutamate binds to the NMDA subtype of the glutamate receptor, the channel opens and allows Na+, Ca++ to enter the cell and K+ to exit
* Flux of these ions depolarize the postsynaptic neuron and initiate an action potential.
* depresses transmission of impulses in the medial medullary reticular formation
* this is important for transmission of the affective-emotional components of nociception from the spinal cord to higher brain centers
* binds with opioid (mu, delta, kappa) → subanesthetic doses (0.2-0.5 mg/kg)
* binds to monoaminergic receptors → antinociceptive (at descending levels)
* binds to cholinergic receptors → acts as an antagonist (antimuscarinic effects)
* inhibits neuronal Na+ channels → produces a modest local anesthetic action
* inhibits Ca++ channels → cerebral vasodilatation
36
Precedex CNS effects?
Dec CBF (no change in ICP/ CMRO2)
Dec MAC of volatile agents and opioid requirements
Depress thermoregulation (depress shivering if hypothermic)
37
Precedex dose?
1 **mcg**/kg bolus over 10-15 min
## Footnote
followed by
0.2-1 **mcg**/kg/**hr**
38
propofol respiratory effects
* Apnea after induction dose
* **Faster** & larger doses will produce more apnea (if given slowly the risk is avoided)
* ↓ TV, ↓ RR
* ↓ ventilatory response to CO2 & hypoxia
* PaCO2 rises → ↓ pH
* Bronchodilation in COPD patients → propofol good these patients
* Unless sodium metabisulfite (generic) is present which can lead to bronchospasms
* Hypoxic pulmonary vasoconstriction (HPV) remains **intact**
39
Etomidate metabolism
Liver hydrolysis by hepatic enzymes or N-dealkylation & plasma esterases
to carboxylic acid
FAST biotransformation
excretion: 85% renal, 13% biliary excretion 2% unchanged
40
How is propofol metabolized?
* clearance exceeds hepatic blood flow
* Conjugated in liver to glucuronide and sulfate by CP450 to water soluble compounds
* Liver function doesn't effect rate of metabolism
* safe for liver and renal patients
* renal excretion
* CRF doesn't affect clearance
* less than 1% excreted unchanged
* first pass effect
* Mostly inactive metabolites
* 4-hydroxy-propofol 1/3 potency
41
propofol onset
20-30 sec
"one arm-brain circulation"
42
What is in the preservative of diprivan?
Disodium edetate (EDTA)
43
Induction drug with the most N/V
Etomidate
44
What is the pH and solubility of etomidate like in solution? In the body?
In solution: pH 6.9, water soluble
In body: pH 8.2 (weak base), lipid soluble
45
Ketamine: respiratory effects?
Minimal, no CO2 response alteration
Bronchial smooth muscle relaxation
Increases PVR (avoid in pulmonary hypertension)
Increases salivation
46
Which drug has a greater decrease in BP propofol or TPL?
Propofol
47
Ketamine doses
premedication (sedative/analgesic), induction, maintenance?
Premed: 0.2-0.5 mg/kg
Induction 0.5-2 mg/kg IV
Maintenance: 1-2 mg/kg/hr
48
Dexmedetomidine pharmacokinetics
PB
E1/2 t
Vd
Highly PB - 90-94%%
E1/2t 2-3h
Vd 3 L/kg
49
Which of these are chiral compounds:
Thiopental, etomidate, ketamine, propofol
All EXCEPT for propofol
50
Dexmedetomidine (precedex) is ____ soluble (water/lipid)
Water
51
Etomidate: CV effects
MINIMAL, lacks SNS effects
HR, BP, PAP, CO, SVR, PVR = unchanged
52
Ketamine: CV effects?
Sympathomimetic NMDA effect & inhibits reuptake of NE
inc BP, HR, CO
Inc myocardial work and O2 consumption
Myocardial DEPRESSANT, especially in sick people with decreased NE stores
53
Etomidate MOA
augumens the inhibitory tone of GABA at the GABAa receptor
Increases affinity of GABA to GABA-a receptor, which increases chloride conductance, hyperpolarizing/inhibiting the postsynaptic cell membrane (same as propofol)
binding at ß2=sedation, other properties
binding at ß3=anesthetic properties
54
Why must an **opioid** be given with Etomidate, Propofol and Barbiturates for the induction of anesthesia
They have **NO** **analgesic** **properties**, and the opioid is needed to blunt the SNS response to laryngoscopy
55
what factors influence propofol's pharmacokinetics?
* weight (calculate dose to IBW)
* co-existing diseases
* age (ex: kids need more of the drug)
* co-administration of other drugs
56
how does age affect propofol dosage
increase dosage with younger patients (they have the highest ED95)
decrease dosage with the elderly
57
Etomidate: Respiratory effects
Ventilatory response to CO2 depressed minimally
Decrease TV Increase RR
(except big fast dose can lead to apnea)
Hiccups, coughing
58
Precedex respiratory effects?
Minimal change in RR
Moderate dec in TV
No change in CO2 responsiveness (good for COPD pts)
Upper airway obstruction possible
59
Precedex CV effects?
Dec HR, SVR, BP
(bolus can cause a transient **increase** in BP and **dec** HR)
Potential for severe bradycardia, heart block, systole
Decreases catecholamine levels during GA
60
Dexmedetomidine antagonist
Antipamezole
it is a specific and selective alpha-2 antagonist that will rapidly and effectively reverse sedative and CV effects of precedex
(also reserached as potential anti-parkinson's)
61
propofol CNS effects
* ↓ CBF, ↓ ICP, ↓ CMRO2, ↓ CPP, ↓ IOP
* cerebral protection
* cerebral protection from antioxidant effects (resembles Vitamin E)
* EEG burst supression
* hiccuping
* myoclonus
* hallucinations
* opisthotonos (weird eye positioning)
* anti-emetic & anti-pruritic effects at (low, sub-hypnotic doses)
62
Etomidate pharmacokinetics
(lipid solubility, onset, peak, DOA, Vd, E1/2t, PB)
highly lipid soluble
onset ≈30-60 sec
peak 1 min
DOA 3-5 min (terminated by redistribution)
Vd 2.5-4.5 (large)
E1/2t 3-5h
High hepatic extraction ratio and clearance (caution in liver patients, prolonged effects)
Highly protein bound (75%)
63
Etomidate: Endocrine effects
Prevents conversion from cholesterol to cortisol by inhibiting 2 enzymes (major: 11-beta-hydroxylase, minor: 17-alpha-hydroxylase)
Adreno**cortical** suppression for 4-8 hrs reduces mineralocorticoid and corticosteroid production
64
Propofol pharmacokinetics
E1/2t? VD?
E1/2t 0.5-1.5h
LARGE VD 3.5-4.5 L/kg
65
Propofol is excreted renally, how is this effected in chronic renal failure
It does not effect clearance d/t inactive metabolites
66
Ketamine: CNS effects
Crosses BBB
Dissociative state
caused by depressed neuronal function in association areas of cortex and thalamus while stimulating limbic/hippocampus (caution with psych patients)
Amnesia (less than benzos),
nystagmus (rapid eye movement),
pupil dilation,
salivation, lacrimation,
myoclonic activity
Increases CBF, metabolic rate/ CMRO2, ICP, IOP
Emergence reactions: dreaming, out of body sensation, illusions, fear
67
Ketamine contraindications?
Inc ICP
Open eye injury
CAD (for sole anesthetic)
Vascular aneurysm
Uncontrolled HTN
pulmonary HTN
Psych diseases/PTSD
Pheochromocytoma
68
What is a **limiting factor** in using etomidate for induction of anesthesia
It depresses aderenocortical function
69
Propofol Vd
3.5-4.5 L/kg
70
Propofol MOA
1. decreases the rate of dissociation of GABA from GABAa
1. increases Cl- influx in the cell → hyperpolarization
2. decreases neuronal excitability
2. potentiates the binding of GABA to GABAa (ß1 subunit)
3. inhibits glutamate action at the NMDA receptor
71
which drug causes hypnosis through locus ceruleus?
Precedex
72
**Prompt awakening** of propofol, ketamine and etomidate is due to
**Etomidate, Ketamine** = **redistribution**
**Propofol** = high drug **metabolism**
73
Dexmedetomidine drug class?
Alpha-2 adrenergic agonist
74
Ketamine metabolism?
Hepatic **enzymes** to ACTIVE metabolite: norketamine (not a significant clinical effect) &
**hydroxilated** to hydroxynorketamine & **conjucated** to water soluble
urinary excretion
Clearance affected by liver blood flow (equal to HBF)
75
propofol redistribution 1/2 time
2-8 minute
CNS actions are terminated by redistribution from the brain to other compartments
76
What is the reason aquavan (fospropofol) isn't used often?
Fospropofol is the prodrug of propofol
once it gets to the plasma, it hydrolyzes to propofol
It effects people differently and is therefore very **unpredictable**
has slower onset, higher Vd, and higher potency
77
Effects of Propofol
1. Sedation/hypnosis
2. Anesthesia
3. Amnesia
4. Antiemetic
5. Antipruritic
6. Anticonvulsant
7. Attenuation of bronchoconstriction
78
Propfol unlike thiopental, etomidate and ketamine is not a ___________ compound
Chiral
