Barbiturates/non-barbiturates Agents Flashcards
(225 cards)
1
Q
Why are barbiturates not classify as either short acting or long acting
A
- Residual plasma concentrations last for hours even after “ultra short-acting” drug are given for anesthesia
- More drug will convert a short acting to long actin
2
Q
Ultra short Barbiturates
A
Methohexital
3
Q
They are _________solutions so they are incompatible with _____, _____ and _______ (NOC)
A
Alkaline salts
Opioids, catecholamines, NMB agents
4
Q
Methohexital usually ___% with a ph of ____-
A
1; 10
5
Q
Barbiturates comes from a combination of the
A
urea and malonic acid.
6
Q
Methohexital ________causes _____activity manifested by __________
A
Methyl radical (methohexital), causes convulsive activity manifesting as involuntary muscle movement
7
Q
**Mechanism of action for Methohexital
A
- Works on neurotransmitter GABA in the CNS/ potentiates effect (inhibitory neurotransmitter)
- Produces sedative-hypnotic effects
8
Q
GABA to cell work by?
A
Hyperpolarize post synaptic cell
9
Q
Barbiturates and propofol on GABA, Mechanism of action
A
Barbiturates and propofol
⇩ dissociation of GABA from receptor
⇧duration of GABA activated opening of chloride channels
10
Q
Barbiturates on RAS ______
• RAS promotes_________
A
- Uniquely depress reticular activating system(RAS)
- wakefulness(⇧ Brain activity)
- leading to hypotension due to venodilation
11
Q
At high doses , barbiturates does what?
A
⇩ sensitivity of postsynaptic membranes to acetylcholine inhibits Ach to bind to Ach receptors enhances muscle relaxation
12
Q
***Fast awakening with methohexital is because
A
*****redistribution from the brain to inactive tissues
13
Q
Elimination of methohexital is dependent on ______%metabolized
A
metabolism• <1% recovered unchanged in the urine (99% metabolized)
14
Q
Methohexital
Effect site equillibration is _________
and Context sensitife half life is ________due to
A
Rapid effect site equilibration
prolonged ; drug sequestered in fat and skeletal muscle reenters the circulation
15
Q
Protein binding parallels_________
• Decreased protein binding due__________ such as aspirin can =
A
- lipid solubility
-to displacement by drugs - enhanced drug effects
⇧ drug sensitivity in pts with uremia and cirrhosis
16
Q
what can decrease protein binding in uremic patients ?
A
⇩ protein binding in uremic pts may be due to
competitive binding of nitrogenous waste products
(displacement by metabolites)
17
Q
_________cause ⇩ protein binding in pts with_________
A
Hypoalbuminemia ;cirrhosis of the liver
18
Q
Most important determinant of DISTRIBUTION
A
Lipid solubility
19
Q
2 Other determinants of distribution other than lipid solubility
A
Ionization
Protein binding
20
Q
For Methohexital the most important determinant of distribution is
A
Lipid solubility
21
Q
__________is a major determinant of delivery- change in blood volume/flow may alter distribution
A
Tissue blood flow
22
Q
***Methohexital in the brain undergo_______within _______
What is the mechanism of early awakening?
A
Methohexital undergo maximal brain uptake within
30 seconds
•Redistribution is the mechanism for early awakening after SINGLE IV dose
23
Q
_________is the most prominent site for initial redistribution of high lipid soluble barbiturates
A
Skeletal muscle
24
Q
During distribution • Initial ____plasma concentration________due to
• Equilibration with skeletal muscle is achieved in _______after IV dose of ________
A
⇩ ; uptake into skeletal muscles
15 minutes after IV does thiopental
25
• Need to ____dose with muscle ______perfusion (shock), _____muscle mass (elderly)
⇩;⇩; ⇩
26
Metabolism of Methohexital
Metabolized where?
Reserve capacity of liver is _______therefore takes ______dysfunction before you have a prolonged effect.
Oxybarbiturates metabolized only in hepatocytes
• Reserve capacity of liver is large -> takes extreme
hepatic dysfunction before a prolonged effect
27
Methohexital vs thiopental which has more rapid metabolism? reflecting less________
Therefore______ remains in plasma= more available for
metabolism
methohexital rapid ;lipid soluble
| More
28
Methohexital Hepatic clearance is______than thiopental
• Early awakening after single IV dose is dependent
on _________
3-4 X more than thiopental
| redistribution
29
For methohexital _________plays a greater role in terminating effects, than________
• Metabolism plays a role in time required for
complete____________
Metabolism; THIOPENTAL ;
psychomotor recovery
30
• Psychomotor functions recover faster with-______than ________
methohexital than thiopental
31
For Methohexital vs Thiopental: recovery time ?
more predictable doses than thiopental
32
What is more dependent on changes in cardiac output and hepatic blood flow ?
Hepatic clearance
33
Barbiturates are excreted where?
Renal system
34
All barbiturates filtered by renal glomeruli:
What limits filtration?
What favors reabsorption into circulation ?
What % is excreted unchanged?
• High degree of protein binding limits filtration
• High lipid solubility favors reabsorption of filtered
drug back into circulation
• <1% methohexital is excreted unchanged in urine
35
_________ and _________are similar for thiopental and methohexital
Distribution half time and Vd
36
_______ and _______differ for methohexital and Thiopental
• Elimination half time and clearance
37
Why is methohexital shorter elimination half time due to ?
• Methohexital’s shorter elimination half time due to
| it’s greater hepatic clearance
38
Elimination half time of methohexital is_____
| Thiopental ______
about 4 hours; 11 hours
39
• Principal uses of methohexital
Induction anesthesia
• Treatment of ⇧ ICP
• Electroconvulsive therapy
• Seizure treatment
40
Barbiturate use is declining due to 5 main reasons among many
Lack specificity of effect in the CNS
Lower therapeutic index than benzodiazepines
Result in tolerance more easily than benzodiazepines
Greater liability for abuse
Paradoxical reaction in elderly
41
What drug has replaced barbiturates?
Propofol has replaced barbiturates
| • Especially when rapid awakening is desired
42
This drug has more rapid recovery of consciousness
Methohexital
43
What is the only barbs with actions sufficient to offer an alternative to other IV induction agents?
Methohexital
44
2 Disadvantages of Methohexital?
⇧ incidence of excitatory phenomena such as involuntary skeletal muscle movements(myoclonus) and hiccough
• High dose associated with seizures in 1/3 patients
45
The involuntary skeletal muscle movement is -_____dependent therefore premedicate with
• Incidence-dose dependent, can ⇩ by premedicate
| with opioids & use optimum dose of (1-1.5mg/kg)
46
Potency and dose
Methohexital vs thiopental? which one more potent and why?
when dose redistribution terminates action ?
Methohexital is 2.5 x more potent than thiopental
⇧ potency is due to lower ionization at physiologic
pH/ Alkaline=burns on injection
- about 8.5 minutes
47
What is the dose of Methohexital dose?
1-1.5mg/kg
48
High dose response curve?
NMB agents, 80-90% of receptors to exert an effect.
49
Alkaline drugs
Burn on injection
50
For uncooperative patients, give methohexital
rectally ; 20-30mg/kg
51
Other uses of Methohexital for neurology ? USe to during
Useful to induce seizures
• ECT
• Temporal lobe resection of seizure producing
tissue
52
Barbs used to_____ICP, along with_____&_______. ⇩
| • Barbs _____metabolic oxygen requirements
⇩ hyperventilation & diuresis
| ⇩
53
How does barb decrease ICP?
by decrease cerebral blood volume through drug
induced cerebral vasoconstriction and associated ⇩
in cerebral blood flow
54
Barb on EEG and head trauma patient
* Isoelectric EEG=max barb effect and ⇩ CMRO2 55%
| * No improved outcomes for head trauma pt
55
Barb High dose =________ = ____cerebral perfusion
| pressure
hypotension;⇩
56
Methohexital
| • Dose required to suppress EEG results in _________ & ___________ similar to isoflurane (2 MAC)
vasodilation & myocardial depression
57
When profound EEG depression is desired? _____ preferred over ____
Barbs is preferred to Isoflurane if profound EEG depression is desired
58
Methohexital Cerebral protection?
Improve brain survival in cardiac patients?
Not recommended for routine _____surgery due to _____ and _________
_______may be protective without prolonging recovery.
No improved brain survival in cardiac arrest
patients
• Not recommended for routine use during cardiac
surgery due to ⇧ need for inotropic support and
prolonged recovery time
• Hypothermia may be more protective without
prolonging recovery
59
Methohexital Side Effects : Cardiac
CV depression
Normovolemic pt- transient 10-20 mmHg ⇩ in BP
and offset by compensatory 15-20BPM ⇧ in HR
Overdose or large dose to ⇩ ICP may cause direct
myocardial depression
60
Methohexital on induction
What happens to BP?
3 reasons?
Induction- mild, transient ⇩ BP due to peripheral
vasodilation (mostly venous), reflecting depression of the medullary vasomotor center and ⇩ sympathetic nervous system outflow
61
Barb and hypovolemic patients?
| 2 classes of drugs that worsen conditions?
Caution , hypotension may occur
Beta blockers and centrally acting alpha 2 agonists
may accentuate this response= more profound
shock
62
For induction of anesthesia, barbs produce a dose
dependent depression of _______and ______ventilatory centers.
• Leads to 3 things?
depression of the medullary and pontine ventilatory centers
⇩ response to hypercarbia
• Low respiratory rate
• Low tidal volumes
63
2 drugs with higher risk for MH
Succinylcholine
| Volatile anesthetics
64
⇧_______when used with other CNS depressant
| drugs used for preop medication
Apnea risk
65
Large doses needed to suppress _____and ________
laryngeal reflexes & cough
66
May occur during intubation?
Laryngospasm or bronchospasm may occur during intubation attempts- no LMA
67
Induction dose doesn’t alter_________
| Induced enzyme induction =
-postop LFT’s
accelerated metabolism of other drugs (oral anticoagulants, phenytoin, tricyclic antidepressants) or endogenous substances (corticosteroids, bile salts and vit K)
68
• Stimulate ________in liver metabolism (____)
| after 2-7 days sustained drug administration
⇧ in liver metabolism (enzyme inducer)
69
Barbiturates stimulate activity of ___________ which leads to _____Production of ______ and may exacerbate which condition ?
• Stimulate the activity of mitochondrial enzyme
• This ⇧ production of Heme, and may exacerbate
acute intermittent porphyria
70
Barbiturates, avoid in pt with _____________
Avoid in pt with Acute Intermittent Porphyria
• Also enhance barbs own metabolism which
contributes to tolerance
71
Barbiturates lead to a Modest _____in renal blood flow and glomerular filtration rate due to
⇩; ⇩ in BP and CO
72
Does barbiturate use for induction of anesthesia produce renal damage?
• Barbiturate use for induction of anesthesia does not
| produce renal damage
73
Barbiturates and placenta?
| Fetal plasma conc vs. maternal concentration
Barbiturates readily cross the placenta
• Fetal plasma concentrations are significantly lower
than maternal plasma concentrations
74
______occurs earlier than enzyme induction
At maximal tolerance the required effective dose
increases _______
- Acute tolerance
| - six-fold
75
Tolerance to the sedative effects occurs
sooner and is greater than the anticonvulsant and lethal effects
76
```
As tolerance to the sedative effects____ the
therapeutic index______(narrow therapeutic index)
```
⇧; ⇩
77
With intra-arterial injection there is ?
Can cause _____ and ________
Risk ___with ___drug concentration
Immediate, intense vasoconstriction and excruciating pain that radiates along the distribution of the artery
Gangrene and permanent nerve damage may result
Risk ⇧ with ⇧ drug concentrations
78
Mechanism of Damage done with intra-arterial injection
```
Precipitation of crystals in the artery leading to inflammation and arteritis, which coupled with the
micro embolization that follows causes
• Occlusion of the distal artery
• Ischemia
• Tissue necrosis
```
79
Intra-arterial injection
Treatment-immediate attempts to dilute drug,
prevention of arterial spasm, general measures to
maintain blood flow
Lidocaine, papaverine, phenoxybenzamine sympathectomy of the upper extremity produced by a brachial plexus block
80
Large role in picking out induction agents
Blood pressure
81
Etomidate doest not
increase or decrease BP or CO
82
Which induction agents will raise BP
Ketamine
83
Which 2 induction agents with analgesic ?
Precedex
| Ketamine (potent analgesic properties)
84
Venous Thrombosis happens because of?
Deposition of barbiturate crystals in the vein
• Less risk because of ⇧ diameter of veins
• Prevented by using dilute concentrations
(1% methohexital )
85
Allergic reactions for IV barbs for induction of anesthesia most likely represent anaphylaxis but can also be anaphylactoid. What is the difference?
• Anaphylaxis- antigen-antibody interaction,
immune mediated and requires prior exposure
• Anaphylactoid- no previous exposure or
sensitization, not a true allergic reaction but results
in histamine release, vasodilation, wheals, and
welts
86
Treatment for allergic reaction of barbiturates
• Treatment- Aggressive fluid replacement & IV EPI
87
What are the NON- BARBITURATE INDUCTION AGENTS ?
```
PDEK
Propofol (Diprivan),
Dexmedetomidine(Precedex)
Etomidate (Amidate)
Ketamine (Ketalar)
```
88
What is PROPOFOL?
| is it chemically different as compared to other IV sedatives?
Emulsion (parental fat formulation intralipid)
1% (10mg/ml)solution in an aqueous solution of 10% soybean oil, glycerol, and purified egg lecithin
FketaminChemically different from all other IV sedative/ hypnotics
89
Equivalence of propofol to thiopental?
1.5-2.5mg/kg IV is equivalent to 4-5mg/kg thiopental or 1.5 mg/kg methohexital
90
Dose of Propofol induction
1.5-2.5 mg/kg rapid IVP=unconsciousness in 30 seconds
91
Advantages of PROPOFOL
Rapid and complete awakening compared to other induction agents
92
```
Continues advantages of propofol include
? effect of CNS
?MH activation
? steroid syntheis, hepatic, histamine release
Comment contxt sensitive half time
Other effects (2)
```
Minimal residual CNS effects
• No MH activation
• Doesn’t affect steroid synthesis or ACTH response
• Does not alter hepatic or fibrinolytic function
• Does not cause histamine release
• Context sensitive half time is minimally influenced by
duration of infusion (<40 minutes for up to 8hr infusion)
• Antiemetic and antipruritic effects
93
MECHANISM of ACTION of PROPOFOL
Modulate what receptors?
When activiated = ________ = ________ =____inhibition
-may also _____the rate of
Sedative-hypnotic effects via GABA activation
• Selective modulator of GABA receptors
• GABA receptor activated= ⇧chloride ions= hyperpolarizes cell= functional inhibition
• Propofol may also ⇩ the rate of GABA dissociation from the GABA receptor
94
Methohexital volume of distribution
Large
95
```
PharmacoKINETICS of Propofol
Clearance?
Metabolism?
Excretion?
Liver and kidney patients effects?
```
Clearance (rapid)from the plasma exceeds hepatic blood flow as well as metabolism
Hepatic oxidative metabolism by cytochrome P-450 to inactive metabolites is rapid and extensive
- <0.3% excreted unchanged in the urine
-No impaired elimination in pt with cirrhosis or renal dysfunction
96
What terminates the action of propofol
Redistribution terminates action
97
What is important for removal of drug (propofol) from plasma?
Tissue uptake (possibly into the lungs) is important for removal of drug from plasma
98
Elimination half life of Propofol?
0.5-1.5 hours
99
Propofol Context sensitive half time is
| • ________effect-site equilibration
<40 minutes for infusions up to 8 hours
| Short
100
For propofol, No evidence of impaired eliminationn
| • Elderly display ⇩ rate of plasma clearance
- in cirrhosis pt
• Renal dysfunction doesn’t influence elimination
- ⇩
101
Clinical uses of Propofol MAC cases
| •
-Induction agent of choice- especially when rapid and complete awakening is needed (MAC cases) - -Continuous IV infusion is commonly used for
conscious sedation or as part of Total Intravenous
anesthesia (TIVA)
102
• ICU sedation- caution in pediatric-reports of
metabolic acidosis, lipemia, bradycardia, &
| progressive myocardial failure
103
Propofol onset of action
10-50 seconds
104
Propofol peak effect
2 min
105
Duration of action
2-5 minutes
106
Advantages short
Short acting, Antiemetic and anxiolytic
107
Some disadvantages of Propofol
```
Dose dependent hypotension
Respiratory Depression
Apnea
NO ANALGESIA/ NO MUSCLE RELAXATION
Burns at injection site.
```
108
Induction dose of propofol
Healthy adults- 1.5-2.5 mg/kg will provide blood levels of 2-6 mcg/ml & unconsciousness
109
For propofol: why do KIDS require HIGHER INDUCTION DOSES?
Kids need higher induction dose due to higher
| central distribution volume and higher clearance rate (3mg/kg)
110
Who require LOWER INDUCTION DOSES and why?
Elderly need lower induction dose (20-25% ⇩) due
to smaller central distribution volume and ⇩
clearance
111
_____effect site equillibration and _____context sensitive half time = ___________
Short effect-site equilibration & short context
| sensitive half time= easy titration
112
Conscious sedation of propofol dose?
| Supplement with _________ for painful procedures
doses of 25-100mcg/kg/min
provide minimal amnestic effects, no analgesic
Supplement with midazolam or short acting opioid for painful procedures
113
Pharmacokinetics comparison of anesthetic agents
not numbers but difference
114
Etomidate can also cause _______another drug that can also cause that is _________
MYOCLONUS; METHOHEXITAL
115
Maintenance of propofol
100-300mcg/kg/min to maintain anesthesia (combined with opiods if need analgesia)
116
General anesthesia with propofol=
Minimal postop nausea/vomiting +Prompt awakening
| Minimal residual sedative effects
117
NONHYPNOTIC THERAPEUTIC USES of PROPOFOL
| What is the subhypnoptic dose?
Antiemetic effects- post op nausea/vomiting is ⇩
when propofol is given regardless of anesthetic
type/drugs used
• Sub-hypnotic doses (10-15mg) may be given in the
post-op area-rapid onset, little side effects
• Effective treatment for chemotherapy induced N/V
118
Propofol ____mg is effective in treating ________associated with _______
10mg is effective in treating pruritus associated with neuraxial opioids
119
Anticonvulsant activity Can terminate status epilepticus- short duration
_________induce seizure activity in epileptic pts
• Doses of >1mg/kg IV ⇩ seizure duration 35-45% in pt
undergoing ECT
• Does NOT
120
_______properties with propofol similar to vitamin ____
Antioxidant properties similar to vitamin E
121
ORGAN EFFECTS- CNS-PROPOFOL
| Effect on CMRO2? ICP? Cerebral blood flow
Decrease, decrease, decrease
122
Neuro effects: Large doses can of propofol can cause _______and a fall in________ and _________
hypotension ; cerebral perfusion pressure
123
• EEG changes similar thiopental_______burst
suppression
• decrease those potentials on EEG?
⇩⇩
somatosensory evoked potentials (SSEP) and
motor evoked potentials (MEP)
124
```
Propofol vs thiopental? CV effect
Systemic BP?
CO and SVR?
BP effects exaggerated in _______, _______and pt with __________ due to _________
Required prior to propofol?
```
⇩ in systemic BP( ⇩ preload) greater than
equivalent thiopental dose
• ⇩ BP often accompanied by changes in cardiac output and SVR
• BP effects exaggerated in hypovolemic, elderly, & pt
with compromised LV function due to CAD
• Adequate hydration recommended prior to administering
propofol
125
Propofol induces _______of smooth muscle and is due to ______________
• Relaxation of smooth muscle is due to inhibition of
| sympathetic vasoconstrictor nerve activity
126
Stimulaiton of ______and _______ does what to BP effects of propofol?
Stimulation of laryngoscopy and intubation reverses
| BP effects of propofol
127
_________ and __________have been seen in
healthy patients despite prophylactic anticholinergics
• Risk- is ____________
•
Profound bradycardia and asystole
| 1.4 in 100,000
128
_________and _________in children in ICU with prolonged use
Severe, refractory and fatal bradycardia
129
What can occur in the pediatric population with propofol?
⇧ in incidence of oculo-cardiac reflex in pediatric strabismus surgery despite prior prophylaxis with anticholinergics
130
Propofol and pulmonary system?
| What can counteract this effect?
Dose dependent depression of ventilation
Apnea occurring in 25-35% of pts after induction
• Effect enhanced with preoperative opioids
• Painful stimuli may counteract this effect
131
Propofol on Vt and RR
Effect on asthma?
effect on ventilatory response to CO2 and arterial hypoxemia?
• Maintenance doses of propofol ⇩ Vt and RR
• Causes bronchodilation and ⇩ incidence of
intraoperative wheezing in asthma pt
• ⇩Ventilatory response to CO2 & arterial hypoxemia
132
Propofol on Liver? Kidneys?
| May cause ____Urine why?
Liver; No adverse effect on the liver
Kidneys :No adverse effect on the kidneys
May cause GREEN URINE due to the presence of phenols in the urine
133
Effects of Propofol on intraoccular pressure?
Associated with SIGNIFICANT ⇩ in IOP which may lead to false readings
134
Caution with Propofol ?
| Prolonged________repored with ________
Allergic reaction to phenol nucleus & diisopropyl side chain
- May lead to anaphylaxis
- May lead to bronchoconstriction
- Prolonged myoclonus has been reported in pt with
meningismus
135
Propofol and bacterial contamination?
• Potential for bacterial contamination. Propofol strongly supports the growth of E-coli and pseudomonas aeruginosa
136
Propofol general aseptic techniques?
Use aseptic technique
•** Discard unused portion in 6 hours
•*** Change infusion line q 12 hours
• HIGH abuse potential- high risk of death
137
Propofol infusion syndrome
Symptoms
Dose associated with PIS
* s/s Lactic acidosis, bradycardia unresponsive to treatment, fat infiltrated liver,rhabdomyolysis
* Pediatric and adults
* High dose infusions (>75mcg/kg/min) for longer than 24 hours
* Reversible if discontinued
138
Propofol airway?
Airway Protection
Inhaled and IV anesthetics alter pharyngeal function with associated risk of impaired upper airway protection and pulmonary aspiration
139
Propofol pain at injection site
Occurs <10% of pts if large vein is used
• Precede injection with lidocaine
• Precede with potent short acting opioid
• Incidence of thrombosis or phlebitis is <1%
• Arterial inject= severe pain but no vascular
compromise
140
Etomidate, Amidate
Carboxylated imidazole-containing compound
chemically unrelated to other anesthesia induction
agents
141
Disadvantage of etomidate
Decrease ability to produce cortisol
142
Aqueous solution is unstable at __________ pH and
| is formulated in a________% solution with 35%__________________ (pH6.9)
Aqueous solution is unstable at physiologic pH and is formulated in a 0.2% solution with 35% propylene glycol (pH6.9)
143
ETOMIDATE and Injection site
Contributes to high incidence of pain at injection site and occasional venous irritation
144
Which isomer is active with EtomIDATE , ? potency?
• Only D-isomer is active and 5 times as potent
145
Etomidate MECHANISM OF ACTION
| What does etomidate not do?
* Binds GABA and enhances the affinity of the inhibitory neurotransmitter (GABA) for these receptors
* Etomidate does not modulate other ligand gated ion channels at clinically relevant concentrations
146
Pharmacokinetics of Etomidate?
Vd?
pka_____, ___% ionized at physiologic ph
• Large Vd, suggesting considerable tissue uptake
• Distribution into body water is favored by moderate
lipid solubility and existence as a weak base
• pKa 4.2, 99% unionized at physiologic pH
147
Etomidate Penetrates brain _____reaches peak levels__________
______%protein bound to albumin
rapidly, within 1 minute
| 76%
148
Prompt awakening with ETOMIDATE is the result of
redistribution to inactive tissues
149
```
****Metabolism of Etomidate
MEtabolized by ?
What is responsible for hydrolysis?
Clearance compared to thiopental? =
Elimination half time is ____hours
```
Rapidly metabolized by hydrolysis of the ethyl ester
side chain to water-soluble, inactive compound
• Hepatic microsomal enzymes and plasma esterases are responsible for hydrolysis
• Clearance is about 5 times that of
thiopental=shorter elimination half time of 2-5
hours
150
KETOFOL
Combined ketamine and propofol to prevent hypotension cause by ketamine.
151
Precedex is a
Centrally acting alpha 2 antagonists
152
Induction dose of Etomidate
• Induction dose- 0.2-0.4 mg/kg IV
153
Excellent amnestic
ETOMIDATE
154
• Can result in loss of airway reflexes
ETOMIDATE
155
Etomidate Onset of unconsciousness occurs in______________circulation
one arm-to-brain circulation
156
Involuntary myoclonic movements are common with ________can be attenuated by ________
awakening compared to barbiturates?
***Attenuated by opioids
Awakening- more rapid than barbs, with little/no
hangover or cumulative drug effects
157
PRINCIPAL LIMITING FACTOR of ETOMIDATE
Principle limiting factor is transient depression of
| adrenocortical function
158
ETOMIDATE on PONV
• May ⇧ PONV
159
No need to know half life of_____know that it is
propofl ; short
160
ETOMIDATE on CBF, CMRO2, ICP?
| Maintain what? ideal for?
• ***⇩ cerebral blood flow and CMRO2
•*** ⇩ ICP
• Maintains cerebral perfusion pressure
Ideal for head injury pt
161
Caution of etomidate in those neuro patients ? because it is used to __________in patient undergoing _________
Caution in pt with history of seizures, and focal
epilepsy
Used to facilitate localization of seizure foci in pt undergoing cortical resection of epileptogenic
tissue
162
For ETOMIDATE, what is the dose for CV stability ?
CV stability is characteristic with 0.3mg/kg IV
| induction dose
163
****ETOMIDATE on HR, stroke volume or cardiac
| output? BP?
BEST FOR PATIENTS with HR and OTHER HEART DISEAS
Minimal changes• Minimal effects on myocardial activity with induction doses in pt with little/no cardiac reserve
• Mean BP may ⇩ 15% due to fall in SVR
164
Propofol, worried about recall may give
VERSED
165
Who can have sudden hypotension with ETOMIDATE?
• Acutely hypovolemic pt could have sudden
| hypotension
166
What dose of ETOMIDATE can cause decrease in BP and CO?
• Dose of 0.45mg/kg may cause a significant ⇩ in BP
| and CO
167
ETOMIDATE effect on Resp system? compared to barb?
TV, RR
how long does the effect last?
Ventilatory depressant effects are less than with
barbs but apnea may occur after rapid IV injection
• Causes a ⇩ in tidal volume that is offset by ⇧in RR
• Effects on breathing are transient, lasting 3-5
minutes
168
ETOMIDATE on renal ?
Does not ⇩ renal blood flow
169
ETOMIDATE at injection site?
| What is recommended?
* Pain on injection
* Pain with IV inject is frequent (80%)
* Administration of lidocaine or opioid prior to injection recommended (Stabilize myocardium, Not to require Increase O2)
170
MYOCLONUS
Excitatory effects that manifest as spontaneous movements, dystonia and tremors
171
• MOA of myoclonus
| What % of patients affected?
Inhibition of subcortical structures that normally suppress extrapyramidal motor activity
• Occur in >50% of pts
172
How can you decrease the incidence of myoclonus?
• Can ⇩ myoclonus incidence with 1-2mcg/kg fentanyl or a benzodiazepine prior to etomidate injection
173
Not good for LMA
Etomidate
174
Etomidate and ENDOCRINE ?
| How long does that effect lasts?
ADRENAL CORTICOL SUPPESSION
Produces a dose dependent inhibition of the conversion of cholesterol to cortisol
Effects last 4-8 hours
175
Use Etomidate in those endocrine patients? 2 types of patients
Use with caution or avoid in pt that may require an
intact ****cortisol response(Sepsis or hemorrhage patients)
May result in “stress free” surgery
176
Incidence of allergic reaction with ETOMIDATE
Very low
| ETOMIDATE KEEPS EVERYTHING EVEN
177
What is Ketamine?
Phencyclidine derivative that produces a “dissociative anesthesia”
KETAMINE INCREASES EVERYTHING
178
Good with asthma 2
Propofol
Ketamine (Bronchodilator) and Respiratory depression
Ketamine cause amnesia
179
What is dissociative anesthesia?
• Dissociative anesthesia resembles cataleptic state
• Eyes open, slow nystagmic gaze
• Appears awake, non communicative
• Varying amounts of hypertonus and purposeful skeletal
muscle movement
180
Ketamine causes
Amnesia
| And INTENSE ANALGESIA with SUB anesthetics
181
Ketamine concentrations
Supplied in 10, 50, 100mg/ml(IM injection )
182
Ketamine concentration for IM injection
100mg/ml
183
Ketamine structures resembles
Phencyclidine
184
S isomer of Ketamine associated with
intense analgesia more than S
185
MOA of Ketamine
Interacted with N-Methyl-D aspartate (NDMA) receptors, and may affect opioid receptors, monoaminergic receptors, muscarinic receptors, voltage sensitive NA channels and calcium channels
186
NDMA is a member of
glutamate recepotr, ligand gates ion channle. EXCITATORY neurotransmitter with glycine as an obligatory coagonist
187
Ketamine
inhibits activation of the NMDA receptor by
glutamate, ⇩presynaptic release of glutamate and
potentiates GABA
188
Ketamine and opioid receptor activiety
Mu, delta, kappa receptors•
189
Some studies have suggested that ketamine may be
| an
antagonist at mu receptors and an agonist at
| kappa receptors
190
Ketamine is Partially antagonized by
| This suggests ketamine is an
anticholinesterase drugs
| antagonist at the muscarinic receptor
191
Ketamine produces anticholinergic symptoms
(emergence delirium, bronchodilation, sympathomimetic action)
192
Ketamine Pharmacokinetics
Resembles?
Onset, duration of action, lipid solubility, pka
Resembles thiopental
• Rapid onset of action, short duration of action, high lipid solubility
pK 7.5 at physiologic pH
High lipid solubility (5-10x thiopental)= rapid
transfer across BBB
193
Protein binding of Ketamine?
Peak plasma concentration after 1 minute IV, 5
| minutes IM Not highly protein bound
194
Ketamine redistribution
Hepatic clearance Vd
Hepatic Extraction?
```
Redistributed
• High hepatic clearance- 1 liter/minute
• Large Vd- 3 liters/kg
• High hepatic extraction ratio suggests alterations in
hepatic blood flow may effect clearance
```
195
Ketamine metabolism
Active metabolites yes or no?
what slows metabolism of Ketamine?
Metabolized-liver microsomal enzymes(CYP-450)
• Norketamine-active metabolite 1/5-1/3 as potent
and may contribute to prolonged effects
• Diazepam slows the metabolism
• Chronic use = enzyme induction and may explain
tolerance of analgesic effects
• Tolerance can occur with >2 short interval
exposures
196
Ketamine unique induction agents why?
recommended to administer_________why?
Which agent is preferred?
What may increase emergency
Recommend to administer antisialagogue
preoperatively to prevent coughing and
laryngospasm due to ketamine induced salivary
secretions
GLYCOPYRROLATE may be preferred(doesn’t cross
BBB) atropine, scopolamine may ⇧emergence
delirium
197
Always want to give
Versed before Ketamine
198
Ketamine and analgesia dose
• Dose of 0.2-0.5mg/kg can produce intense
| analgesia
199
Induction dose of KETAMINE
which dose is higher?
CAREFUL
1-2mg/kg IV or 4-8mg/kg IM
• Consciousness lost 30-60 seconds after IV, 2-4
minutes after IM
KNOW IM vs IV dose
200
with Ketamin return of consciouness_____
| fulll orientation______
Return of consciousness usually in 10-20 minutes
• Return of full orientation, additional 60-90 minutes
• Emergence times are ⇧ after repeated dose or
continuous infusion
• Useful for burn dressing changes
• Useful in hypovolemic pt due to CV stimulating
effects
201
Ketamine induction
May be a __________if endogenous____________
Induction of anethesia with ___________ and _________followed by ________is proposed For _______ patient
May be a myocardial depressant, especially if endogenous catecholamine stores are depleted and sympathetic nervous system responses are impaired
• Induction of anesthesia with diazepam 0.5mg/kg, &
ketamine 0.5mg/kg IV followed by 15-30 mcg/kg/min is proposed anesthesia for CAD pt
• Sub anesthetic doses + propofol for TIVA = more
stable hemodynamics then propofol + fentanyl,
without emergence reactions that may occur with
high dose ketamine
202
Ketamine may cause
Nystagmus not ideal for eye surgery
203
Only drugs of Induction causing induction delirum
Ketamine
204
Ketamine side effects include
Unique in its ability to stimulate the CV system
• Unique in its ability to cause emergence delirium
• May ⇧ ICP placing pts with intracranial pathology at
risk
205
CV effects of Ketamine
Produces CV effects that resemble sympathetic nervous system stimulation
• ⇧ systemic and pulmonary arterial pressure, cardiac
work and myocardial oxygen requirements
• ⇧ in systolic BP 20-40mmHg
206
Ketamine Direct stimulation of CNS leads to ______
| May enhance the _________of Epi (make myocardial more sensitive)
Direct stimulation of CNS leads to sympathetic nervous system outflow
• Evidence =ability of inhaled anesthetics, ganglionic
blockade, cervical epidural anesthesia and spinal
cord transection to prevent ketamine induced
increases in systemic BP and HR
• May enhance the dysrhymogenic ability of
epinephrine
207
Hallmark with KETAMINE
No SIGNIFICANT RESPIRATORY DEPRESSION effect.
208
Ketamine + VA may =
hypotension
• VA depresses the sympathetic nervous system outflow,
unmasks the direct myocardial depressant effects of
ketamine
209
****Ketamine and Diazepam and midazolam-
also effective in preventing the cardiac stimulating effects of ketamine
210
Verapamil attenuates
the BP elevating effects, drug induced ⇧in HR is enhanced
211
Ketamine and NDNMB
Succinylcholine
Pancuronium
Seizure
Enhances action of nondepolarizing neuromuscular- blocking agents due to interference with calcium ion binding or its transport
• Decreases sensitivity of post junctional membranes
to neuromuscular blockers
• Duration of apnea after succinylcholine is ⇧ due to
inhibition of plasma cholinesterase
• Pancuronium enhances the cardiac stimulating
effects of ketamine
• Seizures have been reported in asthmatic pts
receiving aminophylline after ketamine
212
Ketamine Emergencen delirium
| % of patients
Dreams and hallucinations can occur up to 24
hours after administration
5-30%
213
WHat are the factors that increase the incidence of Emergence delirium?
* Factors that ⇧incidence
* Age > 15yrs
* Female
* Doses >2mg/kg
* History of personality disorder or frequent dreaming
214
No significant long term personality differences with which drugs?
present in adults receiving ketamine
215
Emergence delirium is less frequent when
ketamine is repeated
216
PREVENTION OF EMERGENCE DELIRIUM with KETAMINE
Benzodiazepine- most effective
• Midazolam > diazepam
Give benzo 5 min prior to induction
Inclusion of thiopental or inhalational agents may⇩
incidence
Atropine or droperidol may ⇧ incidence of
emergence delirium with ketamine
Pt easily aroused but appear calm and comfortable
217
DEXMEDETOMIDINE, PRECEDEX
• Highly selective, specific and potent full alpha 2
adrenergic agonist(1600 times the affinity for the
receptor)
• Indicated as an adjunct for anesthesia and ICU sedation
Produces hypnotic, sedative and analgesic effects
Produces pharmacologic effects similar to
clonidine-clonidine is partial alpha 2 agonist
Initial dose 1mcg/kg IV, load over 10 minutes
then 5-10mcg/kg/hour= TIVA without ventilatory
depression
0.2-1.5mcg/kg/hr -postop sedation
218
No significnat resp depression associated with
Precedex
219
Pharmacokinetics of Precedex
```
2-3 hours compared to clonidine 6-10 hours
• Large Vd
• Highly protein bound (>90%)
• Undergoes extensive hepatic metabolism
• Renal excretion
```
220
Precedex side effects
Most serious reactions
• Hypotension, severe bradycardia, sinus arrest, arrhythmias atrial fibrillation
Common reactions
hypotension, TRANSIENT HTN, NAUSEA< BRADYCARDIA
Nausea, bradycardia, fever, vomiting, hypoxia
Tachycardia, anemia, DRY MOUTH thirst
221
Depresses transmission in the sympathetic nervous
| system ganglia -
hypotension due to venodilation
222
Comparative thiopental to methohexital Rapid distribution time
Metho 5.6
| Thio 5.6
223
minimal effect on hemodynamics
Etomidate
224
Comparative thiopental to methohexital elimination half time
3. 9 hours metho
| 11. 6 thio
225
Comparative thiopental to methohexital: clearance
Metho 10.9
| Thio 3.4
