2. Sedative, Hypnotics, IV Anesthetics Flashcards
(193 cards)
1
Q
sedation
A
calming and drowsiness
decreases activity
moderates excitement
calms pt
2
Q
hypnosis
A
produces drowsiness
facilitates the onset/mx of sleep
3
Q
anesthesia
A
global but reversible CNS depression results in loss of response to and perception of external stimuli
“deafferentation”
changes in behavior and perception
4
Q
anesthetic effects
A
amnesia
decreased/diminished pain response
immobility to noxious stimuli
analgesia
unconsciousness
5
Q
anesthetic drugs can
A
enhance inhibitory synaptic activity
(GABA/Glycine)
or
diminish excitatory activity
(Glutamate)
6
Q
glutamate anatomy
A
relay neurons all levels and some interneurons
7
Q
glutamate receptors
A
NMDA
AMPA
Kainate
metabotropic
8
Q
NMDA (gultamate)
A
excitatory
increase cation conductance
(esp Ca++)
9
Q
AMPA (glutamate)
A
excitatory
increase cation conductance
10
Q
Kainate (glutamate)
A
excitatory
increase cation conductance
11
Q
metabotropic (glutamate)
A
inhibitory (presynaptic)
- decrease Ca conductance
- decrease cAMP
excitatory
- decrease K+ conductance
- increase IP3
- increase DAG
12
Q
glycine anatomy
A
spinal interneurons and some brainstem interneurons
13
Q
glycine receptors
A
glycine
14
Q
glycine receptor MOA
A
inhibitory
increase Cl conductance
15
Q
GABA anatomy
A
spuraspinal and spinal interneurons
pre and postsynaptic
16
Q
GABA receptors
A
GABAa
GABAb
17
Q
GABAa
A
inhibitory
increase Cl conductance
18
Q
GABAb
A
inhibitory
presynaptic:
- decrease Ca conductance
postsynaptic:
- increase K conductance
19
Q
drug catetogies
A
sedatives
hypnotics
anesthetics
20
Q
potential drug effects
A
amnesia
analgesia
anticonvulsant
muscle relaxation
respiratory
depression
21
Q
drug classes
A
benzodiazepines
non-bz sedative hypnotics (Z drugs)
barbituates
melatonin congeners
IV anesthetics
inhaled anesthetics
22
Q
balanced anesthesia
A
combination of agents to limit dose and toxicity of each agent
23
Q
triad of general anesthesia
A
unconsciousness
analgesia
muscle relaxation
24
Q
IV agent uses:
A
- sedation-based
- monitored anesthesia care
- regional anesthesia
- conscious sedation
- deep sedation
- light general anesthesia
25
monitored anesthesia care (MAC)
regional or local anesthesia delivered with supplemental sedation
26
conscious sedation
small doses
pt mxs airway
pt responds to commands
ICU for prolonged mechanical ventil
27
light state of general anesthesia
loss of protective reflexes
inability to mx airway
lack responsiveness to sx stimuli
28
IV induction side effects
(non-anesthetic)
CV (?)
pain at injection site
movement
hiccups
apnea
29
IV recovery side effects
(non-anesthetic)
restlessness
nausea
vomiting
30
GABA type
inhibitory CNS neurotransmitter
31
GABAa receptor
pentameric structure
- subunits: aby
major isoform has
- 2 alpha 1
- 2 beta 2
- 1 gamma 2
32
GABA binding site (GABAa)
2 sites (one on each lobe)
located between a1 and b2
33
BZ binding site (GABAa)
between a1 and y2
34
BZ binding is
allosteric modulation
35
BZ effects GABAa by
attracting more GABA to the receptor to bind
36
barbituates effect GABAa by
increasing the duration the channel is open
37
allosteric agonist
different binding site
enhance effect
38
allosteric antagnoist
different binding site
inhibit effect
39
onset time
how quickly the drug takes to get from blood to tgt organ
(brain/viscera)
40
continuous infusion half life
pt may take longer to recover from a continuous infusion compared to a single dose due to a prolonged half life
41
barbiturates
methohexital (Brevital)
thiopental (Pentothal)
thiamylal
42
barbituates MOA
-allosteric modulation
-enhance Cl conductance
-increased duration of GABA-gated Cl channel opening
43
barbituates structure
derived from barbituric acid
44
methohexital will elicit
epilectiform activity
used in electroconvulsive therapy or surgeries where seizures are desired
45
barbituates admin
- IV
- rectally (peds)
46
barbituates lipid solubility
high
47
barbituates distribution
plasma:brain equilibrium rapidly
- onset within 30 sec
rapid diffusion to other tissues
- limited duration of induction
(20 min)
48
barbituates and elderly
reduce induction dose
slower redistribution
longer duration of action
49
barbituates repeated doses
(or continuous infusion)
saturates peripheral compartments
minimize redistribution effect
increases duration of action
50
barbituates metabolism
metabolized by CYP enzymes
no active metabolites
51
barbituates elimination
some renal elim of metabolites
some excretion in feces
methohexital cleared rapidly by liver
52
barbituates formulations
alkaline solution for solubility
will precipitate when mixed w/weak bases
- roc, lidocane, labetalol, morphine
53
barbituates site of action
CNS
54
barbituates CNS onset
10-20 sec
bolus lasts 8-20 min
half life: 3-12 hrs
55
barbituates CNS impacts
constrict cerebral vasculature
-decrease BF/ICP
-decrease cerebral O2 consumption
anticonvulsant (except methohexital)
-decreases EEG
decrease pain threshold
involuntary muscle movements
-hiccups, myoclonus
56
barbituates cardiovascular impacts
peripheral vasodilation: BP decreas
neg ionotropic effects (CO decrease) venous vasodilation
- (decrease BP/CO)
vagolytic compensatory responses
- HR and contractility
57
barbituates contraindications
Pt w/o adequate baroreceptor response
- hypovolemia
- beta blocker therapy
- congestive heart failure
asthma pt (histamine response)
acute intermittent porphyria
58
barbituates respiratory impacts
dose related respiratory depression
incomplete suppress of airway reflex
apnea
bronchospasm
hiccup
laryngospasm
59
barbituates histamine release
may cause hypotension/tachycardia
rare allergic reactions
60
barbituates pharmacodynamics
no muscle relaxation
injection pain
no analgesia
no renal/hepatic toxicity
induce ALA-S (may trigger porphyrins)
61
acute intermittent porphyria
neurological disease cause by inadequate porphyrin metabolism
62
porphyrins
highly reactive oxudants
cause toxic neurological seueqlae
63
porphyrias symptoms
nausea
vomiting
abdominal pain
psychosis
lower motor neuron palsies
64
barbituates status
being replaced by propofol
methohexital used for ECT
thiopental not used in US
65
barbituates interactions req dose reduction
opioid
alpha 2 adrenergic agonist
benzodiazepine
acute ethanol
66
barbituate dose reduction for pts w/
anemia
low protein
decreased cardiac output
shock
elderly
67
benzodiazepines (BZ)
diazepam
lorazepam
midazolam
68
BZ mechanism of action
potentiate GABA inhibition
increase efficiency of GABA
increase freq of Cl channel openings
GABA must be present
binds to BZ receptor
69
flumazenil
BZ receptor antagonist
70
BZ structure
3 ring structure
water soluble
- affects parenteral prep
71
BZ lipid solubility
high
speeds up CNS onset
72
diazepam absorption/admin
oral
- 1-2 hr onset
IM
- painful/erratic absorption
73
lorazepam absoprtion/admin
oral
- 1-2 hr onset
IM
- well absorbed
- 90 min peak
74
midazolam absorption/admin
oral
IM
- well absorbed
- 30 min peak
IV
- short onset (minutes)
75
BZ lipid solubility
M>D>L
76
BZ distibution to brain
time to onset:
M
77
BZ redistribution
rapid
3-10 min
short duration of effect
78
BZ protein bound
high
>= 90%
79
BZ metabolism
hepatic
phase 1 oxidation
active metabolites (D/M)
Phase 2 rxns = metabolite
conjugation for elimination
80
BZ half life
D>L>M
81
BZ excretion
renal
enterohepatic recirculation
- Diazepam
82
enterohepatic recirculation
the process by which biliary excreted drug is reabsorbed in the intestine instead of being removed from the body
83
high dose midazolam accumulation
accumulation of active metabolite in pts w/kidney failure
84
high lipid solubility =
high volume of distribution
85
volume of distribution
the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma
86
BZ Vd
L
87
BZ hepatic extraction
Low: D/L
High: M
88
BZ CNS effects
sedation
hypnosis
anesthesia
amnesia
anticonvulsant
muscle relaxation (not paralysis)
tolerance
dependence
decreased CBF/O2 consumpt/ICP
muscle relaxation at spinal cord
anterograde amnesia
antianxiety
stupor/unconsciousness (induction)
control seizure activity
no analgesia
89
BZ cardiovascular impacts
minimal
lg doses may decrease BP
w/opioids may decrease BP
possible increase HR
90
BZ respiratory impacts
minimal respiratory depression
decrease ventilatory resp to CO2
induction apnea
thrombophlebitis
(D>M>>L)
91
BZ drug interaction
drugs that induce/inhibit CYP P450
opioids - decrease SVR = hypotension
decrease MAC (incr potency of IA)
additive effects w/sedative/resp dep.B
92
BZ status
perioperative period
sedation-hypnosis
procedure not req analgesia/full anes
seizure control
ICU sedation
93
BZ receptor antagonist
flumazenil
reversal agent for midazolam
competitive antagonist
no impact to BZ elimination/conc
half-life: 54 min
duration of action: 20 min
re-sedation may occur
94
Ketamine MOA
inhibit NMDA receptor complex
95
NMDA complex
glutamate receptor
affects CNS/spinal cord
dissocaitive anesthesia
- dissociates thalmus to limbic
appears awake but unable to respond to stimuli
no global CNS depression (some stimulation)
96
Ketamine potency
0.1
some psychotomimetic effects
97
Ketamine isomers
S+: potent anesthetic w/o psychotomimetic effects
- greater affinity for NMDA = greater potency
98
Ketamine absorption
IV
or
IM
99
Ketamine distribution
lipophilic
fast onset
short duration (10-15min)
100
Ketamine metabolism
induction of CYP enzymes
extensive hepatic extraction (oral)
101
Ketamine active metabolite
Norketamine
(less potent)
102
Ketamine excretion
renal elimination of metabolites
(aka renal elimination of norketamine)
103
Ketamine analgesic
excellent analgesic at subanesthetic doses (2.5-15 mcg/kg/min)
104
Which drug can be a complete anesthetic?
ketamine
analgesia
amnesia
unconsciousness
105
"complete" anesthetic
analgesia
amnesia
unconcsciousness
106
Ketamine CNS effects
cerebral vasodilator
- increase blood flow
- increase ICP
does not lower seizure threshold
anticonvulsant alt for status epilepticus
107
Ketamine onset
15-30s
108
Ketamine duration
10-15 min
109
analgesia/amnesia onset/duration
immediate onset
duration: 40 min
110
Ketamine emergenc reactions
occur in 10-30% of adults
- delirium, excitement, confusion, euphoria, fear, vivid dreaming, hallucinations
- 1st hour of emergence
- lower rate in peds
111
how to minimize ketamine emergence reactions
benzodiazepine
112
Ketamine cardiovascular reactions
central sympathetic stimulation
- inhibits NE
- increase NE in synaptic cleft
- increase HR, BP, CO
113
Ketamine contraindications
coronary artery disease
uncontrolled hypertension
congestive heart failure
arterial aneurysms
114
Ketamine CV exceptions
may see direct myocardial depression in pts w/ depleted catecholamines/spinal cord transection
w/ very lg doses
(Ca++ channel blocker)
115
Ketamine respiratory effects
minimal effect on RR
minimal effect on ventilatory drive (CO2)
bronchodilator (racemic)
increase salivary/trachiobronchial secretions
116
Ketamine muscular effects
myoclonic activity (uncontrollable twitching)
stimulates uterine muscle contract
no risk for malignant hyperthermia
117
Ketamine drug interactions
a/b adrenergic receptor antagonists
- block ketamine sympa effects
- direct myocardial depress. effects
118
Ketamine drug additives
inhaled anesthetics
propofol
BZ
GABA acting agents
119
Ketamine status
used w/BZ in emergent/trauma situations
severe depression
120
Propofol MOA
interacts w/GABAa receptor
- binds to beta subunit
allosterically increases binding
affinity of GABA for GABAa receptor
- hyperpolarization of membrane
binds to multiple ion channels
- glutamate related
121
Propofol formulation
Not water soluble
1% solution oil/water emulsion
lipophilic (10% fat emulsion)
122
Propofol absorptions
IV only
123
Propofol distribution
rapid onset
short duration
124
Propofol initial distribution half life
2-8 min
125
Propofol metabolism
hepatic &
extra hepatic clearance
hepatic conjugation to inactive metabolites --> renal clearance
126
Propofol Cerebral/CNS effects
decrease cerebral BF, BV, ICP
antiemetic
antipruritic
no analgesic effects
127
Propofol contraindications
pts w/elevated ICP
- can cause critical reduction in ICP unless steps are taken to support BP
pts w/porphyrias
128
Propofol CNS effects
dystonic movements
- excitatory mvmt w/induct/emerg
seizures
- some anticonvulsant properties
- epileptogenic in pts w/seizure diag
129
Propofol tolerance
does not occur w/repeated doses
130
Propofol addiction
not common
131
Propofol cardiovascular effects
decrease BP by 15-40%
- decreased SVR/cardiac filling
- effects contractility
- inhibits baroreceptor response
(HR unchanged w/BP decrease)
132
Propofol BP impacts are greater in
pts w/
hypovolemia
elderly
LV dysfunction
beta blockers
133
Propofol respiratory effects
respriatory depression
decreased CO2 response
30-60 sec apneic period post-induct
inhibits airway reflexes
minimal histamine release
lees impacts to asthmatics
134
Propofol muscle effects
NO muscle relaxation
135
Propofol pain w/injection
burning/stinging
can give lidocaine before/with
opioid before
136
Propofol other effects
sedative/anxiolytic
antiemetic (subanesthetic doses)
antipruritic
OB/GYN safe
137
Propofol porphyrinogenic
increases ALA reductase activity
138
Hypertriglyceridemia
high blood lipids
can be caused by prolonged/continuous propofol
critical care/peds at higher risk
139
Propofol infusion syndrome
metabolic acidosis
lipemic plasma
myocardial failure
hepatomegaly
rhabdomyolysis
140
Propofol status
induction
anesthetic mx
ICU
141
Propofol onset
10-20 seconds
142
Propofol awakening
2-8 min
143
Propofol induction
use w/midazolam
additive effect w/midazolam/opioids
- decrease propofol by 10%+
144
Propofol TIVA
use w/remifentanil and ketamine
145
Propofol and fentanyl
increase concentrations of fentanyl/alfentanil
may be able to decrease propofol dose
146
Propofol dosing (elderly)
smaller induction dose
147
Fospropofol formulation
water soluble prodrug
(no lipid emulsion)
sterile aqueous clear solution
148
Fospropofol metabolism
metabolizes to:
- propofol
- phosphate
- formaldehyde
149
Fospropofol onset/recovery
slower onset than propofol
longer duration than propofol
150
Fospropofol uses
monitored anesthesia care
w/O2
151
Etomidate MOA
enhances GABA
- binds to GABAa (increase affinity)
- increase Cl- conductance
152
Etomidate absorption
IV only
153
Etomidate distribution
high-protein binding
high lipid solubility
large non-ionized fraction
rapid onset
154
Etomidate metabolism
metabolized by:
plasma esterases
hepatic CYP enzymes
155
Etomidate clearance
renal clearance
156
Etomidate CNS/Cerebral effects
potent
hypnotic
decrease cerebral metabolic rate
decrease CBF/ICP
well mx cerebral perfusion
EEG changes
- no seizures during ECT
- seizures in pts w/epilepsy
involuntary muscle movements
157
Etomidate onset
20-30 sec
158
Etomidate duration
5 min
159
Etomidate cardiovascular effects
reduced sympa/barorecept response
decline in SVR
no histamine release
low rate incidence of hypersensitivity
160
Etomidate indication
pts w/
impaired LV function
cardiac tamponade
hypovolemia
emergent tracheal intubation
high risk CV pts
161
Etomidate respiratory effects
less depression
no apnea (unless +opioids)
162
Etomidate endocrine effects
suppress adrenal cortical function
- inhibit 11-b-hydroxylase
(enzyme needed for steroid biosynt - cortisol
- body cant make cortisol 4-8 hrs post sedation
163
Etomidate analgesia
None
164
Etomidate contraindication
not used in ICU sedation
- cortisol not produced 4-8hrs post
165
Etomidate status
typically used w/BZ for induction
- neurosurgical case
- CV risk pts
166
Dexmedetomidine
Alpha 2 receptor agonist
greatest affinity for Alpha 2 in CNS
167
Alpha 2 receptor
stops stimulating NE
168
Dexmedetomidine FDA indications
- sedation of intubated and ventilated pt in ICU
- sedation prior to and/or during surgical procedures of non-intubated pts
169
Dexmedetomidine MOA
selective alpha 2 adrenergic agonist
<24 hr sedation (prolonged use can cause withdrawl)
170
Dexmedetomidine Uses
- presedation
- procedural sedation
- GA supplementation
- ICU sedation
- withdrawl treatment/prevention
- Epidural regional
** No amnesia
171
Dexmedetomidine CV effects
hypotension (25-50% pts)
bradycardia (5-15% pts)
withdrawal effects > 24 hrs
nausea
172
Dexmedetomidine withdrawal effects
BP
nervousness
agitation
headache
173
Dexmedetomidine respiratory effects
little effect on ventilation
174
Dexmedetomidine dosing
loading dose: 1 mcg/kg over 10 min
infusion: 0.2-0.7 mcg/kg/hr
175
Dexmedetomidine onset/duration
rapid onset
half-life: 2 hrs
176
Dexmedetomidine drug interaction
vasodilators
cardiac depressants
drugs that decrease HR
hypnotics
177
Dexmedetomidine reduce dose for
combo w/hypnotics/volatile agents
- offsets hypotensive effects
renal/hepatic insufficiency
178
Dexmedetomidine other uses
post-op shivering
premed for Ketamine/intubation
179
Dexmedetomidine pt candidates
drug/alcohol withdrawal
chronic pain
unwilling/able to take opioids
hypertension
if you need hypotension for sx
ophthalmic surgery
ketamine anesthesia
180
doxapam
respiratory/CNS stimulant
given for respiratory depression
181
doxapam MOA
selective activation of carotid chemoreceptors by low doses
- stimulates hypoxic drive (low PO2)
182
doxapam adverse effects
seizures
muscle fasciculation
HA
dizzy
tachycardia
arrythmia
nausea/vomiting
183
doxapam contraindictions
epilepsy
cerebrovascular and CAD
acute head injury
hypertension
asthma
184
doxapam dosing
IV bolus
0.5-1 mg/kg
185
doxapam onset
1 min
186
doxapam duration
5-10 min
187
doxapam continuous infusion
1-3 mg/min
Max: 4mg/kg
188
malignant hyperthermia
rare (1:15000 peds, 1:40000 adults)
acute hypermetabolic state
mostly on induction
189
malignant hyperthermia signs
profound MMR
tachycardia
hypercarbia
hyperthermia
190
malignant hyperthermia MOA
uncontrolled release of intracellular Ca++ in skeletal muscle
VA or Succ bind to nAChR causing depolarization
depolarization is prolonged in MHR
191
malignant hyperthermia treatment
stop VA/Succinycholine
hyperventilate
bicarbonate
dantrolene
cooling measures
192
dantrolene MOA
binds to Ryr1 receptor of Ca channel
inhibits Ca release from SR
193
dantrolene dosing
20 mg/60mL water
initial dose: 2.5mg/kg every 5 min until episode terminated
Max: up to 10 mg/kg
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