Sedatives/Hypnotics Flashcards
1
Q
first recorded parenteral agent to produce a hypnotic state
A
Christopher Wren
1657
injecting an aqueous opium solution into a dog
2
Q
first hollow needles
A
Francis Rynd
1845
injected a morphine solution around nerves to treat neuralgia
3
Q
Why were hollow needles significant?
A
could now be sterilized
instead of using porcupine needles lol
4
Q
first recorded IV anesthetic
A
chloral hydrate
Pierre Ore’
1872
5
Q
IV administration of inhalational anesthetics
A
unsuccesful
6
Q
changed everything in the early 1900’s
A
specific agents
barbiturate testing
7
Q
opened the era of IV anesthesia
A
first administration of thiopental in 1934
8
Q
When was ketamine released?
A
1970
“ketamine: hallucin8ing is very 70s”
9
Q
When was etomidate released?
A
1974
10
Q
When was midazolam released?
A
mid 70’s
11
Q
most used benzo in anesthesia
A
Midazolam
12
Q
T/F
inhalationals are the preferred anesthetic
A
False
IV preferred
partially d/t less equipment needed
13
Q
When was propofol released in its current form?
A
1986
Diprivan
problems with formulation d/t its high lipid solubility
14
Q
Drugs take about ____ years to bring to market, costing about ____ dollars
A
10-15 Y
~1 billion
15
Q
T/F
“Sedative/Hypnotics” accurately describe the class of medications it encompasses.
A
False
old terms
not specific
16
Q
Sedative
A
mild suppression of arousal and behavior
slight decrease in alertness and response to stimuli
17
Q
T/F
Sedatives produce certain degrees of CNS depression, but not anesthetic levels.
A
True
18
Q
Hypnotic
A
pronounced sedative effects
induction of sleep
19
Q
T/F
Sedatives can cause sleep in the proper dose
A
False
hypnotics cause LOC in proper doses
20
Q
T/F
Hypnotics can provide anesthesia level LOC
A
False
not quite anesthesia level b/c still arousable to strong stimuli
21
Q
T/F
Most sedatives become hypnotics in higher doses
A
True
22
Q
Sedative/Hypnotics
example agents
A
alcohols
barbs
BZD
misc (meprobamate, meathqualone, Droperidol, etomidate, propofol)
23
Q
T/F
Alcohol is considered a sedative/hypnotic.
A
True
24
Q
Why can’t ethanol alone be used for anesthesia?
A
level that causes LOC can cause death
too many side effects
25
Chloral Hydrate is still often used in which pt population?
children
26
Thiopental was optimal for (short/long) duration cases.
short
27
T/F
Thiopental and methohexital are considered similar.
true
28
T/F
Pentobarbital & Phenobarbital are part of different families but have the same effects.
False
same family
different effx
29
T/F
Phenobarbital was once commonly used a sleeping pill, but not as common now d/t side fx.
False
Pentobarbital
Phenobarb: seizures, psych disorders
30
induces its own metabolism
phenobarbital
31
T/F
The phenobarbital dose for a chronic user may be fatal to a person who has never taken it before.
True
phenobarbital induces its own metabolism
body builds resistance
32
BZDs have largely supplanted the BARBs, except for ____
methohexital
33
T/F
BZDs can be the solo agent used in short procedures.
False
used as an adjunct
34
Use of preop BZDs (increases/decreases) anesthetic requirement.
decreases
produces some CNS depression
35
Known as Quaaludes
Methaqualone
36
T/F
Methaqualone is still available on the market.
False
heavy abuse caused issues in distribution
37
T/F
Sedative/Hypnotics' MoA is similar, but not identical.
True
38
Sed/Hyps mainly act on _____.
polysynaptic pathways
39
Sed/Hyps usually fxn to _____.
increase presynaptic inhibition
40
T/F
Sedative/Hypnotics all lead to CNS depression.
True
41
Why is our understanding of sed/hyps limited?
it works in the brain
anything working in brain is hard to ID all mechanisms
42
T/F
Different brain areas have different levels of susceptibility
True
43
Most Sedative/Hypnotics are believed to enhance...
pre- and post-synaptic effects of GABA (gamma-aminobutyric acid)
44
polysynaptic pathways
go thru multiple nerves
45
monosynaptic pathways
one nerve going one place to another
46
We tend to block thses with compounds
interneurons
47
GABA is an (excitatory/inhibitory) (compound/NT) because it...
inhibitory
NT (neurotransmtr)
decreases the ability of depolarization
48
Sedative/Hypnotics Mechanism of action:
GABA ___ Augmentation
Ionophore
(ionophore = ligand gated)
49
How many GABA sites on the GABA receptor?
2
50
Which GABA binding site are we most concerned with?
GABA A
51
GABA receptors came from ...
5 subunit protein structure
52
T/F
GABA receptors are quadrameric in structure.
False
**penta**meric
53
Cl- is higher in the (ICF/ECF)
ECF
54
Na is higher in the (ICF/ECF)
ECF
55
K is higher in the (ICF/ECF)
ICF
56
Ca is higher in the (ICF/ECF)
ECF
extremely small amount in ECF and ICF
57
At which voltage can Cl- no longer move into the cell?
-90
58
Na stops moving into cells @ which voltage?
-30/-40
59
When ICF is extremely (+/-), it is harder to depolarize.
negative
60
T/F
Cl- ions cannot flow into the cell if the ICF is at -70 mv.
False
the Cl gradient (ECF vs ICF) is so large, that it overcomes the repelling - charge from ICF
until about -90 mv
61
Depolarization occurs when membrane potential is closer to ___.
0
62
BZDs ___ GABA fxn by....
augment
increasing CNS depression
63
Lowering ICF voltage makes it (easier/harder) to depolarize.
harder
64
T/F
A single GABA molecule can open the channel completely.
False
need two! Two sites
65
T/F
A single molecule of GABA can bind and cause some Cl- to enter the cell.
True
not as much Cl- will enter as when 2 GABA molecules bind tho
66
How many GABA molecules need to bind to change the ionophores structure?
only 1
1 =changes structure; some Cl- influx
2 = full effect
67
T/F
most ionophores need 2 molecules to bind for full effect
True
68
T/F
Most brain pathways are excitatory.
False
inhibitory
69
Too much excitatory activity may result in...
excessive neuron firing
epileptic conditions
70
Picrotoxin
strong stimulant
**prevents GABA from binding**
epilieptic type/stimulatory effects
71
Anything blocking GABA causes...
epilieptic type/stimulatory effects (ie: picrotoxin)
72
T/F
GABA only acts when we introduce sed/hyps into the body.
False
GABA acts brain all the time by providing inhibition at certain times
73
T/F
The GABA A receptor complex spans the membrane.
True
allows Cl- to pass thru bilayer & enter ICF
74
T/F
The GABA A receptor complex is mostly composed of B-pleated sheets inside the channel.
False
Mostly alpha helices inside channel
75
Form the "mouth" of the GABA A receptor complex.
spiral helices
76
Ach receptors at the NMJ are ____.
ionphores
77
Twist more or less to open/close channel of GABA A receptor complex.
spiral helices
78
T/F
Glutamate is an inhibitory neurotransmitter.
False
Glutamate is an excitatory neurotransmitter
glutamate = excite
GABA = inhibit
79
voltage-dependent ionophoric system
Glutamate
80
Sed/Hyps works by (agonizing/antagonizing) the Glutamate Receptor.
antagonizing
81
NMDA glutamate receptor complex
Which ions to enter?
Which exit?
Calcium and Sodium IN
Potassium OUT
82
T/F
NMDA glutamate receptor complex works independently of the membrane potential
False
allows Ca & Na in; K out
*depending on local membrane potential*
83
T/F
Ketamine appears to act primarily at the PCP binding sites on the GABA A receptor complex
False
84
Which receptor has a QUADRAmeric structure (4 subunits)?
NMDA
85
Ca and Na entering cell causes (repolar/depolarization)
depolarization
they're + ions
86
Ketamine and PCP both cause hallucinations. Why?
Ketamine and PCP act on same site = hallucin8 with ketamine
(gen class: Ketamine is an analog of PCP)
87
angel dust
PCP
88
glycine allows ___ to act properly
glutamate
89
Glycine vs. GABA
which is most present in the brain?
which is most present in the SC?
brain: GABA
SC: glycine
90
T/F
Nicotinic receptors have a pentameric structure.
True
91
Glycine receptor
Inhibitory neurotransmitter complex similar to GABAA
2 sites for glycine
92
2 phases of sleep (that we discussed)
Slow wave sleep (SWS)
Rapid eye movement sleep (REM)
93
Rapid eye movement sleep (REM)
skeletal muscles are relaxed (inhibited) and the eyes move back and forth rapidly.
94
Slow wave sleep (SWS)
EEG shows mainly high-voltage synchronous activity
95
How much of sleep is REM?
~25%
1-2 H
96
Hypnotic sleep differs...
SWS altered & shortened
REM depressed
Total sleep time longer
97
T/F
Without SWS, people can become psychotic.
False
REM
98
Which drug class is known to inhibit REM sleep?
BZDs
99
T/F
Hypnotics can produce longer, deeper sleep.
False
longer but not very deep
inhibited REM
100
Twitching/movement seen during REM sleep
Breakthrough
101
Barbiturates
Onset and duration of effect generally predictably based on...
lipid solubility (higher partition coefficient)
102
Barbiturates
more lipid soluble agents (higher partition coefficient) usually have the more ___ onset and ___ duration
rapid
shorter
103
Inhibits oxidative phosphorylation
BARBs
cell fxns requiring energy slows down
Slows down whole body
104
Overdoses with BARB sleeping pills
awaken thinking they didnt take pill
could happen multiple times in a night
OD
105
T/F
BARBs have a wider T.window than BZDs.
False
BZDs have wide TW; harder to OD
106
Barbiturates MoA
-Bind to GABAA receptor
-(diff site than BZDs)
-Decreases the dissociation rate of GABA
-increase Cl conductance
-**inhibits excitatory glutamate AMPA receptors
-inhibits Ca mediated glutamate release**
107
T/F
BZDs and BARBs bind to the same site on the GABA receptor.
False
they have separate sites
108
Barbiturates MoA
outside of GABA receptor
inhibits:
1) excitatory glutamate AMPA receptors
2) calcium mediated glutamate release
109
T/F
Barbiturates mimic the action of GABA at the GABAA receptor to the same extent.
False
mimicking is minimal
major effects require GABA
110
T/F
Barbituric acid has no sedative powers of the parent compound.
True
111
structure we get all BARBS from
Barbituric acid
Exists in keto and enol forms (tautomers)
112
Replacement of C-2 oxygen with sulfur results in (2)
thiobarbiturates
&
greater lipid solubility
113
Addition of various functional groups onto position ___ alters sedative/hypnotic properties
5
114
Addition of a ___ group at C-5 enhances anticonvulsant activity and produces ___.
phenyl
Phenobarbital
phenyl @ 5 = pheno
115
Addition of a ___ group to the ring N atom shortens duration of action and produces ___.
methyl
Methohexital
Methyl to N =methohex
116
117
118
which positions are 1, 2 & 5?
what are their significance?
sites of substitution
119
Which class exists in tautomer forms?
BARBs
120
Barbiturates by duration
Long: Phenobarbital
Intermediate: Pentobarbital & Secobarbital
Short/Ultra-short: Methohexital & Thiopental
121
T/F
Complications and side effects lead to the discontinuation of Thiopental by the FDA.
False
DC’ed by manufacturer
refused to sell to US b/c we use it to kill ppl
122
Position 5 increases ...
lipid solubility/mvmt into tissues
123
T/F
Barbiturates are weak bases.
False
Barbiturates = weak **acids**
124
What is the basic form of BARBs?
sodium salt (carboxylate form)
125
BARBs are packaged as ___.
sodium salt, which is the basic form
(carboxylate form)
126
The ___ pH of BARB sodium salt solution makes it ____.
high
bacteriostatic
126
T/F
We can remove multiple doses of a BARB out of its packaging.
True
pH = bacteriostatic
however, only **stable for a couple weeks or else precipitates**
127
lipid soluble agents
__ onset due to rapid increase in ____ concentration, followed by rapid ___ to other body fatty tissues.
shorter
brain
redistribution
128
T/F
BARBs are lipid soluble.
True
129
As a drug redistributes, the brain [ ] (increases/decreases)
decreases
130
primary mechanism of cessation of action of lipid sol Rx in the brain
Redistribution (to fat)
131
What does this chart tell us?
Thiopental
brain uptakes the fastest
balances with plasma [ ]
moves into other tissues
brain [ ] drops
Fat [ ] increases as [ ] in all other compartments drop
132
Thiopental
As fat [ ] increases, [ ] in other tissues (increases/decreases)
decreases
133
Primary metabolic pathway for BARB metabolism is...
hydroxylation to inactive metabolites
(Phase I)
134
phenobarbital t1/2
86 hours
slowly metabolized
135
BARB metabolism
occurs to a larger extent in oriental populations
N-glucosylation
136
Potent inducers of the hepatic microsomal enzyme system
BARBs
137
BARBs can increase metabolic rates of drugs metabolized by ____. These include....
hepatic microsomal enzyme (CYPs)
oral anticoagulants, phenytoin, TCA’s
138
Hydroxylation is a Phase ___ reaction.
I
its a CYP
139
Your pt is taking phenobarbital regularly for epilepsy. For their anesthesia, you would use drugs that ...
Use phase II/renal metab
140
Cerebral edema occurs when...
prolonged hypoxia
cell damage/death causes swelling
141
What can cause cerebral edema?
drowning
OD
ilicit drugs
142
How does cerebral edema cause an impedance to blood flow?
Brain swelling impinges upon bony structure
closes off blood flow d/t pressure
143
Do BARBs cross the placenta?
Yes
144
BARB is mostly Phase ___ metabolism.
I
145
BARBs are less used now b/c...
BZDs safer and equally effective
**Drug interactions (enzyme induction)
Tolerance development
Greater abuse potential
Less CNS specificity than BZDs**
146
BZDs advantages over BARBs
higher specificity
safer (wider T.window)
equally effective
147
BARBs primary use
-Therapeutic/diagnostic (psych)
-cerebral edema (surgery, head injury, cerebral ischemia)
-Antiepileptic
148
What causes BARB tolerance
enzyme induction (CYP)
149
T/F
BARBs offer extensive pain relief and muscle relaxation.
False
150
Repeated administration of thiopental
will fill the body's storage sites (fats) and can lead to long duration of action
(already some in fat, less [ ] differential btwn blood and fat; does not go into fat as quickly
Additional doses = longer duration
Not so much on second dose)
151
T/F
Thiopental increases sensitivity to pain
True
lowers pain threshold
152
Thiopental can induce in ____
10-15 seconds
153
2-3 times as potent as Thiopental
Methohexital
154
Methohexital metabolism
primarily via P-450 oxidation
metab faster than thio
(due to less lipid solubility)
155
T/F
Thiopental is more lipid soluble than methohexital.
True
156
Which has longer effect?
Methohexital
Thiopental
Thiopental
methohexital = less lipid-sol
-metabolized faster
-redistribution
157
Methohexital is more potent than thiopental, but its effect is lost mainly d/t ...
due to re-distribution (even though less lipid soluble)
158
Which has faster recovery?
Thiopental
Methohexital
Methohexital
metabolized faster (due to less lipid solubility) primarily via P-450 oxidation
159
BZDs were first introduced for the treatment of
anxiety
160
BZD properties (4)
sedative
antianxiety
anticonvulsant
muscle relaxant
161
T/F
BZDs can achieve hypnosis and unconsciousness in large doses
True
162
BZDs used to supplement or to induce and maintain anesthesia
**Diazepam (VALIUM)**
lorazepam (ATIVAN)
midazolam
163
1/2 L of midazolam vs diazepam
M: 1H
D: >24 H
164
T/F
BZDs are mostly metabolized via glucuronide conjugation.
False
Many = microsomal N-demethylation (diazepam)
some (oxazepam) rapidly via glucuronide conjugation.
Midazolam: microsomal hydroxylation
165
Midazolam metabolism
rapidly mainly via microsomal hydroxylation
166
T/F
Caution with liver Dz pts & BZDs
True
167
T/F
1/2 life determines how long the effects of a medication will last.
False
1/2 life of effect
168
T/F
Lorazepam (Ativan) does not undergo Phase I metabolism.
True
169
⭐️
BZD receptor site
specific receptor sites
GABA receptor α and γ subunits
CNS
(ONE BZD site
Has TWO GABA sites)
170
BZDs primarily affects cells in the ___
brain
171
BZD MoA
-**α and γ subunits (GABA receptor; CNS)**
-**enhance GABA binding to its receptor**
-more Cl- in
-hyperpolarization
-resistant to excitation
(Vs BARBs: decrease GABA dissociation rate)
172
T/F
BZD receptors are found only in post-synaptic regions in the CNS
False
almost exclusively
173
T/F
BZDs have minimal effects in other areas of the body other than the CNS.
True
(except effects caused via CNS control)
174
BZDs receptor is greatest in the ______ & areas associated with ____.
cerebal cortex
memory formations
175
T/F
BARBs cause amnesia
False
BZDs do
176
T/F
BZDs have a smaller side effect profile
True
177
Area responsible for memory/consciousness/thinking
Neo Cortex
178
T/F
Anesthetic agents work in a bottom-up fashion.
False
work top-down
Neo cortex to lower brain
179
T/F
neo cortex regulates breathing/autonomic fxns
False
lower brain/lizard brain
180
Benefits of anesthetics affecting neo cortex before lower brain
affects memory/consciousness/thinking
before breathing & autonomic fxns
181
What do patients forget when we give then BZDs in preop?
don’t remember things just prior to surgery (exposure to OR)
182
BZD
CV effects
mild
minor decrease BP & SVR
183
T/F
BZDs increases heart rate.
True
Heart rate *may* decrease or increase somewhat, probably reflexively
depends on a person's state
184
Rapid infusion of ____ risks ____, so resp support should be available.
Diazepam
transient apnea
(BZDs all carry risk of transient apnea, but rapid IV Diazepam especially)
185
BZDs induces relaxation of spastic skeletal muscle activity via ____
central inhibition
186
T/F
BARBs treat delirium tremens
False
BZDs
187
BZD Clinical Uses
Pre-op meds
Induction
sedation
Anticonvulsant
**delirium tremens
Skeletal muscle relaxation**
188
T/F
BZDs provide smooth muscle relaxation.
False
skeletal
189
T/F
BZDs are used as anesthetics.
False
190
T/F
BZDs cross the placenta well and leads to fetal depression.
True
191
Which BZD can lead to true physical dependance?
diazepam (long DoE d/t desmethyl metabolite)
“Diazepam dependance”
192
Flumazenil (Romazicon)
**Competitive Benzo antagonist**
IV
treat OD
almost immediate reversal
193
We must give Flumazenil (Romazicon) cautiously b/c...
give too much = seizure
194
astringent
Locally cause dehydration of cell **proto**plasm
195
Alcohol produces a cooling effect on skin due to
rapid evaporation
196
Applying alcohol & rubbing the skin
Rubbing: increases blood flow
alcohol: cools more blood at a time
197
T/F
Alcohol efficiently makes your body warmer in cold weather.
False
cutaneous vasodilation brings heat closer to surface = *feel* warmer
but
cold environment can suck this heat off you quickly
deadly
198
High dose alcohol injections near nerves
blocks conduction by decreasing Na+ and K+ conductance
but
we don't do this b/c high doses needed
199
Alcohol **bactericidal** effect
ethanol penetrates lipid BL
increases fluidity of membrane
friction/shear tears bacterial membranes
200
T/F
Alcohol is considered a potent CNS depressant
True
201
Ethanol has a (wide/narrow) T.window as a general anesthetic.
narrow
why we dont use it for that
202
Raises pain threshold and causes euphoria
ethanol
203
Ethanol
resp effects
Depresses medullary sensing of plasma CO2
Long periods between respirations
204
T/F
Ethanol has anticonvulsant activity and may be used for these purposes if the patient is unresponsive to other means.
False
Anticonvulsant at [ ]s that depress other CNS functions
205
T/F
Ethanol causes cardiac depression by both central and direct mechanisms at high plasma [ ].
True
cardiac depression
central & direct
206
T/F
Ethanol can damage your muscles.
True
Small doses: increase work ability via central mechanisms
larger doses: decrease work; directly damage
207
T/F
Ethanol [ ] 10% and higher increases gastric blood flow and secretions
False
20%
208
What causes vomiting from ethanol?
large ingestions due to local irritant effect (gastric irritation and erosion)
209
Why do alcoholics have problems with fatty livers?
Increases synthesis of fat in liver
210
Cirrhosis seen in (short/long) term abuse
long
211
____ [ ] ethanol suppresses appetite.
high
212
Ethanol metabolism
ethanol --alcohol dehydrogenase--> acetaldehyde
213
alcohol dehydrogenase
liver enzyme
contains zinc
requires NAD cofactor
214
Acetaldehyde metabolism
using aldehyde dehydrogenase
becomes acetic acid
215
T/F
acetaldehyde is an energy source
False
acetic acid
216
T/F
Methanol is converted via same enzymes as ethanol.
True
Give ethanol drip for methanol poisoning
Occupies eznymes for methanol metab and use for ethanol instead
Excrete methanol in urine
217
Using alcohol dehydrogenase, methanol becomes _____ . It then becomes ____ using the enzyme ____.
formaldehyde
formic acid
aldehyde dehydrogenase
218
T/F
Ethanol can cause blindness in a dose of 15 ml.
False
METHanol
219
Formic acid cannot be used by the body, and its build up causes...
acidosis, which can be fatal
220
fomepizole (Antizol)
**inhibitor of alcohol dehydrogenase**
may replace ethanol use
resistance d/t cost = longer stay using ethanol drip
221
Why is making alcohol yourself dangerous?
methanol is produced in the process
222
Why is alcohol high in calories?
converted directly to acetic acid, an energy source
223
Which is most potent?
Zaleplon (Sonata)
Zolpidem (Ambien)
Eszopiclone (Lunesta)
224
Zaleplon (Sonata)
Zolpidem (Ambien)
Eszopiclone (Lunesta)
have similar action to ____ in action on ____ receptor complex
BZD
omega 1 portion of GABA A receptor (on alpha 1 subunit)
225
governs anti-anxiety and anticonvulsant effects
weak alpha-2 agonist
226
What did these medications have over BZDs for sleep?
Zaleplon (Sonata)
Zolpidem (Ambien)
Eszopiclone (Lunesta)
did not interfere with tomorrow's activities
vs. "benzo hangover"
227
Which medications' side fx included sleep eating/driving?
Zaleplon (Sonata)
Zolpidem (Ambien)
Eszopiclone (Lunesta)
228
the first hollow needles were used to treat
neuralgia using a morphine solution
229
Release date (earliest to latest):
Thiopental
midazolam
propofol
etomidate
ketamine
1934: thiopental
1970: ketamine
1974: etomidate
1975: midazolam
1986: propofol
TKEMP
230
Sedative
cause mild suppression of arousal and behavior, and a slight decrease in alertness and response to stimuli
231
Hypnotic
- pronounced sedative effects (ex: inducing sleep)
- usually arousable by strong stimuli (ie pain)
232
Most hypnotics are...
-most agents are sedatives given in larger doses
233
Which BARB was used as a sleeping pill?
Pentobarb
234
Which BARB induces its own metabolism?
Phenobarb
doses for chronic user could be fatal to novel user
235
Misc. category of Sed/hyps
**Meprobamate**
Methaqualone
**Droperidol**
Etomidate
Propofol
236
T/F
Most anesthetic agents work via same mechanism as the sed/hyps.
True
237
Most act mainly on
**polysynaptic pathways (interneurons)**
goes thru multiple nerves to get one place to another
more nerves = more receptors = greater chance drug can inhibit
238
presynaptic inhibition
2 methods:
1) NT released acts on receptor on presynaptic membrane to shut off/reduce release
2) neuron impinges on another (at terminal, axon, etc) to prevent signal passage
239
Can help control amount of NT released
presynaptic inhibition
240
SNS can shut off PNS via
presynaptic inhibition
241
T/F
Most sed/hyps work by inhibiting excitatory signaling via post-synaptic inhibition.
False
pre synaptic
242
T/F
Similar receptors in the brain work the same throughout the brain.
False
the different areas of the brain respond differently to the same compound, even if the receptors are similar
243
most are believed to enhance
the pre- and post-synaptic effects of GABA (gamma-aminobutyric acid)
244
ICF usual voltage
-50 to -70 mv
245
Cl influx brings ICF voltage to ____ mv. At this voltage...
-90
no more Cl- can flow in; repulsive force too strong
246
GABA receptors are located
between A1 and B2 subunits
247
prevents GABA from binding
Picrotoxin
248
T/F
90% of brain mechanisms are inhibitory.
True
249
T/F
the BZD site only allows antagonists to bind.
False
250
T/F
Steroids can augment GABA fxn.
True
251
Does ethanol excite or inhibit?
affects both "evenly"
but since most of brain is inhibitory, the inhibitory processes are affected the most
"drinking diminishes inhibitions"
252
the GABA receptor complex is similar to
ACh at the NMJ
both ionophores & pentameric
253
Glutamate acts at which receptors?
NMDA
AMPA
254
NMDA receptor structure
voltage-dependent ionphoric system
QUADRAmeric structure (4 subunits)
different than GABA ionophore!
255
Ways we can control ion passage thru channel
change charge at both ends of the channel (will repel/attract)
change diameter of channel
256
Ketamine MoA
primarily at PCP binding sites on **NMDA glutamate receptor** complex
blocks Calcium entrance → blocks excitation
257
similar to GABA and allows glutamate to act properly
glycine
258
T/F
Glycine attaches the the NMDA glutamate receptor allosteric site to alter Ketamine's ability to bind and block Ca.
false
glycine has its own site
other ligands can bind to allosteric site and cause this effect tho
259
increased K outflow will cause
hyperpolarization (losing + charge)
260
the different mechanisms of action (7)
-GABA Ionophore Augmentation
-Glutamate Receptor Antagonism
-**Two-pore domain K leakage channel activation**
-Glycine receptor augmentation
-Sodium and Calcium ionophore inhibition
-Nicotinic ACh receptor inhibition
-Opiate Receptors
261
Sodium and Calcium ionophore inhibition
block these + ions that depolarize
262
**Nicotinic** ACh receptor inhibition
blocks action at NMJ
muscle relaxation
esp BZDs
263
nerves that go to skeletal muscle are ___ in nature
cholinergic
uses NT ACh to start contraction
using nicotinic ionophore (pentameric)
264
T/F
The muscle relaxant effect seen esp from BZDs is d/t muscarinic ACh receptor inhibition.
False
**Nicotinic** ACh receptor inhibition
265
T/F
Some sed/hyps act on opioid receptors
True
266
T/F
A dream (REM sleep) in which you're running uses the same pathways as if you're actually running IRL.
True
the brain inhibits the motor pathways during sleep; twitches = breakthrough
267
Long-term BZD & sleeping pill use affects sleep by...
Which- leads to...
inhibiting REM sleep
developing certain psychiatric disorders
REM sleep deprivation = psychotic
268
T/F
Hypnotics prolong sleep and enhance overall sleeping
True
but
not very deep
REM inhibited
269
Sleeping pills now vs back then
50's/60's: BARBs
now: BZDs d/t wider T. window
270
T/F
The primary effect of BARBs is their inhibition of oxidative phosphorylation.
False
BARBs do this, but isn't primary effect
**primary effect:**
Bind to GABA receptor
Decrease dissociation of GABA
increase duration of action of GABA
increase chloride conductance
271
conductance
movement of ions thru a channel
272
Which position affects lipid solubility and DoA?
5
273
How do we achieve salt form of BARBs?
Remove H+ and replace with Na+
Na+ attaches to O-
O-[Na+]
274
What happens when we draw up additional doses from the same vial? (BARBs)
inserts air:
CO2 dissolves in water --> carbonic acid
H ions protonate --> back to (weak) acid form (RCOOH)
BARB structure can precipitate out (its no longer ionized)
&
decrease bacteriostatic effects
275
RCOOH vs RCOO-
which is water soluble?
RCOO-
ionized
(will make solutions basic; mechanism used to make BARB into salt form)
276
Use of BARBs in the Wada speech test
inject BARB into either L or R carotid
garbled speech = dominant language hemisphere
shows us which side NOT to use when doing NeuroSx
277
BARB coma mechanism
decreases [O] phosphryltn > decreased metabolism > decreases swelling
gives tissues time to heal
reduces swelling (which causes ichemia)
278
Should BARBs be used in pregnancy? why?
avoid
fetal elimination slower than mom's
279
T/F
BZD receptors are found in fewer places than BARBs.
True
BZD have higher specficity
280
T/F
redistribution is an alteration of duration.
False
alteration of effect
281
Which causes greater skeletal muscle relaxation?
BARBs
BZDs
neither
BZDs
282
Oxazepam
use
metabolism
sleep indxn
eliminated rapidly primarily via glucuronide conjugation (phase II) >>> much shorter HL
283
Should we give BARBs with BZDs?
No
BARBs induce CYP 450 (increased metab)
BZDs mostly use this system for metabolism
284
T/F
Extended use of Versed may result in a -longer duration of effect d/t higher levels of inactive glucuronide.
True
high [ ] can increase duration of effect
also can happen in RF
285
Midazolam --> 1-Hydroxymidazolam
is what type of rxn?
hydroxylation
286
T/F
If a metabolite has Double the HL & half potency => doubles duration of effect
False
Double HL but half potency = extends effect but not greatly
287
Shorter DoE of all BZDs
Midazolam (even tho Lorazepam does not have active metabolite)
288
Region of brain distinctive to humans
neo cortex
289
T/F
Amnesia effect of BZDs is considered beneficial
True
decreases anxiety for future procedure bc they don't remember the scary OR
290
Where do BZDs act?
interface of the α and γ subunits of the GABA receptor in the CNS
291
T/F
BZDs will decrease BP to the same extent as propofol.
False
BZDs do not drop BP as much
292
Drug of choice for status epilepticus
Diazepam
293
T/F
BZDs are contraindicated in pregnancy
False
cross placenta; fetal depression
but
can be used
294
Ethanol is ____ soluble
lipid
penetrates into lipid bilayer
increases fluidity
295
When are Ethanol's effects greatest?
“up-swing” of the plasma [ ] curve
On downswing, the brain becomes accustomed to the alcohol, and we can perform the same task at higher blood [ ]
(Same effect/outcome has lower [ ] on upswing vs downswing)
296
T/F
acetic acid can greatly affect the body
False
formic acid; can lower pH; hard to remove
body mechanisms quickly removes acetic acid
(enters Krebbs cycle)
297
How is methanol eliminated?
urine
298
Z class of sed/hyps
Zaleplon (Sonata) – potency = 1
Zolpidem (Ambien) – potency = 1
Eszopiclone (Lunesta) – potency = 7X
299
T/F
Zaleplon (Sonata)
Zolpidem (Ambien)
Eszopiclone (Lunesta)
bind to alpha 2 receptors
False
they bind to the omega-1 portion of the GABA A receptor (on alpha 1 subunit)
"alpha 2 agonist" describes their actions on the SNS binding sites (norepi/epi type binding site)
