Chapter 12: CNS Depressant Drugs Flashcards
1
Q
what type of receptors are GABA a receptors?
A
ligand ion channels
2
Q
when GABA binds to GABA A receptors it causes an opening of the channels and ___ions enter, resulting in membrane ___
A
Cl-; hyperpolarization
3
Q
when cl hyper polarizes the cell after GABA a activation, does this make the cell more or less excitable?
A
less
4
Q
when GABA binds to GABA A receptors, the opening of the channel is ___ and will close once __
A
transient; GABA dissociates
5
Q
when GABA A channels are exposed to GABA for a prolonged period of time, what happens to them?
A
they inactivate
6
Q
there are ___ known allosteric binding sites on GABA A receptors
A
several
7
Q
benzodiazepines, zolpidem and barbiturates are all __ modulators of GABA
A
positive allosteric
8
Q
flumazenil is a ____ that competes with benzodiazepines at the GABA A receptor
A
allosteric antagonist
9
Q
allosteric modulators act in a ____ way with the endogenous agonist
A
non-competitiive
10
Q
when GABA A receptors become inactivated, it requires ____ before it can be reactivated
A
removal of GABA
11
Q
most drugs acting on GABA A receptor are ____ modulators of GABA actions
A
positive allosteric
12
Q
barbiturates such as phenobarbital bind GABA A and increase ___
A
duration of channel opening
13
Q
when benzodiazepines and Z-hypnotics bind to the GABA A, they influence the ___ of the channel
A
frequency of opening
14
Q
compare the Cl influx into GABA A when bound to barbiturates and benzos/Z-hypnotics
A
benz/Z: burst-like entrance of Cl
barb: more prolonged entrance of Cl
15
Q
what is propofol?
A
anesthetic with similar activity to barbiturates
16
Q
do benzo’s/Z-hpnotics, barbiturates, and propofol all bind to the same allosteric site on the GABA A receptor?
A
no, all different
17
Q
the effects of GABA A modulators are ___ dependent
A
dose
18
Q
at low to moderate doses, the effects of GABA A modulators are similar: ___ and ___
A
sedation and hypnosis (Sleep)
19
Q
at higher doses, GABA A modulators induce ____ and many are used in combinations for ___
A
anesthesia; surgery
20
Q
at high doses, barbiturates can open GABA A w/o GABA present, which has a higher risk of ___
A
over-activation of GABA A, leading to coma or death
21
Q
increasing amounts of GABA, increases the amount of ___ ion entering the neuron
A
Cl
22
Q
at high doses, can barbiturates still open GABA A channels even if no GABA is present? Can benzodiazepines?
A
yes; no
23
Q
what are 2 examples of barbiturates?
A
pentobarbital and phenobarbital
24
Q
why are barbiturates not used very often today?
A
largely replaced by Benzodiapenes which have better safety
25
give 2 examples of where barbiturates are still used today
anti seizure and surgical anesthesia
26
barbitaues are typically very ___ (hydrophilic / lipophilic) and have ___(high/low) distribution through the CNS
lipophilic; high
27
prolonged duration of action for barbiturates may be observed in patients with ___
poor organ function (renal / hepatic) and old age
28
barbiturates are known to induce ___ enzymes, including those involved in ____ metabolism
CYP450 enzymes; their own
29
t/f there are MANY drug-drug interactions with barbiturates
true
30
barbiturates are primarily metabolized by the ___
liver
31
barbiturates are primarily excreted by the __
renal system
32
barbiturates are absorbed ___ (slowly/rapidly)
rapidly
33
give 4 examples of benzodiazepines
diazepam, alprazolam, oxazepam, lorazepam
34
the differences among benzodiazepines stems from differences in the ways they are ____
metabolized
35
t/f all benzodiazepines have the same MOA
true
36
lorazepam has ___ (#) active metabolites, undergoes phase __ metabolism and is excreted by the __
0; 2; urine/kidneys
37
alprazolam has ____(#) active metabolites formed by phase 1 metabolism, which means each dose lasts as long as __
some; the active metabolites are present
38
diazepam has ___(#) active metabolites, including ___which can also be given on its own
several; oxazepam
39
diazepam has a very ____duration of action. Why?
long; has many active metabolites that all need to be cleared before effect wears off
40
___ is an example of a benzodiazepine pro-drug
clorazepate
41
on its own, clorazepate is not active @ GABA, but when hydrolysed in the stomach, it become the active ___
desmethyldiazepam
42
what type of benzodiazepines have active metabolites?
long-acting
43
how many active metabolites does oxazepam have?
none
44
clorazepate is activated in the stomach and has been seen to be activated less when the patient is also taking __
antacids
45
Z-hypnotics are a ___ class of agents that were designed specifically to act as __
newer; sleep aides
46
in patients with insomnia or disrupted sleep, sleep cycles can be __ and can result in the patient feeling ___ and may result in __ issues
irregular; unrested; cognitive
47
how do Z-hypnotics work?
act to speed up onset of sleep to reestablish sleep cycles
48
Z-hypnotics bind to similar but different sites on the GABA as ___
benzodiazepines
49
z-hypnotics increase the ___ of GABA channels
opening frequency
50
Z-hypnotics are similar to many benzodiazepines in theta they have ___ onsets of action and ___ duration of action
fast; short
51
why do z-hypnotics and many benzodiazepines have rapid onset and short duration?
no active metabolites
52
the onset and duration of z-hypnotics compared to benzo
faster and shorter
53
what is the onset time for z-hypnotic?
1-3 hours
54
what is the duration for z-hypnotics?
1.5-3 hours
55
z-hypnotocs are metabolized by ___ enzymes
CYP3A4
56
the presence of ____ can prolong the duration of action for z-hypnotocs
inhibitors
57
theoretically, benzodiazepines, z-hypnotics, and barbiturates can all cause sedation, hypnosis ad anesthesia, however in most practical cases, the therapeutic indications between them are delineated based on ___ properties of the agents
kinetic
58
at low doses, benzodiazepines have ___ and ___ effect
sedative and anxiolytic
59
whether z-hypnotics, benzodiazepines, and barbiturates have a sedative, hypnotic, or anesthetic outcome is based on the ___ given
dose
60
in anesthesia, we want rapid onset and predictable duration, meaning the drug used should g=have no ___
active metabolites
61
give 2 examples of drugs used as anesthetics
midazolam and propofol
62
t/f the retrograde amnesia effects of anesthesia are often beneficial
true
63
what are the 4 stages of CNS depression and anesthesia?
1. analgesia
2. excitement/delirum
3. surgical anesthesia
4. medullary depression and death
64
surgical anesthesia occurs when the CNS is suppressed to the point where a patient is ___ and ___
non-responsive to verbal commands (unconscious) and feeling is lost
65
if CNS depression goes beyond the level of surgical anesthesia, ___ and ___ become impaired and ___ will happen if intervention is not made
respiration and brain function; death
66
why are surgical anethtics typically given by continuous IV
want rapid onset and predictable duration
67
midazolam and propofol are typically used in surgical anesthesia bc they have ___
short duration of action
68
general anesthetics act to dress the CNS by either ___ or __
increasing inhibitory input or decreasing excitatory input
69
what are 2 ways gaseous anesthetics such as NO and desflurane are believed to work
1. interact w/ membrane proteins to influence neuron excitability
2. interact w/ ion channels such as nicotinic Ach receptors to reduce excitably of neuron
70
the precise MOA and interactions of gaseous anesthetics is ___
unclear
71
give 3 examples of IV anesthesia cocktails
1. propofol
2. benzodiazepines
3. opioids
72
the effects of inhaled anesthetics are ___ dependent
dose
73
at moderate doses, nitrous oxide causes __
delirium effects (laughing gas)
74
nitrous oxide is useful in what type of procedures?
minor; such as dentistry, where full anesthesia is not needed, but is beneficial to have patient less aware
75
in most cases during surgery, both ___ and ___ types of anesthesia and used and are monitored closely by the anesthesiologist
inhaled and IV
76
most ADR of sedatives are related to extensions of their ____
pharmacologic effects
77
moderate CNS depression can cause __ and higher doses can cause
amnesia; cognitive and respiratory impairment
78
benzodiazepine OD can be reversed by __
flumazenil
79
flumazenil is a ___ of the benzodiazepine GABA A receptor
competitive antagonist
80
flumazenil cannot reverse the OD of __ or ___
barbiturates or other binding site of the GABA A
81
additive sedative effects can occur when patients take multiple drug with this type of action and this can be hard for HCW to control bc ___
many don't require an Rx (such as alcohol)
82
ethanol is ___ in size and has ___ CNS actions
small; many
83
ethanol has ___ (high/low) penetrance of th eCNS
high
84
ethanol is known to CNS suppressive effects similar to __ and __
sedatives and general anesthesia
85
ethanol interacts with many ___ pathways and ___ processes
NT; cellular
86
ethanol has particularly high effects on __ and __
GABA and NMDA
87
ethanol ___ the effects of GABA A
enhances
88
ethanol ___the effects of glutamate s
reduces
89
what general inhibitory effects are associated with ethanol use?
slowed reaction time, poor coordination, acute cognitive impairment and memory loss
90
ethanol follows ___ order elimination kinetics, meaning there is a ___ amount of alcohol lost over time
0th; constant
91
is ethanol elimination concentration dependent?
no
92
the linear elimination of ethanol is the basis for ___testing and allows extrapolation back to a certain time to see how much alcohol would have been in their blood then
blood-alcohol
93
ethanol metabolism occurs primarily in the ___
liver
94
what are the 3 ways alcohol can be metabolized in the liver?
1. alcohol dehydrogenase
2. aldehyde dehydrogenase
3. CYPP450 metabolism by the microsomal ethanol oxidizing system (MEOS)
95
___ is the primary enzyme responsible for metabolizing ethanol into acetaldehyde
alcohol dehydrogenase
96
the CYP MEOS pathway for metabolizing alcohol is minor unless
alcohol levels are high
97
the CYP MEOS pathway is seen more in cases of ___alcoholism and contributes to ___
chronic, tolerance
98
t/f induction of the CYP enzymes in the MEOS pathways can influence the metabolism of other drugs
treu
99
once acetlyadehyde is produced, ____ oxidizes it into acetate
aldehyde dehydrogenase
100
the accumulation of acetaldehyde metabolite causes systemic effects such as :
nausea, facial flushing, headaches and tachycardia
101
a polymorphism in ___ can cause some people/certain ethnicities to accumulate more acetaldehyde and have more adverse effects of alcohol
aldehyde dehydrogenase
102
what patient population is most at risk of adverse effects of sedatives? why?
elderly, have impaired clearance and more likely to be taking multiple medications that may result in additive effects
103
can tolerance to benzodiazepines and z-hypnotics happen?
yes, if used over long period of time
104
what is one of the possible reasons for tolerance to benzodiazepines / z-hypnotics relating to the GABA receptor?
GABA A receptors can become down regulated
105
if tolerance is caused by a down regulation of the GABA A can it be fixed by increasing the dose?
no, there are fewer receptors available no matter the dose
106
what is a non-receptor way that patients can become tolerant to benzodiazepines / z-hypnotics?
increased metabolism to more rapidly clear the drug
107
if tolerance is caused by increased metabolism, would increasing the dose help?
yes bc more drug would be at the action site and nothing is wrong with the receptor
108
what is the best practice for avoiding benzodiazepine / z-hypnotic tolerance?
starting at the lowest possible therapeutic dosing (start low, go slow)
109
what is psychologic dependence?
the patient shows drug-seekiing behaviour, once effect wears off they want more, can lead to misuse or overuse
110
what type of drugs often are associated with psychologic dependence>
addictive
111
what is physiological dependence?
involves withdrawal symptoms such as anxiety and agitation that is often worse than original symptoms
112
physiological dependence is more common when drugs are used for ____ amount of time and drugs with ___ half lives
extended; shorter
113
why do drugs with shorter half-lives have a higher incidence of physiological dependence?
the drop in effect is more pronounced
