CNS Depressants Flashcards
1
Q
GABA A Receptor Complex
A
Cl channel within the CNS that is opened by GABA.
- there are five accesory receptors that can be activated with drugs (benzo, barb, ETOH) to speed the influx of Cl
- as it becomes more negative (hyperpolarized) it becomes harder to depolarize and conduct the AP
- Each CNS depressant activates different combinations of these accessory sites to produce different profiles of CNS depression by making it easier for GABA to bind
- All CNS depressants are POSITIVE ALLOSTERIC MODULATORS of the GABA A receptor
2
Q
Dose Dependency in CNS Depressants
A
- Every CNS depressant can cause the full range of CNS depression (anxiolysis to death) depending on how the accessory sites affect hyperpolarization and dose
- order of CNS depression is anxiolysis, euphoria, sedation, muscle relaxation, anticonvulsant, coma, and death
- It is very costly to get drugs approved for different indications, so keep in mind that any CNS depressant can achieve any effect of CNS depression.
3
Q
Barbiturates (general aspects)
A
- are classified by rate and duration of action
- At higher doses Barbs can open the channel spontaneously, which gives them a narrow therapeutic window
4
Q
Pharmacokinetics of Barbiturates
A
- Rate of distribution depends on lipid solubility
- metabolized more slowly with hepatic impairment (risk of OD)
- tolerance, physical dependence, psychological dependence
- additive effect with other CNS depressants
5
Q
Ultrashort Acting Barbiturates
A
sodium thiopental, thiamylal, methylhexital
- these are primarily used for induction of anesthesia
- very lipid soluble so they enter and leave the brain quickly (very fast onset)
- HL range from 4-12 hours (although therapeutic effect is long gone, drug remains in body)
6
Q
Short to Intermediate Acting Barbiturates
A
-these are rarely used today
secobarbital- first sedative/hypnotic
pentobarbital- first anxiolytic
7
Q
Long Acting Barbiturates
A
phenobarbital- anticonvulsant with 80-120 hour HL
8
Q
Side Effects of Barbiturates
A
CNS and respiratory depression (more pronounced than Benzo), tolerance, dependence, abuse
9
Q
Withdrawal from CNS depressants
A
- withdrawal symptoms are the opposite of therapeutic effect (CNS hyperstimulation)
- withdrawal is a life threatening occurrence (can seize to death)
10
Q
Benzodiazepines (general aspects)
A
- unlike Barbs, these cannot open the Cl channel alone
- have a wider therapeutic window and better SE profile than Barb
- more likely to pass out before apnea occurs
- have a reversal agent
11
Q
Flumazenil
A
aka romazicon
- reversal agent for benzos
- outcompetes other benzos at the site but has no effect
- 1 hour HL (many benzos have much longer HL, so may need repeated doses of flumazenil
12
Q
Pharmacokinetics of Benzodiazepines
A
- MOA is similar to that of barbs
- benzos are metabolized to less effective, but still potent, metabolites
- therefore, drugs that need to be repeatedly metabolized have longer HLs
- temazepam, oxazepam, and lorazepam only need a phase II reaction to become inactive so they are most gentle on liver
13
Q
Short Acting Benzodiazepine
A
midazolam and triazolam
14
Q
midazolam
A
- short acting benzodiazepine
- used for conscious sedation and same-day surgery
- comes in a sucker (children)
15
Q
triazolam
A
- short acting benzodiazepine
- approved as sedative/hypnotic but is often used for conscious sedation
16
Q
Intermediate acting Benzodiazepine
A
lorazepam, oxazepam, temazepam, alprazolam, chlordiazepoxide
17
Q
lorazepam
A
- intermediate acting benzodiazepine
- used for a wide variety of anxiety issues
- most water soluble which makes it easy for IV or IM injection
- first choice for status epilepticus
- part of the B52
18
Q
oxazepam
A
- intermediate acting benzodiazepine
- used for short term or situational anxiety that is debilitating (afraid of flying but must take a flight)
19
Q
temazepam
A
- intermediate acting benzodiazepine
- sedative hypnotic for sleep maintenance disorder
20
Q
alprazolam
A
- intermediate acting benzodiazepine
- used for anxiety, depression, and panic disorder
- is very widely prescribed and many practitioners become concerned with dependency
- it is key to give clear administration instructions rather than “prn anxiety”
21
Q
chlordiazepoxide
A
- intermediate acting benzodiazepine
- the oldest benzo (that’s why it doesn’t end in pam or lam)
- used for anxiety but rarely seen
22
Q
Long acting benzodiazepine
A
diazepam and clonazepam
23
Q
diazepam
A
- long acting benzodiazepine
- manages anxiety with a long HL
- also commonly used in status epilepticus, but is more viscous than lorazepam
24
Q
clonazepam
A
- long acting benzodiazepine
- manages anxiety with a long HL
- can be used for aggressive behavior/sundowning
25
Uses of Benzodiazepine
- used for the widest range of CNS effects because they are much safer than barbs
- anxiety, sedation, muscle relaxant, anticonvulsant, and anesthesia induction agent
26
Adverse Effects of Benzodiazepines
- CNS depression, anterograde amnesia, respiratory depression (less pronounced than barbs), tolerance, dependence, abuse
- Have additive effects with other CNS depressants
27
anxiety disorder
generalized anxiety disorder- constantly increased anxiety, muscle tension, and autonomic hyperactivity
panic disorder- recurrent and discrete periods of of intense anxiety, fear, and discomfort with autonomic arousal
28
Treatment of Anxiety Disorder
- depends on type and severity of anxiety
- alprazolam is only one approved for panic disorder
- benzos are used for immediate anxiolysis and to reduce the sympathetic response
- for generalized, buspirone is a good first choice (no dependence, long effect) SE include HA, nausea, dizziness
- for panic, an SSRI or tricyclic is a good first choice
- beta blocker can be used for performance anxiety
29
Treatment of Insomnia
benzos, non-benzos, antidepressants, antihistamines, melatonin, and meprobamate/carisoprodol
-chloral hydrate SHOULD NOT BE USED
30
benzos used for insomnia
triazolam and temazepam
31
non-benzodiazepines used for insomnia
- these work at the benzo binding site but have different structure
- zolpidem, zaleplon, eszopiclone
32
antidepressants used for insomnia
trazadone and doxepin
33
antihistamines used for insomnia
hydroxyzine and diphenhydramine
| -OTC meds with PM
34
melatonin for insomnia
-binds to MT receptor and has long onset
35
meprobamate and carisoprodol for insomnia
meprobamate- originally an anxiolytic that became sedative-hypnotic
carisoprodol- skeletal muscle relaxant that is metabolized to meprobamate. Has abuse potential.
36
causes of insomnia
stress, illness, drugs, ETOH, jet lag
37
Monitored anesthesia care and its fundamental elements
- combination of local anesthesia, sedation, and analgesia
| - fundamental elements include safe sedation, control of anxiety, and pain control
38
Conscious Sedation
- depress the LOC without compromising airway or ability to respond to stimuli
- good conscious sedation should be safe, cheap, readily absorbed, fast acting, wear off quickly, be reversible, not irritate GI, and be rapidly excreted
