Sedative-hypnotics Flashcards
1
Q
Define sedative vs hypnotic
A
Sedative = anxiolytic; calms the patient
Hypnotic: promotes drowsiness and sleep
2
Q
T/F: Sedative-hypnotics (SH) are lipid soluble
A
True. This allows them to cross BBB
3
Q
Sedative-hypnotics are absorbed in ____
A
GIT
4
Q
How are the CNS effects of sedative-hypnotics terminated?
A
by rapid REDISTRIBUTION of the drug from
brain to other highly perfused tissues
the higher rate of drug redistribution, the less its effect
5
Q
All BDZs are absorbed completely, except
A
clorazepate
6
Q
decarboxylated rapidly in gastric juice to N-desmethyldiazepam
A
nordiazepam
7
Q
How are sedative-hypnotics metabolized?
A
via hepatic metabolism
8
Q
Give examples of drugs that are converted initially to active metabolites with long half-lives
A
diazepam, flurazepam
Diazepam(28hrs) to Nordiazepam(60hrs) to Oxazepam(6hrs)
Flurazepam (2hrs) to N-desalkylflurazepam (50hours)
9
Q
Undergo extrahepatic metabolism, and therefore do not form active metabolites
A
Lorazepam , tamezapam, and oxazepam
10
Q
Main classes of drugs in sedative-hypnotics
A
Benzodiazepines
Barbiturates
11
Q
Barbiturates are extensively metabolized Except
A
phenobarbital
12
Q
Arrange the SH drugs in sequence based on increasing duration of action
A
zaleplon
13
Q
It is a non-BDZ with biphasic release form
A
zolpidem
14
Q
Examples of long-acting SH
A
chlordiazepoxide, clorazepate, diazepam, phenobarbital
15
Q
Site of action of BDZ and barbiturates
A
GABA A receptor
16
Q
Differentiate GABA A vs GABA B receptor
A
GABA A activation: ↑ Cl- influx; Ionotropic (fast)
GABA B activation: ↑ K+ efflux Metabotropic (slow)
Both mechanisms result in membrane hyperpolarization
17
Q
GABA A receptor has how many subunits
A
5 subunits
o 4 transmembrane domains
o 2 α1, 2 β2, and 1 γ2 subunits
18
Q
binding site for benzodiazepines is
A
between an α1 and the γ2
subunit
19
Q
BDZ vs Barbiturates based on mechanism of action on GABA A receptor
A
BOTH increase the potency of GABA but by different mechanisms:
BDZ: increased FREQUENCY of opening of GABA receptor
Barb: increased DURATION of opening of GABA receptor
20
Q
Is it okay to combine BDZ and Barbiturate?
A
No. they could have ADDITIVE effects. They can both stimulate the receptor. DO NOT MIX THESE DRUGS TOGETHER.
21
Q
Antagonist of BDZ
A
Flumazenil
hence used as antidote for BDZ poisoning
22
Q
Which has GABA-mimetic activity?
A
Barbiturates. They can mimic GABA esp at high doses
BDZ has NO GABA-mimetic activity.
23
Q
Additional MOA of barbs
A
Inhibit complex I of the Electron Transport Chain
24
Q
Give examples of SH that are neither BDZ or Barb
A
zolpidem, zaleplon, and esZopiclone
Z drugs
25
Adv of Z drugs
Less effect on cognitive function
| Less tolerance and abuse liability
26
Give the dose-dependent effects of SH
Sedation (lowest dose)
Hypnosis
Anesthesia
Coma (highest dose)
27
What is paradoxical inhibtion?
Its a benzodiazepine induced hyper-reactive phenomenon. It takes the person to the extreme end of emotions, removes all inhibitory and suppressed signals resulting in extreme pychosis and agitation, paranoia and depression. Its a rare occurence in pts taking the drugs.
It is due to inhibition of inhibitory subcortical neurons during initial doses of BZ.
28
How does SH affect sleep?
Reduced REM duration
| Increased of Non-REM (Stage II) duration (ex: Diazepam)
29
Used for anesthesia
Thiopental
Midazolam
Anesthesia can be produced by short acting barbiturates (eg,
thiopental) and certain benzodiazepines (eg,midazolam).
30
Can cause anterograde amnesia
benzodiazepines
31
Examples of SH with selective anticonvulsant action
Phenobarbital
| Clonazepam
32
Used in status epilepticus
diazepam, lorazepam, or phenobarbital
33
Muscle Relaxation occurs only with high doses of most sedative-hypnotics Except
diazepam and Meprobamate (they can be used as muscle relaxant even at low doses)
34
Can cause medullary depression
Alcohols and barbiturates
| BDZs are safe and rarely cause medullary depression
35
There is cross-tolerance between
BZ, barbituates, and ethanol
36
T/F Benzodiazepines are less toxic compared to all sedatives.
T
37
DOC for anxiety states
Alprazolam and clonazepam
38
DOC for sleep disorders
estazolam, flurazepam, and triazolam
39
T/F: Sedative hypnotic drugs recommended for breathing-related
sleep disorders
False. Sedative hypnotic drugs NOT recommended for breathing-related
sleep disorders
40
Used for induction of anesthesia
thiopental
41
components of anesthesia protocols
diazepam, midazolam
42
used for seizure disorders
clonazepam, phenobarbital
43
used for bipolar disorcer
clonazepam
44
used for muscle spasticity
Diazepam
45
used in management of withdrawal states
chlordiazepoxide, diazepam
46
benzodiazepines that have active metabolites
| with long half-lives
DIAZEPAM, FLURAZEPAM
47
Barbiturates: Enzyme inducer or inhibitor?
Barbiturates are ENZYME INDUCERS
Mnemonic: PRC
Phenobarbital (barbiturates), phenytoin
Rifampicin
Carbamazepine, Chronic Alcohol use
48
Adverse effect associated with barbiturates
Acute intermittent porphyria
49
Mickey Finn is aka
Chloral hydrate
50
May displace coumarins from plasma protein
chloral hydrate
51
occasionally increases the incidence of nightmares
flurazepam
52
Examples of ATYPICAL sedative-hypnotics
Buspirone
| Ramelteon
53
MOA of buspirone
Partial agonist of 5-HT1A serotonin receptors
54
T/F Buspirone affects GABA
False. It is partial agonist of 5-HT1A serotonin receptors
55
Use of buspirone
anxiolytic ONLY
| it has NO anticonvulsant or muscle relaxant properties
56
Disadvantage of using buspirone
slow onset of action (>1 week) since it is only partial agonist
57
Advantage of using buspirone
Tolerance development is minimal with chronic use
little rebound anxiety or withdrawal symptoms on discontinuance
Minimal abuse
58
Metabolism of buspirone is Increased or decreased by erythromycin?
Decreased metabolism (leading to increased plasma levels)
```
Enzyme inhibitors: MEDVICK-A
Metronidazole
Erythromycin
Valproic acid
Isoniazid
Cimetidine, ciprofloxacin
Ketoconazole
Acute Alcohol use
```
59
Novel hypnotic drug
Ramelteon
60
MOA Ramelteon
activates melatonin receptors in the suprachiasmatic nuclei
61
Effect of Rifampin on metabolism of Ramelteon
Increased metabolism
ENZYME INDUCERS
Mnemonic: PRC
Phenobarbital (barbiturates), phenytoin
Rifampicin
Carbamazepine, Chronic Alcohol use
62
Effect of fluconazole and fluvoxamine on ramelteon
Decreased metabolism
(azoles are enzyme inhibitors)
```
Enzyme inhibitors: MEDVICK-A
Metronidazole
Erythromycin
Valproic acid
Isoniazid
Cimetidine, ciprofloxacin
Ketoconazole
Acute Alcohol use
```
63
Which one of the following statements is correct regarding
benzodiazepines?
A. Benzodiazepines directly open chloride
channels.
B. Benzodiazepines show analgesic actions.
C. Clinical improvement of anxiety requires 2 to 4
weeks of treatment with benzodiazepines.
D. All benzodiazepines have some sedative effects.
E. Benzodiazepines, like other CNS depressants,
readily produce general anesthesia.
Correct answer = D. Although all benzodiazepines can
cause sedation, the drugs labeled “benzodiazepines” in
Figure 9.1 are promoted for the treatment of sleep disorder.
Benzodiazepines enhance the binding of GABAA to its receptor,
which increases the permeability of chloride. The benzodiazepines
do not relieve pain but may reduce the anxiety
associated with pain. Unlike the tricyclic antidepressants and
the monoamine oxidase inhibitors, the benzodiazepines are
effective within hours of administration. Benzodiazepines do
not produce general anesthesia and, therefore, are relatively
safe drugs with a high therapeutic index.
64
```
Which one of the following is a short-acting hypnotic?
A. Phenobarbital.
B. Diazepam.
C. Chlordiazepoxide.
D. Triazolam.
E. Flurazepam.
```
Correct answer = D. Triazolam is a short-acting drug. It has
| little dayt
65
Which one of the following statements is correct regarding
the anxiolytic and hypnotic agents?
A. Phenobarbital shows analgesic properties.
B. Diazepam and phenobarbital induce the cytochrome
P450 enzyme system.
C. Phenobarbital is useful in the treatment of acute
intermittent porphyria.
D. Phenobarbital induces respiratory depression, which
is enhanced by the consumption of ethanol.
E. Buspirone has actions similar to those of the
benzodiazepines.
Correct answer = D. Barbiturates and ethanol are a potentially
lethal combination. Phenobarbital is unable to alter the
pain threshold. Only phenobarbital strongly induces the synthesis
of the hepatic cytochrome P450 drug-metabolizing
system. Phenobarbital is contraindicated in the treatment of
acute intermittent porphyria. Buspirone lacks the anticonvulsant
and muscle-relaxant properties of the benzodiazepines
and causes only minimal sedation.
66
A 45-year-old man who has been injured in a car accident
is brought into the emergency room. His blood alcohol
level on admission is 275 mg/dL. Hospital records show a
prior hospitalization for alcohol-related seizures. His wife
confirms that he has been drinking heavily for 3 weeks.
What treatment should be provided to the patient if he
goes into withdrawal?
A. None.
B. Lorazepam.
C. Pentobarbital.
D. Phenytoin.
E. Buspirone.
Correct answer = B. It is important to treat the seizures
associated with alcohol withdrawal. Benzodiazepines, such
as chlordiazepoxide, diazepam, or the shorter-acting lorazepam,
are effective in controlling this problem. They are less
sedating than pentobarbital or phenytoin.
67
```
Which one of the following is a short-acting hypnotic
and better for sleep induction compared to sleep
maintenance?
A. Temazepam.
B. Flurazepam.
C. Zaleplon.
D. Buspirone.
E. Escitalopram.
```
Correct answer = C. Zaleplon has the shortest half-life and
duration of action. Buspirone and escitalopram are not
effective hypnotic agents. Temazepam and flurazepam have
longer durations of action and will reduce nighttime awakenings
but will have a greater risk of daytime sedation or
hangover effect compared to zaleplon.
68
Which of the following agents has a rapid anxiolytic effect
and would be best for the acute management of anxiety?
A. Buspirone.
B. Venlafaxine.
C. Lorazepam.
D. Escitalopram.
E. Duloxetine
Correct answer = C. The benzodiazepines have same-dose,
first-dose efficacy for anxiety, whereas the other agents
require 2 to 8 weeks for clinically significant improvement
in anxiety.
69
```
Which of the following sedative–hypnotic agents utilizes
melatonin receptor agonism as the mechanism of action
to induce sleep?
A. Zolpidem.
B. Eszopiclone.
C. Estazolam.
D. Ramelteon.
E. Diphenhydramine.
```
Correct answer = D. Ramelteon is the only melatonin receptor
agonist to promote sleep, especially in sleep-phase
disrupted sleep. Zolpidem, eszopiclone, and estazolam all
utilize the benzodiazepine receptor, and diphenhydramine
is a histamine receptor antagonist.
70
```
All of the following agents for the management of
insomnia are controlled substances and may have a risk
for addiction or dependence except:
A. Zaleplon.
B. Flurazepam.
C. Doxepin.
D. Zolpidem.
E. Triazolam.
```
Correct answer = C. Only doxepin, a tricyclic agent with
significant antihistaminergic properties, is considered to
have no risk of addiction or dependence, whereas the other
agents listed all have DEA schedule IV designations with
some risk for addiction or dependence, especially when
used for extended periods.
71
```
All of the following agents may cause cognitive
impairment, including memory problems when used at
recommended doses except:
A. Diphenhydramine.
B. Zolpidem.
C. Alprazolam.
D. Phenobarbital.
E. Ramelteon.
```
Correct answer = E. All of the above listed agents, except
ramelteon, have been associated with cognitive impairments,
including memory impairment. Diphenhydramine
likely causes its cognitive problems from its anticholinergic
and antihistaminergic effects. Zolpidem, alprazolam, and
phenobarbital are well-known causes of cognitive impairment,
including anterograde amnesia. Ramelteon has
safety data extending to 6 months and is a noncontrolled
hypnotic agent acting as a melatonin receptor agonist. It is
not considered to have a risk for cognitive impairment as
compared to the other agents listed.
72
Which agent is best used in the Emergency Room
setting for patients who are believed to have received
too much of a benzodiazepine drug or taken an
overdose of benzodiazepines?
A. Diazepam.
B. Ramelteon.
C. Flumazenil.
D. Doxepin.
E. Naloxone.
Correct answer = C. Flumazenil is only indicated to reverse
the effects of benzodiazepines via antagonizing the benzodiazepine
receptor. It should be used with caution due to a
risk of seizures if the patient has been a long time recipient
of benzodiazepines or if the overdose attempt was with
mixed drugs. Naloxone is an opioid receptor antagonist.
The other agents are not efficacious in reversing effects of
benzodiazepines.
