CNS Depressants BZ1 mediates Do not act through

sedation BZ receptors
Addiction BZ2 mediates anti- Have on binding sites
 State of response or drug taker feels anxiety & on GABAa complex
compelled to use the drug suffers when impairment of
cognitive fxns
separated
Also inhibit complex
Anesthesia 1 of electron
transport chain
 Loss of consciousness associated w/ an (NADH coenzyme Q
absence of response to pain reductase
Anxiolytic
Sedative Hypnotics
 Drug reduces anxiety; a sedative
 Chemically heterogeneous class of
Dependence
drugs w/c produce dose-dependent
 Removal of drug evokes unpleasant & CNS depressant effects
possible life-threatening symptoms  Ranges from sedation, to anesthesia, to
after the opposite of the drugs effect respiratory depression, & death
 Major subgroup is benzodiazepines
Hypnosis
 Other subgroups are still in use
 Induction of sleep o Barbiturates
o Miscellaneous agents
REM sleep
(carbamates, alcohols, & cyclic
 Associated w/ rapid eye movement; ethers)
most dreaming takes place during this
MECHANISM
stage
Activation of:
Sedation
GABAa  inc. CI influx
 Reduction of anxiety
GABAb  inc. K influx
Tolerance
- Both result in hyperpolarization

Benzodiazepines
Principles
 Potentiate GABA
 Increase frequency of CI channel
Benzodiazepines Barbiturates opening
Potentiate GABA Prolong GABA  Act through BZ receptors (part of
activity GABAa complex)
Increase frequency of Increase duration of o BZ1 – mediates sedation
CI channel opening CI channel opening o BZ2 – mediates anti-anxiety &
Act through BZ Have GABA-mimetic impairment of cognitive fxns
receptors (part of activity @ high doses
GABAa complex) Barbiturates
  Prolong GABA activity o Thiopental
 Increase duration of CI channel opening
Short
 Have GABA-mimetic activity @ high
doses o Pentobarbital
 Don’t act through BZ receptors o Secobarbital
 Have own binding sites of GABAa
complex Intermediate
 Also inhibit complex 1 of electron o Aprobarbital
transport chain (NADH coenzyme Q o Butabarbital
reductase)
Long
Sedatives & Hypnotics
o Phenobarbital
Sedatives
Barbiturates
 Drugs that have an inhibitory effect on
the CNS  Narrow therapeutic
 They reduce: MOA:
Nervousness
Excitability  Potentiate GABA (gamma-amino butyric
Irritability acid)
Without causing sleep
Site of Action:
Hypnotics
o Brainstem (reticular formation
 Calm or soothe the CNS to the point o Cerebral cortex
that they cause sleep
Drug effects:
Sedative-Hypnotics
Low doses – sedative
 Effects are dose-dependent
High doses – hypnotic (also lowers RR)
Low doses? Calm/sooth the CNS
Notorious enzyme inducers
High doses? + sleep
Therapeutic uses:
Barbiturates
 Hypnotics
 1st introduce in 1903
 Sedatives
 Standard agents for insomnia &
 Anticonvulsants
sedation
 Surgical procedures
 Habit-forming
 Only a handful are use today d/t safety Side effects
& efficacy of Benzodiazepines
 CNS? Drowsiness, vertigo, lethargy,
 Have 4 categories according to mental depress, coma
duration of action:  Respiratory? Respiratory depression,
apnea, bronchospasms, cough
Ultrashort  GI? Nausea, vomiting, diarrhea,
o Thiamylal
  Others? Agranulocytosis, vasodilation,
Steven-Johnson syndrome, hypotension
Toxicology
Overdose leads to respiratory
depression  respiratory arrest
o Midazolam (Versed)
Note: Zolpidem (Ambien) and Zaleplon (Sonata)
are non-BZ agents w/c share the same
characteristics as hypnotic agents
MOA:

Therapeutic: anesthesia induction  Depress CNS activity

 Affect hypothalamic, thalamic, and
Uncontrollable seizures
limbic systems of the brain
(Phenobarbital coma)  Bezodiazepine receptors

Drug interaction Drug effect

 Additive? ETOH, antihistamines,  Calming effect on CNS

narcotics, benzodiazepines
 Inhibited metabolism? MAOIs
(prolong its effects)
 Increase metabolism? Reduces
anticoagulant response (clots form)
Benzodiazepines
 Commonly prescribe of the drug classes
 Favorable side effects
 Use for controlling agitations & anxiety
Therapeutic uses:
 Sedation, sleep induction
 Skeletal muscle relaxation, anxiety relief
 Treatment of alcohol withdrawal
 Agitation, depression, epilepsy
 Balanced anesthesia

Classified as either: Drug Indications

Alprazolam Anxiety, panic,
o Sedative-hypnotic
phobias
o Anxiolytic Diazepam Anxiety, pre-
Sedative-hypnotic operative
sedation, muscle
Long relaxation, &
withdrawal
o Flurazepam (Dalmane) states
o Quazepam (Doral) Lorazepam Anxiety, pre-
operative
Short
sedation, &
o Eztazolam status epilepticus
o Temazepam (Restoril) (IV)
o Triazolam (Italcion) Midazolam Pre-operative
sedation,
Anxiolytics anesthesia (IV)
Temazepam Sleep disorders
o Alprazolam (Xanax) Oxazepam Sleep disorders
o Chlordiazepoxide (Librium) & anxiety
o Diazepam (Valium)
o Lorazepam (Ativan)

Benzodiazepines
Side effects:
 Mild & infrequent (HA, drowsiness,
dizziness, vertigo, lethargy, paradoxical
excitement nervousness) hangover er
effect
NSG. Implication
 Before beginning perform thorough
history regarding allergies, use of other
meds, health history & medical history
 Obtain baseline VS & I & O including
supine & erect BPS
 Assess potential disorders/conditions
may be contraindicated & for potential
drug interaction
 patient should be instructed to avoid
alcohol & other CNS depressants
 check w/ physician before taking other
meds, including OTC meds
 may take 2-3 weeks to notice improve
sleep when taking barbiturates
 abruptly stopping may cause insomnia
 safety is important (side rails up, don’t
allow smoking, assist pt w/ ambulation
(esp. the elderly) keep call light within
reach
 monitor for side effects
 monitor for therapeutic effects
 increase ability to sleep @ night
 fewer awakenings
 shorter sleep induction time
 few side effects; such as hangover
effects
 improve sense of well-being because of
improved sleep
Atypical Sedative-Hypnotic
Buspirone
 selective anxiolytic w/ minimal CNS
depressant effects (doesn’t affect
driving skills)
 no anticonvulsant
 interacts w/ brain serotonin receptors
as partial agonist
 specific MOA for its anxiolytic is
unknown
 minimal tolerance w/ chronic use
 little rebound anxiety/withdrawal
symptoms upon discontinuance
 safe in pregnancy
Ramelteon
 activates melatonin receptors
(suprachiasmatic nuclei of the CNS) &
decrease latency of sleep onset
 minimal rebound insomnia/withdrawal
symptoms
 no direct effect on GABA-ergic
neurotransmission in the CNS
 minimal abuse liability (not a controlled
substance)
Similar to Ramelteon
Tasimelteon
 similar melatonin receptor agonist
 recently approved
Orexin Antagonists
Orexin
 peptide found in the hypothalamus
 involved in wakefulness
 suvorexant
 recently approved antagonist & orexin
receptors
 has hypnotic properties
Facts
Dose-dependent CNS fluvazetin