Sedative Flashcards
Which anxiety disorders are treated with benzodiazepines
- acute anxiety
- generalized anxiety disorder
what class of medications are used to treat generalized anxiety disorder
- benzodiazepines
- buspirone
DOC for tx of enuresis (bed wetting)
tricyclic antidepressants
What type of medications are most useful for short term insomnia, which occurs with situational stress
- sedative-hypnotics
MOA of GABA
- CNS depressant
- major inhibitory neurotransmitter
- relieves anxiety and promotes sedation
describe GABA receptors
-
Cl- channels
- activation allows Cl- to enter cell hyperpolarizing membrane
The majority of sedative-hypnotics and anxiolytics (barbiturates, benzodiazepines, and the “z-drugs”) act by binding to a modulatory site on
GABAA receptor complex, to either intensify or prolong the actions of GABA.
MOA of Barbiturates
- Bind to GABAA receptor, and increase the duration of GABA action.
- At high concentrations, they may increase Cl- influx and produce inhibition independent of GABA.
- Marked CNS depressant effect -> produce hypnosis
why are Barbiturates a drug of abuse
they cause euphoria
What drug class is Thiopental in? Use?
- short acting Barbiturate
- induction of anesthesia
What drug class is Phenobarbital in? Use?
- Long acting Barbiturates
- anticonvulsant
List the barbituates
- Pentobarbital
- Phenobarbital
- Secobarbital
- Thiopental
Barbituates are metabolized in what organ
liver
with chronic use, Barbituates induce what liver enzymes
- CYP450s
Side effects of Barbituates
- CNS depression
- paradoxical excitement
- severe physiological and psychological dependence
contraindications to use Barbituates
- Porphyria: enhance porphyrin synthesis
- Pulmonary insufficiency: may cause respiratory depression
- Supra-additive effects when combined with alcohol
Why do barbituates have No ceiling effect
- because the action of barbiturates is not dependent on GABA, as the dose increases, the effect continues to increase; it does not plateau
- Especially dangerous when combined with alcohol.
Do the elderly metabolize benzodiazepines more slowly or more quickly
more slowly
Duration of action of benzodiazepines is very clinically relevant. BZs that are converted to active metabolites have what duration of action
longer duration of action
List the benzodiazepines with long duration of action
- Diazepam : 75 hrs
- Chlordiazepoxide
- Flurazepam
List the benzodiazepines with intermediate duration of action
- Alprazolam (6 hr)
- Oxazepam
- Lorazepam
List the benzodiazepines with short duration of action
- Midazolam
List the Benzodiazepines
- Diazepam
- Chlordiazepoxide
- Flurazepam
- Midazolam
- Temazepam
- Alprazolam
- Lorazepam
- Oxazepam
MOA of benzodiazepines
- bind to specific BZ receptor on the GABAA receptor complex.
- Intensify the actions of GABA by enhancing its binding to the GABAA receptor.
- effect is dependent on GABA
explain why benzodiazepines have a ceiling effect
-
Act only when GABA is present.
- As the concentration increases, GABA release is inhibited. This produces a ceiling to the effect, and respiratory depression is far less likely than with barbiturates. This is why benzodiazepines are relatively safe drugs.
List the anxiety disorders for which benzodiazepines are not used
- obsessive compulsive disorder
- Agoraphobia and panic disorders
- Post traumatic stress
- anxiety in children and adolescents
DOC anxiety
benzodiazepines
Which benzodiazepines are commonly used as hypnotics.
- Flurazepam (Dalmane®)
- may cause a drug “hangover” effect
- Temazepam (Restoril®)
Which benzodiazepines are commonly used for status epilepticus
- Diazepam
- Lorazepam
which benzodiazepine is frequently used in preparation for anesthesia and for short surgical procedures
- Midazolam
route of administration of Midazolam
IV
In addition to sedation and a calming effect, midazolam causes
- anterograde amnesia
- the patient will be unable to recall events that occurred after the drug was administered.
Which benzodiazepine can be used for acute muscle spasm and pain as a result of injury
Diazepam
Long-term use of alcohol or barbiturates can produce physical dependence and result in
- withdrawal that is very severe and can be life threatening
- Abrupt discontinuation of BZs can cause rebound increases in insomnia and anxiety
- BZ shoulde be tapered very slowly following chronic use
which benzodiazepines are used to provide a more tapered withdrawal?
- Long acting benzodiazepines
- Chlordiazepoxide
- Diazepam
- Lorazepam
side effects of benzodiazepines
- CNS depression
- paradoxical excitement: dis-inhibition of suppressed behavior
- supra-additive: CNS depression more profound when BZs are combined with alcohol
- sleep-related behaviors: sleep driving, eating, walking
contraindications to benzodiazepines
- pregnancy: category D
- sleep apnea: may decrease tone of upper airway
- elderly
overdose of benzodiazepines causes
- BZs are relatively safe
- overdose results in long deep sleep (24-48 hrs)
- fatalities occur in people with respiratory difficulties, children, and when combined with alcohol
MOA of Flumazenil
-
Benzodiazepine antagonist
- competes with BZs for GABA receptor
- reverses the effects of BZs
- ex: reverses effect of Midazolam (versed)
adverse effect and CI of Flumazenil
- triggers withdrawal and seizures in patients who are physically dependent upon BZ
- do not used in patients with h.o. seizures
List the “Z” drugs used for insomnia
- Zolpidem (Ambien®)
- Zaleplon (Sonata®)
- Eszopiclone (Lunesta®
MOA of Zolpidem (Ambien®) Zaleplon (Sonata®) Eszopiclone (Lunesta®
- bind to the BZ1 subtype of the GABA receptor to increase GABA-mediated inhibition
- very strong and rapid sedative effects
- no anxiolytic, anticonvulsant or muscle relaxant properties
route of administration and duration of action of Zolpidem (Ambien®) Zaleplon (Sonata®)
- oral
- short duration of action
- morning drowsiness is unlikely
route of administration and duration of action of Eszopiclone
- oral
- long half life
- used in long term treatment
side effects of Zolpidem (Ambien®) Zaleplon (Sonata®) Eszopiclone (Lunesta®
- GI: diarrhea and nausea
- CNS: drowsiness and dizziness
- sleep related behaviors
- confusion and memory loss in elderly
- rebound insomnia after rapid discontinuation
abrupt cessation after long term use of Eszopiclone (Lunesta®) can cause
- withdrawal
- CNS sitmulation
- anxiety
- seizures
MOA of Ramelteon
- melatonin analogue
- resets sleep-wake cycle
- promotes sleepiness with out GABA effect
what happens when Ramelteon is taken with alcohol or other sedative hypnotics
additive sedation
side effects of Ramelteon
- drowsiness
- dizziness
- nausea
MOA of Chloral Hydrate
- converted to tricholorethanol which causes sedation
- acts similarly to barbiturates on GABAA receptor
adverse effects of Chloral Hydrate
-
low margin of safety
- high doses induce respiratory and vasomotor depression
- long term use -> liver damage and fatal intoxication
use of Chloral Hydrate
- cheap
- in children for sedation during dental procedures
- use as a sedative-hypnotic not recommended
MOA of Buspirone
- partial agonist at the postsynaptic 5-HT1A (serotonin) receptor -> inhibition of cell signaling
- full agonist at the presynaptic 5-HT1A (serotonin) receptor -> decreased release of 5-HT
Use of Buspirone
- relieves anxiety without producing sedation
- no muscle relaxant or anticonvulsant properties
- does not potentiate CNS depression with alcohol or BZs
- very low addiction potential: excellent choice for anxiety in recovering alcoholics/addicts
