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For each of the following sedative-hypnotic-induced CNS effects, place in order from effect caused by lowest to highest does of drug: coma; anesthesia; hypnosis; sedation/anxiolysis; medullary depression
Sedation/anxiolysis; hypnosis; anesthesia; medullary depression; coma
Which medication produces CNS depression when converted to its active metabolite trichloroethanol
Chloral hydrate
What is the first step in ethanol metabolism
Alcohol dehydrogenase converts ethanol to acetaldehyde
None
What is the second step in ethanol metabolism
Acetaldehyde dehydrogenase converts acetaldehyde to acetate
What enzyme does disulfiram inhibit
Acetaldehyde dehydrogenase
Which metabolite of ethanol is responsible for causing headache, hypotension, nausea, and vomiting (“hang over”)
Acetaldehyde
What does GABA stand for
Gamma-aminobutyric acid
How many subunits make up the GABA receptor
Five subunits
Which subunit does GABA bind to
α subunit
Which subunit on the GABA receptor do benzodiazepines bind to
γ subunit (binding potentiates the affinity of the GABA receptors for GABA; does not activate the receptor alone without GABA); multiple benzodiazepine receptors subtypes exist (i.e. BZ1 receptors and BZ2 receptors)
Which subunit on the GABA receptor do barbiturates bind to
β subunit (binding potentiates the affinity of the GABA receptor for GABA; does not activate the receptor alone without GABA)
None
What physiologic process takes place when GABA binds to the GABAa receptor
Increased chloride ion influx into cells leading to membrane hyperpolarization and subsequent decreased neuronal firing
What physiologic process takes place when GABA binds to the GABAb receptor
Increased potassium ion efflux out of the cell leading to membrane hyperpolarization and subsequent decreased neuronal firing
What medication binds specifically to the GABAb receptor
Baclofen
What is baclofen used for
Muscle relaxation
Do benzodiazepines potentiate GABA by increasing the duration or frequency of chloride ion channel opening
Frequency
Do barbiturates potentiate GABA by increasing the duration or frequency of chloride ion channel openings
Duration
Binding to which benzodiazepine receptor subtype is responsible for mediating sedative-hypnotic actions of the drug class
BZ1 receptor subtype
Name three nonbenzodiazepine sleep aids that specifically bind to the BZ1 receptor subtype
Eszopiclone
Zolpidem
Zaleplon
None
Does zolpidem display anticonvulsant, antianxiety, or muscle relaxant properties
No (selective hypnotic along with zaleplon and eszopiclone)
None
Do benzodiazepines have good analgesic properties
No
What types of actions do benzodiazepines display
Muscle relaxant
Anticonvulsant
Antianxiety
Sedative-hypnotic
Anterograde amnesia (midazolam)
Alcohol withdrawal
None
Give examples of benzodiazepines
Chlordiazepoxide
Diazepam
Flurazepam

Lorazepam
Temazepam
Alprazolam

Midazolam

Flunitrazepam
Clonazepam
Triazolam
Oxazepam
Clorazepate
None
What is the name of the prototype benzodiazepine
Chlordiazepoxide
What is another name for flunitrazepam
Rohypnol
Which benzodiazepine is the longest acting
Diazepam
Which benzodiazepine is the shortest acting
Midazolam
What benzodiazepines undergo phase II metabolism
Lorazepam
Temazepam

Oxazepam
None
Which benzodiazepines are commonly used as anticonvulsants
Diazepam
Clonazepam
None
Which benzodiazepines are commonly used to treat alcohol withdrawal
Chlordiazepoxide
Diazepam
Lorazepam

Oxazepam
None
Which benzodiazepines are commonly used as sleep aids
Flurazepam
Temazepam

Triazolam
None
Which benzodiazepines are commonly used as anxiolytics
Diazepam
Lorazepam
Alprazolam
None
Why is alprazolam not the drug of choice when treating patients with chronic anxiety
Short half-life; therefore, may cause withdrawal symptoms, such as anxiety, which subsequently worsens the condition
Give examples of long-acting benzodiazepines (duration of action of 1 to 3 days)
Chlordiazepoxide
Diazepam
Flurazepam

Clorazepate
None
Give examples of intermediate-acting benzodiazepines (duration of action of 10 to 20 hours)
Lorazepam
Temazepam
Alprazolam
None
Give examples of short-acting benzodiazepines (duration of action of 3 to 8 hours)
Midazolam

Oxaxepam
Triazolam
None
What types of dependence can develop in patients treated with benzodiazepines
Physical dependence; psychological dependence
Give examples of benzodiazepine withdrawal signs and symptoms
Insomnia
Anxiety
Agitation
Seizures
Restlessness
Confusion
None
What are the adverse effects of benzodiazepines
Confusion
Drowsiness
Ataxia
Cognitive impairment
Amnesia
Respiratory depression
None
Is withdrawal more likely to occur with long-acting or short-acting benzodiazepines
Short-acting benzodiazepines (abrupt withdrawal may ensue as drug levels are rapidly decreased vs. long-acting benzodiazepines offer a “self-tapering” mechanism which decreases the chance of withdrawal)
What is the antidote for benzodiazepine-induced CNS depression
Flumazenil (short half-life; therefore, multiple administrations may be necessary)
What is the mechanism of action of flumazenil
Benzodiazepine receptor antagonist
Will flumazenil decrease the effects of barbiturates
No (barbiturates act at a different GABA receptor subtype than benzodiazepines)
Which two sedative-hypnotic drug classes are potentially fatal with overdose and/or withdrawal
Barbiturates; alcohols (benzodiazepines may be potentially fatal but to a lesser extent than barbiturates and alcohols)
Give an example of a long-acting barbiturate (duration of action of 1-2 days)
Phenobarbital
Pentobarbital
None
Give examples of short-acting barbiturates (duration of action of 3 to 8 hours)
Amobarbital; Secobarbital
Give an example of an ultra-short-acting barbiturate (duration of action of 30 minutes)
Thiopental
What is Phenobarbital commonly used to treat
Seizures (generalized tonic-clonic and partial seizures)
What is thiopental commonly used for
Induction anesthesia
What are short-acting barbiturates commonly used for
Sedation and hypnosis
What kind of drug interactions can barbiturates produce
Induction of cytochrome P-450 enzymes
What are the adverse effects of barbiturates
Drowsiness
Impaired cognitive function (especially in pediatric patients)
“Hang over” effect
Nausea
Dizziness
Increased heme synthesis (contraindicated in patients with acute intermittent porphyria)
Coma
Respiratory depression
Cardiovascular depression
Addiction
None
Give exampes of barbiturate withdrawal signs and symptoms
Insomnia
Tremors
Anxiety
Restlessness
Nausea
Vomiting
Seizures
Cardiac arrest
Delirium
Hyperreflexia
Agitation
None
What drug class is used to prevent barbiturate withdrawal
Long-acting benzodiazepines
Over-the-counter (OTC) sleep aids have what types of medications in them
Sedating antihistamines
Give examples of sedating antihistamines
Diphenhydramine
Doxylamine

Hydroxyzine (prescription only)
None
Give examples of antidepressants that have been used for sedation and hypnosis
Trazodone
Amitriptyline
None
Which medication is a partial agonist at 5-HT1a receptors and is effective in treating generalized anxiety disorder
Buspirone
Does buspirone have anticonvulsant and muscle relaxant properties
No
Is buspirone sedating
No
How long does it take for buspirone to exert its anxiolytic effects
1 to 2 weeks (therefore, not useful in treating an acute anxiety attack)
Does buspirone cause physical and psychological dependence
No
What types of withdrawal signs and symptoms does buspirone cause
None