CNS Anxiolytics, Sedative and Hypnotic Drugs - Kelly 4

Question 1

Sedative drug

Answer 1

Reduce person’s response to external stimuli

Reduces anxiety and has calming effect with minimal depression of motor or mental functions

Question 2

Hypnotic drug

Answer 2

Cause drowsiness and sleep-like state

Question 3

Anxiety

Answer 3

Changes in mood, physiological arousal and increased perceptual acuity
Tachycardia, sweating, trembling, palpitations, unpleasant state of tension, apprehension, uneasiness
Disorders involving anxiety and sleep are the most common mental disturbances

Question 4

Classes of sedative-hypnotics

Answer 4

Benzodiazepines
Barbiturates
Sedative-autonomic (Beta-blockers, clonidine, TCA’s, antipsychotics - short or long and action based on need/intention)
All anxiolytic drugs also cause sedation (based on dose)

Question 5

Ceiling effect of benzodiazepines

Answer 5

Not found in barbiturates, causing higher mortality and coma

Question 6

Benzodiazepines pharmacokinetics

Answer 6

Absorbed in gut
Rate where BZ crosses CSF depends on protein binding, lipid solubility and ionization constant
Usually easily cross BBB and placental barrier
Extensively metabolized by the hepatic microsomal metabolizing system to active compounds
Excreted in urine
Psychological and physiological dependence with prolonger use
Tolerance
Additive manner with alcohol, barbiturates and anticonvulsants
Smokers need higher dose of drug
SSRI increase levels

Question 7

Long acting BZ

Answer 7

Diazepam, chlordiazepoxide, flurazepam
Form active metabolites with long half-life
Drowsy in morning

Question 8

Intermediate acting BZ

Answer 8

Alprazolam, lorazepam, temazepam

Question 9

Short acting BZ

Answer 9

Oxazepam, triazolam

Question 10

Adverse reactions of BZ

Answer 10

Drowsiness and confusion, ataxia and cognitive impairment at higher doses
Abrupt discontinuation results in confusion, anxiety, agitation, restlessness, insomnia and tension
Onset of withdrawal relates to half life of BZ

Question 11

BZ pharmacodynamics

Answer 11

Allosteric modulator

Increase GABA binding to channel, inducing Cl influx

Question 12

Therapeutic uses of BZ

Answer 12

Anxiety disorders
Muscular disorders (spasticity from degenerative disorders)
Seizures (chronic treatment of epilepsy)
Acute treatment of alcohol withdrawal
Sleep disorders (shorter duration BZ)

Question 13

Barbiturates

Answer 13

Well absorbed orally, distributed widely throughout body
Metabolized in liver into inactive metabolites that are excreted into urine
Mainly replaced by BZ
CNS depressants, which is additive with alcohol and opioids
No significant analgesic affects
Anticonvulsant effects

Question 14

Barbiturate pharmacodynamics

Answer 14

In high doses, can activate GABA receptor

Allosteric modifier

Question 15

Therapeutic uses of barbiturates

Answer 15

Anesthesia
Anticonvulsant (phenobarbital used in long term management of tonic-clonic seizure)
Anxiety (mostly replaced by BZ)

Question 16

Thiopental

Answer 16

Ultra-short acting

Barbiturate used IVE to induce surgical anesthesia

Question 17

Busiprone

Answer 17

5-HT1A receptors
Also has affinity for DA2 receptors
Treatment of generalized anxiety disorders, little sedation, no anti-convulsant or muscle-relaxant properties

Question 18

Zolpidem

Answer 18

Imidazopyridine derivative
Unrelated to BZ
Hypnotic actions
Binds directly to BZ receptor and increases GABA-mediated inhibition
Used for short-term treatment of insomnia

Question 19

Ramelteon

Answer 19

Activated melatonin receptors in the superchiasmic nuclei of the CNS and decreases the latency of sleep onset
Minimal rebound insomnia and abuse potential

Question 20

Orexin antagonists

Answer 20

Orexin is a peptide found in the hypothalamus and is involved in wakefulness
Suvorexant is an antagonist at orexin receptors, acts as a hypnotic