L7- Sedatives, Hypnotics (benzodiazepines)

Question 1

describe the goals of Sedatives

Answer 1

• reduce anxiety
• exert calming effect
• no change in motor / mental functions
• should not cause sleep (minimum dose with therapeutic efficacy)

Question 2

describe the goals of Hypnotics

Answer 2

• produce drowsiness + encourage onset and maintenance of sleep to resemble natural sleep
• more pronounced depression of CNS than sedation

Question 3

describe the dose-response relationships for benzodiazepines and barbituates

Answer 3

Barbituates: linear curve; sedation –> hypnotic –> anesthesia –> coma

Benzodiazepines: non-linear curve; sedation (low doses) –> hypnotic (high doses)
Note- benzos never cross into anesthesia stage if used alone but used in combination
**therefore benzos are safer + more affective

Question 4

list the sedative-hypnotics

Answer 4

• benzodiazepines
• barbituates
• non-benzodiazepine receptor agonists
• 5-HT-1A receptor partial agonists
• melatonin agonists
• • others as secondary effects

Question 5

GABA-a receptors:

• (1) subunits
• (2) ion channel
• (3) site of GABA binding
• (4) site of Benzodiazepines

Answer 5

1- 2α, 2β, γ
2- Cl-
3- between α/β
4- between α/γ

Question 6

list the defined benzodiazepine receptors

Answer 6

BZ1- α1 subunit

BZ2- α2 subunit

Question 7

describe the effect benzodiazepines have on GABA-a receptors

Answer 7

• allosteric binding

- increases the frequency of channel opening events

Question 8

describe briefly the 3 benzodiazepine-receptor interactions

Answer 8

i) agonists- pos. allosteric modulators // clinically useful benzos exerting anxiolytic, anticonvulsant effects
ii) antagonists- Flumazenil
iii) inverse agonists- neg. allosteric modulators // causes anxiety, seizures

Question 9

(1) is the benzodiazepine antagonist and is used in (2) and (3) situations

Answer 9

1- Flumazenil
2- Tx for benzodiazepine overdose
3- quickens recovery from anesthesia and diagnositic procedures when benzos are used

Question 10

list the benzodiazepine actions

Answer 10

• **reduction of anxiety
• sedative hypnotic actions
• anticonvulsant
• muscle relaxant
• anesthesia (in combination)

Question 11

how can benzodiazepines have different clinical actions

Answer 11

each drug in this class have varying effects at varying doses

Question 12

describe the pharmacokinetics of benzodiazepines

Answer 12

• lipophilic –> rapidly and completely absorbed, distribution throughout the body
• 1/2 lives differ among different agents (short, intermediate, long)

Question 13

list the benzodiazepines (separate by half-lives)

Answer 13

Long (1-3 days): diazepam, flurazepam

Intermediate (10-20h): alprazolam, lorazepam, temazepam

Short (3-8h): oxazepam, triazolam

Question 14

______ benzodiazepines are used for anxiety disorders

Answer 14

short-term- oxazepam, triazolam
intermediate: alprazolam, lorazepam, temazepam

Note- not long-term as it can cause dependence

Question 15

______ benzodiazepines are used in muscular disorders, explain

Answer 15

Diazepam: Tx of skeletal muscle spasms and spasticity from degenerative disorders (MS, cerebral palsy)

Question 16

(1) benzodiazepine(s) is/are used for epileptic seizures

2) benzodiazepine(s) is/are used for status epilepticus (successive seizures w/o recovery

Answer 16

1- Clonazepam

2- Lorazepam (drug of choice), Midazolam, Diazepam

Question 17

______ benzodiazepines are used for withdrawal symptoms of ethanol

Answer 17

diazepam

oxazepam

Question 18

list the most popular benzodiazepines used for sleep disorders

Answer 18

Short, Triazolam: for falling asleep

Intermediate, Temazepam: for staying asleep, and maybe for falling sleep too

Long, Flurazepam: extreme cases

Question 19

list the most common AEs for benzodiazepines

Answer 19

• **drowsiness, confusion
• ataxia (don’t operate heavy machinery)
• cognitive impairment

Question 20

describe the psychological AEs for benzodiazepines

Answer 20

paradoxical effects are rare, but result in: anxiety, irritability, hostility / rage, paranoia, depression, suicidal ideation (aka disinhibition)

Question 21

describe the effects of dependence with benzodiazepines

Answer 21

depends of specific agent, worse with long acting agents => withdrawal Sxs w/ abrupt discontinuation:

• confusion, anxiety, agitation
• restlessness, insomnia, tension

Question 22

Flumazenil:

• (1) functions
• (long/short) 1/2 half-life
• can precipitate (3) reaction in benzodiazepine users or cause (4) with specific benzodiazepine use

Answer 22

1- benzo OD, recovery from anesthesia with benzo
2- short, must be given frequently
3- withdrawal in dependent users
4- seizures in users using for seizure control