Sedative-Hypnotic Drugs

Question 1

Uses of sedative-hypnotic drugs

Answer 1

Induce sleep; acute tx of anxiety disorders (anxiolytic) including GAD, acute anxiety disorder, panic disorder, OCD, phobic disorders; muscle relaxation; anticonvulsant; pre-anesthetic; recreation

Question 2

Most sedative-hypnotic drugs bind to some site on this receptor complex and potentiate this nt’s mediated inhibition. Activation by the nt at this receptor does what?

Answer 2

GABA-A receptor complex. Opens Cl channel, hyperpolarizing the cell thus inhibiting it

Question 3

These different agents allosterically enhance GABA binding to GABA-A receptors

Answer 3

Benzos, barbs, and etoh

Question 4

Most clinically used benzos bind to both of these sub-types of receptors

Answer 4

BDZ1 (omega1) and 2

Question 5

The model benzo diazepam binds both BDZ1 and BDZ2 generally producing varying degrees of what properties?

Answer 5

Sedation»hypnosis (dose-related, thus anti-anxiety AND sleep); muscle relaxation, anticonvulsant activity, often anterograde amnesia. [*Very little CV or resp effects]

Question 6

The barbs (& etoh, general anesthetics) exhibit a linear dose-response effect, which progresses from sedation to resp depression, coma, and death. They augment the action of GABA, and in high doses can also do what biochemically?

Answer 6

Directly open the Cl channel, leading to full CNS depression

Question 7

Benzos exhibit limited CNS depression with oral admin,, an effect known as?

Answer 7

Ceiling effect, i.e. no resp depression, coma and death when augmenting action of GABA

Question 8

List some benzos

Answer 8

Diazepam (valium), chlordiazepoxide (librium), lorazepam (ativan), flurazepam (dalmane), alprazolam (xanax), midazolam (versed iv or im), triazolam (halcion)

Question 9

Metabolism of benzos creates what two general types of benzos?

Answer 9

Longer-acting vs shorter-acting depending on phase I metabolite activity or direct metabolism to inactive glucuronides

Question 10

Sleeping pills are selective to what?

Answer 10

BDZ1-selective = “omega1 agonists” (“pseudobenzos”)

Question 11

What’s the main omega1 agonist and what does effect does it produce and not produce?

Answer 11

Zolpidem (Ambien). Sedation and hypnosis, without muscle relaxation or anticonvulsant activity

Question 12

What synthetic drug is used as a benzo-antagonist to reverse overdose of benzo?

Answer 12

Flumazenil

Question 13

Name the two barbs

Answer 13

Phenobarbital and thiopental

Question 14

Differences betw the two barbs

Answer 14

Pheno is less lipid-soluble where Thio is highly lipid-soluble, pheno is slowly elim’d whereas thio is fast on/off

Question 15

What does phenobarbital have some use as?

Answer 15

Anti-epileptic/anticonvulsant

Question 16

What is thiopental used to do?

Answer 16

Induce anesthesia

Question 17

The elimination half-life of all barbs except thiopental (I think) are too long to be useful for hypnosis i.e. all will accumulate during repetitive administration, thus we should use…

Answer 17

Benzos (or omega1’s)

Question 18

For long-term tx of anxiety, use..

Answer 18

Antidepressants (notably SSRIs)

Question 19

For acute anxiety, use..

Answer 19

Benzos

Question 20

For GAD, use..

Answer 20

Antidepressants (SSRIs) and/or benzos. Also buspirone.

Question 21

Relieves anxiety without marked sedation and does not interact with GABA-A receptor cpx but rather may act as a partial agonist at the 5-HT1A receptors?

Answer 21

Buspirone

Question 22

For Panic Disorder, use..

Answer 22

Antidepressants (SSRIs) or benzos

Question 23

For OCD, use..

Answer 23

SSRIs

Question 24

For PTSD, use..

Answer 24

Various antidepressants, etc (?benzos too?)

Question 25

For sedation, use shorter-acting benzos such as?

Answer 25

Alprazolam, lorazepam

Question 26

To induce sleep, use..

Answer 26

Triazolam (very short-acting benzo) or zolpidem

Question 27

To induce anesthesia, use..

Answer 27

Thiopental (barb), benzos for calming and producing anterograde amnesia (very short-acting benzo midazolam)

Question 28

For anticonvulsant effects (like in status epilepticus), use..

Answer 28

Lorazepam, diazepam, phenobarbital

Question 29

For muscle relaxation, use..

Answer 29

Diazepam

Question 30

AEs for benzos

Answer 30

Daytime sedation and drowsiness, additive or synergistic depression with other drugs like etoh, dose-related anterograde amnesia, psychologic and physiologic dependence with chronic use

Question 31

AEs for sedative-hypnotics

Answer 31

Drowsiness and hangover, falls, additive CNS depression with more than one agent, tolerance, psychologic and physiologic dependence can be life-threatening (seizures and death)