L33 - Sedatives, anxiolytics

Question 1

What are sedatives?

Answer 1

Drugs that calm or relax anxious or restless patients without actually inducing sleep. However, these drugs may produce sleepiness and sleep may follow.

Question 2

Do anxiolytics notably impair consciousness?

Answer 2

No – ideally it should also not cause sleepiness; however, distinction between a sedative and an anxiolytic is not entire clear.

Question 3

Is insomnia a disease entity or a symptom?

Answer 3

Symptom

Question 4

2 cycles of sleep

Answer 4

First, you go into non-REM sleep that has 4 stages (60 – 90 minutes). This is when GH is released, protein synthesis. Physical regeneration.

Next REM sleep (20 minutes) – Rapid eye movement (eyes are closed by eyeballs move fast under the closed eyelids. This is when we dream – escape reality or else without it, we get psychotic symptoms when awake. Psychological regeneration.

Question 5

EEG of people sleeping shows that REM sleep looks like?

Answer 5

Synchronised waves – looks like a regular pattern similar to wakefulness

Question 6

What drugs are barbituarates classified as? Side effects?

Answer 6

Hypnotic, sedatives, anti-epileptic – but now BZ more popular

SE: Anaesthetic (High lipid solubility hence goes into CNS immediately but goes back out and absorbed into muscle and fat), anti-epileptic

Question 7

Barbituates or BZ – which is harder to commit suicide with?

Answer 7

BZ

Question 8

What effects do Barbituates and BZ have on REM sleep?

Answer 8

Suppress REM sleep and increase non-REM sleep periods

Question 9

What happens when you stop taking barbituates and BZ?

Answer 9

You get rebound REM– excessive dreaming, hence preferably to only take them for a few days as it causes physical (e.g. convulsants) and psychological dependence

Question 10

How does tolerance develop with barbituate and BZ intake?

Answer 10

Tolerance develops because they are potent inducers of liver microsomal enzymes that break down the barbituates and pharmodynamic tolerance (cells getting used to drug and needing more to produce same effect)

Question 11

What drug are BZ classified as?

Answer 11

Sedative, hypnotic and anxiolytic, anticonvulsant, muscle relaxant and amnesic actions

Question 12

a) Example of 2 BZ
b) Onset of action after oral administration
c) Elimination half life of parent drug – long or short?
d) Active metabolites – yes or no?

Answer 12

a) Diazepam (trade name Valium), Oxazepam (trade name Benzotran)
b) Rapid, Slow
c) 24—70 hours, 6 – 12 hours
d) Yes- long acting, broken down to another substance that also acts as BZ e.g. Oxazepam, No – short acting

Question 13

Date rape drug

Answer 13

Flurazepam

Question 14

Long acting agent (BZ) preferable in 3 situations

Answer 14

Speedy onset, when daytime anxiety is present and for muscle tension

Question 15

Mechanism of Action of BZ

Answer 15

Increased affinity of GABA for GABA A receptor -> increase Cl- permeability -> increase Cl- flux -> hyper pola nd diminished excitability

Question 16

Subunits of GABA A R

Answer 16

2 alpha, 2 beta, 1 gamma

Question 17

Which subunit of GABA is associated with BZ’s anxiolytic actions? Sedative?

Answer 17

a2 - anxiolytic

a1 - sedative

Question 18

Which subunits do GABA bind to? What about BZ?

Answer 18

GABA - a1, b2

BZ - a1/2/3. gamma 2

Question 19

List one non-BZ – what is it used for? Mechanism of action? How are effects reversed?

Answer 19

Zolpidem (Stillnox) is used in short treatment of insomnia, binding to a1 subunit of GABA A R. Has little anticonvulsant or muscle relaxant activity

All identified effects of Zolpidem are reversed by the benzodiazepine antagonist Flumazenil