Anxiolytics and Hypnotics Flashcards

1
Q

What are the four main proteins that make up the GABA-A receptor?

A

GABA receptor protein

Benzodiazepine receptor protein

Barbiturate receptor protein

Chloride channel protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What protein links the GABA receptor proteins and the benzodiazepine receptor protein?

A

GABA modulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the normal physiological action of GABA.

A

GABA binds to the GABA receptor protein

GABA modulin links the GABA receptor protein and the benzodiazepine receptor protein

This results in opening of the chloride ion channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name a competitive antagonist of the GABA receptor protein.

A

Biciculline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Name a competitive antagonist of the benzodiazepine receptor protein.

A

Flumazenil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the two main effects of benzodiazepines that facilitate GABA neurotransmission?

A

They facilitate the GABA-mediated opening of the chloride channel

They facilitate the binding of GABA to its receptor protein (increase theaffinity of GABA to the GABA binding site) – this is reciprocated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the three main effects of barbiturates that facilitate GABA neurotransmission?

A

They enhance the normal physiological action of GABA

They enhance GABA binding to the GABA receptor protein (NOT reciprocated)

At higher concentrations, barbiturates can have a direct action on the chloride channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the key difference in the mechanism of action of barbiturates and benzodiazepines?

A

Benzodiazepines – increase the frequency of chloride channel opening

Barbiturates – increase the duration of chloride channel opening

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the relative difference in selectivity between barbiturates and benzodiazepines?

A

Barbiturates are LESS selective

This may explain why barbiturates induce surgical anaesthesia and why barbiturates are less safe than benzodiazepines

NOTE: barbiturates also reduce excitatory transmission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Name a barbiturate that is used as an anaesthetic.

A

Thiopentone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Name three barbiturates and benzodiazepines that are used as anti-convulsants.

A

Diazepam- benzodiazepine

Clonazepam- benzodiazepine

Phenobarbital- barbiturate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Name a benzodiazepine that is used as an anti-spastic.

A

Diazepam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are two other clinical uses of benzodiazepines and barbiturates?

A

Anxiolytics

Hypnotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Define anxiolytic.

A

Remove anxiety without impairing mental or physical activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Define sedative.

A

Reduce mental and physical activity without producing loss of consciousness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Define hypnotic.

A

Induces sleep

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What structure is common to all barbiturates?

A

Six-membered ring (4 carbons and 2 nitrogens)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Barbiturates have been largely superseded by benzodiazepines. Which barbiturate is still used relatively commonly?

A

Amobarbital

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the unwanted effects of barbiturates?

A

Low safety margin (overdose can be lethal)

Alters natural sleep (reduced REM)

Enzyme inducers

Potentiate the action of other CNS depressants (e.g. alcohol)

Tolerance

Dependence

20
Q

What structure is common to all benzodiazepines?

A

They are tricyclic

21
Q

What are the three key benzodiazepines?

A

Diazepam

Oxazepam

Temazepam

22
Q

What is the difference between all the benzodiazepines that are in clinical use?

A

Their pharmacokinetics

23
Q

Describe the administration of benzodiazepines.

A

Well absorbed per orally

Peak plasma concentration after about 1 hour

24
Q

When would you give IV benzodiazepines?

A

Treatment of status epilepticus

25
Q

Describe the distribution of benzodiazepines.

A

Bind strongly to plasma proteins

Highly lipid soluble

26
Q

Describe the metabolism of benzodiazepines.

A

Extensively metabolised in the liver

27
Q

Describe the excretion of benzodiazepines.

A

Excreted in the urine as glucuronide conjugates

28
Q

Describe the duration of action of benzodiazepines.

A

Varies a lot

This allows classification as short-acting and long-acting benzodiazepines

29
Q

What makes long-acting benzodiazepines have a long duration of action?

A

They have slower metabolism

They generate active metabolites

30
Q

Name two short-acting benzodiazepines.

A

Oxazepam

Temazepam

31
Q

Name a long-acting benzodiazepine.

A

Diazepam

32
Q

Describe the metabolism of oxazepam.

A

It is metabolised straight to its glucuronide conjugate (t1/2 = 8 hours)

33
Q

Describe the metabolism of temazepam.

A

Metabolised to oxazepam and then to the glucuronide conjugate

34
Q

Describe the metabolism of diazepam.

A

Metabolised via temazepam and oxazepam to the glucuronide conjugate

Some diazepam is metabolised to nordiazepam and then oxazepam

35
Q

Name three drugs that are used as anxiolytics.

A

General rule – long-acting benzodiazepines

Diazepam
Chlordiazepoxide
Nitrazepam

36
Q

Under what condition would you use a short-acting benzodiazepine as an anxiolytic?

A

Hepatic impairment – this means that the benzodiazepines and metabolised more slowly – drug of choice = oxazepam

37
Q

Name two drugs that are used as sedatives/hypnotics.

A

General rule – short-acting benzodiazepines

Oxazepam
Temazepam

38
Q

Name a long acting drug that might be used as a sedative/hypnotic.

A

Nitrazepam (t1/2 = 28 hours)

39
Q

What are the advantages of benzodiazepines over barbiturates?

A

Wide margin of safety

 Overdose causes prolonged sleep (but this is rousable)

 Flumezanil can be given IV if a patient has overdosed

Mild effect on REM sleep

Do NOT enhance liver enzymes

40
Q

What are the unwanted effects of benzodiazepines?

A

Sedation

Confusion

Ataxia

Potentiate other CNS depressants (e.g. alcohol)

Tolerance

Dependence

Free plasma concentration of benzodiazepines can be increased by giving aspirin and heparin

41
Q

Name a sedative/hypnotic that isn’t a benzodiazepine. What class of drug does this fall into?

A

Zopiclone – this is a cyclopyrrolone and it’s short-acting (t1/2 = 5 hours)

NOTE: it acts on the benzodiazepine receptor but it is not a benzodiazepine

This has fewer hangover effects but dependency is still an issue

42
Q

What drug is used to control the physical symptoms of anxiety?

A

Propranolol

43
Q

Name a new drug that has started being used as an anxiolytic.

A

Buspirone – 5HT1A agonist

This has relatively few side effects and causes less sedation than benzodiazepines

Downside: slow onset of action (maximal anxiolytic effects are not seen for a number of days/weeks)

44
Q

how is GABA synthesised

A

GLUTAMATE–> GABA via GAD(glutamate decarboxylase)

45
Q

how is GABA metabolised?

A

GABA–> Succinate semialdehyde–> Succinic acid

GABA-T and SSDH are the enzymes

46
Q

what other drugs shoudnt be taken with BDZs and why?

A

Alcohol- synergistic CNS depression

Aspirin and heparin- increase amount of free unionised BDZs in blood (bind to same plasma proteins)

47
Q

which GABA receptors do BDZ’s enhance the action of GABA at

A

GABA-A