Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Y2 - PHARM > Anxiolytics > Flashcards

Anxiolytics Flashcards

1
Q

GABA is the most important ….. NT in the brain

A
  • GABA is the most important inhibitory NT in the brain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is GABA synthesised from and what enzmye carries out this reaction, also what must be present for the enzyme to function properly?

A
  • Glutamate (+GAD enzyme) → GABA
  • GAD enzyme requires the presence of vitamin B6 to function properly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

1) What are the 2 GABA receptors, where are they located, and what type of receptors are they?
2) What is the function of the one not involved in the inhibitory action of GABA?

A

1)

  • GABA-A - on post-synaptic membranes - type 1 ion-channel-linked chloride ionophores
  • GABA-B - on pre-synaptic membranes - type 2 (G-protein coupled)

2)

  • GABA-B receptors are regulatory receptors located on the pre-synaptic membranes - they regulate GABA transmission
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Outline how GABA has its inhibitory effect, mentioning detail on the GABA receptor involved

A

GABA acts on GABA-A receptors on post-synaptic membranes to induce chloride influx - hyperpolarises the neurone - therefore has an inhibitory effect

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

Outline the metabolism of GABA, and then circle round to GABA formation (describe how it is linked to the TCA cycle)

A
  • GABA reuptake either into glial cells surrounding the synapse or back into the pre-synaptic neurone occurs - thereby reducing the synaptic concentration of GABA and allowing its metabolism
  1. GABA (+GABA-Transaminase) → Succinic semi-aldehyde
  2. Succinic semi-aldehyde (+Succinic semi-aldehyde dehydrogenase) → Succinic Acid
  • Succinic acid goes back into the TCA cycle
  • In the TCA cycle you eventually form glutamate
  • This glutamate is then used for conversion into GABA using GAD in the presence of vitamin B6
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Name 2 anxiolytic drugs that target GABA metabolism and outline their modes of action

A
  1. Sodium valproate
    * GABA-Transaminase and Succinic Semi-Aldehyde Dehydrogenase inhibitors, thereby preventing both stages of GABA metabolism, so preserves and potentiates the inhibitory efffects of GABA
  2. Vigabatrin
    * GABA-Transaminase inhibitor, thereby preventing the first stage of GABA metabolism, so preserves and potentiates the inhibitory effects of GABA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the 4 main proteins that GABA-A receptors are composed of?

A
  1. GABA receptor protein
  2. Benzodiazepine receptor protein
  3. Barbiturate receptor protein
  4. Chloride channel protein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe in detail how GABA has its inhibitory effect, knowing the complexes within the GABA-A receptor

A
  1. GABA binds the GABA receptor protein complex on the GABA-A receptor on the post-synaptic membranes of target neurones
  2. When this happens, GABA receptor protein complex links with the benzodiazepine receptor complex - this is mediated by GABA modulin
  3. This linkage causes temporary opening of the cloride channel within the GABA-A receptor
  4. There is therefore Cl- inclux which causes hyperpolarisation which makes it harder for depolarisation to occur for an action potential - hence the inhibitory effects of GABA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Name a GABA-A receptor antagonist and expand further on its mode of action

A
  • Bicuculline
  • Competes with GABA for its binding site on the GABA receptor protein complex on the GABA-A receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe in detail how benzodiazepines have their effect to potentiate GABA, knowing the complexes within the GABA-A receptor

A
  • Benzodiazepines bind the benzodiazepine receptor protein complex on the GABA-A receptor. It then has its effects:
  1. Binding of benzodiazepines to its receptor on GABA-A facilitates binding of GABA to the GABA receptor protein complex on the GABA-A receptor. This is a reciprocal effect (i.e. subsequent GABA binding also facilitates benzodiazepine binding to their receptor complexes on the GABA-A receptor)
  2. Directly facilitates GABA’s ability to open the calcium ion channels in the GABA-A receptors - it increases the frequency of chloride channel opening
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is Flumezanil - what does it do?

A
  • Competitive benzodiazepine antagonist - competes with benzodiazepines for the benzodiazepine receptor protein on the GABA-A receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

1) Describe in detail how barbiturates have their effect to potentiate GABA, knowing the complexes within the GABA-A receptor
2) Describe how barbiturates can have a depressant effect in isolation, which is not via GABA transmission, and when does this occur?
3) Apart from promoting inhibition, how else can barbiturates have an inhibitory / depressant effect?

A

1)

  • Barbiturates bind the barbiturate receptor protein complex on the GABA-A receptor. It then has its effects including:
  1. Facilitating GABA’s ability to open chloride channels within the GABA-A receptor - increases the duration of chloride channel opening
  2. Facilitates the binding of GABA to the GABA receptor protein complex on the GABA-A receptor

2)

  • At high barbiturate concentration, the barbiturates can have direct effects on opening of calcium channels

3)

  • Barbiturates can have a direct antagonistic effect against the action of glutamate (an excitatory NT) - so inhibits the excitatory signals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

1) Why do barbiturates and benzodiazepines only have an effect in the presence of GABA neurotransmission - why wouldn’t it work in isolation?
2) What is an exception to this rule - when would you get isolated effect?

A

1)

  • Because they work by allosteric binding in order to potente GABA transmission in order to indirectly have an inhibitory / depressant effect - they do not have direct inhibitory effects

2)

  • At high concentrations, barbiturates have a direct effect to open the chloride channels on the GABA-A receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

1) Which are less selective - barbiturates or benzodiazepines?
2) How does the reduced selectivity make it useful - give a use
3) Which are more dangerous - barbiturates or benzodiazepines and why?

A

1)

  • Barbiturates are less selective than benzodiazepines

2)

  • It has other uses - for example as a surgical anaesthetic

3)

  • Barbiturates due to its lower selectivity and also because it causes respiratory depression upon overdose unlike benzodiazepines
  • Also benzodiazepines can be antagonised using flumezanil in the event of OD, unlike barbiturates
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Give 5 clinical uses of barbiturates / benzodiazepines - one of them is ONLY a BARBITURATE use

A
  1. Anaesthetics - only barbiturates
  2. Anti-convulsants
  3. Anti-spastics
  4. Anxiolytics
  5. Sedatives / hypnotics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Define what anxiolytics do, and what is another name for them?

A
  • Remove anxiety without impairing physical or mental health
  • ‘Minor tranquilisers’
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Define what sedatives do

A
  • Reduce mental and physical activity without causing loss of consciousness
18
Q

Define what hypnotics do

A
  • Induce sleep
19
Q

Name a powerful barbiturate sedative / hypnotic

A
  • Amobarbital - used for severe insomnia
20
Q

Give 3 basic structural features of the chemical structure of barbiturates

A
  • 6 ring structure
  • 4 C’s in a ring
  • 2 N’s
21
Q

What are the unwanted effects of barbiturates?

A
  • Low safety margins as they depress respiration → lethal
  • Alter natural sleep (decrease REM sleep) → hangovers and irritability
  • Enzyme inducers - barbiturates induce microsomal enzymes - so avoid co-administration
  • Potentiate other CNS depressants (e.g. alcohol)
  • Tolerance
  • Dependence: withdrawal symtoms, insomnia, anxiety, tremor, convulsion, death
22
Q

Give a characteristic chemical structural feature of benzodiazepines

A
  • Tricyclic - i.e. three ring structure
23
Q

Give 3 key benzodiazepines

A

DOT

  • Diazepam
  • Oxazepam
  • Temazepam
24
Q

What does Flumezanil do, and how does the structure of Flumezanil allow it to have its effect?

A
  • Flumezanil is a competitive benzodiazepine receptor antagonist
  • It has the same tricyclic (3-ring) structure as benzodiazepines which enables it to compete for the benzodaizepine receptors
25
Q

What is the main use of benzodiazepines - excluding sedative / hypnotic?

A
  • Anti-convulsant - epilepsy - status epilepticus
26
Q

Describe the distribution of benzodiazepines in terms of its pharmacokinetics

A
  • Bind plasma proteins strongly
  • Highly lipid soluble
27
Q

Describe the main route of phase 2 metabolism of benzodiazepines

A
  • Mainly glucuronide conjugates
28
Q

Describe the excretion of benzodiazepines

A
  • Excreted in the urine as glucuronide conjugates
29
Q

Describe the duration of action of benzodiazepines

A
  • Short-acting vs long-acting
30
Q

How are long-acting benzodiazapines, long-acting?

A
  • Slow metabolism
  • Generate active metabolites
31
Q

1) Name 2 short-acting benzodiazepines
2) Name 1 long-acting benzodiazepines

A

1)

  1. Oxazepam
  2. Temazepam

2)

  • Diazepam
32
Q

Describe how oxazepam is metabolised

A
  • Oxazepam is metabolised in the liver into its glucuronide conjugate
33
Q

Describe how temazepam is metabolised

A
  • Temazepam is metabolised into oxazepam
  • Oxazepam is then metabolised into its glucuronide conjugates
34
Q

Describe how diazepam is metabolised and thus explain why it is a long-acting benzodiazepine

A

There are 2 routes:

EITHER:

  • Diazepam is metabolised into Temazepam
  • Temazepan is then metabolised into Oxazepam
  • Oxazepam is then metabolised into its inactive glucuronide conjugate

OR:

  • Diazepam is metabolised into nordiazepam - an active metabolite
  • Nordiazepam also is reversibly converted into chlordiazepoxide which is another active metabolite
  • Ultimately nordiazepam is then metabolised into oxazepam which is then metabolised into its inactive glucuronide conjugate

THEREFORE IT IS CONSIDERED A LONG-TERM METABOLITE BECAUSE…

of the active metabolites that it generates because then you take longer to metabolise both the diazepam AND the active metabolites it is metabolised into

35
Q

Name three benzodiazepines used particularly for their anxiolytic effects

A
  • Diazepam
  • Chlordiazepoxide
  • Nitrazepam
36
Q

Apart from for its short-acting metabolic effects, when else could it be preferential to use short-acting benzodiazepines rather than long-acting ones?

A
  • If a patient has hepatic impairment, this would impair the ability to metabolise the benzodiazepines, thereby prolonging their effects, so you give a short-acting benzodiazepine such as oxazepam
37
Q

What are the advantages of using benzodiazepines over barbiturates?

A
  • Wider margin of safety - in the event of overdose this does not lead to fatal consequences as readily like respiratory distress as with barbiturates
    • You can also administer flumazenil in the event of overdose which is a competitive benzodiazepine antagonist to counter the overdose
  • Does not alter REM sleep as much as barbiturates - so less ‘hangover’ feeling
  • Do not induce liver (microsomal) enzymes like barbiturates do so less danger with co-adminstering with other drugs
38
Q

Give the unwanted effects of benzodiazepines (5)

A
  1. Confusion / ataxia
  2. Potentiate other CNS depressants like alcohol
  3. Tolerance - only tissue tolerance not pharmacokinetic tolerance
  4. Dependence
  5. Free plasma concentration of benzodiazepines increases when you co-administer aspirin and heparin because these are also plasma protein bound and so compete with them for the plasma proteins
39
Q

1) Name a drug that is a sedative / hypnotic but is neither a benzodiazepine nor a barbiturate and describe its mode of action
2) What class of drugs does it belong to?
3) Give an advantage of this drug

A

1)

  • Zopiclone
  • Benzodiazepine receptor agonist (but it is NOT a benzodiazepine)

2)

  • Cyclopyrrolone

3)

  • Minimal hangover effects - as it does not alter REM sleep much
40
Q

Name some drug types and some named examples or directly name some drugs that can also be used as anxiolytics that are neither benzodiazepines nor barbiturates

A
  • Anti-depressants
    • SSRIs
  • Anti-epileptics
    • Valproate
    • Tiabigine
  • Anti-psychotic drugs
    • Olanzapine
    • Quetiapine
  • Propranolol
    • Non-selective beta-blocker - improves the physical symptoms of anxiety
  • Buspirone
    • 5-HT1A agonists

Y2 - PHARM (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions