sedatives and anxiolytics Flashcards Preview

Yr 2 - Pharmacology > sedatives and anxiolytics > Flashcards

Flashcards in sedatives and anxiolytics Deck (86):
1

What is a neurotransmitter?

A chemical substance released at the end of a nerve fibre by the arrival of a nerve impulse to another nerve fibre, muscle fibre or some other structure

2

What is an excitatory neurotransmitter?

Increases the probability that the target cell will fire an action potential

3

Give an example of an excitatory neurotransmitter:

Glutamate

4

What is an inhibitory neurotransmitter?

Decreases the probability that the target cell will fire and action potential

5

Give two examples of inhibitory neurotransmitters:

GABA (fast, found in virtually every part of the brain = short interneurones e.g. pain modulation)

Glycine (the inhibitory transmitter in the spinal cord)

6

Anxiety is a disorder of the...

CNS

Too few GABA = Anxiety

7

What was GABA first discovered as?

A product of microbial and plant metabolism

8

Which drug enhances the effects of GABA?

Valium

9

What causes epilepsy?

When GABA is lacking in certain parts of the brain

10

Where are there long GABAergic tracts to?

Cerebellum

Striatium

11

Which enzyme produces GABA?

Glutamic Acid Decarboxylase (GAD) -> found primarily in CNS

 

Co-enzyme = Vitamin B6

12

Which reaction produces GABA?

Glutamate -> GABA + CO2

13

How many isoforms of Glutamic Acid Decarboxylase are found in the brain?

Two

(GAD1 & GAD2 -> evolved separately but do same job!)

14

What is a glial cell?

A helper axillary cell = mop up and release neurotransmitter

15

What breaks GABA down?

GABA-Transaminase (GABA-T)

Co-factor = Vitamin B6= located in the mitochondria

16

What does GABA-T break GABA down into?

L-glutamate

17

Which drug is the most potent inhibitor of GABA-T?

Gabaculine (used more in lab than clinically)

18

What happens inside the cell after Gabaculine is given?

- Lots of GABA in cleft

- Eventually it stops vesicles containing GABA (relies on action of GAD to package produce GABA from glutamate and package into vesicle) = action potential = no release of GABA = no inhibition = Anxiety

19

Which cells express GABA receptors?

- Most neurones in the CNS

- Glial cells (astrocytes) = ANS neurones

20

When GABA binds what happens to the neurone?

Shift in membrane permeability to Chloride ions

 

postsynaptic inhibition = hyperpolarisation

presynaptic inhibition = depolarisation

21

How many types of GABA receptor are there?

What are they called?

Two

GABA-A & GABA-B

22

What type of receptor is GABA-A?

Ligand-gated ion (chloride) channel

23

What type of receptor is GABA-B?

GPCR

24

Which drug does GABA enhance the binding of?

Benzodiazepine

25

Why does GABA enhance binding of benzodiazepine?

GABA-A and Benzodiazepine (BDZ) receptor make up 2 separate parts of the same complex

26

Which is the most prevalent GABA receptor?

GABA-A

27

How many subunits does the GABA-A receptor have?

5 (pentameric)

N.b. subunit composition varies between brain regions and neuronal subpopulations (how we get sensitivity to specific regions)

28

Between which two subunits on the GABA-A receptor do benzodiazepines bind?

Alpha & Gamma

29

Which subunit of the GABA-A receptor binds GABA?

Alpha

30

Whats the birds eye view subunit arrangement for the GABA-A receptor?

A image thumb
31

What are the two types of allosteric modulators that act on GABA-A receptors?

Channel blockers (picrotoxin)

Channel modifiers (ethanol, volatile anaesthetics & neurosteroids)

32

What is the most common arrangement of subunits in GABA-A receptors?

1 X Alpha

2 X Beta

2 X Gamma

33

What are the different effects of benzodiazepine on GABA-A receptors with different subunits?

No effect = Alpha 4 & 6

Sedation and Amnesia = Alpha 1

Anxiolytic = Alpha 2 &3

For sensitivity to benzodiazepine = Gamma 2

34

Where are GABA-A receptors found?

Postsynaptic membrane

35

Where are GABA-B receptors found?

Presynaptic terminals

(many sites in brain & periphery)

36

When GABA binds to GABA-B receptors what happens?

- inhibition of voltage sensitive Ca channels

- inhibition of transmitter release

37

What type of receptor is the Glycine receptor?

Ligand gated Cl channel

38

What is the role of Glycine in interneurones?

High in ventral horn

Low in ventral root fibres= associated with inhibitory interneurones

 

N.B. inhibitory effect of glycine is restricted to spinal cord, lower brain stem and retina

39

What is the role of Glycine in the CNS?

inhibitory hyperpolarisation

N.B. inhibitory effect of glycine is restricted to spinal cord, lower brain stem and retina

40

What type of neurotransmitter is Glycine?

Inhibitory

41

Name 3 amino acids that activate the glycine receptor:

Glycine

Beta alanine

Taurine

42

Name two competitive agonists of the Glycine receptor:

Strychnine (high affinity)

Caffiene= block the receptor

43

Which receptors mediate the excitatory responses facilitated by Glycine?

NMDA receptors

44

What effects do glycine/NMDA receptor antagonists have?

Anxiolytic

45

What 4 features characterise anxiety disorders?

- Excessive rumination

- Worrying

- Apprehension

- Fear

46

Which four aspects of experiences does "anxiety" cover?

- mental apprehension

- physical tension

- physical symptoms

- dissociative anxiety

47

What are the (5) somatic and autonomic clinical manifestations of anxiety?

- Restlessness and agitation

- Tachycardia

- Increased sweating

- Weeping

- GI disorders

48

Which three disorders can anxiety disorder be divided into?

- Generalised anxiety disorder

- Phobic disorder

- Panic disorder(characterised by own symptoms and have own treatment)

49

What are the 6 clinically recognised anxiety disorders?

  1. generalised anxiety disorder = ongoing anxiety lacking any clear reason or focus
  2. social anxiety disorder = fear of being with/interacting with other people
  3. Panic disorder = sudden attacks of overwhelming fear
  4. Phobias = song fears of specific objects/ situations
  5. Post traumatic stress disorder = anxiety triggered by recall of past stressful experiences
  6. Obsessive compulsive disorder = compulsive ritualistic behaviour driven by irrational anxiety

50

Which types of drugs are used to treat anxiety disorders?

Anxiolytics -> anxiety

Sedatives -> sedation (calming effect)

Hypnotics -> insomnia (induce sleep)

51

How does dose effect anti-anxiety drugs?

Effect can be dose dependent

= same drug can be classified as anxiolytic/sedative/hypnotic at different dose

52

Too much anti-anxiety drugs =

seizures/ anxiety

53

What are the two possible mechanisms for anxiety?

  1. over activation of brain neurotransmission and neuronal firing (too much excitation e.g. excess glutamate & calcium)
  2. under-inhibition of brain neurotransmission and neuronal firing (insufficient inhibition e.g. insufficient GABA, GABA-A receptor function or enhancement of GABA)

54

How do many sedative/tranquillising drugs work?

Enhance the effects of GABA:

  • increased GABA = blocks repute & increased GABA release
  • increased GABA signalling = Benzodiazepine agonist (partial/total) or blocking benzodiazepine inverse agonists

55

Name 4 groups of anxiolytic drugs:

  • Phenobarbitone :
    • Barbiturate
    • Benzodiazepines
  • Older Tricyclic antidepressants (TCAs)
    • imipramine
    • doxepin
    • amitryptiline
    • trazodone
  • Monoamine Oxidase inhibitors (MAOIs)
    • phenezine
    • tranylcypromine
  • Selective serotonin reuptake inhibitors (SSRIs)
    • sertraline
    • fluoxetine
    • citalopram
    • paroxetine

56

Which receptor do barbiturates bind to?

Beta subunit of GABA-A

(ligand gated Cl channel) = increased duration of Cl channel opening

57

What are the 4 actions of barbiturates?

- potentiate GABA (increased duration of Cl opening)

- block AMPA receptor (glutamate receptor subtype)

- inhibit Ca dependent release of neurotramsmitters

- Binds entire superfamily of ligand gated ion channels

58

What are the 2 side effects of Barbiturates?

Sedation and hypnotic (too much inhibition)

Risk of abuse and addiction is high (rarely used anymore)

59

When are Barbiturates used clinically?

Short-term treatment of severe insomnia

(when benzodiazepines or non-benzodiazepines have failed)

60

What are the 5 clinical uses of benzodiazepines?

- anti anxiety

- sedative

- hypnotic

- anticonvulsant

- muscle relaxant

61

What are the 6 side effects of benzodiazepines?

- Drowsiness

- Confusion

- Amnesia

- Impaired motor co-ordination

- Lack of depth perception

- Reduced REM (rapid eye movement) sleep

62

In which two treatments are benzodiazepines often used?

As a premedication for medical or dental procedures

63

What are the three different categories of benzodiazepines?

Short-acting

Intermediate-acting

Long-acting

64

Which two categories of benzodiazepines are preferred for insomnia?

Short & intermediate-acting

65

Which category of benzodiazepines is preferred for anxiety?

Long-acting

66

What happens following longer term use of benzodiazepines?

Tolerance, dependence & withdrawal

Psychological & physical effects

67

Which receptor interactions with benzodiazepines may contribute to their addictive properties?

inhibits NMDA & nACh receptors

68

Overall which is less toxic... barbiturates or benzodiazepines?

Benzodiazepines

BUT... combination with other CNS depressants (alcohol & opiates) = increased toxicity and potential of fatal overdose

69

Why do we rarely use the older tricyclic antidepressants (TCAs)?

Severe side effects

70

Name 4 different older tricyclic antidepressants (TCAs):

- imipramine

- doxepin

- amitryptiline

- trazodone

71

Name 2 different Monoamine oxidase inhibitors (MAOs):

- phenelzine

- tranylcpromine

 

very effective for anxiety but lots of drug dangers so rarely prescribed

72

What is the main problem with selective serotonin reuptake inhibitors (SSRIs)?

Early in treatment they can produce anxiety due to negative feedback through serotonergic auto receptors

(reduced by combined with a low dose of benzodiazepine)

73

Name a 5HT-1A receptor partial agonist used as an anxiolytic drug:

Buspirone

74

What are the 4 side effects for Buspirone?

Nausea

Dizziness

Headache

Restlessness

 

(less than benzodiazepines)

75

What are the 3 key let downs for Buspirone?

  • Takes days/weeks to develop action
  • Ineffective against panic attacks
  • Prolonged use = adaptive changes/ desensitisation

76

What are the 3 key benefits of Buspirone?

  • No reports of tolerance and physical dependence
  • Less sedation
  • Less motor incoordination

77

Name two hypnotics used to treat insomnia:

  • Zopiclone (non BDZ hypnotic)
  • Zolpidem (non BDZ hypnotic imidazopyridine)

78

Name three antihistamines used for sedation:

Chloral hydrate

Diphenhydramine (nytol)

Promethazine

 

n.b. Drowsiness = side effect due to H1 antagonism in CNS

79

What are the 2 benefits of antihistamines over other sedatives?

Fewer side effects

Safer

80

Name a beta adrenoreceptor antagonist used to remove the peripheral symptoms of anxiety:

Propanalol

81

Why are anxiolytics often used in general dental practice?

As a premedication

82

What are the 6 indications of using anxiolytics in general dental practice?

If individual is:

  • fearful
  • anxious
  • longer appointments
  • especially invasive procedures
  • pronounced gag reflex
  • may help achieve profound local anaesthesia

83

What are the 5 contraindications of using anxiolytics in general dental practice?

  • pregnancy
  • elderly
  • medically unstable (angina/diabetes)
  • medically complex (sever systemic disease)
  • patients already presenting adverse reactions to medications

84

Which anxiolytics are often used in general dental practice?

Chloral hydrate (now replaced with Midazolam)

Barbituates = phentobarbital

Benzodiazepines = Diazepam (valium), Lorazepam (ativan) & Triazolam

Antihistamine H1 - hydroxyzine (vistoril)

Serotonin 5-HT-1A partial antagonists = Buspirone

85

What is the mechanism of action for Benzodiazepines?

Increase the PROBABILITY of channel opening

86

What is the mechanism of action for phenobarbitone (barbiturates)?

Low conc = PROLONG channel opening High conc = open channel in absence of GABA