Transmitters and Receptors

Question 1

What is essential for drugs to do to act in the CNS?

Answer 1

Cross BBB

Question 2

Where do drugs interfere with chemical neurotransmission?

Answer 2

Synthesis
Storage
Release
Reuptake
Metabolism
Receptor

Question 3

Why isn’t the second line of cocaine as good as the first line?

Answer 3

NA depleted from first line

Question 4

What happens to motor nerves in epilepsy?

Answer 4

Excessive discharge

Question 5

What is the function of phenytoin?

Answer 5

Limits excitatory nerve action in epilepsy

Question 6

On what receptor does phenytoin have an action

Answer 6

Na channels on post-synaptic terminals

Question 7

What conformation must Na channels be in for phenytoin to work?

Answer 7

Only blocks Na channels when they’re open

Question 8

What is the challenge of administering phenytoin?

Answer 8

Firing that gives epileptic seizure one day is different to firing on another day
Means that phenytoin concentrations have to be in window

Question 9

What is the function of benzodiazepines?

Answer 9

Enhance GABA receptor activity > enhance inhibitory input in epilepsy

Question 10

What are the therapeutic outcomes of benzodiazepines in epilepsy?

Answer 10

Increased tonic inhibition

Decreased excessive discharge

Question 11

Describe GABA

Answer 11

Main inhibitory transmitter in CNS

• GABA A - ligand-gated receptor
• GABA B - GCPRs

Question 12

What does activating the neuropeptide Y (NPY) 1 receptor do?

Answer 12

Reduce anxiety

Question 13

What is the effect of antagonising the H1 receptor in the CNS?

Answer 13

Sedative

Question 14

20% of the population has a point mutation in the H1 receptor. How do these people respond to antihistamines?

Answer 14

Antihistamines make them hyperexcitable

Question 15

What are benzodiazepines used in?

Answer 15

Epilepsy
Anxiety
Sleep disorders
Premedication - sedation for medical procedures
Acute alcohol withdrawal

Question 16

What is insomnia?

Answer 16

Not being able to sleep when, or as well as one should

Question 17

Is insomnia a disease or a symptom?

Answer 17

Symptom - important to ID and treat underlying cause

Question 18

What is anxiety?

Answer 18

Manifestation of fear response in anticipatory manner, independent of external events

Question 19

What do beta-adrenoceptor antagonists do in anxiety?

Answer 19

Block physical signs
- Sweating
- Tremor
- Tachycardia
Little effect on CNS

Question 20

What are clinically recognised anxiety disorders?

Answer 20

Generalised anxiety states
Panic disorder
Phobias
Post-traumatic stress disorder

Question 21

What are generalised anxiety states?

Answer 21

Excessive anxiety lacking clear reason or focus

Question 22

What is panic disorder?

Answer 22

Overwhelming fear in association with somatic signs

Question 23

What are phobias?

Answer 23

Strong fears of specific things/situations

Question 24

What are the side effects of anxiolytics?

Answer 24

Degree of sedation

Drowsiness

Question 25

What are three classes of sedative, hypnotic and anxiolytic agents?

Answer 25

Benzodiazepines Non-benzodiazepines Barbiturates

Question 26

What are some non-benzodiazepines?

Answer 26

Beta-adrenoceptor antagonists Buspiron Zopiclone Zolpidem

Question 27

Describe barbiturates

Answer 27

General depressants - produce all levels of CNS depression Effective but - Very toxic - Low therapeutic index - Induction of liver enzymes - Abrupt withdrawal could cause death Obsolete as anxiolytics/hypnotics - used now in controlled situations - Anaesthetics for people who have prior history of being allergic to other anaesthetics - Anticonvulsant

Question 28

Why are benzodiazepines safer to administer than barbiturates?

Answer 28

Wider therapeutic index - Less depression of respiratory and cardiovascular centres - Less dependence - Safe in overdose

Question 29

When aren't benzodiazepines safe in overdose?

Answer 29

Additive effect when taking multiple benzodiazepines

Question 30

What responses do benzodiazepines elicit?

Answer 30

``` Sedation and induction of sleep - Reduce time to fall asleep - Increase duration of sleeep Reduction of anxiety and aggression Reduction of muscle tonee - Anticonvulsant but reduces coordination Obliterate memory - Use as premedicant ```

Question 31

What effect do benzodiazepines have on neurons?

Answer 31

Interfere with GABAergic transmission

Question 32

Which receptor do benzodiazepines interact with?

Answer 32

GABA A only

Question 33

What do allosteric molecules modulate?

Answer 33

Orthosteric ligand affinity Orthosteric ligand efficacy Receptor activating level

Question 34

What drug class does diazepam belong to?

Answer 34

Benzodiazepines

Question 35

How does diazepam work?

Answer 35

Has specific binding sit on GABA A > increase in receptor affinity for GANA Increases frequency of GABA receptor Cl channel opening

Question 36

What is the mechanism of action of benzodiazepines?

Answer 36

Bind regulatory site - Increase GABA affinity for receptor - Allosteric modulators Enhance response to GABA - Facilitate opening of Cl channels - Increase frequency - no change in conductance/mean opening time - Increase sensitivity of receptor with no change in maximum response

Question 37

What is the mechanism of action of barbiturates?

Answer 37

Bind GABA receptor > prolongs opening of channel | Increases sensitivity and maximum responses

Question 38

What are the advantages of allosteric modulators?

Answer 38

Ceiling of effect of inhibitors - Increased therapeutic window Positive modulation of endogenous agonist effect rather than continuous effect of exogenous agonist - Physiological regulation continues Great receptor subtype selectivity possible

Question 39

What is the pharmacodynamic profile of benzodiazepines?

Answer 39

Similar

Question 40

What are the unwanted effects of benzodiazepines?

Answer 40

Drowsiness Confusion Impaired coordination

Question 41

What are the disadvantages of benzodiazepines?

Answer 41

``` Interaction with - Alcohol - acts on GABA receptors dysregulating them > synergistic - Antihistamines - Barbiturates Long lasting hangover effects Withdrawal symptoms Dependence ```

Question 42

Can you develop tolerance to benzodiazepines?

Answer 42

Yes

Question 43

What are the signs of physical and psychological withdrawal from benzodiazepines?

Answer 43

``` Nausea Tremor Anxiety Depression Insomnia ```

Question 44

What determines the use of benzodiazepines?

Answer 44

Pharmacokinetic profile - Active orally but differ in duration of action - Generation of active and inactive metabolites

Question 45

What is potency?

Answer 45

Relative position of dose-effect curve along dose axis

Question 46

Does potency have clinical significance?

Answer 46

Not really | More potent drug not clinically superior

Question 47

When is low potency a disadvantage?

Answer 47

If dose so large that it's awkward to administer

Question 48

Why are barbiturates more potent than benzodiazepines?

Answer 48

Increase frequency of Cl ion channel opening at GABA A receptor

Question 49

Why are barbiturates more efficacious than benzodiazepines?

Answer 49

Increase duration Cl channel is open

Question 50

Why are barbiturates more toxic than benzodiazepines in overdose?

Answer 50

Direct opening of Cl ion channel

Question 51

Describe zolpidem

Answer 51

Short-term treatment for insomnia Non-benzodiazepine but binds to benzodiazepine site Very little anticonvulsant activity Short duration of action

Question 52

Describe zopiclone

Answer 52

Short-term treatment of insomnia | Non-benzodiazepine

Question 53

Describe buspirone

Answer 53

``` Antiolytic Non-benzodiazepine Partial agonist at 5HT 1A receptor - Inhibitory autoreceptors regulating transmitter release Slow onset - Up to 2 weeks Little dependence Side effects - Nausea - Dizziness - Headache ```