19 - Transmitters and Receptors

Question 1

Basic mechanism of epilepsy

Answer 1

Synapsing at a motor neuron body are inhibitory GABA and excitatory glutamate neurons.
Overstimulation of motor neuron.

Question 2

Phenytoin mechanism

Answer 2

Decreases excitatory fibre activity (glutamate) by inhibiting Na+ channels.
Only can do this when channel is open (ie: when there is abnormally high firing rate, such as in an epileptic seizure)

Question 3

Benzodiazepine mechanism

Answer 3

Allosteric modulators of GABA A receptors.
Increase GABA A receptor affinity.
Increases Cl- influx to cell through GABA A channel.

Question 4

Role of neuropeptide Y in mood

Answer 4

NPY 1 receptor activation reduces anxiety

Question 5

On which group are H1 antagonists used for sedation?

Answer 5

Children

Question 6

What are benzodiazepines used to treat?

Answer 6

Epilepsy, anxiety, sleep disorders, pre-medication for surgery, acute alcohol withdrawal

Question 7

Barbituates

Answer 7

General depressants (mild sedation, surgical anaesthesia, coma, death)
Very toxic
Highly addictive
No longer used as anxiolytics/hypnotics

Question 8

Aspects of benodiazepines that are preferable to barbituates

Answer 8

• Wider therapeutic Index
– Less depression of respiratory & cardiovascular centres
– Less dependence
– Considered safe in overdose
• Elicit
– Sedation and induction of sleep
• Reduce time to fall asleep
• Increase duration of sleep
– Reduction of anxiety & aggression
– Reduction of muscle tone
• anticonvulsant but reduce co-ordination
– Obliterate memory
• Use as premedicant

Question 9

GABA A

Answer 9

Receptors that are ligand gated ino channels

Question 10

GABA B

Answer 10

GPCR

Question 11

GABA receptor that bennodiazepines interact with

Answer 11

GABA A

Question 12

Possible effects of allosteric modulators
1
2
3

Answer 12

1. Modulation of orthosteric ligand affinity
2. Modulation of orthosteric ligand efficacy
3. Modulation of receptor activation level

Question 13

Difference between function of barbituates and benzodiazepines

Answer 13

Benzodiazepines allosterically increase affinity of GABA A receptor for GABA to increase frequency of Cl- channel opening.

Barbituates increase duration of opening of Cl- channel. This can be more toxic

Question 14

Advantages of allosteric modulators
1
2
3

Answer 14

• 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 15

Ceiling effect with benzodiazepines

Answer 15

Cl- takes time to open and close.

Question 16

Suffix of benzodiazepines

Answer 16

-pam (EG alprazolam, clonazapam)

Question 17

Disadvantages of benzodiazepines
1
2
3
4

Answer 17

– Interaction with alcohol, antihistamines & barbiturates
– Long lasting hang over effects
– Withdrawal symptoms
– Dependence
• Abuse potential
• Patients / doctors should be counseled1) Interaction with alcohol, antihistamines and barbituates

Question 18

Why does alcohol, antihistamines, barbituates alter benzo function?

Answer 18

Alcohol interacts with GABA A receptors, increasing effect (depression of respiratory centres).
Antihistamines change conformation of GABA receptor

Question 19

Short acting benzos

Answer 19

Oxazepam, temazepam

Question 20

Medium/long-acting benzos

Answer 20

Clonazepam, diazepam

Question 21

When is low potency a problem?

Answer 21

Only when the dose required is so large as to be difficult to administer.

Question 22

Pharmacological efficacy

Answer 22

The strength of the receptor activation.

Question 23

Clinical efficacy

Answer 23

The strength of the beneficial effect of a drug.