Transmitters and Receptors

Question 1

5 places that CNS drugs can act on

Answer 1

1. Synthesis
2. Storage
3. Release
4. Inactivation: Re-uptake/Metabolism
5. Receptor

Question 2

Problems with drug in the CNS re: mechanisms:

Answer 2

molecular mechanisms known

therapeutic mechanism not always known.

Question 3

SSRI, Cocaine and Anti-AChE affect what?

Answer 3

reuptake of NTs

Question 4

Cocaine and amphetamines affect NA but also:

Answer 4

dopaminergic

serotonergic

Question 5

Which drug in epilepsy limits excitatory nerve activation?

Answer 5

phenytoin: binds to OPEN sodium channel, decrease Glutamate action

Question 6

What drug enhances inhibitory input for epilepsy?

Answer 6

benzodiazepines enhance GABA receptor activity

Question 7

Two NTs implicated for sedation/anxiety?

Answer 7

GABA

Serotonin

Question 8

3 NTs implicated for anxiety?

Answer 8

serotonin
NA
Neuropeptide Y

Question 9

NT implicated for Sedation in children

Answer 9

Histamine

Question 10

Benzodiazepines used in treating what 5 main things:

Answer 10

epilepsy
anxiety
sleep disorders
premedication
acute alcohol withdrawal

Question 11

Beta-adrenoceptor antagonists do what for anxiety?

Answer 11

block physical signs

nothing for CNS though

Question 12

4 clinically recognized anxiety disorders?

Answer 12

general anxiety
panic disorder
phobia
PTSD

Question 13

Barbiturates, hypnotic/anxiolytics used much today?

Answer 13

pretty much obsolete

Question 14

What is Zolpidem?

Answer 14

direct non-benzodiazepine GABA agonist at orthosteric site

Question 15

What do barbiturates do? why bad?

Answer 15

General depressants
toxic: narrow therapeutic window
induce liver enzymes
abrupt withdrawal = death
addictive

Question 16

2 situations where you anxiolytics/hypnotics are still used?

Answer 16

anaesthetic

anticonvulsant

Question 17

Why choose benzodiazepines over barbiturates?

Answer 17

wider therapeutic index
less cardioresp depression
less addictive
‘safer’ in overdose

Question 18

benzodiazepines interact with GABA A or GABA B receptors?

Answer 18

GABA A receptor only

Question 19

three ways benzodiazepines interact with GABA A receptor?

Answer 19

1. modulate orthosteric ligand affinity
2. modulate orthosteric ligand efficacy
3. modulate receptor activation level

Question 20

benzodiazepines modulate at which site?

Answer 20

allosteric modulators

Question 21

diazepam a benzodiazepines does what to the GABA A receptor?

Answer 21

1. increase frequency of Cl- channel opening

2. increase sensitivity with no change to maximal response

Question 22

difference between benzodiazepines and barbituates in terms of receptor channel? how does this affect overdose?

Answer 22

1. benzodiazepines: open and close/frequency: hits ceiling, safer
2. barbituates: keeps the channel open, can overdose easily

Question 23

why are allosteric modulators better?3 big ones:

Answer 23

1. increase therapeutic window
2. positive modulation of ENDOGENOUS agonist, not exogenous
3. more receptor subtype selectivity

Question 24

unwanted side effects of benzodiazepines?

Answer 24

drowsiness
confusion
impaired coordination

Question 25

disadvantages of benzodiazepines?

Answer 25

interact with alcohol,
antihistamines/barbituates
withdrawal,
dependence

Question 26

Can you take the same dose of benzodiazepines always?

Answer 26

develop tolerance: need to increase dose

Question 27

How long is short vs. long acting benzodiazepines?

Answer 27

short: 6-12 hours
Long: >24 hours

Question 28

Does low potency matter?

Answer 28

only if awkward to administer, low potency does not = inferior drugs

Question 29

what is pharmacological efficacy?

Answer 29

strength of receptor activation: full vs. partial agonist

Question 30

what is clinical efficacy?

Answer 30

strength of beneficial effect

Question 31

benzodiazepines vs. barbituates: 3 big points in terms of efficacy/potency

Answer 31

1. both affect GABA receptors
2. Benzo: increase channel frequency (increase potency)
3. barbituates increase duration of Cl- channel opening (increase efficacy)

Question 32

What is Buspirone? where does it act?

Answer 32

non benzo anxiolytic: partial agonist at 5HT1 receptors