Neuropharmacy II

Question 1

What is an allosteric modulator?

Answer 1

Binds to receptor but to different site to agonist
Causes an allosteric change in the receptor which alters the affinity for the agonist
This accordingly alters the receptor occupancy for the agonist, altering the extent of agonist action

Question 2

How does benzodiazepines alter GABAergic transmission?

Answer 2

Benzodiazepines are positive allosteric modulators, so increase GABAergic transmission

Question 3

How does dosage of benzodiazepine affect pharmacological outcome?

Answer 3

Large dose

Anaesthesia 
Muscle relaxation
Hypnosis 
Sedation 
Ataxia
Anticonvulsant 
Anxiolytics

Small dose

Question 4

What is the name and time span of a short term benzodiazepine?

Answer 4

Triazolam

8-16h

Question 5

What is the name and time span of a medium acting benzodiazepine?

Answer 5

Diazepam

32h

Question 6

What is the name and time span of a long acting benzodiazepine?

Answer 6

Clonazepam

55 h

Question 7

What is the cellular effect of GABA(A)-R activation?

Answer 7

Cl pore opens
Cl ions flow into cell
Cell is hyperpolarised

Question 8

Which benzodiazepine would you use for hypnosis?

Answer 8

Triazolam

Question 9

Which benzodiazepine would you use as an anxiolytic?

Answer 9

Diazepam

Question 10

Which benzodiazepine would you use as an anticonvulsant?

Answer 10

Clonazepam

Question 11

What effects are seen from barbiturates at low doses?

Answer 11

Anxiolytic and sedative

Question 12

What effects are seen from barbiturates at high doses?

Answer 12

Fatality due to respiratory depression and cardiovascular collapse

Question 13

Why are barbiturates no longer used as anxiolytics?

Answer 13

Anxiolytic effects are only seen at sedative doses
Induction of P(450) in the liver causes drug tolerance
Dangerous in overdose (problem in suicide prone patients)
They have additive effects with other CNS depressants (e.g. Alcohol)

Question 14

How is serotinergic transmission targeted in anxiolysis

Answer 14

Busiprone:

Agonist to 5HT(1A) presynaptic autoreceptors to reduce 5HT exocytosis

Question 15

How is noradrenergic transmission targeted in anxiolysis?

Answer 15

Clonidine:

Agonist to alpha 2 autoreceptors to reduce NA exocytosis

Question 16

what are the two major categories of epilepsy?

Answer 16

Partial

Generalised

Question 17

How do the two different types of epilepsy differ?

Answer 17

For partial:
Seizures begin in a particular area of the brain involving only one side

For general:
Seizures begin with an electrical discharge involving both sides of the brain

Question 18

What ion channels can be targeted to reduce neuronal excitability?

Answer 18

Na-VGIC

T-type Ca-VGIC

Question 19

Give examples of sodium channel blockers

Answer 19

Phenytoin
Carbamazepine
Valproate

Question 20

Give an example of a T-type Ca- channel blocker

Answer 20

Ethosuximide

Question 21

What does valproate do?

Answer 21

Blocks Na channel

Inhibits GABA transaminase (increases brain GABA)

Question 22

What role does diazepam have as an anticonvulsant

Answer 22

Increases efficacy of Postsynaptic GABA transmission by allosteric modulation

Question 23

What role does Phenobarbitone have in anti-epileptics?

Answer 23

Increases efficacy for GABA transmission

Directly increases Cl influx

Question 24

How can the NMDA receptor be targeted for epilepsy?

Answer 24

Felbamate:
Blocks NMDA
Binds to glycine site

Question 25

How can the AMPA receptor be targeted for epilepsy?

Answer 25

Parampanel: | Non-competitive antagonist of AMPA

Question 26

Name 3 currently used volatile anaesthetics

Answer 26

Halothane Isoflurane Nitrous oxide

Question 27

How do you increase anaesthetic potency?

Answer 27

Unsaturation Halogenation Ether groups

Question 28

What is a MAC?

Answer 28

Minimum alveolar concentration | The concentration of anaesthesia in the air air inspired giving a safe level of anaesthesia in 50% of patients

Question 29

Does a potent anaesthetic have a low MAC?

Answer 29

Yes, | Potency is inversely proportional to the MAC

Question 30

Name 4 intravenous anaesthetics

Answer 30

Thiopentone Propofol Etomidate Ketamine

Question 31

Which general anaesthetics work through potentiation of GABA(A) receptor transmission

Answer 31

``` Halothan Isoflurane Thiopentone Propofol Eromidate Nitrous oxide ```

Question 32

Which general anaesthetics work through inhibition of excitatory transmission

Answer 32

``` Halothane Isoflurane Nitrous oxide Thiopentone Propofol Ketamine ```

Question 33

Which nerve fibres transmit the perception of pain?

Answer 33

C fibres

Question 34

Which types of tissue damage produces pain?

Answer 34

Inflammation | Neuropathy

Question 35

How might hypersensitivity be produced at spinal level?

Answer 35

Repetitive painful stimulation on the c-fibres can cause them to enter a high state of excitability Different pain states then converge on common pathways to the spine

Question 36

What voltage channels can be blocked to alleviate pain?

Answer 36

NMDA | AMPA

Question 37

What drugs block the NMDA channel?

Answer 37

Ketamine | Gabapentin

Question 38

What drugs block the AMPA channel

Answer 38

Carbamazepine | Lignocaine

Question 39

How might pain be reduced by suppression of excitatory NT release?

Answer 39

Inhibition of presynaptic Ca channels would prevent NT vesicle exocytosis K channels may be open hyperpolarising the cell so Ca channels won't open

Question 40

What are the endogenous opioids and receptors?

Answer 40

Mu- endorphin Delta- enkaphalin Kappa- dynorphin Orl-1- nociceptin

Question 41

Name some exogenous opiates used for analgesia

Answer 41

Morphine | Codeine

Question 42

Which transmitters are involved in the descending pathways that regulate nociception?

Answer 42

Substance P CGRP glutamate Aspartate