Lecture 1 And 2

Question 1

One person trials

Answer 1

Focus on individual response to treatment rather than average from group

Question 2

Drawback of imprecision medicine

Answer 2

Very few people derive benefits from the drugs they take

Question 3

100,000 genome project

Answer 3

NHS genome sequencing programme

Some patients will benefit as a conclusive diagnosis can be given for rare/inherited diseases or because most suitable treatment can be chosen

Question 4

Pharmacokinetics

Answer 4

What the body does to a drug
Measures changes in drug concentration with time in one or more regions of body
Focuses on how much drug you should take

Question 5

Pharmacodynamics

Answer 5

What drug does to the body

Biological effects and mechanisms of action

Question 6

3 classes of GPCR

Answer 6

Rhodopsin like
Secretin and adhesion
Glutamate

Question 7

4 major classes of drug targets

Answer 7

Receptors
Ion channels
Enzymes
Transporters

Question 8

Most GPCRs are

Answer 8

Class A

Rhodopsin like

Question 9

How are the classes of GPCRs different?

Answer 9

Have different orthosteric sites

Question 10

First crystal structure of GPCR bound to diffusible ligand

Answer 10

Human beta2 adrenoceptor

Target for salbutamol- asthma

Question 11

Purinergic receptors

Answer 11

P2Y1
P2Y12
Bind ADP in very different binding pockets despite belonging to same family

Question 12

How do we study nociceptor activation?

Answer 12

DRG neuron culture

Electrophysiology eg. Patch clamp

Question 13

Key molecular target in nociceptors

Application

Answer 13

Na channels
Targeted by local anaesthetic- LAs block channel and stop APs firing. Enter cell and bind to site inside pore- very effective

Question 14

Problem with local anaesthetic

Answer 14

Not selective

Systemic application would have many toxic effects

Question 15

Voltage gated sodium channels are encoded by….different genes and are……., giving a opportunity for

Answer 15

9
Structurally diverse
Selectivity

Question 16

Which sodium channel is the target for pain disorders and where is it expressed?

Answer 16

Nav1.7

Spinal cord

Question 17

Relationship between Nav1.7 and SCN9A

Answer 17

SCN9A encodes Nav1.7

Question 18

Carbamazepine

Answer 18

Anti epileptic drug
Na channel inhibitor
IEM patients with 2 different types of mutation in Nav1.7 experiences reduced pain time

Question 19

Pfizer

Answer 19

Trialed a Nav1.7 antagonist on subjects with 4 different Nav1.7 mutations
Heat pad elicited pain and rates on scale
Significant but variable results

Question 20

Largest drug class

Answer 20

Small molecules 
Eg diazepam (Valium)

Question 21

Antibody-drug conjugate

Answer 21

mAb targets toxic drug to its target