12 Properties of Drug Targets and their Biological Processes

Question 1

Drug target definition

Answer 1

molecules usually proteins, which play a pivotal role in existing physiological or biochemical process, the function of which can be modulated by a drug to produce a biological effect

Question 2

Drug target examples

Answer 2

receptors / ion channels / transporters / enzymes

Question 3

What are ion channels formed of

Answer 3

3-5 subunits

Question 4

Regulation of ions

Answer 4

Ligands bind to an extracellular domain. Part of each subunit (pore domain) forms a hydrophilic (water filled) channel to selectively allow ions to flow through the membrane

Question 5

2 types of ion gated channels

Answer 5

Ligand gated ion channel receptors

Voltage gated ion channels

Question 6

Voltage gated ion channel process description

Answer 6

Action potential

Voltage gated Ca2+ channel open

Synaptic vesicles + Ach diffuse across the synapse

Nicotine Ach receptor (ligand gated ion channel is open)

Na+ influx, depolarisation and muscle contraction

Question 7

Ion channel blcokers

Answer 7

Permeation blocked

Question 8

Ion channel modulators

Answer 8

Increased or decreased opening probability

Question 9

Voltage gated calcium channel blockers physiology

Answer 9

Ca2+ currents drive signalling in vascular smooth muscle cells and some cardiac cells

Question 10

Voltage gated calcium channel blockers Pharmacology

Answer 10

Ca2+ channel blockers are used to treat cardiac disorders

Question 11

Ion channel blocker example

Answer 11

1. Muscarinic M3 acetylcholine G protein coupled receptor signalling
2. Contraction of vascular smooth muscle
3. Ca2+ channel blockers
4. Treatment for Hypertension
5. Lowers risk of cardiovascular events resulting from vascular damage

Question 12

G-protein coupled receptors - what are they

Answer 12

Single protein polypeptide

7 transmembrane domains (alpha helices)

G protein is a guanine nucleotide binding protein made of 3 subunits (alpha, beta, gamma)

Question 13

What do ligands bind to on g-protein coupled receptors

Answer 13

extracellular domain or within transmembrane domain (depending on type)

Question 14

What happens upon ligand binding with g-protein coupled receptors

Answer 14

The alpha subunit binds GTP and dissociates (to GDP) from the complex

A subunit is then free to activate target ion channel or enzyme

Question 15

What have endogenous chemical molecules evolved to do

Answer 15

fine-tune the control of cells and physiological functions

(eg. Neurotransmitters and hormones / stimulate and inhibit (mood) / contract and relax (muscle) / reduce and increase (heart beat)

Time - rapid (seconds)

Question 16

Transporters / carriers use

Answer 16

Transporters move ions and chemicals against their electrochemical (concentration/voltage) gradient

This requires energy provided by ATP hydrolysis “active transport”

Question 17

Primary active transport

Answer 17

Direct

Question 18

Secondary active transport

Answer 18

C o-transport

Doesn’t require a chemical source of energy such as ATP, uses an electrochemical gradient generated by primary active transport. Ion is then transported back together with an additional molecule

Question 19

Example - antidepressant transport

Answer 19

Drug - Fluoxetine (SSRI)

Block the reuptake of serotonin (5HT) back into the presynaptic neuron and recycling into vesicles, increase the exposure time od serotonin (5HT) in the synaptic cleft. Prolongsthe activation of serotonin receptors in different regions of the brain

Improve mood, emotion and sleep

Question 20

What do enzymes catalyse

Answer 20

Enzymes catalyse the conversion of a substrate into a produce

Question 21

Most drugs acting at enzymes are…

Answer 21

Inhibitors

Question 22

What can drugs do (2)

Answer 22

Drugs can also potentiate enzymes (eg. Increase their activity)

Drugs can be converted from their inactive form to their active form

Question 23

Example - Anticholinesterases and anaesthesia (drugs acting on receptors)

Answer 23

Nicotine acetylcholine receptor signalling
Drug - Neostigmine

Block the enzymatic clearance of Ach, increase the exposure time of Ach in the synaptic cleft, prolongs the activation of nicotine Ach receptors, reverses muscle relaxation