Drug Targets

Question 1

Regarding extracellular signalling explain endocrine signalling

Answer 1

Glands produce hormones = signalling molecules, 100 known, Secreted into blood stream, Highly potent,
Hydrophilic I –> amines (millisecs to secs),
Hydrophilic II –> peptides to proteins (mins to hrs),
Lipophilic –> steroids (hrs to days),
Therapeutic –> adrenaline IV, insulin derivatives

Question 2

Give examples of paracrine extracellular signalling

Answer 2

neurotransmitters (more than 100 known) –> excitatory, inhibitory = acetylcholine OR cytokines: interleukins, interferons

Question 3

What are the main drug targets?

Answer 3

receptors, ions, transporters, enzymes

Question 4

Give examples of receptors and explain them: KING

Answer 4

K –> kinase linked receptors: mediate signals of wide variety of proteins, growth factors, via phosphorylation,

I –> ion channels (ligand gated): allow ion current across membrane and regulate voltage change, action potential, regulated by phosphorylation of intracellular sites on channels via GPCR,

N –> Nuclear/intracellular: activates/inactivates genes, thyroid hormone, Vit D,

G –> G-protein coupled receptors: largest group, Gs Gi Gq, activates intracellular signalling routes

Question 5

What is an example of a drug target that is a transporter?

Answer 5

Proton pump inhibitor: PPIs, omeprazole: inhibits H+ efflux into stomach

Question 6

Give an example of a therapeutic drug that targets enzymes

Answer 6

Aspirin

Question 7

What is autocrine extracellular signalling?

Answer 7

cell respond to molecules they release themselves, cytokines, growth factors

Question 8

What is the difference between hydrophilic I, hydrophilic II and lipophilic?

Answer 8

Hydrophilic I –> amines (millisecs to secs),
Hydrophilic II –> peptides to proteins (mins to hrs),
Lipophilic –> steroids (hrs to days)

Question 9

What does RITE stand for?

Answer 9

Signalling molecules targets: R - receptors, I - ion channels, T - transporters, E - enzymes

Question 10

What are the properties of catacholamine hormones?

Answer 10

Hydrophilic, half-life = seconds, course of action = milliseconds, receptor location = plasma membrane, mechanism = cause change in membrane potential, trigger synthesis of second messenger

Question 11

What are the properties of protein hormones?

Answer 11

Hydrophilic, half-life = mins to hours, course of action = hours to days, receptor = plasma membrane, mechanism = trigger synthesis of second messenger, trigger protein kinase activity

Question 12

What are the properties of steroidal hormones?

Answer 12

Lipophilic, half-life = hours to days, course of action = hours to days, receptor location = cytosolic/nuclear, mechanism = controls transcription and stability of mRNA