Lecture 11 - Signalling Molecule And Drug Targets

Question 1

What is a ligand?

Answer 1

A signalling molecule that binds to a target/receptor

Question 2

Are nearly all of the Antagonists endogenous or exogenous?

Answer 2

Exogenous

There are very few endogenous antagonists

Question 3

What is the pneumonic for the target of signalling molecules/drugs?

Answer 3

RITE

Question 4

What does the pneumonic for drug targets RITE stand for?

Answer 4

Receptors
Ion channels (Voltage gated)
Transporters
Enzymes

Question 5

Receptors can be further categorised, what is the pneumonic for these categories?

Answer 5

K(L)ING

Question 6

What does the pneumonic K(L)ING for the categories of receptors stand for?

Answer 6

Kinase linked receptors
Ion channels (Ligand gated)
Nuclear/intracellular
G Protein Coupled Receptor

Question 7

How can the activity of an ion channel be changed?

Answer 7

Allosteric phosphorylation

Question 8

What Voltage gated ion channels are normally targeted by drugs?

Answer 8

VGSCs (Voltage gated sodium channels)
VGCC (Voltage gated calcium channels)

Question 9

What state are the Voltage gated Sodium channels in when they get blocked by drugs?

Answer 9

Open (Depolarised)
Inactivated

Question 10

What drug is often used to treat Epilepsy?

Answer 10

Lamotrigine
Phenytoin

Question 11

How does Lamotrigine help treat epilepsy?

Answer 11

Allows normal levels of CNS by preventing over firing of AP

Blocks the central pores of VGSCs while open or inactive preventing excess Na+ influx

Question 12

What drug is often used as a local Anaesthetic?

Answer 12

Lidocaine/lignocaine
Bupivacaine (Longer half life than lidocaine)

Question 13

How does Lidocaine act as a local anaesthetic?

Answer 13

Blocks central pore of VGSCs while open/depolarised or while inactivated

Question 14

What drug can help treat chronic pain by blocking VGSCs?

Answer 14

Lamotrigine

Question 15

What Voltage gated ion channels can be targeted by drugs to help treat Hypertension?

Answer 15

Voltage gated Ca2+ Channels (VGCCs)

Question 16

How does drug blocking of VGCCs on vascular smooth muscle help treat hypertension?

Answer 16

Blocked VGCCs means Reduced Ca2+ influx into cell
Reduced [Ca2+] intracellularly
This means less Ca2+ released for the SR
Smooth muscles of blood vessels relax = Vasodilation

Question 17

What is a drug which acts to block voltage gated ion channels to treat hypertension?

Answer 17

Amlodopine

Question 18

What are the key roles of transporters?

Answer 18

Transporting ions and molecules
Setting up and maintaining electrochemical gradients
Important in acting as an energy source for 2º active transport

Question 19

What is the energy source for 1º active transport?

Answer 19

ATP hydrolysis

Question 20

What is the energy source for 2º active transport?

Answer 20

Pre established electrochemical gradient (usually established by a Na+/K+ ATPase)

Question 21

What clinical condition is low synaptic 5-HT levels linked to?

Answer 21

Depression

Question 22

What is 5-HT also called?

Answer 22

Serotonin

Question 23

How do Selective Serotonin Re-Uptake Inhibitors (SSRIs) help treat depression?

Answer 23

It reduces the re-uptake of the neurotransmitter serotonin/5-HT
This leads to increased synaptic levels of serotonin/5-HT

Question 24

What drug is an example of a Selective Serotonin Re-Uptake Inhibitor?

Answer 24

Fluoxetine

Question 25

What do drugs that treat Diabetes Mellitus target?

Answer 25

SGLT2 (inhibitors)

Question 26

How does inhibition of the SGLT2 co-transporter in gut cells help treat diabetes Mellitus?

Answer 26

Less glucose absorbed into the blood cells and therefore into the blood reducing glucose intake

Question 27

What are the 3 possible drugs used to treat Diabetes Mellitus?

Answer 27

Dapagliflozin Empagliflozin Metoformin

Question 28

What is the mechanism of action of Dapagliflozin and Empagliflozin in treating Diabetes Mellitus?

Answer 28

Inhibits the SGLT2 transporters in the gut reducing glucose absorption into the body

Question 29

What is the mechanism of action for Metformin treating Diabetes Mellitus?

Answer 29

Alters cell metabolism by reducing the amount of Gluconeogenesis performed by hepatocytes Acts against glucagon

Question 30

What are the 2 types of ways drugs can act as inhibitors to enzymes?

Answer 30

Directly: -Competitive inhibitors -Non-competitive inhibitors Indirectly: -Targets receptors that affect enzyme activity

Question 31

Where do competitive inhibitors bind to an enzyme?

Answer 31

Active site

Question 32

Where do non-competitive inhibitors bind to an enzyme?

Answer 32

Allosteric site

Question 33

What type of drugs act as Antihypertensives (treat hypertension) by acting on enzymes?

Answer 33

ACE Inhibitors

Question 34

What do ACE Inhibitors do?

Answer 34

Reduce conversion of Angiotensin I to Angiotensin II Less Angiotensin II = Less vasoconstriction and Na+ and water reabsorption So reduced BP

Question 35

What are some ACE Inhibitors?

Answer 35

Trandolapril Captopril Ramipril

Question 36

Broadly, what do Tyrosine kinase linked receptors do to other proteins to cause a cell change?

Answer 36

Phosphorylates proteins triggering a phosphorylation cascade

Question 37

What happens to a Tyrosine kinase linked receptor once a ligand binds to both separate monomers?

Answer 37

Dimer forms (Both monomers come together) Each monomer Phosphorylates the others Tyrosine residues Fully phosphorylated = fully active receptor Phosphorylated tyrosines allow proteins to bind to them and transfer the phosphate to the protein Phosphorylated protein then goes on in a cascade triggering a cellular change

Question 38

What hormone is a good example of a hormone that binds to a Tyrosine Kinase receptor?

Answer 38

Insulin

Question 39

In terms of receptors, what is abnormal about cancer cells?

Answer 39

Have many tyrosine kinase receptors which cause over activation of growth factor

Question 40

How can Herceptin be used to treat cancer?

Answer 40

Block the Tyrosine kinase receptors preventing the over expression of growth factor