Lecture 3

Question 1

What are the most common binding sites for drugs?

Answer 1

Proteins, particularly enzymes, carrier proteins, ion channels and receptors

Question 2

What are the three types of ligands that are recognised by receptors?

Answer 2

Neurotransmitters such as noradrenaline
Hormones such as adrenaline
Local Hormones such as prostaglandins

Question 3

What are ligands?

Answer 3

Chemicals that bind to a receptor

Question 4

What is efficacy?

Answer 4

The ability to create a signal by binding to a receptor

Question 5

What features must a ligand have to produce its intended effect?

Answer 5

Must bind to the target receptor with some selectivity, which is determined by the shape, charge and size of the ligand and the receptors binding sites

Question 6

What is affinity with respect to a receptor?

Answer 6

The attraction of a ligand for a receptor

Question 7

How is efficacy measured?

Answer 7

On a scale of 0 (no activity) to 1 (maximum possible activity)

Question 8

What is the difference between agonists and antagonists?

Answer 8

Agonists are mimics which have both affinity and efficacy while antagonists are blockers which have affinity but NO efficacy

Question 9

Why do side effects occur when drugs are taken?

Answer 9

No drug is totally specific for a receptor family which will lead to unwanted side effects

Question 10

What is important about receptor structure?

Answer 10

Specificity for ligand
Verification of receptor family subtypes
Structure confers functionally important characteristics for intracellular signalling
Structure is fluid

Question 11

What is a family with respect to receptors?

Answer 11

Families all have one endogenous ligand

Question 12

what is Drug action is dependant on?

Answer 12

Drug properties (selectivity for receptor subtypes)
Tissue properties (Distribution of receptor subtypes throughout tissues)

Question 13

What are the different histamine receptors?

Answer 13

H1= Skin, Allergic reactions
H2= Stomach and acid secretion
H3= CNS, ileum and cardiac tissue often pre-synaptic and autoregulatory

Question 14

What is selectivity?

Answer 14

Preferential binding to a certain subtype leading to a greater effect on that subtype to help avoid side effects

Question 15

Why is salbutamol used as opposed to fenoterol and propranolol?

Answer 15

Salbutamol is selective for Beta1 receptors which affects the lungs while, fenoterol would affect both beta 1 and beta 2 receptors to cause vasodilation and slowing of the heart
Propranolol affects both beta receptors to slow down the heart but will also block airways

Question 16

What are the different antagonists for each of the histamine receptor subtypes?

Answer 16

H1= antihistamines (chloropheniramine, loratidine)
H2= Inhibition of gastric acid secretion (cimetidine)
H3= typically experimental but could be used for treating pain and inflammation (thioperamide)

Question 17

How does the two isoforms of COX show the importance of selectivity?

Answer 17

COX I is used in homeostatic mechanisms while COX II is only induced in inflammation
NSAIDs which universally inhibited COX therefore caused problems like ulcers and uncontrollable bleeding not seen with the more modern rofecoxib or celecoxib which are selective for COX II

Question 18

What are the four receptor theories?

Answer 18

Receptor occupancy theory, rate theory, two state model, floating receptor model

Question 19

What is the receptor occupancy theory?

Answer 19

The drug effect is directly proportional to the number of receptors occupied

Question 20

What is the rate theory?

Answer 20

The drug effect is directly proportional to the rate of occupancy

Question 21

What is the two state model?

Answer 21

Receptors exist in active or inactive form

Question 22

What is the floating receptor model?

Answer 22

The D-R complex may interact with a variety of effectors in the membrane to produce its effect

Question 23

What is the underlying principle of occupancy theory?

Answer 23

When a drug is present in the body there is an equilibrium present, of free receptor + unbound drug to drug-receptor complex
causing there to be a logarithmic fractional occupancy-concentration relationship

Question 24

What is Ka/Kd?

Answer 24

The association/dissociation constant

Concentration of the ligand which gives 50% occupancy

Question 25

What is the two state receptor model?

Answer 25

Receptors can exist in two states, inactive and active which causes an equilibrium independent of agonist presence, which in the absence of agonist strongly favours the inactive position
Full agonists bind only to the active form and fix it in this position
Partial agonists bind mostly to the active form, but some to the inactive form
Antagonists bind to either the inactive or active form with no preference