Drug Mechanisms and Receptor Interactions

Question 1

Explain the term “drug”

Answer 1

Chemical substance –> interaction –> physiological effect

Question 2

Explain the term “drug target site”

Answer 2

Examples include: receptors, ion channels, transport systems and enzymes

Question 3

What are the 2 types of ion channel?

Answer 3

Voltage-gated; receptor-linked

Question 4

What is blocked by the drug lidocaine?

Answer 4

VGSCs

Question 5

Give 2 examples of common antagonists

Answer 5

Atropine

Hexamethonium

Question 6

What is the ‘affinity’ of a drug?

Answer 6

The avidity with which it seeks out and binds to receptors

Question 7

What is the potency of a drug determined by?

Answer 7

Its affinity and efficacy

Question 8

Explain the term “drug selectivity”

Answer 8

A drug has a preference for a specific type of receptor (but it NOT specific to it)

Question 9

Describe the term “structure activity relationship”

Answer 9

Basis of the ‘lock and key’ analogy –> describes close relation of activity and structure of a drug, and how sensitive a drug’s pharmacokinetics are to structural changes

Question 10

List the 4 main categories of drug target sites

Answer 10

Receptors
Ion channels
Transport proteins
Enzymes

Question 11

What sort of ion channels are blocked by lidocaine?

Answer 11

VGSCs

Question 12

Why is the Na+/K+ pump not classed as a receptor?

Answer 12

Does not produce a physiological response

Question 13

Give an example of a drug class and its mechanism that has an ion channel as its target site

Answer 13

Tri-Cyclic Antidepressants (TCAs)

Slow down reuptake of NA and 5HT at the serotonin receptor

Question 14

Give an example of a drug that inhibits enzymes

Answer 14

Anti-cholinesterases

Question 15

Give an example of a drug that acts as a false substrate

Answer 15

Methyl-DOPA (generates methyl-NA)

Question 16

Differentiate between a full and partial agonist

Answer 16

Full = full efficacy
Partial = part efficacy

Question 17

How can full agonists differ in their level of action?

Answer 17

Whilst they all have full efficacy they can differ in affinity

Question 18

Describe the shape and relative positioning of full agonists with high affinity, full agonists with lower affinity and partial agonists on a log dose-response curve

Answer 18

Slightly sigmoid shape
Full agonist goes through origin
FA with lower affinity –> right, same shape
Partial agonist crosses x at same point as FAWLA but has lower gradient

Question 19

Describe the shape and relative position of full agonists and partial agonists on a dose-response curve

Answer 19

Curve with decreasing gradient

Full agonist has higher gradient

Question 20

Give an example of a competitive and an irreversible antagonist

Answer 20

Competitive: atropine/ propanolol
Irreversible: hexamethonium

Question 21

Differentiate between log dose-response curves to a specific agonist in the absence and presence of a competitive antagonist and an irreversible antagonist

Answer 21

Slightly sigmoid shape
Agonist alone goes through origin
+ Comp. antagonist = curve moves right
+ irr. antagonist = moves further right and gradient reduced

Question 22

Recall and summarise the 4 main types of antagonism

Answer 22

1. Receptor blockade
2. Physiological antagonism (interact with diff. receptors to have opp. effects in same tissue)
3. Chemical antagonism (2 ligands interact in solution)
4. Pharmacokinetic antagonism (one drug changes effect of an other)

Question 23

Describe the interaction of warfarin and barbiturates

Answer 23

When barbiturates are administered for a long period of time, the liver enzyme that metabolises them is upregulated. This same enzyme is used to metabolise warfarin. Therefore, when warfarin is given a higher dose is required as it will be metabolised more quickly.

Question 24

What is the “receptor reserve” phenomenon?

Answer 24

Stimulation of only a fraction of the whole receptor population apparently elicits the maximal effect achievable

Question 25

List the 4 main families of receptors

Answer 25

1: channel-linked
2: GPCR
3: Tyrosine - Kinase-linked
4: controllers of gene transcription

Question 26

Describe the structure of a type 1 (channel-linked) receptor

Answer 26

Subunits and TM segments

Question 27

Give 2 examples of type 1 receptors

Answer 27

nicotininc ACh receptors

GABA

Question 28

Give 2 examples of type 2 receptors

Answer 28

muscarinic ACh receptors

Adrenoceptors

Question 29

Give 3 examples of type 3 receptors

Answer 29

Insulin receptors
Growth Factors
Cytokine receptors

Question 30

Give 2 examples of type 4 receptors

Answer 30

Steroid receptors

Thyroid receptors

Question 31

Define “drug tolerance”

Answer 31

Gradual reduction in response to the drug over a period of days or weeks

Question 32

Give an example of a drug which patients commonly show tolerance to

Answer 32

Benzodiazapenes eg diazepam

Question 33

Recall 5 cellular mechanisms which may account for the phenomenon of drug tolerance

Answer 33

1. Increased rate of metabolism (eg with alcohol)
2. Loss of receptors (endocytosis)
3. Change in receptors (desensitised by conformational change)
4. Exhaustion of mediator stores
5. Physiological adaption (tolerance to side effects whilst efficacy of drug maintained)