Pharmacodynamics

Question 1

Pharmacology definition and the 4 levels

Answer 1

The science that studies the interactions between chemical substances and living organisms

Molecular, Cellular, Organ, Organism

Question 2

Pharmacodynamics definiton

Answer 2

The action of drugs on the body

how the drugs interact with cells and resultant physiological changes

Question 3

Drug targets - regulatory proteins (4)

Answer 3

Enzymes

Carrier proteins

Ion channels

Receptors

Question 4

Drug targets - others (3)

Answer 4

Nucleic acids

Lipids

Ions

Question 5

3 ways drugs can interact with enzymes

Answer 5

Enzyme inhibitors

False substrates (drug is converted and then disrupts pathway)

Pro-drugs (inactive precursors activated by enzyme action)

Question 6

How do drugs interact with carrier proteins (eg ATP pumps)

Answer 6

They block the binding sites preventing movement of substances across the cell membrane

Question 7

How do drugs interact with Ion channels (2)

Answer 7

Both ways block the channel

• Entering and binding to recognition site
• Diffuse across membrane and bind to an intracellular recognition site

Question 8

How do drugs interact with receptors?

Answer 8

Act on the ligand binding domain of the receptor

the change activates an intracellular effector domain

triggering a transduction mechanism - eg changes in cellular response or gene expression

Question 9

4 main types of receptors

Answer 9

Ligand-gated ion channels (ionotropic)

G-protein coupled receptors

Kinase-linked receptors

Nuclear receptors

Question 10

Where do drugs bind to on ionotropic receptors?

Answer 10

a binding site on the extracellular domain (blocking channel in milliseconds)

Question 11

What are the 2 effectors drugs interact with on G-protein coupled receptors

Answer 11

Enzyme

Ion channel

(100ms - seconds response to due cascade of intracellular reactions)

Question 12

How do drugs interactive with Kinase-linked receptors & the 2 ligands

Answer 12

Binds to binding domain blocking normal ligands (insulin or growth factor) from binding hampering intracellular catalytic domain activation

response in minutes

Question 13

How do drugs interactive with intracellular receptors (proteins in nucleus)

Answer 13

ACT on DNA (‘zinc fingers’ domain) prevent protein synthesis (alter gene expression)

responses hours - days

Question 14

Drug agonists explained

Answer 14

agonist + binding site = drug-receptor complex

a change in the receptor is induced and a response of the cell initiates

Question 15

Affinity & efficacy definitions in relation to agonist drugs

Answer 15

Affinity - chemical forces of the binding

Efficacy - drugs ability to activate the receptors & induce a response

Question 16

dose - response link

Answer 16

drug effect is proportional to drug concentration until maximal response is achieved (all receptors bound)

Question 17

dose - response units

Answer 17

the % of maximal response (Emax) induced in relation to logarithmic concentration of drug

Question 18

EC50 = ?

Answer 18

drug concentration that produces 50% of the maximal response

Question 19

3 types of agonist effects

Answer 19

Full agonists - normal rule

Partial agonists - cant reach maximal response

inverse agonists - exerts opposite effect by supressing spontaneous receptor signalling

Question 20

How is EC50 practically used

Answer 20

to compare the potency of different drugs acting on the same receptor (conc differences)

Question 21

Agonist drug potency = ?

Answer 21

Agonist drug potency = affinity + efficacy

Question 22

Antagonist drug definition

Answer 22

a drug that binds to a receptor but does no induce a conformational change or biological response

Question 23

Receptor antagonist examples

Answer 23

Competitive (reversible & irreversible)

Non-competitive

Question 24

Non-receptor antagonists

Answer 24

Chemical

Physiological

Pharmacokinetic

Question 25

How does competitive antagonism work

Answer 25

Antagonist drugs have higher affinity than agonists

agonist potency = only affinity

Question 26

^ agonist concentration = ?

reversible competitive antagonism

Answer 26

^ agonist concentration = reduced antagonist effect

Question 27

how does Irreversible competitive antagonist work

Answer 27

antagonist dissociates very slowly or not at all

synthesis of new receptors may be required

Question 28

How does non competitive antagonism work

Answer 28

drug binds to allosteric site preventing receptor activation (inhibits agonist response)

Question 29

Chemical antagonism definition

Answer 29

a drug binds to a receptor ligand resulting in an inactive product lacking affinity & efficacy for the receptor

Question 30

Physiological antagonism definition

Answer 30

2 Drugs have opposing actions via different receptor son the same tissue

Question 31

Pharmacokinetic antagonism definition

Answer 31

Antagonism alters the pharmacokinetics of the agonist (^ metabolism rate or reducing absorption rate