W2 L2 - Pharmacology Principles

Question 1

what’s pharmacology

Answer 1

Pharmacology is the science of drugs and their effect on living systems

Question 2

define pharmacotherapeutics

Answer 2

the use of drugs to prevent and treat disease

Question 3

How does a drug cause an intracellular response?

Answer 3

1. unoccupied receptor
2. drug binds to receptor
3. receptor activated
4. signal transduced
5. biological response

Question 4

define affinity

Answer 4

• degree of attraction

Question 5

define efficacy

Answer 5

• degree of response

Question 6

what properties will functional groups determine

Answer 6

• How it interacts with target
• Mechanism of action
• Route of administration
• Route of metabolism
• Ability to cause side effects / adverse effects
• They will also determine the 3D shape

Question 7

what’s target interaction dependent on

Answer 7

• functional groups and charge distribution
• this is due to ions, dipoles and Van der Waals forces

Question 8

Terms describing effects at proteins for receptor, enzyme, transporter, ion channel

Answer 8

Receptor: agonists and antagonists

Enzyme: activator and inhibitor

Transporter: activators and inhibitors

Ion channels: openers and blockers

Question 9

Why do we need to understand drug-receptor interactions and behaviours?

Answer 9

help us understand how a drug works, what effects it will have, how side effects occur and what potential interactions there may be

Question 10

define intrinsic efficacy

Answer 10

• capacity to excite
• excitation refers to the process where ligand binding induces a conformational or functional change in the receptor, leading to an active or stimulated state
• Full agonists have high intrinsic efficacy (produce a full response)
• Partial agonists have lower intrinsic efficacy (produce a submaximal response)
• Antagonists have zero intrinsic efficacy (bind but don’t activate)
• Inverse agonists have negative intrinsic efficacy (reduce baseline activity)

Question 11

define orthosteric binding

Answer 11

Molecules bind to main active binding site

Question 12

define rate of dissociation

Answer 12

How quickly the drug comes off the receptor

Question 13

what are agonists

Answer 13

• they activate
• have affinity and efficacy
• biased agonists - bind to a receptor and selectively activate specific signalling pathways over others. They “bias” the receptor’s response, potentially enhancing therapeutic effects while reducing side effects
• inverse agonists produce opposite effect of natural ligand
• all bind to same active site

Question 14

what are antagonists

Answer 14

• prevent agonist binding
• competitive - bind to same site as agonist
• non-competitive - binds to diff site
• could be reversible or irreversible (covalent bonds)

Question 15

what are allosteric modulators

Answer 15

• Bind to different site on receptor to alter affinity and / or efficacy (degree of response) of the drug binding to the main site
• Can be
  Positive (PAM)
  Negative (NAM)
  Neutral (SAM)

Question 16

what’s occupation governed by

Answer 16

affinity

Question 17

rate constants for binding and dissociating respectively

Answer 17

• K+1
• K - 1

Question 18

what’s activation governed by

Answer 18

• efficacy
• activation leads to a response

Question 19

2 conformational state of receptors

Answer 19

R - resting state
R* - active state
There’s an equilibrium between the two
KR is the rate constant

Question 20

what happens at the active state

Answer 20

• ligand binds to active site
• biological effect
• ligand then dissociates returning receptor back to R

Question 21

what happens when inverse agonists bind to receptor

Answer 21

• receptor remains in resting state
• they reduce its constitutive (baseline) activity, pushing the receptor into an inactive state. This leads to less signalling than would occur without any ligand bound.

Question 22

what are constitutively active receptors

Answer 22

• receptors that allow for a biological response to occur without ligand binding
• baseline (constitutive) activity is the level of receptor activity that occurs without any ligand (agonist) bound—some receptors are naturally active even in the absence of a stimulus. Inverse agonists reduce this intrinsic activity, while antagonists only block external activation.

Question 23

What does a dose-response (or a concentration response) graph tell us?

Answer 23

• The effects of increasing dose / concentration of drug to see what it does to the size of the response
• dose dependent effect usually seen
• semi log scale helps look at beginning of graph more easily (easier to compare effect)
• EC50 - concentration of a drug that produces 50% of its maximum effect. It indicates drug potency—a lower EC₅₀ means higher potency.
• Properties of drugs can also be determined

Question 24

what’s potency

Answer 24

• measure of drug needed to produce a given effect
• usually quantified by EC50
• allows comparisons between drugs at the same receptor
• affinity more important than potency
• in a graph, curve furthest to the left is more potent

Question 25

competitive vs noncompetitive antagonism

Answer 25

- in competitive increasing conc of agonist allows for maximal response - in non-competitive antagonism increasing conc of agonist won't allow maximal response to be reached

Question 26

what's IC50

Answer 26

- IC50 - inhibitory conc - how much drug is needed to inhibit a biological process by half

Question 27

what is Functional (Physiological) Antagonism

Answer 27

- Drugs can bind to different receptors and produce opposing functional effects - Contraction of smooth muscle - Relaxation of smooth muscle