Pharmacology

Question 1

Definition of pharmacology

Answer 1

Study of effects of drugs on function of living systems

Question 2

What is a drug?

Answer 2

Chemical substance with biological effects

Question 3

What are receptors?

Answer 3

Proteins that recognise and respond to a chemical signal with a binding and functional site

Question 4

What is a ligand?

Answer 4

A chemical that binds to a receptor. Can be endogenous (hormone) or exogenous (applied drug)

Question 5

Agonist vs Antagonist

Answer 5

Agonist: ligand that activates a receptor
Antagonist: ligand that blocks an agonist and doesn’t activate a receptor

Question 6

Specificity

Answer 6

Receptors that are only activated by one endogenous agonist

Question 7

Potency

Answer 7

Amount of agonist needed to induce a given response. Expressed as a dose or concentration

Question 8

Affinity

Answer 8

How effective a ligand binds to its receptor

Question 9

Efficacy

Answer 9

How effective a ligand activates its receptor

Question 10

Size of response is proportional to…

Answer 10

Number of receptors occupied by an agonist

Question 11

What is the strength of ligand-receptor determined by?

Answer 11

Electrical charge interactions, hydrogen bonding and hydrophobic interactions

Question 12

Law of mass action

Answer 12

Rate of chemical reaction is proportional to the product of concentrations of reactants

Question 13

What does acute mean?

Answer 13

Single drug that induces immediate response due to direct action to receptor

Question 14

What does chronic mean?

Answer 14

Repeated drug treatment that induces a delayed response due to indirect action on receptor

Question 15

Tolerance

Answer 15

• Gradual decrease in effectiveness of drug
• Chronic treatment can cause tolerance
• Tolerance occurs because the drug has an effect on homeostasis which minimises drug effects

Question 16

Downregulation vs Upregulation

Answer 16

Downregulation: decrease in the number of receptors on a cell surface
Upregulation: increase in the number of receptors on a cell surface

Question 17

Desensitisation vs Super sensitivity

Answer 17

Desensitisation: reduction in functional response with binding to receptors
Super sensitivity: increase in functional response with binding to receptors

Question 18

Withdrawal

Answer 18

Avoiding drugs completely leading to adverse effects. Avoided by removing drugs gradually

Question 19

Receptor classification

Answer 19

Classified based on differences in how functional responses are induced when drug binds to receptors

Question 20

Signal transduction

Answer 20

Mechanism involved in translating signal to a response

Question 21

What are receptor subtypes?

Answer 21

Endogenous agonists that can bind to and activate more than one receptor

Question 22

What do ion channels do?

Answer 22

Mediate very fast synaptic transmission in nervous system and communicate between neurones or between a neuron and a muscle cell

Question 23

How does agonist binding effect ion channels?

Answer 23

Allows ions to pass through using proteins to prevent the membrane being hydrophobic

Question 24

What is ion movement based on?

Answer 24

Electrochemical gradient where concentration of ions on either side determines movement

Question 25

Name the 3 ion channels

Answer 25

Cation channels (positive), anion channels (negative) and ion specific (sodium and potassium)

Question 26

What do G-protein-coupled receptors (GPCRs) do?

Answer 26

Involved in fast synaptic transmission. Agonist binding to receptor induces functional response indirectly through G-proteins present in membrane

Question 27

Why are they called G-proteins?

Answer 27

Association with guanine nucleotides GTP and GDP and are comprised of a trimetric structure with three units (α, β, and γ)

Question 28

GPCR structure

Answer 28

Long third cytoplasmic loop of receptor coupled to G-proteins

Question 29

GPCR activation

Answer 29

- GDP binds with alpha - GDP is converted to GTP causing dissociation with complex - Resulting in α-GTP with βγ complex - These are active forms of G-protein and bind to various effectors in membrane

Question 30

GPCR inactivation

Answer 30

Reverse reaction

Question 31

Kinase-linked receptors

Answer 31

Mediate slow forms of communication by altering gene transcription and target peptides and hormones

Question 32

What is kinase?

Answer 32

An enzyme that phosphorylates proteins

Question 33

What is phosphatase?

Answer 33

An enzyme which de-phosphorylates proteins

Question 34

Kinase-linked receptors structure

Answer 34

Single large polypeptide chain with one transmembrane domain and large extracellular ligand-binding domain and an intracellular catalytic domain

Question 35

What is dimerization?

Answer 35

Two receptors become associated together in membrane

Question 36

Auto-phosphorylation

Answer 36

Two receptors phosphorylating themselves

Question 37

Kinase-linked receptors activation

Answer 37

Dimerization results in auto-phosphorylation of tyrosine which serves as a binding site for other enzymes

Question 38

Nuclear receptors

Answer 38

Mediate very slow forms of communication by altering gene transcription which target hormones and fat-soluble vitamins

Question 39

Orphan receptors

Answer 39

Receptors with an unknown ligand

Question 40

How many classes of nuclear receptors are there?

Answer 40

2

Question 41

Homodimers vs Heterodimers

Answer 41

Homodimers: two identical receptors associate and function together and act outside nucleus Heterodimers: two different receptors associate and function together and act inside nucleus

Question 42

Class 1 of nuclear receptors

Answer 42

Located in cytosol and form homodimers

Question 43

Class 2 of nuclear receptors

Answer 43

Located in nucleus and form heterodimers

Question 44

Structure of nuclear receptors

Answer 44

- N-terminal domain (contains co-activator region that binds to transcription factors) - DNA binding domain (binds to specific DNA sequences known as hormone response element to alter gene transcription) - Hinge region (binding site for two nuclear receptors during dimerization) - Ligand binding domain (binding site for ligand that is specific for different receptors).