Pharmacodynamics

Question 1

1. Membrane potential change opens the channel
2. Inactivation occurs after
3. Channel returns to closed state

Answer 1

• voltage-gated ion channels

Question 2

1. Binding to receptor
2. Transient increase in permeability to a particular ion
3. Negative membrane potential
   - influx of Na+
   - depolarization of cell
   - possible AP

Answer 2

• ligand gated ion channel

Question 3

Nicotinic ACh, GABA type A and glutamate

Answer 3

• ligand gated ion channel examples

Question 4

1. Inhibition of adenylate cyclase (AC)
2. decrease of cAMP in cell
3. Increase in K+ efflux
4. Decrease in Ca+ influx

Answer 4

• Gi/Go protein coupled receptors

Question 5

Muscarinic ACh (M2), Alpha-2 adrenoceptors, serotonin receptors: 5-HT1

Answer 5

• Gi/Go protein coupled receptors examples

Question 6

1. Activation of phospholipase C
2. Increase in InsP3 and Ca2+
3. Conversion of PIP2 into DAG
4. Increase in protein kinase C

Answer 6

• Gq protein coupled receptors

Question 7

Muscarinic ACh (M1, M3), Alpha-1 adrenoceptors, serotonin receptors: 5-HT2, Histamine H1

Answer 7

• Gq protein coupled receptors examples

Question 8

1. Activation of adenylate cyclase

2. Increase of cAMP in the cell

Answer 8

• Gs protein coupled receptors

Question 9

1. Ligand binds receptor
2. Protein phosphorylation occurs
3. Gene transcription
4. Protein synthesis
5. Cellular effects

Answer 9

• Kinase-linked receptors

Question 10

Insulin, growth factor and cytokine receptors

Answer 10

• kinase linked receptors

Question 11

1. Ligand enters the nucleus
2. Gene transcription
3. Protein synthesis
4. Cellular effects

Answer 11

• nuclear receptors

Question 12

Steroids receptors (oestrogen receptor)

Answer 12

• nuclear receptors

Question 13

Two most important things for drug-receptor interaction

Answer 13

1. A close fit between the drug and receptor is essential

2. Strong binding forces

Question 14

Binding forces

Answer 14

• Covalent > ionic > hydrogen > van der waals > hydrophobic

Question 15

Excellent receptor fit and elicits a therapeutic response

Answer 15

• agonist

Question 16

Strength of binding between drug and receptor

Answer 16

• affinity

Question 17

Weak binding forces means

Answer 17

• short interaction with the receptor

and vice versa with strong binding forces

Question 18

Measured by the dissociation constant Ko (50% occupancy)

Answer 18

• affinity

Question 19

Tendency to activate the receptor and the strength of response after binding to the receptor

Answer 19

• efficacy

Question 20

Drugs with a high ______ usually have a high affinity and occupy a significant proportion of receptors EVEN at LOW concentrations

Answer 20

• potency

Question 21

Measured for example as EC50 (concentration that leads to 50% of the maximum effect)

Answer 21

• drug potency

- > more to the left on the graph

Question 22

Agonists

Answer 22

• lead to a response

Question 23

Antagonists

Answer 23

• lead to no response

Question 24

Activation is governed by ____

Answer 24

• efficacy

Question 25

Occupation is governed by ____

Answer 25

- affinity

Question 26

Antagonist binds with the active site of the enzyme molecule and prevents the binding of a substrate molecule (no product molecules generated)

Answer 26

- competitive antagonist

Question 27

Antagonist binds with the inhibitor site of enzyme molecule. Molecule may still bind with the enzyme molecule, but the reaction is hindered.

Answer 27

- non-competitive antagonist

Question 28

When an antagonist is added there is a parallel shift to the right, an increase in the EC50(potency) and no change in maximum effect (efficacy)

Answer 28

- competitive inhibition | - > can overcome antagonist by increasing dose of agonist

Question 29

When an antagonist is added there is a decreased maximum response (efficacy) and no change in EC50(potency)

Answer 29

- non-competitive inhibition | - > can NOT overcome antagonist by increasing dose of agonist

Question 30

Acts on receptors that always lead to a response and lowers the constitutive level of receptor activation

Answer 30

- inverse agonists

Question 31

Prolonged use of an agonist leads to? Prolonged use of an antagonist leads to?

Answer 31

- receptor down-regulation | - receptor up-regulation