Pharmacodynamics

Question 1

What is pharmacology ?

Answer 1

The science of the effects of drugs on healthy or sick organisms or the study of the interactions between chemicals and biological systems

Question 2

What are pharmacodynamics and pharmacokinetics ?

Answer 2

• Pharmacodynamics deals with the interaction of chemicals with receptors
• Pharmacokinetics deals with the stages by which chemicals pass through the body
  -> Absorption
  -> Distribution
  -> Metabolism
  -> Excretion

Question 3

Which two aspects of a drug must be known for the risk assessment of toxicity ?

Answer 3

1. The dose level at which the drug is effective#
2. The dose level at which damage is likely to occure

Question 4

Name five points on which the sensitivity of an organism to a pharmaceutical substance depends.

Answer 4

1. Age
2. Gender
3. Genes
4. Diseases
5. Tolerance

Question 5

What do the abbreviations ED and LD stand for?

Answer 5

ED: Effective (single) dose
LD: Lethal dose

Question 6

In which range of concentration should you start to test a new drug ?

Answer 6

In nM range

Question 7

Which two main characteristics of a drug can be read from a concentration-effect curve ?

Answer 7

1. The maximal possible effect (E max)
2. The concentration which gives the half-maximal effect (EC 50)

Question 8

How are pharmaceutical argonists compared to each other ?

Answer 8

They are compared regarding their potency (pD2) and their maximally possible effect (E max)

Question 9

Which formula can be used to calculate pD2 ?

Answer 9

pD2 = -log (EC 50)

Question 10

What is beside pD2 and E max an important characteristic of a high qualitity drug ?

Answer 10

A small amount of side effects

Question 11

What do the abbreviations ED 50, LD 50 and TD 50 stand for?

Answer 11

ED 50: The dose at which 50% of the tested group shows the observed effect

LD 50: The dose at which 50% of the tested group statistically die

TD 50: The dose at which 50% of the tested group shows side effects

Question 12

What do the abbreviations LD LO / LC LO and TD LO / TC LO stand for?

Answer 12

LD LO / LC LO: Lethal dose / concentration low
-> Lowest dose/concentration of a substance for that a lethal effect has been described

TD LO / TC LO: Toxic dose / concentration low
-> Lowest dose/concentration of a substance for that a toxic effect has been described

Question 13

What is the therapeutic range of a drug ?

Answer 13

It is a range of concentrations in which the drug is effective but not toxic.

Question 14

What is the therapeutic ratio of a drug ?

Answer 14

LD 50 / ED 50

It is the ratio of TD 50 to ED 50; The higher this ratio the safer is the drug.

Question 15

Name three characteristics of unspecifically acting substances.

Answer 15

1. They act only in relatively high concentrations
2. They pruduce similar effects even with their different structures
3. Changes in their structure barely change their effects

Question 16

Name two characteristics of specifically acting substances.

Answer 16

1. They act at very low concentrations
2. Their effect strongly depends on their structure

Question 17

Name the four main kinds of regulatory proteins which are commonly involved as primary drug targets.

Answer 17

1. Receptors
2. Ion channels
3. Enzymes
4. Transporter molecules

Question 18

What does the receptor theory 1 say ?

Answer 18

The receptor and the drug have to fit to each other like a lock and a key in order tro exert a chemical effedt on each other.

Question 19

What does the receptor theory 2 say ?

Answer 19

Bodies do not act if they are not bound.

Question 20

What are the two functions of pharmaceutical receptors ?

Answer 20

1. Signal detection
   -> They bind a drug with high affinity to form a ligand-receptor complex
2. Signal transduction
   -> By conformational change they trigger a follow-up response

Question 21

The more receptors are occupied with an agonist, the greater the effect of the agonist. What is the formula of the association constant KA in this case ?

Answer 21

KA = ([Pf]*[Rf])/[PR]

Pf: free pharameutical
Rf: free receptor
PR: pharmaceutical bound to the receptor

Question 22

How is the concentration of the bound state of receptor and pharmaceutical calculated ?

Answer 22

[PR] = ([Pf]*[Rt])/(KA+[Pf])

PR: pharmaceutical bound to the receptor
Pf: free pharameutical
Rt: total amount of receptors
KA: association constant

Question 23

Name the four types of receptors sorted by the time required for a cellular effect.

Answer 23

1. Ligand-gated ion channels (milliseconds)
2. G-protein coupled receptors (seconds)
3. Kinase-linked receptors (minutes to hours)
4. Nuclear receptors (hours)

Question 24

Name five examples of ligand-gated ion channels.

Answer 24

1. Nicotinic ACh receptor
2. Ionotropic glutamate receptor
3. GABA_A receptor
4. Glycine receptor
5. 5-HT3 receptor

Question 25

Name five examples of G-protein-coupled receptors.

Answer 25

1. Adrenoceptors 2. Dopamine receptors 3. Histamine receptors 4. Opiate receptors 5. Adenosine receptors

Question 26

Name four examples of Kinase-linked receptors.

Answer 26

1. Insulin receptor 2. Immunglobulin E receptor 3. Low-densitiy lipoprotein (LDL) receptor 4. Cytokine receptor

Question 27

Name five examples of nuclear receptors.

Answer 27

1. Steroid hormone receptors 2. Vitamin B receptors 3. Retinoid receptors 4. Thyroid hormone receptors 5. Peroxisome proliferatior-activatred receptor (PPAR)

Question 28

What an agonists function ?

Answer 28

Agonists bind to a receptor to change its conformation, thus leading to signal transduction. Agonists have both affinity and intrinsic activity.

Question 29

What does an antagonist do ?

Answer 29

Antagonists bind to a receptor, but do not result in conformational change.

Question 30

What is the formula to calculate the relative intrinsic activity α ?

Answer 30

α = E_A / E_M E_A: effect triggered by the drug A E_M: maximum possible effect

Question 31

What are typical values of the relative intrinsic activity α of agonists and antagonists ?

Answer 31

- For full agonists is α=1 - For antagonists is α=0

Question 32

Name the five types of antagonists.

Answer 32

1. Competitive antagonists 2. Noncompetitive antagonists 3. Functional antagonists 4. Physiological antagonists 5. Chemical antagonists

Question 33

How do dose-response curves of an agonist change under the effection of a competitive antagonist ? What is the effect on ED_50 and E_max ?

Answer 33

Competitive antagonists lead to a parallel shift in the dose-response curve of the agonist -> ED_50 will increase -> E_max is not affected

Question 34

How are non-competitive antagonists acting ?

Answer 34

- Non-competitive antagonists bind allosterically to the receptor - This leads to a conformational change, which alters the binding conditions and the signal transduction of the agonist

Question 35

How do dose-response curves of an agonist change under the effection of a non-competitive antagonist ? What is the effect on ED_50 and E_max ?

Answer 35

- Non-competitive antagonists lead to a decrease in the E_max of the agonist - The ED_50 of the agonist is not changed

Question 36

How are functional antagonists acting ?

Answer 36

A functional antagonist reverses the effect of an agonist in the same cell system/organ. Thereby a different pathway is used and the effects are mediated by different receptors.

Question 37

How are physiological antagonists acting ?

Answer 37

A physioligical antagonist reverses the effect of an agonist at a different cell system/organ. Thereby, opposing effects are triggered in the overall system.

Question 38

What is chemical antagonism ?

Answer 38

Chemical antagonism means that a substance prevents the effect of another substance through e.g. complex formation. This reaction can usually takes place independently of an organism.