Module 7 - Pharmacodynamics - Dose Response Relationships

Question 1

what is pharmacodynamics

Answer 1

is the study of what the drug does to the body

Question 2

In pharmacodynamics what do we study

Answer 2

we study the biochemical and physiological effects of drugs and the mechanisms by which drugs produce effects.

Question 3

In pharmacokinetics increasing the dose of a drug does what

Answer 3

increases plasma concentrations

Question 4

in pharmacodynamics, increasing the dose does what

Answer 4

increases the response to the drug

Question 5

how do we evaluate the pharmacodynamics of drugs

Answer 5

dose-response curves

Question 6

Monotonic

Answer 6

means that the response increases as the dose increases.

Question 7

how do we look at dose-response curves

Answer 7

dose-response curves are NOT linear, for this reason we usually look at the dose response curve as a semi-logarithmic plot

Question 8

Phase 1 of semi-logarithmic dose-response curve

Answer 8

doses are too low to elicit a clinically relevant response

Question 9

Phase 2 of semi-logarithmic dose-response curve

Answer 9

the response is graded and nearly linear

Question 10

Phase 3 of semi-logarithmic dose-response curve

Answer 10

larger doses do NOT lead to greater response. larger does may cause toxicity

Question 11

What is efficacy

Answer 11

is a measure of how effective a drug is at a given dose

Question 12

what is maximal efficiency

Answer 12

represents the maximum effect that a drug is capable of achieving

Question 13

how is maximal efficacy read on a dose-response curve

Answer 13

by looking at the maximum height

Question 14

Do we always choose the drug with the highest efficacy to treat patients?

Answer 14

NO!! We choose the drug and dose that are therapeutically effective with the fewest side effects.
Health care professionals often titrate the dose of a drug. This means they start with a low dose of the drug and slowly increase the dose while monitoring the patient’s response.

Question 15

what does potency mean

Answer 15

refers to the amount of drug required to elicit a pharmacological response

Question 16

High Potency

Answer 16

• does NOT mean more therapeutically effective
• a more potent drug will require a smaller dose to achieve the desired effect than a less potent drug

Question 17

comparing potency

Answer 17

the drugs must produce the same therapeutic effect.
ex: you can’t compare the potency of a medication used for pain relief with one that lowers blood pressure

Question 18

How is potency determined

Answer 18

by comparing the dose required to produce the HALF maximal response
- this is called ED50

Question 19

Lower ED50 drugs

Answer 19

are said to be more potent than drugs with high ED50

Question 20

How do drugs produce effects

Answer 20

• most drugs act on cellular macromolecules (receptors, enzymes)
• majority of drug targets are receptors but drugs also act on enzymes, ion channels, and transport proteins

Question 21

what cellular macromolecules do drugs act on

Answer 21

receptors, enzymes, ion channels, and transport proteins

Question 22

Typical drug action involves…

Answer 22

binding of drug molecules to the macromolecule target.
- complex is then able to produce a biological effect

Question 23

Mimic Drugs

Answer 23

drugs typically mimic an endogenous compound in the body
- for example norepinephrine binds to receptors in the heart and increases heart rate. There are drugs that mimic the action of norepinephrine by binding to the same type of receptor.

Question 24

do all drugs act on cellular targets

Answer 24

NO! Although most drugs do act on cellular targets, there are a few that do not.
* The best example of drugs that don’t act on cellular targets are antacids.

Question 25

what are endogenous compounds

Answer 25

an endogenous compound are things that our body synthesizes
- our body breaks down for us, whereas an exogenous compound is something our body is not good at breaking down
- endogenous compounds are within our body exogenous are outside our body

Question 26

what are antacids

Answer 26

they are drugs that neutralize stomach acid to provide symptomatic relief from some gastro disorders
- they are bases that neutralize stomach acid - therefore they DON’T bind to any cellular target

Question 27

What are the types of drug receptors

Answer 27

1. ligand-gated ion channels
2. G-protein coupled reactions
3. enzyme-linked receptors
4. intracellular receptors

Question 28

Ligand-Gated ion channels

Answer 28

• The movement of ions into or out of a cell can cause instantaneous changes in function
• As ions are unable to directly cross the cell membrane they utilize specialized channels.
• ligands control the opening and closing of ion channels
• many neurotransmitters bind to these receptors

Question 29

GABA receptor

Answer 29

• is an important example of a ligand0gated ion channels
  when GABA (neurotransmitter) binds to the GABA receptor is causes the opening of a channel that allows the ion chloride to flow into the cells
• benzodiazepine bind to GABA receptor and allow chloride in

Question 30

What happens in the Activation of GABA receptor

Answer 30

• causes sedation and muscle relaxation mediated by the increased intracellular chloride
• responses to these receptors are very rapid (milliseconds)

Question 31

G-Protein coupled receptors (GPCRs)

Answer 31

• binding of a ligand to a GPCR causes activation of the G-protein.
• The G-protein then dissociates from the receptor and activates the effector.
• Activation of GPCRs results in a response that lasts from seconds to minutes in duration.

Question 32

what are GPCRs 3 components (G-protein coupled receptors)

Answer 32

1) A seven transmembrane-spanning protein receptor.
2) A G-protein which has three subunits.
3) An effector molecule (i.e. an enzyme).

Question 33

How do endogenous neurotransmitters mediate their effects

Answer 33

endogenous neurotransmitters such as norepinephrine, serotonin, and histamine mediate their effects by binding to GPCRs

Question 34

Enzyme-Linked receptors

Answer 34

• they span the cell membrane with the ligand binding domain on the outside of the cell and the enzymes catalytic site on the inside
• Binding of a ligand on the outside of the cell activates the enzyme on the inside of the cell.
• occurs in seconds

Question 35

Enzyme linked receptor (Insulin receptors)

Answer 35

• Binding of insulin to the insulin receptor causes enzyme-mediated phosphorylation and activation of an intracellular effector.
• The phosphorylated effector causes an increased translocation of glucose transporters to the cell membrane.
• The net effect of insulin binding to its receptor is increased cellular glucose uptake and utilization.

Question 36

Intracellular receptors

Answer 36

INSIDE the cell (also called transcription factors)

• to access these receptors, ligands must be able to cross cell membrane (diffusion or transport protein)
• Binding of the ligand causes translocation of this complex to the nucleus and binding to DNA.
• When the ligand/receptor complex binds to DNA, transcription of messenger RNA is stimulated.
• Protein synthesis occurs hours or days later.
• ligands to these receptors = highly lipid soluble
• endogenous = testosterone and estrogen

Question 37

Lock and Key hypothesis

Answer 37

• The lock can be thought of as the receptor. The lock requires a key with a specific size and unique shape to open it.
• The drug can be thought of as the key. If it has the right shape and size, it can open the lock.
• Drugs that are selective will bind to only one receptor and therefore will be less likely to produce side effects.

Question 38

Even if drugs bind to only one receptor, why do they still have side effects?

Answer 38

The target for therapy may be in the brain but the receptor may be located in the brain and in the intestine.

Therefore side effects in the intestine may occur.