Pharmacodynamics

Question 1

Pharmodynamics

Answer 1

The action of a drug on a living organism

Question 2

When a drug binds to a receptor, one of the following actions usually occurs:

Answer 2

An ion channel opens or closes
 Biochemical messenger (second messengers) 
Normal cellular function is inhibited 
A cellular function is turned on (DNA transcription)

Question 3

Law of mass action

Answer 3

The amount of drug-receptor complex formed determines the magnitude of the response. as drug concentration increases, the drug-receptor complexes increase and drug effect increases.

Question 4

Relationship between drug-receptor complex formation and concentration of drug

Answer 4

Proportional, but the relationship is not linear. Use semilogarithmic graph.

Question 5

Drug-target interactions are regulated by which two properties

Answer 5

Affinity- How strong is the binding

Efficacy- how well does the drug work to alter the activity of the receptor?

Question 6

Affinity is influenced by what?

Answer 6

Size and shape of drug molecule
Types, number and spatial arrangement of receptor
Intermolecular forces

Question 7

is affinity influenced by concentration?

Answer 7

No

Question 8

Bonds from weakest to strongest

Answer 8

Weakest 
Van der Waal
Hydrophobic 
Hydrogen 
Ionic 
Covalent 
Strongest

Question 9

KD

Answer 9

Dissociation constant. Describes the drug concentration at which 50% of the receptors are occupied. Measure of drug’s affinity.

Does not always indicate half maximal response.

Question 10

relationship between KD and affinity

Answer 10

inverse. High KD means that it takes a high drug concentration to bind 50% of the receptors. Poor affinity.
Low KD means it takes a low concentration to bind 505 of the receptors. Good affinity.

Question 11

KD is found on which graph?

Answer 11

Drug receptor occupancy curve. Semi-log. Found at 50% mark on Y.

Question 12

Beta 1 selective blockers. As concentration increases, the drug will bind

Answer 12

to receptors for which it has a lower affinity.

Question 13

Two types of drug-target relationships

Answer 13

Graded: How much the drug works. Continual.
Quantal: All or none. yes or no.

Question 14

Graded Dose-Response curves

Answer 14

Measures continual effect.
Emax: Maximum drug activity. Measure of efficacy. Any increase in conc will not increase effectivity of drug. Found at top of graph.

EC50: Concentration that has 50% of max effect. Measure of potency/strength. Found in center of each curve.

Question 15

Quantal Dose-Response Curves

Answer 15

Measures responses that are all or none. Gives relationship between drug dose and frequency at which a biologic effect occurs.
Emax: Response in 100% of population
ED50: Response in 50% of population
TD50: Toxic response in 50% of population
LD50: Lethal response in 50% of population

Question 16

Therapeutic Index

Answer 16

A measure of the safety of a drug (larger is better)

Found by dividing TD50 or LD50 by ED50.

Question 17

Agonist

Answer 17

Binds to receptor and elicits a response

Question 18

Antagonist

Answer 18

Binds to a receptor but does not elicit a response. Blocks receptor- prevents something from binding to it.

Question 19

Full agonist vs partial agonist

Answer 19

Full (strong) produces max activation of receptor and elicits max response from tissue.

Partial (weak) produces a weaker response compared to the full agonist. Takes more drug molecules bound to more receptors to produce the same effect as full agonist.

Question 20

Inverse Agonist

Answer 20

Drug that binds to a cell, which in its natural state, is on. Drug turns it off.

Ex: Drug has ion channel always open. Ions always flowing. Drug binds and closes channel.

Technically an agonist bc it caused a response. An antagonist would have prevented it from closing.

Question 21

What does it mean that antagonist have zero intrinsic activity?

Answer 21

They do not cause a reaction- they simply present the receptor from being occupied by another molecule.

Question 22

Competitive reversible antagonist (?? i think)

Answer 22

Antagonist competes directly with the agonist molecule. Increased concentration of agonist will overcome the antagonism.

Emax will be the same, but the curve will shift to the right. Will produce same max response, but will require more molecules to do it.

Question 23

Competitive irreversible antagonist

Answer 23

Compete directly with agonist for receptor binding site. Very strong bond-irreversible. Will reduce the maximal agonist effect since it permanently reduces the number of receptors available to an agonist.

Emax of agonist will decline due to decreased receptors available to bind.

Question 24

Noncompetitive antagonist

Answer 24

Does not compete with agonist for same binding site. Both antagonist and agonist can be bound at the same time (but antagonist is more powerful). Increasing concentration of the agonist will not reverse the inhibitory action!

Similar curve to irreversible antagonist. Emax of agonist will decline due to antagonists bound. EC50 stays the same.

Question 25

4 families of receptor types

Answer 25

Ligand gated ion channel G protein coupled receptor Enzyme linked Intracellular

Question 26

Quickest to slowest response time based on receptor type

Answer 26

``` Quickest: Ligand gated ion channel G protein Enzyme linked Intracellular Slowest ```

Question 27

Flow of ions through a ligand gated channel is depend on

Answer 27

The binding of a ligand to the receptor on the channel. The ligand can include a NT or drug.

Question 28

Two examples of ligand gated ion channels

Answer 28

1. Cholinergic receptors: Binding of agonist opens sodium channel and causes action potential. Excitatory. 2. GABA receptors: binding of agonist opens chloride channels- causes hyperpolarization. Inhibitory.

Question 29

Voltage gated ion channels

Answer 29

Change confirmation in response to changes in membrane voltage Binding of drug causes the channel to open or close. Ex: local anesthetics

Question 30

GPCR activation

Answer 30

Ligand binds. GTP replaces GDP on the alpha subunit of the G protein. The alpha + GTP dissociates and interacts with adenylyl cyclase --> camp production --> second messengers produce further actions

Question 31

Response time difference between ligand gated ion channels and GCPR

Answer 31

GCPR have a slower response, but last longer.

Question 32

Examples of second messengers in GPCR

Answer 32

cAMP regulates protein phosphorylation Phospholipase C Guanylyl cyclase to form cGMP. Relaxes smooth muscle cells.

Question 33

How do enzyme-linked receptors work?

Answer 33

Have systolic enzyme activity as part of their structure and function. Binding of ligand activates or inhibits the activity of the enzyme.

Question 34

2 examples of enzyme linked receptors

Answer 34

Insulin receptor | VEGF

Question 35

Intracellular receptors

Answer 35

Receptors are located inside cell. Ligand must be lipid soluble (steroid hormone) and travel to the receptor inside the cell. Complex will migrate to nucleus and regulate gene expression Response time: 30 mins Can last hours to days

Question 36

Spare receptors

Answer 36

In some cases, maximal response can be achieved when only a fraction of receptors are occupied. EC50 will be lower than KD due to amplification of secondary messengers. Common with GPCR or single ligand interacts with many G proteins.

Question 37

What causes spare receptors?

Answer 37

Common with GPCR or single ligand interacts with many G proteins.

Question 38

Receptor Desensitization

Answer 38

If receptors are continually bound, it may lead to changes in the responsiveness of the receptor- usually causes decreased response. Evolved to prevent cell damage.

Question 39

Two mechanisms of receptor desensitization

Answer 39

Tachphylaxis: Receptor is still present but is unresponsive to the ligands. Light switch unplugged from the wall. Endocytosis: Cell engulfs receptor and is sequestered from further activation. Can be recovered- needs a break.

Question 40

Tolerance

Answer 40

Decreased response to a drug due to desensitization (changes at receptor level), metabolism, or behavioral (ex drinking coffee). Dose must be increased to achieve the same effect.

Question 41

Tolerance can lead to ___ and then ____

Answer 41

Dependence --> withdrawal

Question 42

Dependence

Answer 42

Pt feels abnormal in absence of drug. Ex: dependent on drug. Need coffee. If not, will get headaches or be shaky.

Question 43

Withdrawal

Answer 43

Drug is no longer given to dependent patient. Symptoms are often opposite of the effect of the drug.