Week 2: Pharmacodynamics

Question 1

What is pharmacodynamics?

Answer 1

What the drug does to the body - almost all drugs act through receptors located on or in the cells - drugs combine to a receptor and produce an effect

Question 2

What is a ligand?

Answer 2

a molecule that binds with a molecular target (receptor)

- aka 1st messenger or a signaling molecule

Question 3

What are 2 types of ligands?

Answer 3

Endogenous (comes from within the body) ex: hormones, neurotransmitters
Exogenous (comes from outside the body) ex: drugs

Question 4

What type of ligand can be both endogenous and exogenous?

Answer 4

Insulin - is produced by the body, but can also be given exogenously to diabetics

Question 5

What is an example of a drug that acts through a chemical reaction with other molecules?

Answer 5

antacids that neutralize stomach acids - act directly

Question 6

Can a drug create an effect?

Answer 6

No - drugs modulate functions already present in the cell or tissue

Question 7

What things can affect pharmacodynamics?

Answer 7

• age
• sex
• ethnicity
• individual characteristics of a person

Question 8

What are the three steps of pharmacodynamics/cellular communication?

Answer 8

1) Signal recognition
2) Signal transduction
3) Cellular response

Question 9

What are the four types of cellular communication?

Answer 9

1) Ion Channel Receptors / Ligand Gated Ion Channel
2) G-protein coupled Receptors
3) Transmembrane Receptors
4) Intracellular Receptors

Question 10

How do ion channel receptors transmit signals across the cell membrane?

Answer 10

• a signal molecule activates the ion channel receptor which increases the flow of ions across the cell membrane which alters the electrical potential of the cell or by separating changed ions across the membrane.
• Example: acetylcholine which momentarily opens a central channel allowing sodium to enter a cell and potassium to leave the cell

Question 11

How do G Protein Coupled Receptors (GPCR) transmit signals across the cell membrane?

Answer 11

• most common used by drugs
• Binding on extracellular causes conformational change then signal goes intracellular then interacts with G protein binding receptor to other proteins that control response via 2nd messengers (ie cyclic AMP)
• goal: intracellular effect

Question 12

What is one type of second messenger involved in G-Protein Coupled Receptor cellular communication?

Answer 12

Cyclic adenosine monophosphate (cAMP)

Question 13

G-proteins are made up of what three major subunits?

Answer 13

1) alpha agonist
2) beta agonist
3) gamma agonist

Question 14

How do transmembrane receptors transmit signals across the cell membrane?

Answer 14

• An extracellular hormone binding domain is bound by a ligand
• when an active hormone binds to the binding site, the receptor conformation changes and two receptors bind to each other, activating the intracellular enzyme domain and causing the receptors to catalyze the phosphorylation of tyrosine residues on various downstream signaling proteins

Question 15

How do intracellular receptors work to regulate gene expression?

Answer 15

Hormones that are lipid-soluble and able to readily cross the cell membrane into the cell bind to glucocorticoid receptors in the cell’s cytoplasm. This binding displaces a stabilizing protein and permits the receptor to change into it’s active conformation - the receptor moves into the cell’s nucleus where it binds to specific DNA sequences and alters the transcription of genes

Question 16

What is an agonist?

Answer 16

A ligand that binds to and activates a receptor.

Question 17

What is a full agonist?

Answer 17

• a drug that produces receptor stimulation and a conformational change every time they bind
• don’t need all of the available receptors to produce a maximum result
• ACTIVATOR

Question 18

What is an antagonist?

Answer 18

Drugs that occupy receptors without stimulating them

• occupy a receptor site and prevent other molecules, such as agonists, from occupying the same site and producing a response
• BLOCKER/INHIBITOR

Question 19

What is a partial agonist?

Answer 19

• submaximal/partial benefit even with all receptors activated
• intrinsic activity
• require all of the available receptors to produce their full response
• maximum response for a partial agonist is less that that for a full agonist

Question 20

Affinity

Answer 20

• The strength of attraction between the drug and its receptor
• high affinity = lower dose requirement
• low affinity = higher dose requirement

Question 21

Selectivity

Answer 21

the ability of the receptor to distinguish between drugs

• has the same implications as specificity
• drug selective to a receptor on various organs

Question 22

Specificity

Answer 22

the measure of a receptors ability to respond to a single ligand

Question 23

Saturation

Answer 23

Portion of receptors that are occupied at any time - if all receptors are bound, they cannot take on any more ligands

Question 24

Efficacy

Answer 24

the invivo potency;

• the maximum response achieved from a drug
• an interaction (absorption, metabolism, excretion) of the drug in the body may alter the relative bioavailability and thus, change the theoretical effect/efficacy of the drug

Question 25

Potency

Answer 25

• the relationship between the drug dose and the magnitude of the effect
• when high, it induces a strong effect with a low drug dose
• depends on both affinity and efficacy

Question 26

Synergism

Answer 26

The combining of two drugs that produce a combine effect greater than the sum of their separate effects

Question 27

Additive

Answer 27

The combined effect produced by the action of two or more agents being equal to the sum of their separate effects

Question 28

Graded drug response

Answer 28

• drug effects that can be measured continually
• easier to manage clinically because patient response to the drug is monitored and drug dosages can be changed based on patient response
• example: monitoring a patient’s blood pressure while taking antihypertensive medications and adjusting the dose for continued HTN or hypotension

Question 29

Quantal drug response

Answer 29

• responses that may or may not occur
• example: seizures, pregnancy, sleep
• the response is: either they occur or they don’t

Question 30

Receptors

Answer 30

Proteins (macromolecules) that can be found on cell surfaces or inside the cell that mediate drug activity

Question 31

Therapeutic index

Answer 31

• the ratio of the median effective dose (ED50) to the median toxic dose (TD50)
• the window between the dose which produces a therapeutic benefit and the dose which causes toxicity/harmful effects
• the higher the therapeutic index of a drug, the safer the drug is

Question 32

Downregulation

Answer 32

• The cellular decrease in the number of receptors to a molecule (hormone or NT), which reduces sensitivity to molecule
• occurs because receptors have a lifecycle (drug tolerance) & gets recycled back into cell
• occurs more often with agonists
• ex: taking oxycodone but with time, receptors starting to move into cell = drug tolerance

Question 33

Upregulation

Answer 33

• Increase in the cellular response to a molecular stimulus due to an increase in the number of receptors on the cell surface
• occurs more often with antagonists medications
• can be caused by disease states, pregnancy (due to more oxytocin), or abrupt withdrawal of an antagonist medication