Pharmacodynamics- Quiz 1

Question 1

What is pharmacodynamics?

Answer 1

-What the drugs do to the body

Question 2

Signal transduction

Answer 2

The drug= the signal
The receptor= signal detector

-Are mechanisms in place to protect cell from excess stimulation

Question 3

When is a drug an agonist?

Answer 3

-A substance that binds to a receptor and activates it to start a series of reactions. Agonists can be full (producing maximal effects) or partial (producing a lesser effect).
-They are used to treat various conditions by mimicking the effects of natural compounds, such as neurotransmitters or hormones.

Question 4

What is a second messenger?

Answer 4

-AKA “effector molecules”
-Is a molecule inside the cell that is activated by the binding of a first messenger to a receptor. They amplify and propagate the signal within the cell
-Are part of a cascade that translates agonist binding into cellular response

Question 5

What is a drug receptor complex?

Why do we care?

Answer 5

-Is the interaction that occurs when a drug binds to a receptor, resulting in a biochemical effect that can alter physiological processes.
-Magnitude of this response is proportional to the number of the
drug-receptor complexes.
-This concept involves specificity of the receptor for a given agonist.
-Not ALL drugs exert effects by
interacting with a receptor

Question 6

What are receptor states?

Why do we care?

Answer 6

-Refer to the different functional states a receptor can adopt in response to ligand binding.

1. Two types:
   Active State (R*)
   Inactive State (R)
2. Are in reversible equilibrium to one
   another—usually favoring inactivity
   -Binding with agonists cause the equilibrium to shift from inactive to active to get an effect
3. Magnitude of the biological effect of a drug is directly related to the fraction of active receptors

Question 7

What is an antagonist?

Answer 7

-Are drugs that bind to the receptor but do NOT increase the amount of activity, RATHER they stabilize the amount of inactive receptors

Question 8

What is a partial agonist?

Answer 8

-They shift the equilibrium from inactive to active—but the fraction of active receptors is LESS than that caused by an agonist

Question 9

What is a receptor?

Answer 9

-Any biological molecule to which a
drug binds and produces a response
-Ex: Enzymes, nucleic acids, structural proteins can act as receptors for drugs

Question 10

What are the richest sources of receptors?

Answer 10

-Membrane bound proteins:

-Ligand-Gated Ion Channels
-G Protein-Coupled Receptors
-Enzyme Linked Receptors
-Intracellular Receptors

Question 11

What are the 2 major receptor families?

Answer 11

1. Hydrophilic ligands: interact with receptors found ON the cell surface
2. Hydrophobic ligands: enter cells through lipid bilayers of the cell membrane to interact with receptors found INSIDE the cells

Question 12

Signal amplification

What important concept is associated with this mechanism?

Answer 12

-Typical of G Protein-Linked and EnzymeLinked Receptors
-Only a small amount of receptors need to be occupied for a ligand to get maximal response (ex: Insulin receptors)
-Systems that have this are said t have “spare receptors”

Question 13

Desensitization and down regulation of receptors
(STATED IMPORTANT CONCEPT)

Answer 13

1. Repeated or continuous administration of an agonist or an antagonist often leads to changes in the response of the receptor
2. The receptor may become desensitized due to too much agonist stimulation—causing a diminished response (Tachyphylaxis)
3. Tachyphylaxis: the rapid reduced responsiveness to a drug following its continuous use (from phosphorylation that renders the receptor unresponsive to the agonist)
4. Receptors can be internalized in the cell—making them unavailable for further agonist interaction—this is down-regulation
5. Other receptors require a finite time after stimulation before they can become activated again—during this recovery phase— unresponsive receptors are said to be refractory (i.e. cardiac)

Question 14

Up regulation of receptors

Answer 14

-Repeated exposure of a receptor to an antagonist results in upregulation of the receptors
-The receptor reserves are inserted into the membrane, increasing the number of receptors available—upregulation of the receptors makes the cells MORE sensitive to agonists and/or more resistant to effects of the antagonist

Question 15

Up regulation versus Down regulation of receptors
(In a nutshell)

Answer 15

-Upregulation:
-When a receptor is exposed to insufficient stimulation and cell compensates by increasing the number or sensitivity of receptors.

Downregulation:
-When a receptor is exposed to excessive stimulation and the cell compensates by reducing the number or sensitivity of receptors.

Question 16

Dose-response relationships

What are the determining factors?

Answer 16

-Amount of drug effects depends on receptor sensitivity and drug concentration (is determined by dose, rate of absorption, distribution, metabolism and elimination)

-As the dose of a drug increases, its effect also gradually increases until all of the receptors are occupied [maximum effect]
AKA Epi @ 30 for ten hours ;)

-Potency/ efficacy can be determined by graded dose-response curves

Question 17

Potency of a drug

Answer 17

-Is the Measure of the amount of drug needed to produce an effect

-So, if the concentration of drug producing 50% of maximum effect EC50 is used determine potency

-Therapeutic preparations of drugs reflect their potency

Question 18

Efficacy of a drug

What metric is associated with this concept?

Answer 18

-Is the Magnitude of response a drug has when it interacts with a receptor

-It depends on number of drug- receptor complexes formed and intrinsic activity of the drug (its ability to activate the receptor & cause a response)

-Maximum efficacy of a drug Emax assumes that the drug occupies all receptors and no increase in response is seen with higher
concentrations of the drug

-The max response differs between full agonists/ partial agonists

-For an antagonist—even though it
occupies 100% of receptor sites—no receptor activation occurs (Emax is 0)

-Efficacy is more clinically useful than is potency—a drug with more efficacy is more therapeutically helpful than one that is potent

-

Question 19

Effect of drug concentration on receptor binding:
What is Kd and affinity?

Answer 19

-Kd= the equilibrium dissociation constant for the drug from the receptor (a measure of the binding affinity of a drug to its receptor. The lower the Kd, the higher the affinity, meaning the drug binds more tightly to the receptor)

-Affinity= strength of the binding between a ligand and its receptor (ability to bind)

Ratio: rate of dissociation to rate of association

Question 20

Relationship of Drug Binding
to Pharmacologic Effect

Answer 20

-If a particular group of receptors is crucial for producing the physiological effect, the drug’s potency in inducing that effect should be linked to its affinity for binding to those receptors.

-Many drugs and neurotransmitters can bind to more than 1 type of receptor—thus causing both the
desired effects and unwanted ADEs

Question 21

Intrinsic activity

Answer 21

-An agonist binds to a receptor and triggers a biological response, which depends on the concentration of the agonist, its affinity for the receptor, and the proportion of receptors that are occupied

-Intrinsic activity further determines its ability to fully or partially activate the receptors

-Maximum possible effect that can be produced by a drug

Question 22

Full Agonists

Answer 22

-If a drug binds to a receptor and produces a maximal biologic response that mimics the response of the endogenous ligand, its a full agonist

-Full agonists bind to the receptor, stabilize it in its active form and have intrinsic activity of 1

-All full agonists for a receptor population should produce the same Emax

-Effects of agonists on intracellular molecules, cells, tissues and intact organisms are all attributed to the
interaction between the drug and the receptor

Question 23

Partial Agonist

Answer 23

-Have intrinsic activities > zero but < 1

-Even when all of the receptors are occupied, partial agonists cannot
produce the same Emax as a full agonist

-Partial agonists can have an affinity that is greater than, less than
or equal to that of a full agonist

-A partial agonist can also function as a partial antagonist to a full agonist. As the partial agonist occupies more receptors, fewer receptors are available for the full agonist, resulting in a decrease in Emax until it reaches the Emax of the partial agonist.

-The potential of partial agonists to be both an agonist and an antagonist, may have therapeutic utility (Ex. abilify)

Question 24

Inverse Agonists

Answer 24

-They stabilize the inactive receptor state and promote the conversion of active receptors to the inactive form, reducing the number of activated receptors to levels lower than those observed in the absence of the drug.

-Inverse agonists have intrinsic activity below zero

-By stabilizing the receptor in its inactive state, inverse agonists help modulate inappropriate or excessive physiological responses.

Question 25

Antagonist

Answer 25

-Bind to a receptor with high affinity but have no intrinsic activity

-Has no effect on biologic function in the absence of an agonist (but can decrease the effect of an agonist)

-Blocks the drug’s ability to bind or activate the receptor

Question 26

Competitive Antagonists

Answer 26

-An antagonist that binds reversibly to the same site on the receptor as the agonist

-It interferes with an agonist binding to its receptor and keeps the receptor in its INACTIVE state

-Increasing the concentration of agonist can overcome this inhibition

-reduce agonist potency

Question 27

Irreversible Antagonists

Answer 27

-Binds to the active site of the receptor, permanently reducing the number of receptors available to the agonist

-In contrast to competitive antagonists— addition of more agonist does not overcome
the effect of irreversible antagonists

-noncompetitive antagonists

• reduce agonist efficacy

Question 28

Allosteric Antagonists

Answer 28

-Binds to a site other than [allosteric] the agonist-binding site and prevents activation of the agonist

-Foundation of new and novel ways to antagonize / modulate the effect of drugs

-noncompetitive antagonists

• reduce agonist efficacy

Question 29

Functional Antagonists

Answer 29

-An antagonist that can act on a completely different receptor, producing effects that are functionally opposite to those of the agonist.

-Ex: Epi and histamine induced bronchoconstriction is classic example of this phenomenon

Question 30

Dose-response relationships

Quantal dose

Answer 30

-An important dose-response relationship involves the connection between the drug dose and the proportion of a patient population that exhibits a response to it, known as quantal responses.

-Quantal dose—response curves are useful to determine doses to which MOST of the population responds to

-ED50 is the drug dose that causes a therapeutic response in ½ of the population

Question 31

Therapeutic Index
(IMPORTANT CONCEPT)

Answer 31

-The ratio of the dose that causes toxicity in 50% of the population (TD50) to the dose that produces the desired or effective response in 50% of the population (ED50).

-Is the measure of the drug’s safety

-A larger value means a wide margin between doses that are effective and those that are toxic

-TI of a given drug is determined in drug trials and clinical experience

-High TI is required for most
drugs—yet some drugs with low TI are routinely used to treat serious diseases (In these scenarios, risk of ADEs is not as great as the risk of the leaving the disease untreated)

Question 32

Clinical Usefulness of the
Therapeutic Index

Answer 32

-Drugs with LOW TI that
are often used and require
therapeutic drug monitoring–>

-Phenytoin
-Warfarin
-Lithium
-Digoxin
-Aminoglycosides
-Levothyroxine
-Vancomycin
-Amphotericin B