Intro to Pharmacodynamics

Question 1

What is pharmacodynamics?

Answer 1

“what the drug does to the body”

Question 2

How are receptors strictly defined?

Answer 2

Proteins that normally serve as receptors for endogenous LIGANDS (ex: hormones, NTs, growth factors, cytokines)

Question 3

How are drug receptors broadly defined today?

Answer 3

any cellular constituent ex: enzymes, cell mbs, transport prots, structural prots, DNA, & RNA

Question 4

what are agonists?

Answer 4

drugs that bind to receptors & mimic effect of the endogenous ligand

Question 5

what are antagonists?

Answer 5

drugs that bind to receptors and produce no response (inhibit effect of the endogenous ligand). antagonists can be competitive or noncompetitive

Question 6

What is a partial agonist?

Answer 6

drugs that bind to the receptor & produce a lesser effect than the endogenous ligand

Question 7

What is classical receptor theory?

Answer 7

reversible interaction btwn drug (D) & receptor (R) follows law of mass action & is represented by:
[D] + [R] ,<-> [DR] -> effect
-where [DR] is concentration of activated drug-receptor complexes

Question 8

What are dose-response relationships primarily used for?

Answer 8

To compare drug potencies & efficacies & to determine drug safety.

Question 9

what are the two main types of dose-response relationships?

Answer 9

1. graded
2. quantal

Question 10

all dose-response relationships are plots of?

Answer 10

dose on the independent (x) axis & response on the dependent (y) axis

Question 11

What are graded dose-response relationships?

Answer 11

• show responses of INDIVIDUALS & are continuous responses
• Y axis is usually “percent response” from 0 to 100%
• provides info about INTENSITY OF RESPONSE over a dose range

Question 12

What are quantal dose-response relationships?

Answer 12

• show POPULATION responses & are “all-or-none” responses
• Y axis is usually “ percent of individuals responding” from 0 to 100%
• provides info about # OF PATIENTS EXHIBITING A SPECIFIED EFFECT over dose range

Question 13

What are graded response curves used mainly for?

Answer 13

to compare potency & efficacy

Question 14

What are quantal response curves used mainly for?

Answer 14

to determine drug safety

Question 15

Most patients respond to an average dose, those that dont?

Answer 15

• patients that require a lower dose is often due to ADME
• patients that require a higher dose is often due to things like drug tolerance

Question 16

What is potency?

Answer 16

Potency is a R or L shift on the dose-response curve graph; a drug is more potent if it takes less of that drug to get the desired response

Question 17

What is efficacy?

Answer 17

an up or down shift on the dose-response curve graph; a drug is more efficacious if at it’s max it can get a higher % maximal effect than another drug

Question 18

What is EC50 or ED50?

Answer 18

concentration or dose causing a 50% maximal response; it is used to characterized drugs & compare potencies

Question 19

What else can dose-response curves be used to determine?

Answer 19

Any effective dose (ED1, ED10, ED99) or can be used to determine toxic doses (TD) or lethal doses (LD)

Question 20

What is the therapeutic index (TI)?

Answer 20

TI = TD50/ED50 (or LD50/ED50); want it to be really large, so there is a wide range btwn safe dose & dose that causes death

Question 21

What is the margin of safety?

Answer 21

= TD1/ED99 (or LD1/ED99); margin of safety is more conservative measure of drug safety than therapeutic index b/c it is essentially the ratio of drug dose that causes toxicity/death in 1% of pop to drug dose that causes desired therapeutic effect in 99% of the population

Question 22

upon continuous exposure to a drug, what can happen to receptors?

Answer 22

They can become DESENSITIZED (usually due to downregulation) which is 1 reason for drug tolerance & need for “drug holidays”;

Question 23

what is an example of receptor desensitization?

Answer 23

desensitization of B-adrenergic receptors due to downregulation (decreased receptor concentration - body downregulates receptors in response to drug, so more drug is required to get the same response in future)

Question 24

What can occur due to increased receptor concentration?

Answer 24

upregulation or sensitization (this is rare)

Question 25

modern molecular tools have resulted in the discovery of…

Answer 25

… many receptor subtypes, where only a single type was previously thought to exist

Question 26

Why do so many receptor subtypes occur?

Answer 26

TISSUE SPECIFICITY & SELECTIVITY - which allows the same endogenous signaling agent to act in different tissues

Question 27

our expanding knowledge of receptor subtypes is providing what?

Answer 27

new avenues of drug development

Question 28

What is an orphan receptor?

Answer 28

a receptor w/ no known endogenous ligand

Question 29

What is a classic example of an orphan receptor?

Answer 29

opioid receptors identified using morphine as agonist

Question 30

What is a newer example of an orphan receptor?

Answer 30

cannabinoid receptors identified using THC as agonist

Question 31

What do we now know about opioid and cannabinoid receptors?

Answer 31

that there are indeed endogenous opioids (ex: endorphins) that are involved in analgesia & euphoria, & endogenous cannabinoids that are involved in analgesia, sleep, & hunger

Question 32

Several other orphan receptors have been discovered and are what?

Answer 32

the focus of new pharmaceuticals