Pharmacodynamics

Question 1

Pharmacodynamics

Answer 1

-What the drug does to the body

Question 2

Importance of pharmacodynamics

Answer 2

-provides the basis for therapeutic use of a drug and design of new and superior drugs

Question 3

Receptors strict and broad definition

Answer 3

Strict definition: proteins that normally serve as receptors for endogenous ligands (eg. hormones, NTs, growth factors, cytokines)

Broad definition: any cellular constituent (enzymes, cell membranes, transport proteins, structural proteins, DNA, RNA)

Question 4

Agonists

Answer 4

-drugs that bind to receptors and mimic the effect of the endogenous ligand

Question 5

Antagonists

Answer 5

drugs that bind to receptors and produce no response (inhibit the effect of endogenous ligand)

**can be competitive or non competitive

Question 6

Partial agonists

Answer 6

drugs that bind to receptors and produce a lesser effect than the endogenous ligand

Question 7

Classical receptor theory

Answer 7

The reversible interaction between a drug and receptor following the law of mass action:

concentration of Drug + concentration of receptors <–> (concentration of activated drug-receptor complexes) leading to an effect

Question 8

Dose-response relationships

Answer 8

-used primarily to compare drug potencies and efficacies and to determine drug safety

-can be used to determine toxic doses (TD) or lethal doses (LD)

Question 9

Types of dose-response relationships

Answer 9

1. Graded
2. Quantal

Question 10

Graded dose-response relationships

Answer 10

-shows intensity of responses of individuals = compares potency and efficacy

-continuous

-provides information about the intensity of response

Question 11

Graded response graphs

Answer 11

• y axis is usually percent response from 0-100%
  -x axis= log drug dose

Question 12

Quantal dose-response relationships

Answer 12

-shows population responses
-all or none response
-provides info about the number of patients exhibiting a specified effect over a dose range

Question 13

Quantal response graphs

Answer 13

-y-axis is usually percentage of individuals responding from 0-100%
-x axis= dose (mg)

-used mainly to determine drug safety

Question 14

Potency vs. efficacy

Answer 14

Potency: the strength of the drug. More potent drug will take less to get a desired response
“shift from left to right”

Efficacy: the max effect that a drug can reach. More effective drug higher on graph
“shift up and down”

Question 15

EC or ED50

Answer 15

concentration or dose causing a 50% max response

**can also be altered to be another number eg. ED1, ED99 etc.

Question 16

Therapeutic index (TI)

Answer 16

TI= TD50/ED50

Ratio of dose that kills the animal to the dose that causes desired effect

Question 17

Margin of safety

Answer 17

Margin of safety= TD1/ED99

The ratio of drug dose that causes toxicity/death in 1% of population compared to drug dose causing therapeutic effect in 99% of population

**more conservative number (smaller)

Question 18

ED vs TD vs LD

Answer 18

ED:effective dose

TD:toxic dose

LD: lethal dose

Question 19

Dynamic nature of receptors

Answer 19

-receptors can be desensitized upon continuous exposure to drug (drug tolerance and need for “drug holidays” = addiction (eg. opioid- need more and more to get same high)

**includes downregulation (from increased exposure) or upregulation/sensitization (from increased receptor concentration) of receptors

Question 20

Significance of receptor subtypes

Answer 20

There are many receptor subtypes. Due to tissue specificity and selectivity which allows for the same endogenous signalling agent to act on different tissues and cause different responses

ex. alpha and beta adrenergic receptors binding NE- will have different results depending on where it binds

Question 21

Orphan receptors

Answer 21

A receptor with no known endogenous ligand. Many of them have been identified and are being studied

ex. opioid receptors using morphine as agonist
>now we know that endogenous opiods are involved in analgesia and euphoria

ex. Cannabinoid receptors identified using THC as agonist
>now we known that endogenous cannabinoids are involved in analgesia, sleep, hunger

Question 22

Signal transduction pathways

Answer 22

1. involved in phosphorylation of proteins, often causing activation of enzymes

2.influence gene expression (mRNA production)

Question 23

Major receptors involved in signal transduction pathways

Answer 23

-receptors as enzymes
-multisubunit ligand-gated ion channels
-G-protein coupled receptor systems
-nuclear receptors vs cytosolic receptors = regulation of transcription