Lecture 3- Pharmacodynamics

Question 1

What is pharmacodynamics

Answer 1

-Subfield of pharmacology
-The study of the biochemical effects of drugs and their mechanism of action

Question 2

Drugs do not produce unique biological effects- instead they

Answer 2

Modify the rate of ongoing cellular events

Question 3

Agonists are drugs that

Answer 3

-Cause a biological response
-Have intrinsic activity

Question 4

What do receptors mediate

Answer 4

-The effects of endogenous ligands
-Not the effects of drugs

Question 5

Drug receptor interactions usually involve which kind of bond

Answer 5

Non covalent- weak bonds

Question 6

Affinity:

Answer 6

Kd: Rate of dissociation

Question 7

Lower K values indicate

Answer 7

Low dissociation and high affinity

Question 8

What is intrinsic activity

Answer 8

Degree to which a ligand activates receptors

Question 9

Principles of Drug-Receptor interactions

Answer 9

-The magnitude of the drug effect is proportional to the number of receptors occupied
-Law of Mass Action

Question 10

What is Law of Mass Action

Answer 10

A drug produces maximal effect when all receptors are occupied

Question 11

After a certain point adding more drug

Answer 11

-Does not increase observed drug effect- ED 100
-May continue to increase other drug effects at other receptors

Question 12

ED 50

Answer 12

-Effective dose
-Dose that produces response in 50% of subjects

Question 13

TD 50

Answer 13

-Toxic dose
-Dose that produces a given toxic effect in 50% of subjects

Question 14

LD 50

Answer 14

-Lethal Dose
-Dose that kills 50% of subjects

Question 15

Therapeutic index equation

Answer 15

TI = TD50 / ED50

Question 16

Safety margin equation

Answer 16

Safety margin = LD50 - ED50

Question 17

What are two main characteristics of agonists

Answer 17

-Potency (How much drug is needed to produce an effect)
-Efficacy (Maximum effect)

Question 18

More potent means

Answer 18

They reach 100% elevation of pain threshold at a lower dose than other drugs

Question 19

Affinity is the inverse of

Answer 19

Dissociation

Question 20

Affinity does not determine

Answer 20

The maximum possible effect because at high doses lots of drug molecules are available to take the place of dissociated ones

Question 21

Why do some drugs have higher efficacy than others

Answer 21

-They may act by different mechanisms at different receptors
-They may have more or less intrinsic activity at the same receptor, once bound

Question 22

Antagonists produce their effect by

Answer 22

Blocking the action of an antagonist or an endogenous ligand at the same receptor

Question 23

How do competitive antagonists affect the dose response curve

Answer 23

Shifts the dose response curve to the right

Question 24

Competitive antagonist effect can be overcome by

Answer 24

Increasing the dose of agonist

Question 25

Competitive antagonists bind to

Answer 25

Same receptor site as agonist and competes for available binding sites

Question 26

How do Non-competitive antagonists affect the dose effect curve

Answer 26

Shift the curve to the right and change it’s shape by reducing the maximum effect

Question 27

Non competitive antagonists can NOT be overcome by

Answer 27

Increasing the dose of the agonist as there is a decrease in maximum effect

Question 28

Non competitive antagonists make receptors

Answer 28

Unavailable for drug action

Question 29

What are the effects of alpha bungarotoxin

Answer 29

-Irreversible binding to acetylcholine receptor -Paralysis -Respiratory failure

Question 30

Irreversible antagonists form

Answer 30

Long lasting bond

Question 31

Recovery after irreversible antagonists

Answer 31

Synthesis of new receptors

Question 32

Partial agonists have what effects

Answer 32

Intermediate levels of intrinsic activity at a receptor compared to a full agonist

Question 33

What do partial agonists do in the presence of a full agonist

Answer 33

-Antagonise -Can act as a competitive antagonists by competing for binding sites

Question 34

Partial agonists intrinsic activity can cause

Answer 34

Ceiling effect as the have lower intrinsic activity

Question 35

Inverse agonist affect the does-effect curve how

Answer 35

Produce a descending dose effect curve

Question 36

Inverse agonists produce

Answer 36

-An effect opposite to that of the endogenous ligand or one produced by an agonist

Question 37

How are inverse agonists possible

Answer 37

Some receptors have substantial endogenous activity even when ligands are not bound

Question 38

What is tolerance

Answer 38

Drug effect gets smaller

Question 39

What effect does tolerance have on the margin of safety

Answer 39

Reduces margin of safety as desired effect requires a higher dose which is closer to lethal dose

Question 40

Types of tolerance

Answer 40

-Acute tolerance -Protracted tolerance -Cross-tolerance

Question 41

What is acute tolerance

Answer 41

Drug effect decreases rapidly within a single session

Question 42

What is protracted tolerance

Answer 42

Drug effect decreases with repeated administration

Question 43

What is cross tolerance

Answer 43

Drug effect decreases with repeated administration of another drug

Question 44

In many cases tolerance reflects

Answer 44

Homeostatic adaptations of the body, trying to return to normal despite presence of the drug

Question 45

What is pharmacokinetic tolerance

Answer 45

Changes can be be pharmacokinetic/metabolic such as enzyme induction

Question 46

What is pharmacodynamic tolerance

Answer 46

-Changes occur to receptors and their corresponding signalling pathways -E.g receptors may have fewer in number or change intracellular location

Question 47

Behavioural tolerance

Answer 47

Learning factors can influence such as setting

Question 48

What is sensitisation

Answer 48

If a drug effect gets bigger

Question 49

Examples of cross sensitisation

Answer 49

-Cocaine and amphetamine -Stress can lead to drug sensitivity

Question 50

Sensitisation and tolerance is not to a

Answer 50

Drug but to a drug effect

Question 51

Withdrawal symptoms are typically

Answer 51

Opposite to the acute effects of the drug

Question 52

While tolerance is reversible, withdrawal symptoms are

Answer 52

Transient

Question 53

Tolerance and withdrawal are not necessary for

Answer 53

Addiction