L7 Intro to drug action

Question 1

Describe a receptor

Answer 1

Receptors are specific, complex proteins. Hormones act only on target cells

Question 2

What is pharmacology?

Answer 2

the study of the effects of drugs on the function of living systems

Question 3

Drug Effects Result From Interaction Between ___ And (components of) the ____

Answer 3

Drug
Organism

Question 4

Pharmacokinetics describes the fate of a drug

Answer 4

ADME
What the body does to the drug

Question 5

Pharmacodynamics is the study and measurement of drug effects

Answer 5

What drug does to body

Question 6

Fundamental concepts in drug action (FCDA)
A drug will not work unless it is ____

Answer 6

A drug will not work unless it is bound

Question 7

4 protein targets

Answer 7

1. Receptors
2. Enzymes
3. Carrier molecules
4. Ion channels

Question 8

Receptors as protein targets

Answer 8

• Proteins that allow a chemical agent (drugs,
  hormones, neurotransmitters) to initiate a change
  in cell function
• Receptors are the cell’s ‘sensing elements’
• Receptors provide molecular communication between chemical agent and transduction process

Question 9

(FCDA) Most drugs cause their effects via ___

Answer 9

Most drugs cause their effects via receptors

Question 10

(FCDA) Different cell types have different___ ____

Answer 10

Different cell types have different receptor profiles

Question 11

Acetylcholine example

Answer 11

High densities of muscarinic acetylcholine receptors respond to substances that act on muscarinic acetylcholine receptors

Question 12

Noradrenaline

Answer 12

High densities of alpha-adrenoceptors respond to substances that act on alpha-adrenoceptors e.g., noradrenaline

On vascular smooth cells to cause them to contract

Question 13

Different cell types express different types and ___ of receptor. This determines the___ and___ to which the cell responds

Answer 13

densities
hormones
neurotransmitters

Question 14

FDCA: Drugs can mimic or ____ the actions of___ substances

Answer 14

Block
endogenous

Question 15

Agonist and antagonist are

Answer 15

ligands

Question 16

Ligand

Answer 16

Any molecule that bonds specifically to a receptor site of another molecule.

Question 17

Agonist and antagonist interact with endogeneous ligands how

Answer 17

Agonist mimic the action of ligand
Antagonist block action of ligand

Question 18

FDCA: “Receptors show ligand____”

Answer 18

selectivity

Question 19

Receptor ligand selectivity

Answer 19

• Each receptor type is activated by a small number of substances
• Receptor activation requires a good 3-D “fit” between agonist and receptor
  (paracetamol doesn’t fit a vascular smooth muscle cell but phenylephrine does)
  – each drug activates a certain receptor type

Question 20

endogenous ligand/agonist (noradrenaline) binds to receptor (alpha-adrenoceptor) causing a change in cell function (vascular smooth muscle cell contracts). What if there is an antagonist

Answer 20

Will block the binding of the ligand to receptor

Question 21

FCDA: ___ drugs show selectivity

Answer 21

Useful

Question 22

Selectivity is reciprocal - what does that mean

Answer 22

– each drug only binds to certain receptors
– each receptor recognises only certain drugs

Question 23

Phenylephrine

Answer 23

– binds to a-adrenoceptors in vascular smooth muscle cells – relieves nasal congestion
– binds only weakly to other receptor types
- fewer adverse effects

Question 24

cardiac cell:
adrenaline → b-adrenoceptor → increased___

Answer 24

contractility

Question 25

How most drugs cause their effects via receptors

Answer 25

Chemical agent → receptor → (in cell) signal transduction → change in cell functions

Question 26

FDCA:___ is not absolute

Answer 26

Selectivity

Question 27

Selectivity is not absolute means

Answer 27

- Most drugs act on more than one receptor - Increasing dose activates other receptors --– adverse effects

Question 28

Diphenhydramine

Answer 28

Antagonist and prevents histamine binding - can act on more than 1 receptor

Question 29

Diphenhydramine in vascular smooth muscle cells

Answer 29

Antagonist and prevents histamine binding decongestant

Question 30

Diphenhydramine in salivary gland cell

Answer 30

antagonist of muscarinic acetylcholine receptors dry mouth

Question 31

Drug-induced responses

Answer 31

- Drugs act by binding to specific drug targets - Agonists bind to and activate receptors

Question 32

FDCA: “Agonist or antagonist (?) bind to and activate receptors”

Answer 32

Agonist activate

Question 33

Transducers

Answer 33

the portion of a sensory neuron that is responsible for converting a sensory stimulus into an electrical signal

Question 34

Agonist binding to receptors

Answer 34

- need intermolecular forces between agonist and receptors - Reversible Strong attraction forces (k+1 > k-1) → high affinity for receptor Week attraction forces (k+1 < k-1) → low affinity for receptor

Question 35

Agonist activating receptors

Answer 35

- Bound agonist induces a conformational change in the structure of the receptor → it binds to and stimulates transducers - Bound agonist induces high degree of receptor activation → agonist has *high* efficacy - Bound agonist induces low degree of receptor activation → agonist has *low* efficacy

Question 36

Agonist affinity and efficacy

Answer 36

Ability of an agonist to induce a response depends on two agonist- dependent, graded properties - affinity and efficacy

Question 37

Ability of an agonist to induce a response depends on

Answer 37

two - agonist- dependent, - graded properties

Question 38

Affinity

Answer 38

Tendency of agonist to bind to receptors

Question 39

Efficacy

Answer 39

Ability of agonist receptor complex to initiate a change in cell function

Question 40

Agonist-induced response example asthma

Answer 40

Asthmatic takes salbutamol – relaxes airway smooth muscle – eases breathing Salbutamol + beta 2 adrenoceptor + adenylate cyclase → relaxation of air way smooth muscle AC is tranducer

Question 41

FDCA: Drug dose is related to___ occupancy and effect

Answer 41

receptor

Question 42

Positive relationship between drug dose and

Answer 42

– number of receptors occupied – effect produced

Question 43

With increasing concentrations of the agonist

Answer 43

– more receptors are bound and activated – response is increased

Question 44

Organ bath

Answer 44

a chamber in which isolated organs or tissues can be administered with drugs, or stimulated electrically, in order to measure their function

Question 45

Concentration-response curves has

Answer 45

* Measure size of response at each agonist concentration Plot concentration-response data as Log dose (x-axis) vs Response (y-axis) – log-linear or semi-log graph – sigmoidal shape, exhibits saturation, maximum effect is Emax

Question 46

Agonist potency

Answer 46

- Concentration required to produce 50% of maximal agonist response (EC50) - The lower the EC50, the more potent the agonist - Potency depends on affinity and efficacy and tissue-dependent parameters (e.g., receptor density)

Question 47

EC50

Answer 47

Concentration of drug that produces 50% of maximal response

Question 48

ED50

Answer 48

The effective dose of a chemical that causes 50 percent of the individuals in a dose-response study to display a harmful, but nonlethal, effect

Question 49

Partial agonists

Answer 49

- Partial agonists produce submaximal responses – low efficacy – low level activation a drug that binds to a receptor and causes a response that is less than that caused by a full agonist

Question 50

Agonists with low efficacy

Answer 50

An agonist with low efficacy may act as a – partial agonist - partial agonist causes < maximum response Antagonist - tissue exposed to both low and high efficacy agonists - competition for receptor - full agonist binding inhibited

Question 51

Receptor antagonists 1. afinity and efficacy 2. what do they do

Answer 51

Antagonists bind to, but do not activate receptors – have affinity, but no efficacy - Since antagonists bind to the receptor, they compete with the agonist for the receptor - Antagonists inhibit agonist-induced responses

Question 52

Surmountable antagonists

Answer 52

- Bind reversibly to the receptor - Agonist concentration-response curves shifted -– no change in slope or maximum response - Size of the shift is proportional to the -– antagonist concentration -– affinity of the antagonist

Question 53

Insurmountable antagonists

Answer 53

- Bind irreversibly to the receptor -– reduces number of receptors the agonist can occupy - Reduce the maximum response and slope of agonist concentration-response curve - The higher the antagonist concentration, the larger the response