Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Foundation > Pharmacodynamics 1 > Flashcards

Pharmacodynamics 1 Flashcards

1
Q

Identify molecular targets for drug action

A

receptors, ion channels, enzymes and transporters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Drug interactions with target depend on two factors:

A
  1. Shape - this determines the ability of the drug to bind - ‘lock and key’ mechanism
  2. Charge distribution - this determines the type of bonds that holds the drug to the target

weakest ——–> strongest

van der Waals forces < hydrogen bonds < ionic interactions < covalent bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Define the terms agonist, antagonist and partial agonist

A 
Agonist
A ligand (a drug or an endogenous molecule e.g. neurotransmitter, hormone) that binds to a receptor to elicit a cellular response.

Antagonist
A drug which binds to a receptor and inhibits the receptor from responding to the endogenous ligand.

Partial agonist
Cannot evoke maximum response the system is capable of producing, even when occupying all the available receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Define the terms affinity, efficacy and potency

A

Affinity describes the strength with which a ligand binds to a receptor. A high affinity drug has a much greater tendency to bind to the receptor relative to its dissociation from the receptor
Kd = equilibrium dissociation constant = measure of affinity

Efficacy
= Emax = the maximum effect
the drug can elicit)

Potency = the concentration of drug needed to produce an effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Pharmacodynamics is

A

the effect of a drug on the body

  1. Mechanism of action of drugs
    - Targets for drug action
    - How drugs act at the target
    - How the drug produces an action within a cell
  2. Influence of drug concentration on the magnitude of response
    - Graphical representation of concentration-effect relationships
    - Therapeutic versus toxic effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Example of an agonist

A

e.g. epinephrine/adrenaline acts as an agonist at the β1 adrenoreceptor in the heart to increase cardiac output.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Example of an antagonist

A

e.g. bisoprolol acts as an antagonist at the β1 adrenoreceptor in the heart to decrease cardiac output

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Receptors within a given family generally occur in several molecular varieties (subtypes)

They have similar structure but significant differences in their sequences, and often in their pharmacological properties

Identified either:

  • On the basis of selectivity of agonists and/or antagonists
  • Or by cloning techniques

explain the different receptor subtypes for adrenoceptors

A

a1 =
ag epin
anta doxazosin

b1 =
ag epin
anta bisoprolol

b2 =
ag salbutamol
anta = propranolol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Receptors in a family may occur in different subtypes - similar structure but differences in their sequences, and in pharmacological properties.

Identified either:

  • On the basis of selectivity of agonists and/or antagonists
  • Or by cloning techniques

explain the different receptor subtypes for adrenoceptors

A

a1 =
ag epin
anta doxazosin

b1 =
ag epin
anta bisoprolol

b2 =
ag salbutamol
anta = propranolol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Receptors subtypes elicit many different cellular effects due to:

A
  1. different specificities for what activates or inhibits them and
  2. different signal transduction mechanisms
  • Receptor with bound agonist is activated
  • The activated receptor has altered physical and chemical properties
  • This leads to changes within the cell to cause a biological response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Based on different molecular structure and signal transduction mechanisms, 4 receptor types which respond to drugs: LEGI

A
  • Ligand gated ion channels
  • G-protein coupled receptors
  • Enzyme (kinase) linked receptors
  • Intracellular receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Based on different molecular structure and signal transduction mechanisms, 4 receptor types which respond to drugs: LEGI

A
  • Ligand gated ion channels
  • G-protein coupled receptors
  • Enzyme (kinase) linked receptors
  • Intracellular receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Ligand gated ion channels = ionotropic receptors

work by :

A

ligand binds to the receptor, and a channel nearby opens up to allow ions in.
then it may cause
hyperpolarisation
or depolarisation of the cell, and then cellular effects.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

G-protein coupled receptors = metabotropic

work by :

A

GPCR’s have 7 transmembrane alpha helices, with a binding site.

interact with g proteins. all g proteins have 3 subunits. alpha beta and gamma. Specificity of response is achieved through molecular variation in α subunits -
α subunits variation gives rise to 3 main families of G-protein
Galpha-s, Galpha-i, Gq

alpha and gamma are attached by lipid anchors to the CSM.

inactive protein means it binds GDP to alpha subunit.

when ligand binds –> conformational change.
when it is activated Gs protein releases GDP and binds GTP.

alpha subunit of Gs protein dissociates and regulates target proteins/activates adenylylcyclase –> catalyze formation of cAMP from ATP. cAMP is a second messenger.

target protein can relay a signal.

when hormone or drug is no longer present the receptor reverts to its resting state. GTP on alpha subunit is hydrolyzed to GDP, and adenylyl cylase is deactivated

eg adrenoceptors are types of GPCRs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Explain how in G-protein signal transduction there are different alpha subunit variations in the G protein which give different responses:

A

Galpha-s = stimulatory
Activates adenylyl cyclase Activates Ca2+ channels

Galpha-i =
inhibitory
Inhibits adenylyl cyclase
Activates K+ channels

Gq =
Activates phospholipase C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

eg adrenoceptors are GPCR - explain mechanism

A

alpha 1 - Gq - activates PLC - vasoconstriction

alpha 2 - Gi - Inhibit
adenylyl cyclase
- Auto-inhibition of neurotransmitter release

beta 1 and 2 - Gs - Stimulate adenylyl cyclase - b1 Accelerated heart rate
- b2 Bronchodilation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

___________ is a b2 receptor agonist

A

SALBUTAMOL

18
Q

___________ is a b1

receptor antagonist

A

Bisoprolol

19
Q

enzyme linked receptors

work by :

A

extrcellular site can bind ligand. intracellular part can be an enzyme. eg receptor tyrosine kinases. protein phosphorylation –> gene transcription –> protein synthesis –> cellular effect

20
Q

intracellular receptors

work by :

A

receptor in the nucleus. ligand enters and binds to the receptor. affects gene transcription. protein synthesis. cellular effects.

21
Q

Dr A knelt on a bee and was stung on the knee. She took ibuprofen tablets to counteract the pain and inflammation of the sting. What type of target protein is the ibuprofen acting on?

Receptor
Enzyme
Ion channel
Transporter

A

B

22
Q

What dose of aspirin is required to relieve a headache?

25-50mg
300-600mg
5-10g

A

B

23
Q

Drug dose and response pathway:

A

agonist –> receptor –> agonist receptor complex –> action –> effect.

eg. salbutamol –> binds to adrenoceptor b2 –> salbutamol-b2 adrenoceptor complex –> increased cAMP –> bronchodilation

24
Q

Graded dose response curves help to measure ____________

A

dose-response relationships .

The response of a particular system (individual patient, animal or isolated tissue) measured against agonist concentration

e.g. increasing bronchodilation in a rabbit trachea preparation in response to increasing doses of salbutamol

25
Q

Graded dose-response curve

are plotted a ______________

A

Concentration-effect curve : agonist concentration (log scale) VS maximal effect %

Semi-logarithmic plot of agonist concentration against effect/response

26
Q

Graded dose-response curve - log axis used is base ________

A

Base 10 logarithms (log10) are used for dose response curves

 There is a 10 fold increase from one unit to the next

27
Q

Why plot dose response curves?

A

To determine EFFICACY - Emax

POTENCY - EC50

28
Q

Efficacy is -

A

the maximum effect

the drug can elicit

29
Q

Potency is -

A

the concentration of drug needed to produce an effect

Potency – measure of the end effect, not just receptor binding

Although binding can be measured directly, it is usually a biological response, such as a rise in blood pressure, contraction or relaxation of a strip of smooth muscle in an organ bath, the activation of an enzyme, or a behavioural response, that we are interested in, and this is often plotted as aconcentration-effect curve(in vitro) or dose-response curve(in vivo)

30
Q

Affinity is -

A

the strength with which a ligand binds to a receptor

A high affinity drug has a much greater tendency to bind to the receptor relative to its dissociation from the receptor.

31
Q

Affinity is measured by Kd. explain Kd.

A

Kd = equilibrium dissociation constant. it is the concentration of ligand at which 50% of the available receptors are occupied

Kd is an intrinsic property of any drug-receptor pair

There is an inverse relationship between Kd and affinity

32
Q

The ________ the Kd value the more easily the agonist binds to the receptor = greater affinity.

A

lower

the lower the Kd value (on concentration/x axis) the greater the affinity

33
Q

The effect an agonist produces depends on: 1. the drug binding
2. the drug-bound receptor then producing a biological response.

It is measured by ___________

A

EC50 = concentration of ligand which produces 50% of the maximal biological effect of that system

EC50 is a measure of potency (based on the actual effect, not just the binding).

34
Q

Potency is the __________ of a drug that is needed to produce a given effect

A

AMOUNT

35
Q

**Potency depends on 4 factors:

Potency = amount of drug needed to produce a desired effect.

A

Potency dependent on:
1. Affinity = strength of binding = Kd

  1. Efficacy = activation = Emax, Ec50(=potency), full/partial agonist
  2. The number of receptors
  3. Efficiency of stimulus-response mechanisms used.
36
Q

**Potency depends on 4 factors:

Potency = amount of drug needed to produce a desired effect.

A

Potency dependent on:
1. Affinity = strength of binding = Kd

  1. Efficacy = activation = Emax, Ec50(=potency), agonist/antagonist
  2. The number of receptors
  3. Efficiency of stimulus-response mechanisms used.
37
Q

General rules

A

Agonists with high potency tend to have high affinity

The lower the Kd value the greater the affinity

The lower the EC50 value the greater the potency.

38
Q

Efficacy is __________.

how does it work? explain the agonist-receptor complex and its 2 states.

A

Refers to the maximum effect an agonist can produce regardless of dose

When an agonist binds to a receptor, this induces a conformational change that sets off a chain of biochemical events - an ‘action’.

The agonist-receptor complex can exist in 2 states:

  1. AR = unactivated AR complex (no conformational change)
  2. AR* = activated receptor (i.e. has undergone conformational change)
39
Q

OCCUPATION d/b AFFINITY

ACTIVATION d/b EFFICACY

A

-

40
Q

There are two types of agonist, d/o EFFICACY

A
  1. Full agonist
    • AR* very likely
      (high efficacy)
      Can produce a maximum response while occupying only a small % of receptors available
  2. Partial agonist
    – AR* less likely

Cannot evoke maximum response the system is capable of producing, even when occupying all the available receptors

41
Q

SUMMARY

A

The shape of the drug/receptor is a major determinant of interaction

There are four main targets of drug action
Receptors
Ion channels
Enzymes
Carriers

The four major receptor subtypes are:

  1. Ligand gated ion channel
  2. G-protein
  3. Enzyme linked receptor
  4. Intracellular receptor

The affinity of an agonist is the likelihood that it will bind to and form a stable complex with the receptor

Potency of different agonists can be compared by assessing the EC50 values – the lower the EC50 value the higher the potency

Efficacy describes the ability of an agonist, once bound, to activate the receptor

Full agonists have high efficacy and can produce a maximal response in the system

Partial agonists have lower efficacy and can not produce a maximal response in the system

Foundation (26 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions