Pharmacodynamics

Question 1

What is pharmacodynamics?

Answer 1

Pharmacodynamics involves the understanding of how drugs interact with the body, exploring the biochemical and physiological effects of drugs and their mechanisms of action

Question 2

Define affinity

Answer 2

Strength of the interaction between a drug and its molecular target

Binding affinity is measured by equilibrium inhibition constant (Ki); lower Ki, higher the binding affinity

Question 3

The site at which a drug binds is called a MOLECULAR TARGET.

What are the 4 molecular targets?

Answer 3

-Receptors
-Enzymes
-Ion Channels
-Transporters

New therapeutics may have different targets such as DNA (cancer, anti-microbial)

Question 4

What is an agonist?

Answer 4

An agonist binds to the receptor and produces a biological response

Question 5

What is an antagonist?

Answer 5

An antagonist binds to the receptor without eliciting a response

Question 6

What is an allosteric antagonist?

Answer 6

Allosteric antagonists modulate the affinity and/or efficacy of agonists for receptors.

Question 7

What is an allosteric site?

Answer 7

Sites different from the active site of an enzyme where a molecule can bind and change the shape of the active site is called allosteric site.

Question 8

What is competitive antagonism?

Answer 8

Binding of the antagonist to the receptor prevents binding of the agonist to the receptor

Question 9

What is an example of competitive antagonism?

Answer 9

Naloxone and Opioids (morphine, fentanyl, heroin)

Naloxone has a lower Ki = higher binding affinity than opiods

Question 10

What is non-competitive antagonism?

Answer 10

Agonist and antagonist can be bound
simultaneously (so they are not competing for the receptor), but
antagonist binding reduces or prevents the action of the agonist

Question 11

What is reversible competitive antagonism?

Answer 11

agonist and antagonist form
short-lasting bonds with the receptor, and a steady state among
agonist, antagonist, and receptor is reached. Such antagonism can be
overcome by increasing the concentration of the agonist

Question 12

FACT

Answer 12

Receptors have several downstream targets

Question 13

Efficacy vs potency definitions

Answer 13

Efficacy: the maximum
effect that a given drug
will produce, regardless
of drug concentration

Potency: the amount of
a given drug that is
required to produce a
given effect

*see diagram

Question 14

What pathway do adrenoceptors work on sympathetic or parasympathetic?

Answer 14

sympathetic = fight or flight

Question 15

Example of adrenoceptor agonist

Answer 15

Endogenous catecholamines

• Noradrenaline
  -Adrenaline
  -Dopamine

Question 16

Which receptors does adrenaline work on?

Answer 16

Adrenoceptors: A1, A2, B1 and B2

Question 17

What does A1 affect?

Answer 17

-Arterial vasoconstriction
-Vascular smooth muscle contraction
-Pupil Dilation
- Gluconeogenesis

Question 18

What does A2 affect?

Answer 18

-Pre-synaptic inhibition of NA (sodium)

Question 19

What does B1 affect?

Answer 19

-Increase HR
-Increase force cardiac contraction
-Increase Renin

Question 20

What does B1 affect?

Answer 20

• Bronchodilation

Question 21

Give an example of a paramedic drug which is an agonist to B2

Answer 21

Salbutamol

Question 22

What is selectivity

Answer 22

the number of molecular targets the drug interacts with

Question 23

what is specificity

Answer 23

the ability of a drug to produce its action at specific site

Question 24

What pathway do cholinergic receptors work on sympathetic or parasympathetic?

Answer 24

Parasympathetic = rest and digest

Question 25

What are the 5 subtypes of cholinergic receptors?

Answer 25

M1 – Increase gastric acid secretion and
motility
M2 – Decrease heart rate and force of
contraction
M3 – Increase saliva and sweat, bronchi
contraction and secretion
M4 – Constriction of pupils
N – Skeletal muscle contraction

Question 26

Describe enzymes and their role

Answer 26

Enzymes are biological catalysts that control chemical reactions

They are a molecular drug target, involved in almost every physiological process

Substrate - gets broken down by enzyme = product

Question 27

What is an example of a drug which inhibits enzyme activity?

Answer 27

Aspirin

*see notes for more details

Question 28

Describe transporters and their role

Answer 28

They are drug molecular targets

Transporters (membrane transport/carrier proteins) are specialized membrane-spanning proteins that assist in the movement of ions, peptides, small molecules e.g DRUGS

Question 29

Why do we need transporters?

Answer 29

Small molecules and ions are often too polar (i.e. lack sufficient lipid solubility) to enable them to passively diffuse across lipid membranes

Transporters facilitate diffusion or active transport across membranes

Question 30

Example of a drug which alters transporters normal function

Answer 30

Furosemide

*see voice recording for further details

Question 31

What are ion channels?

Answer 31

Drug molecular targets

Ion channels are pore-forming protein complexes, that are embedded in the cell membrane

Question 32

what do ion channels do?

Answer 32

control ion movement in and out of cell maintaining:

-Nerve impulse
-Muscle contraction/relaxation
-Neurotransmitter release
-Hormone secretion
-Sensory transduction
-Blood pressure control

Question 33

what is an example of an ion channel

Answer 33

Sodium channel

Example of drug associated with sodium channel is opioids which block these ion channels

Question 34

Antiarrhthmics block sodium ion channels, what class are antiarrhythmics as per VW classification

Answer 34

Class I: Sodium channel (ion channel)
eg. flecainide, amiodarone