Drug receptor interactions

Question 1

Define pharmacokinetics and pharmacodynamics

Answer 1

Pharmacology is split into two divisions:

Pharmacokinetics
-the effect of the body on the drug (e.g. absorption,
distribution, metabolism, excretion)

Pharmacodynamics
-the effect of the drug on the body (responses produced,
mechanism of action

Question 2

Definition of a drug

Answer 2

a chemical substance that interacts with a biological system to
produce a physiological effect

Question 3

What are the 4 main drug target sites

Answer 3

There are FOUR main drug target sites:
•Receptors
•Ion Channels
•Transport Systems
•Enzymes
NOTE: these are ALL PROTEINS

Question 4

Receptors:

• where are they found? (+exception)
• what are they activated by?
• the receptors are defined as?
• how many types of receptors
• example

Answer 4

Proteins within cell membranes (usually
-exceptions = steroid receptors)
•Activated by neurotransmitters or hormones
•The receptors are defined by particular agonists and antagonists that interact
with a particular receptor type
•’Agonist’ and ‘Antagonist’ are specific to receptors
-you wouldn’t use it for the
other classes like enzymes
•There are FOUR
main families of receptors with different structures and
transduction systems
•Examples of drugs that target receptors:
oAtropine
-muscarinic cholinoceptor antagonist used as anaesthetic premedication to dry up secretions

Question 5

Ion channels

• what do they allow?
• what are the two types/
• give two examples

Answer 5

Ion Channels
•The lipid bilayer is impermeable to ions but within the membrane there are these selective pores
that allow the passage of ions in or out of the cell depending on the electrochemical gradient
•TWO types of ion channel:
oVoltage-sensitive
(e.g. VGSC)
oReceptor-linked (e.g. nicotinic acetylcholine receptor)
•Drugs can interact with the ion channels rather than with the receptors themselves
•Examples:
oLocal Anaesthetics
•Work by blocking voltage gated sodium channels in the sensory axons
Blocking these channels in sensory axons means that fewer action
potentials are propagated along those axons and so the perception of pain is reduced
oCalcium Channel Blockers
•Usually end in -dipine
•These block the voltage sensitive calcium channels

Question 6

Transport systems:

• what do they transport against
• they have what for certain species?
• examples

Answer 6

Transport Systems
•Systems of carriers that transport substances against their concentration
gradient e.g. glucose ions, neurotransmitters
•The transport systems show specificity for certain species
•Transport systems are NOT receptors
-they don’t mediate a response, all they
do is allow the NT to bind to a protein and then move it somewhere else
•Examples of transport systems:
oNa+/K+ pump
oNoradrenaline uptake 1
•Examples of drugs:
oTricyclic antidepressants (TCAs)
oCardiac Glycosides
-these are cardiac stimulant drugs e.g. digoxin
•Interact with the Na+/K+ pump
•If you give digoxin to a patient with heart failure, it will
slow down
their Na+/K+ pump and that has a knock on effect that
INCREASES
the intracellular calcium concentration
•This, in turn,
increases the force of contraction
•So, overall, digoxin increases the contractility of the heart

Question 7

What are the three ways in which a drug interacts with enzymes?

Answer 7

• enzyme inhibitors
• false substrates
• prodrugs

they are catalytic proteins that increase the rate of reactions

Question 8

How do enzyme inhibitors work?

Answer 8

Enzymes Inhibitors
•E.g.
anticholinesterases
-neostigmine
-increases the concentration
of acetylcholine in the synapse by decreasing the rate of breakdown of acetylcholine

Question 9

How do false substrates work?

Answer 9

False Substrates
•E.g.
Methyldopa
-antihypertensive
-works by subverting the
normal pathway that produces NA
•If you give a patient with hypertension some methyldopa then the
methyldopa will be taken up by the noradrenaline terminal and it’ll take the place of DOPA in the synthesis pathway so it’ll reduce the amount of DOPA being converted to dopamine
• Methyl noradrenaline is worse at causing vasoconstriction than NA so you get reduced TPR and hence reduced blood pressure
• This is a FALSE TRANSMITTER

Question 10

How do prodrugs work?

Answer 10

Prodrugs
•E.g.
chloral hydrate
-insomnia
-chloral hydrate needs to go to the liver and be metabolised into trichloroethanol
before it is effective
so technically chloral hydrate must interact with an enzyme system before it becomes useful

Question 11

what unwanted effects can you get with paracetamol?

Answer 11

Unwanted effects with enzymes:
oParacetamol
-if you take an overdose then you saturate the liver’s
microsomal enzymes so another set of enzymes (P450) starts breaking
down the paracetamol and the metabolites interact with the liver and
kidneys
oThere is a delay in onset, you may not experience the symptoms until 24
-48 hours after the overdose
oThis is also irreversible

Question 12

Non-specific drug action

-what are the few exceptions to the four target site rule

Answer 12

Non-Specific drug Action
•There are a few exceptions to the four target site rule
•Some drugs produce responses due to their physicochemical properties:
oGeneral Anaesthetics
-dampen synaptic transmission but they do not
interact with a specific transport system or receptor
oAntacids
-reduces the acidity of the stomach contents
-they are basic
and so can neutralise the stomach acid
oOsmotic Purgatives
-stimulate the voiding of gut contents
-osmotic purgatives draw water into the stomach contents and this softens the
stool and stimulates voiding

Question 13

What do plasma protein binding do?

Answer 13

Plasma Protein Binding
-drugs bind to plasma proteins but this does
NOT generate a response so it is not a drug target site
-it is just a reservoir of
the drug

Question 14

define agonist

Answer 14

a molecule that binds to a receptor and stimulates it to generate a
response (e.g. nicotine)

Question 15

define antagonist

Answer 15

substances that interact and bind to receptors but do NOT
produce a response
-they just get in the way of the agonist (e.g. atropine)
(inhibitory)

Question 16

define potency

Answer 16

how powerful the drug is
-depends on:
oAffinity-
how willingly the drug binds to its receptor
oEfficacy
-also called intrinsic activity
-the ability of a drug to
generate a response
once it has bound to the receptor
-usually involves some sort of
conformational change

Question 17

define full agonist

Answer 17

Full Agonist
-an agonist that generates the
maximal response

Question 18

define partial agonist

Answer 18

an agonist that generates less than the maximal response
•
NOTE: if you administer a partial agonist with a full agonist you will get an
effect similar to an
antagonist because the partial agonist interferes with the
ability of the full agonist to generate a response

Question 19

define selectivity

Answer 19

Selectivity
they have a preference for interacting with a particular receptor
type (receptors are
rarely specific
they normally interact with a few other
receptors)

Question 20

define structure-activity relationship

Answer 20

Structure-Activity Relationship
oEmphasises the relationship between the structure of the drug and its
activity
oPharmaceutical companies can take an agonist and make a small
structural change to make it an antagonist
oAnalogy
-lock and key
-key has a very specific structure

Question 21

How do full and partial agonist differ in they way they work?

Answer 21

Full Agonist
-reaches maximal tissue
response eventually as you increase the
agonist concentration
•Partial Agonist
-it can
NEVER
generate a
maximal response because it doesn't have
sufficient efficacy

Question 22

Explain what a log dose response curve looks like

Answer 22

Log Dose-Response Curve
•This is going up in powers of 10
•This is more useful for pharmacologists
because you can more easily see where
the maximal response is
•Full agonists with
lower affinity
will still
generate a maximal response but it will
need a much
higher concentration
•The partial agonist curve will peak before
it gets anywhere near the maximal tissue
response

Question 23

Antagonists have HIGH?

but NO?

Answer 23

•Antagonists
have AFFINITY
but NO EFFICACY

Question 24

What are the two types of receptor antagonists?

Answer 24

There
are TWO main types of antagonist:
oCompetitive
•Binds to the same site as the agonist on the receptor
•This means that their responses are
surmountable
•By increasing the concentration of the agonist you can overcome
the effect of the competitive antagonist
•This shifts the D-R curve to the RIGHT
•Examples:
atropine
-competitive muscarinic cholinoceptor
antagonist,
propanolol
-competitive beta blocker

oIrreversible
•If they do bind to the same site as the agonist they bind
more tightly with covalent forces and so they can’t be shifted
•Some irreversible antagonists may bind to a different site from the
agonist and this causes an
insurmountable antagonism
because it is not competing with the agonist
•Example:
hexamethonium
-irreversible nicotinic cholinoceptor
antagonist (it waits until the ion channel is open and then blocks the ion channel rather than just blocking a receptor)

Question 25

what are receptor reserves and why are they useful?

Answer 25

Spare receptors’
oIn some tissues, you don’t have to occupy 100% of the receptors to
generate a maximal response
In some tissues, as little as 1% of the receptor may have to be activated
to generate a maximal response
oThe advantage of this is that it increases the sensitivity
of the tissue to
the agonist and increases the speed of response

Question 26

effects of antagonists

Answer 26

Effect of Antagonists
•Competitive
-surmountable
-just means that
you need a higher concentration of the agonist
to generate a maximal response
•Irreversible
-the curve falls away and you wont be able to generate the maximal response
regardless of agonist concentration
oWe are essentially knocking out a load of
receptors so less response can be generated