3. Drug-Receptor Interactions

Question 1

What is the difference between pharmokinetics and pharmacodynamics?

Answer 1

• Pharmokinetics - effect of the body on the drug i.e. absorption, metabolism etc.
• Pharmacodynamics - effect of drug on body i.e. responses, mechanism of action

Question 2

What are the 4 main drug target sites?

Answer 2

• Receptors
• Ion channels
• Transport systems
• Enzymes

Question 3

Summarise receptors as a drug target site

Answer 3

• Proteins within cell membranes
• Activated by neurotransmitters or hormones
• Receptors are defined by particular agonists/antagonists that interact with them

Question 4

What is atropine?

Answer 4

• Muscarinic cholinoreceptor antagonist

* Anaesthetic premedication to dry up secretions

Question 5

Summarise ion channels as a drug target site

Answer 5

• Selective pores
• Allow the passage of ions depending on the electrochemical gradient (as they can’t pass through bilayer)
• 2 types: voltage-sensitive and receptor-linked (ligand gated)

Question 6

Give 2 examples of drugs that interact with ion channels and describe how

Answer 6

Local anaesthetics
• usually end in -caine
• block VG sodium channels in sensory axons
• Fewer action potentials - perception of pain reduced

Calcium Channel Blockers
• usually end in -dipine
• "clean drugs" - very few side effects
• Block VGCCs
• help treat angina, arrhythmias and hypertension

Question 7

What is a transport system?

Answer 7

• System of carriers that transport substances across their conc. grad
• Specific
• Not receptors
• Don’t mediate a response - just allow the NT to bind to a protein and move somewhere else

Question 8

Give 2 examples of drugs that interact with transport systems and describe how

Answer 8

Tricyclic antidepressants (TCAs)
• Disrupt NA uptake 1
• Prolong NA effect in synaptic cleft
• Improves clinical depression (as this works sub-optimally in a depressed person)

Cardiac Glycosides
• Cardiac stimulant drugs e.g. digoxin
• Interact with the Na+/K+ pump
• If you give digoxin to someone with heart failure - slows down the pump => increases intracellular [Ca2+] => increases force of contraction

Question 9

What are the 3 ways in which drugs interact with enzymes, giving an example of each

Answer 9

• Enzyme inhibitors
- e.g. anticholinesterases (e.g. neostigmine)
- decreases rate of breakdown of ACh
- increases [ACh] in synapse
• False substrates
- e.g. methyldopa - antihypertensive
- methyldopa taken up by NA terminal => replaces DOPA in synthesis pathway => less DOPA converted to dopamine
- methyl NA produced is worse at causing vasoconstriction
• Prodrugs
- e.g. chloral hydrate - insomnia
- metabolised into trichloroethanol in the liver before effective
- therefore only useful after interacting with an enzyme system

Question 10

How does an overdose of paracetamol damage the liver?

Answer 10

• Saturated microsomal enzymes
• P450 breaks down paracetamol instead
• Metabolites of this interact with liver and kidneys causing damage
• Delay onset (symptoms may appear 24-48 hours after)
• Irreversible
• Antidote can be used within 12 hours to soak up metabolites, preventing damage

Question 11

Give 3 examples of drugs that do not follow the four target site rule, following a non-specific action

Answer 11

• General anaesthetics - dampen synaptic transmission, no interaction with specific targets
• Anatacids - reduces acidity of stomach contents e.g. aluminium or magnesium hydroxide
• Osmotic purgatives - stimulate the voiding of gut contents by drawing water in (also softens the stool)

Question 12

What is an antagonist?

Answer 12

Substance that binds to a receptor but does not produce a response (therefore it’s just in the way)

Question 13

What is potency and what does it depend on?

Answer 13

• How powerful the drug is
• Depends on:
- affinity: how willingly the drug binds to its receptor
- efficacy (intrinsic activity): ability of drug to generate a response once bound to the receptor (involves some sort of conformational change)

Question 14

What is a full and partial agonist?

Answer 14

• Full - agonist that can generates the maximal response when concentration is increased
• Partial - agonist that generates less than maximal response and can never generate a maximum response due to insufficient efficacy

Question 15

What happens if you administer a partial agonist with a full agonist?

Answer 15

• Effect similar to antagonist

* Partial agonist interferes with the full agonist

Question 16

Why is the dose in Log in a dose-response curve?

Answer 16

Easier for pharmacologists to see where the maximal response is

Question 17

How does a full agonist with a lower affinity generate a maximal response compared to one with a higher affinity?

Answer 17

• Both can reach maximal response
• Higher concentration needed for one with lower affinity
• Further right on log dose-response curve

Question 18

Do antagonists have affinity and/or efficacy?

Answer 18

• Have affinity

* No efficacy

Question 19

Compare the 2 types of antagonists

Answer 19

Competitive
• Binds to same site as agonist on receptor
• Response is surmountable - increased agonist can overcome this antagonist
• e.g. atropine (muscarinic cholinoreceptor antagonist) and propanolol (beta blocker)

Irreversible
• Can bind to the same site as agonist, more tightly with covalent forces - can’t be shifted
• May bind to a different site - causes insurmountable antagonism (no competition)
• e.g. hexamethonium - nicotinic cholinoreceptor antagonist (waits until ion channel is open)

Question 20

What is the use of a receptor reserve (‘spare receptors’) and what does this mean?

Answer 20

• 100% of receptors don’t need to be occupied for maximal response
• Less than 1% can be activated in some tissues
• This increases the sensitivity of the tissue to the agonist
• Increased speed of response

Question 21

How do the 2 different types of antagonists effect the log dose-response curve (compared to agonist alone) and why?

Answer 21

• Competitive - shifts right (therefore higher [agonist] needed to reach maximum)
• Irreversible - shifts further right and response is lower (higher [agonist] for any kind of response but can’t reach maximum)