3. Drug-Receptor Interactions Flashcards
What is the difference between pharmokinetics and pharmacodynamics?
- 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
What are the 4 main drug target sites?
- Receptors
- Ion channels
- Transport systems
- Enzymes
Summarise receptors as a drug target site
- Proteins within cell membranes
- Activated by neurotransmitters or hormones
- Receptors are defined by particular agonists/antagonists that interact with them
What is atropine?
- Muscarinic cholinoreceptor antagonist
* Anaesthetic premedication to dry up secretions
Summarise ion channels as a drug target site
- 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)
Give 2 examples of drugs that interact with ion channels and describe how
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
What is a transport system?
- 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
Give 2 examples of drugs that interact with transport systems and describe how
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
What are the 3 ways in which drugs interact with enzymes, giving an example of each
• 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
How does an overdose of paracetamol damage the liver?
- 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
Give 3 examples of drugs that do not follow the four target site rule, following a non-specific action
- 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)
What is an antagonist?
Substance that binds to a receptor but does not produce a response (therefore it’s just in the way)
What is potency and what does it depend on?
• 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)
What is a full and partial agonist?
- 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
What happens if you administer a partial agonist with a full agonist?
- Effect similar to antagonist
* Partial agonist interferes with the full agonist
Why is the dose in Log in a dose-response curve?
Easier for pharmacologists to see where the maximal response is
How does a full agonist with a lower affinity generate a maximal response compared to one with a higher affinity?
- Both can reach maximal response
- Higher concentration needed for one with lower affinity
- Further right on log dose-response curve
Do antagonists have affinity and/or efficacy?
- Have affinity
* No efficacy
Compare the 2 types of antagonists
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)
What is the use of a receptor reserve (‘spare receptors’) and what does this mean?
- 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
How do the 2 different types of antagonists effect the log dose-response curve (compared to agonist alone) and why?
- 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)
