Drug-receptor interactions Flashcards
Define drug
A chemical substance that interacts with a biological system to produce a physiological effect.
What are drug target sites?
Receptors
Ion channels
Transport systems
Enzymes
All proteins! RITE
What are agonists and antagonists?
Antagonists - block receptors (don’t produce a response when bound to receptor: they just get in the way of agonists)
Agonists - ligands that stimulates the receptors to generate a response
Receptors are defined by agonists and antagonists
How many types of receptors are there?
4
What are the two different types of acetylcholine receptors?
Nicotinic receptors
Muscarinic receptors
Give an example of an agonist and antagonist
Agonist - ACh
Antagonist - Atropine (used an anaesthetic premedication to dry up secretions)
What are the two types of the ion channels?
1) Voltage-sensitive e.g VSCC Voltage sensitive calcium channel
2) Receptor-linked e.g nAChR Nicotinic ACh Receptor
Give an example of a calcium channel blocker?
Nifedipine (-dipine; means calcium channel blocker)
What is meant when we talk about transport systems?
Transport systems against concentration gradients (glucose, ions, NTs). E.g Na+/K+ATPase
What type of drug can target ion channels?
Local anaesthetics - Sodium/Calcium channel blockers –> fewer action potentials = pain reduced
What type of drug targets transport systems?
TCAs (Tricyclic anti-depressants) - targets NA uptake 1. Act as inhibitors of NA uptake 1 reducing NA reuptake into the neurone
Cardiac glycosides
What are the three methods which drugs can interact with enzymes to produce a response in the body?
i) enzyme inhibitors
ii) false substrates
iii) prodrugs
Give an example of an enzyme inhibitor drug?
Anticholinesterases (neostigmine)
Give an example of a false substrate drug?
methyldopa (antihypertensive)
Give an example of a prodrug?
chloral hydrate (insomnia)
What are PPB drugs?
Plasma protein binding drugs. They create a reservoir of of drugs within the blood - does not create a physiological response. Warfrin
What does the potency (power) of a drug depend on?
Affinity - the avidity of the drug to its binding site. High avidity = good affinity. How willing the drug binds to the receptor
Efficacy - the ability of the drug to cause a conformation change in the receptor. The ABILITY of the drug to GENERATE A RESPONSE.
What can describe a drug with a high affinity and avidity?
Powerful agonist
Define full agonist?
A drug that can produce the maximum response of a tissue
Define partial agonist?
A drug can produce a response but not the maximum response of the tissure
What happens when you have a full an partial agonist together?
The partial agonist has some antagonist activity against the full agonist because it occupies some of the receptors so the full agonist cant occupy this space to generate a maximum response.
Define seletivity
Drugs that have a preferential action towards a specific receptor. This becomes a problem when you try to increase the dose and the drug starts stimulating other receptors.
How do cardiac glycosides work?
Drug that targets Na+/K+ transport pump system. They are cardiac stimulant drugs - digoxin slows Na+/K+ pump down resulting in a knock on effect that increases the intracellular calcium concentration. Increases the force of contraction
What is the difference between receptors and transport system?
The transport system does not mediate a response, all they do is allow a NT to bind to a protein and move it somewhere else.
How does methyldopa work?
It works as an antihypertensive. The enzymes think that it is producing NA but in reality Methyl NA is produced. Methyl NA is a worse vasoconstrictor than NA = Reduced TPR = Reduced BP. The Methyl NA is a false transmitter
Give an example of an unwanted effect of drug interaction with enzymes.
Paracetamol overdose
What drugs produce responses due to their physiochemical properties?
General anaesthetics
Antacids
Osmotic Purgatives
These are all non-specific drug action
Draw the dose-response curve of a full and partial agonist
See diagram: Agonist concentration against tissue response
Draw the log dose-response curve of a full, partial and full with low affinity agonist
See diagram
In terms of potency how can an antagonist be described as?
It has affinity but NO efficacy
What are the two main types of antagonists and examples?
Competitive: Atropine and Propanolol
Irreversible: Hexamethonium
What are the two main mechanisms of irreversible antagonism?
They can bind more tightly with covalent forces so they can’t be shifted or they may bind to a different site from the agonist (not competing - could be inside the channel of an ion channel)
Surmountable vs Insurmountable antagonism
Describe what is meant by receptor reserve?
‘Spare receptors’ - Some tissues don’t require all the receptors to be occupied to generate a maximal response. This increases the sensitivity of the tissue to the agonist and increases the speed of the response
Draw the effect of the antagonist graph
See diagram
What is propanolol used for?
Competitive Beta Blocker
What is atropine used for?
Used as anaesthetic premedication to dry up secretions
Also used to treat organophosphate poisoning - see lecture on Cholinomimetics
