3 - Drug-receptor interactions Flashcards
Define Pharmacokinetics and Pharmacodynamics.
Pharmacokinetics – the effect that the body has on the drug (ADME)
Pharmacodynamics – the effect of the drug on the body
Define ‘drug’.
A chemical substance that interacts with a biological system to produce a physiological response
State the four main target sites for drugs.
Receptors Ion Channels Transport Systems Enzymes (note that these are all proteins)
What are receptors (where are they found)?
proteins within cell membranes (usually - exception=steroid receptors) activated by neurotransmitter and hormones
Define ligand
any molecules that interact with receptors
Give an example of a drug that target receptors and state what it is used for
atropine - muscarinic cholinoreceptor antagonist - used as an anaesthetic premedication to dry up secretions
What are the two types of ion channels? Give an example of each
Voltage-Gated e.g. VGSCs
Receptor Linked/ligand-gated - e.g. nAChr
How do drugs target ion channels?
interact with the actual ion channels, not the receptors
Give an example of a drug that acts by targeting ion channels
- local anaesthetics - block VGSCs (by lodging inside them) in the sensory axons
- calcium channel blockers
What is meant by transport systems as a target site for drugs?
Systems of carriers that transport substances against their concentration gradient
e.g. glucose ions, neurotransmitters
NOT receptors - don’t mediate a response, they only allow the NT to bind to a protein and then move it somewhere else
Give some example of transport systems
o Na+/K+ pump
o Noradrenaline uptake 1
Give an example of a drug that acts on transport systems.
- Tricyclic antidepressants
- Cardiac glycosides – it slows down the Na+/K+ pump —> increases intracellular calcium ion concentration—> increased force of contraction
What are the three ways in which drugs can interact with enzymes?
- Enzyme inhibitors
- False transmitter
- Prodrugs (e.g. chloral hydrate)
Give an example of an enzyme inhibitor
neostigmine - inhibits acteylcholinesterases
Give an example of a false transmitter
methyldopa (an antihypertensive)
replaces DOPA in the NA pathway -> reduces the amount of DOPA being converted to dopamine (methyl NA produced)
Give an example of the prodrug pathway of enzyme-drug interaction
chloral hydrate (sleeping tablet) - insomnia
chloral hydrate needs to go to the liver and be metabolised into trichloroethanol before it is effective
What is a common example of the unwanted effects of drug interaction with enzymes?
Paracetamol overdose – this will saturate the microsomal enzymes in the liver so the paracetamol is then broken down by another set of enzymes (P450) which generates toxic metabolites
Name three groups of drugs that are exceptions to the four target site rule and produce responses due to their physiological properties
General anaesthetics – reduce synaptic transmission without interacting with transport systems or receptors
Antacids – these are basic so they simply neutralize some of the stomach acid
Osmotic purgatives – draw water into the bowel due to its physicochemical properties
Define agonist.
A molecule that binds to a receptor and generates a response
Define antagonist.
A molecule that binds to a receptor but do NOT generate a response
Define potency. What is it dependent on?
How powerful the drug is
It depends on affinity (how willingly the drug binds to the receptor) and efficacy (the ability of a drug to generate a response once bound)
What is a full agonist?
An agonist that generates a maximum response
What is a partial agonist?
An agonist that generates a less than maximum response
What is selectivity?
Drugs have a preference for binding to certain receptors (it is rarely specific – they normally bind to a few different receptors)
What is the difference between full agonists with a high affinity and full agonists with a lower affinity?
Full agonists with a lower affinity can still generate a maximum response but requires a higher dose than the full agonist with lower affinity
Describe antagonists in terms of affinity and efficacy.
Antagonists have affinity but NO efficacy
What are the two types of antagonist?
Competitive – they bind to the same site as the agonist on the receptor – they are surmountable
Irreversible – could bind to the same site as the agonist but will bind more tightly with covalent forces so that they can’t be moved – some irreversible antagonists will bind to sites different to the site that the agonist binds to – insurmountable
Give examples of the 2 types of antagonist
competitive
- atropine - competitive muscarinic cholinoreceptor antagonist
- propanolol
irreversible
- hexamethonium - irreversible nicotinic cholinoreceptor antagonist
What effect do the two types of antagonist (competitive and irreversible) have on dose-response curves?
Competitive – shifts the D-R curve to the RIGHT
Irreversible – shifts the D-R curve to the RIGHT and LOWERS the response elicited (it can no longer generate a full response)
What is receptor reserve?
In some tissues, not all the receptors need to be stimulated to generate a maximum response (sometimes as little as 1% of receptors may need to be activated)
This increases the sensitivity of the tissue to the agonist
True or false: full agonists that are selective for a given receptor will have the same efficacy.
True
They are full agonists so they all elicit a maximum response hence they have the same efficacy
Calcium channel blockers drugs end in ______
-dipine
All drug target sites are ________ .
PROTEINS
