2. Drug-receptor interactions Flashcards
what is a drug?
a chemical substance that interacts with a biological system to produce a physiological effect
what are the 4 drug target sites and what do they have in common?
- receptors
- ion channels
- transport systems
- enzymes
all drug target sites are proteins
what is the only instance when receptors are intracellular instead of within cell membranes?
steroid receptors
what are receptors activated by?
neurotransmitters or hormones - namely agonists (which stimulate receptors) or antagonists (which inhibit receptor-mediated responses)
what are the 4 main groups of receptors defined by?
similarities in structure and transduction systems
give 2 examples of drugs acting on receptors
ACh which is a non-selective agonist that acts on nicotinic and muscarinic receptors
atropine which is a muscarinic antagonist
what are the 2 types of ion channels and how do they differ?
voltage sensitive e.g. voltage sensitive calcium channel
receptor-linked (ligand gated) e.g. nicotinic acetylcholine receptor (nAChR)
they differ in their gating methods
give 2 examples of drugs that act on ion channels
- local anaesthetics
2. calcium channel blockers
how do local anaesthetics act on ion channels?
block VGSCs in the sensory axons -> reduced sodium influx -> fewer action potentials are propagated along those axons -> perception of pain is reduced
how do calcium channel blockers act on ion channels?
block VGCCs -> cause relaxation of smooth muscle -> reduces resistance to blood flow and decreases BP
what are transport systems?
systems of carriers that transport substances against their concentration gradients (glucose, ions, NTs) which show specificity for certain species
give 2 examples of transport systems
- Na+/K+ATPase
2. noradrenaline ‘uptake 1’
give an example of a drug that acts on transport systems and describe how it works
tricyclic anti-depressants (TCAs) bind to and inhibit NA uptake 1 to slow down reuptake into the presynaptic fibre, prolonging the action of NA in the synaptic cleft
what is digoxin and how does it work?
cardiac glycoside
interacts with the Na+/K+ pump and slows it down, which results in a knock on effect that increases the concentration of intracellular calcium and increases the force of contraction of cardiomyocytes
used to treat heart failure
what are the 3 ways that drugs can interact with enzymes?
- enzyme inhibitors
- false substrates
- prodrugs
give an example of an enzyme inhibitor and describe how it works
anticholinesterases
decreases ACh breakdown by inhibiting ACh-esterase
give an example of a false substrate and describe how it works
methyldopa
messes up normal NA production pathway -> reduces amount of dopamine production -> methylNA produced which is a worse vasoconstrictor so tone of blood vessel is not maintained -> increased relaxation -> reduced TPR -> decreased BP
give an example of a prodrug and what it requires to be activated
prodrugs need to interact with enzymes in the body before they are activated
e.g. chloral hydrate is metabolised into trichloroethanol in the liver where it then becomes effective as a sleeping drug
describe the unwanted effects of paracetamol
paracetamol overdose occurs when you saturate the liver’s microsomal enzymes so another set of enzymes (P450) start metabolising the paracetamol. the different metabolites produced interact with the liver and kidneys and damage them
which drugs produce responses due to their physiochemical properties and what responses do they produce?
general anaesthetics - dampen synaptic transmission but don’t interact with a specific transport system/receptor
antacids - reduce acidity of stomach contents
osmotic purgatives - stimulate voiding of gut contents by drawing water into the stomach which softens stool
why are plasma proteins not a drug target site?
they do not generate a physiological response, they are just a reservoir of the drug and the drug remains inactive
what is an agonist?
ACh; nicotine
a molecule that binds to a receptor and stimulates it to generate a response, usually involving a conformational change in the receptor
what is an antagonist?
atropine; hexamethonium
interacts with receptors, doesnt produce a response
what is potency and what does it depend on?
the powerfulness of a drug
it depends on
- affinity - how willingly the drug binds to its receptor
- efficacy - the ability of a drug to generate a response once receptor bound (ability to cause a conformational change of receptor)
