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)
