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 types of drug targets? Are there any additional ways a drug can work?
(All proteinaceous)
- Receptors
- Ion channels
- Transport systems
- Enzymes
Non-specific physicochemical properties
Binding to plasma proteins to create a reservoir of inactive drug
Where are drug receptors located?
Most are on the cell surface.
Steroid receptors are inside the cell.
What is the role of drug receptors?
They are activated by neurotransmitters or hormones.
How are drug receptors categorized?
They are defined by their selective agonists and antagonists.
How many types of drug receptors are there?
4 types, categorised by structure (transduction system)
Examples of drugs that drug receptors?
ACh (agonist), Atropine (antagonist of muscarinic)
Use of atropine?
Pre-surgery to dry up secretions
How many types of ion channels are there?
2 types, voltage sensitive (VSCC) and receptor linked (nAChR)
nicotinic acetylcholine receptor
How are voltage sensitive channels opened?
By a change in membrane potential.
What are examples of drugs that target ion channels?
Local anaesthetics (lidocaine) - block voltage sensitive sodium channels
Ca2+ channel blockers, anti-hypertensives (-dipine) - relaxes sympathetic tone of heart to decrease BP
What are the roles of transport systems?
They transport substances against their conc. gradient (e.g. glucose, ions, T)
What are examples of drugs that target transport systems?
Tricyclic antidepressants (inhibit NorA uptake 1)
Cardiac glycosides - is a cardiac stimulant during heart failure
(inhibits Na+/K+ ATPase, improves contractility through increase in intracellular calcium)
How can drugs interact with enzymes and give an example of a drug for each?
Enzyme inhibition (anticholinesterases [glaucoma])
False substrate to false neurotransmitter (methylDOPA to methylNorA [lowers BP])
Prodrugs (chloral hydrate to trichloroethanol [hypnotic drug])
N.B. Enzyme systems can also mediate unwanted effects e.g. paracetamol (methionine as antidote)
How can drugs have a non-specific action?
Through their physicochemical properties
e.g. antacids (bases), osmotic purgatives (ability to draw water into gut to soften stool)
How do drugs interact with plasma proteins?
Drugs can bind to plasma proteins such as albumin creating a reservoir of inactive drug.
What is an agonist?
Something that stimulates or activates a receptor e.g. ACh, nicotine
What is an antagonist?
Something that blocks the receptor e.g. atropine (musc), hexamethonium (nico)
What two factors determine drug potency?
Affinity - the avidity of which it binds
Efficacy ‘intrinsic activity’ - its action e.g. conformational change of receptor
What is avidity?
The sum of the total individual binding interactions or affinities. e.g. low individual affinity but high avidity
What is the difference between a full and partial agonist?
Full agonists can generate the maximal agonist response of tissue.
Partial agonists have antagonist activity when administered in the presence of a full agonist e.g. beta blockers.
What is ‘selectivity of action’?
The receptor population which the drug interacts with. Will overlap more as drug dosage is increased causing unwanted side effects.
Not the same as specificity as as drugs will overlap to some degree.
What is the meaning and importance of the ‘structure activity relationship’?
The activity of a drug is strongly dependent on its structure. ‘Lock and key’ is a good analogy for affinity and efficacy.
Small changes in structure can produce big changes in activity. This can also have a large change in the pharmacokinetics e.g. metabolism and duration of action. It is common to create new antagonists from agonists.
What is a ligand?
Any substance that binds to a receptor
