Pharmacology Flashcards
What is a receptor?
A macromolecule in the membrane or inside the cell that chemically binds a ligand (drug).
What are different receptors activated by?
Different (sometimes the same) signalling molecule
How many different receptors exist?
4
What are the four different types of receptors?
Ionotropic receptor channel
Receptor enzyme
Integrin receptor
G-Protein coupled receptor
What is an ionotropic receptor?
A receptor that is also an ion channel
What is a receptor enzyme?
Receptor that functions as an enzyme
What is an integrin receptor?
Receptor that directly affects an enzymes activity
What does a G-protein coupled receptor look like?
7 transmembrane spanning segments
What type of response can a receptor evoke?
Membrane permeability
Metabolism
Secretory activity
Rate of proliferation or differentiation
contractile activity
The process is called signal transduction
What type of chemical messenger binds to an intracellular receptor?
A lipid soluble receptor, steroid hormones
Where are the receptors found that can influence the transcription of DNA?
Within the nucleus
What response can steroids have on transcription?
They are a transcription factor and can alter the rate of transcription
What are the tyrosine kinase receptor enzymes involved in?
Proliferation and differentiation
Define affinity
The extent which a drug binds to receptors at any given drug concentration or the firmness with which the drug binds to the receptor.
It is the strength of chemical attraction between the drug and the receptor
Define efficacy
The maximum response that can be achieved with a drug.
It determines how good the drug is at activating the receptor
When will you get the maximum response from a drug?
When all the relevant receptors are bound to the drug
Why is the concentration / response graph curved?
Because it is more likely for a ligand to hit a free receptor at the start of a reaction then the end
What is the EC50?
It is the concentration of a drug at half of its maximal response
What graph is used to determine the EC50?
The log of drug concentration against the increasing response
What does the EC50 indicate?
The affinity of the drug for the receptor, a smaller EC50 indicates a smaller amount of drug is needed to evoke the same response, therefore the drug has a higher affinity
How does efficacy affect the EC50?
It doesn’t
What is an agonist?
It mimics the normal effect of the receptor
What is an antagonist?
It blocks the normal effect of the receptor
How many different receptors can a strand of drug bind to?
As many as the drug has conformational shapes to the receptor
What are the sources of calcium ions?
Internal stores via inisitol triphosphate
From outside the cell via ligand or voltage gated channels
Via inhibition of calcium transport out the cell
What are the effects of calcium in the cell?
Can regulate the activity of the target protein e.g of Protein Kinase C
Can bind to calmodulin which directly activates a target protein
Works via some other calcium binding protein e.g troponin
What is a secondary messenger?
Second messengers are small molecules and ions that relay signals received by cell-surface receptors to effector proteins.
What are the possible effects of a secondary messenger?
Make channels open wider
Regulate protein synthesis
Regulate the release of calcium
Regulate the synthesis of RNA in the nucleus
Might act on microtubules making things secrete things out of the cell
What is intracellular calcium?
Intracellular calcium ([Ca2+]i) is a secondary messenger which regulates numerous cellular processes and, therefore, its concentration is tightly regulated.
Intracellular calcium storage
Organelles which repetitively release and then reaccumulate Ca2+ ions in response to specific cellular events
eg - mitochondria and the endoplasmic reticulum.
What does the size of the response depend on?
Drug affinity - does it bind to a receptor?
Drug efficacy - does it activate the receptor?
What happens to a subunit of a G protein when the G protein coupled receptor is activated?
It regulates an enzyme that produces a secondary messenger, e.g
Regulates adenyl cyclase, which in turn produces the second messenger cAMP (cyclic AMP)
This in turn regulates the activity of another enzyme, PKA (protein kinase A) which then goes off to phosphorylate proteins
What happens when phospholipase C is regulated?
Two secondary messengers are regulated, these (diacylglycerol and Inisitol triphosphate) - These are responsible for activation of Protein Kinase C and the release of calcium ions from internal stores
Give examples of receptors with intrinsic enzyme activity
Tyrosine kinases
Receptor guanylyl cyclases - retina
What type of enzyme can receptors interact with directly?
JAK kinases
What are JAK kinases involved in?
Protein synthesis
What is the result of activation of Adenylyl cyclase by a G protein?
Makes cAMP (secpndary messenger) which activates a protein kinase
What can one signalling molecule act on?
Several receptor subtypes
What is an example of one signalling molecule that can act on several receptor subtypes?
Adrenaline – the endogenous agonist activates all adrenoceptors (α1, α2, β1, β2) like a “master key”
What are selective agonists?
Drugs that activate only some of those receptors
What is an example of a selective agonist?
Salbutamol - a β2 agonist
Used in treatment of asthma
What is a selective antagonist?
Drugs that block only some of those receptors
What is an example of a selective antagonist?
Propranolol - a β1 and β2 antagonist
Used in treatment of arrythmias
An antagonist at a pharmacological receptor is likely to have what combination of affinity and efficacy?
High affinity and no efficacy
Pharmacological antagonists are characterised by having high affinity (so bind readily to the receptor) but low or no efficacy (so have no effect, and stop the ligand binding to prevent its effect too).
An agonist at a pharmacological receptor is likely to have what combination of affinity and efficacy?
High affinity and high efficacy
Why do agonists have high efficacy?
They are able to cause a conformational change in the receptorwhereas regular drugs don’t necessarily cause any changes
Describe some of the sources of drugs
Natural products from nature
Synthetic drugs from the pharmaceutical industry
Biotechnology using living systems to make therapeutic agents.
Gene therapy
How do drugs act?
Interfering with a binding site - a receptor
Give examples of binding sites
Cell surface and intracellular receptors
Ion channels
Carriers
Enzymes
Nucleic acids
What is transmembrane signalling?
Recognition and binding of an extracellular signal by an integral membrane receptor protein and the generation of intracellular signals by one or more effector proteins.
