Drugs And Receptors Flashcards
Defintion of a drug and routes of administration
Medicine or other substance which has either a local or systemic physiological effect
- enteral (GIT - involved e.g oral/PO)
- parenteral (non-GIT e.g IM,IV,SC, injections)
- other (inhaled, topical, rectal)
Pharmacology defintion
The branch of medicine concurred with the uses, effects and modes of action of drugs
Name 4 different drug targets
Receptors
Enzymes
Transporters
Ion channels
Definition of a receptor
A component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligand observed effects
Example of an exogenous ligand
Drugs (extrinsic)
Example of an endogenous ligand
Hormones,
Neurotransmitters (intrinsic)
Receptors are the principal means by which chemicals communicate. Give 3 examples of these chemicals with names.
Neurotransmitters - acetylcholine, serotonin
Autacoids - cytokines, histamine
Hormones - testosterone, hydrocortisone
Example of when there is an imbalance of chemicals
Allergy - increased histamine
Parkinsons - reduced dopamine
Example of when there is an imbalance of receptors
Myasthenia gravis - loss of Ach receptors
Mastocytosis - increased c-kit receptors
Types of receptors
Ligand-gated ion channels
G-protein coupled receptors
Kinase-linked receptors
Cytosolic/nuclear receptors
Cholinergic receptors
Example of ligand-gated ion channels
Nicotinic
Example of a G-protein coupled receptor
Beta-adrenoreceptors
Example of a kinase-linked receptor
Receptors for growth factors
Examples of cytosolic/nuclear receptors
Steroid receptors
How do ligand gated ion channels work?
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore so that the cell undergoes a shift in electric charge distribution.
The change in charge can be mediated by an influx of any kind of cation or efflux of any kind of anion.
How do g-protein coupled receptors work?
Also known as G protein - guanine nucleotide-binding proteins
Their activity is regulated by factors that control their ability to bind to and hydrolyse GTP to GDP
G proteins (GTPases) act as molecular switches (GDO=ON, GTP=OFF)
Targeted by more than 30% of drugs
Ligands include light energy, peptides, lipids, sugars
How do kinase-linked receptors work?
Kinases are enzyme that catalyse the transfer of phosphate groups between proteins - process is known as phosphorylation.
The substrate gains a phosphate group ‘donated’ by ATP
Transmembrane receptors activated when the binding of an extracellular ligand causes enzymatic activity on the intracellular side.
They are receptors for growth factors
How do cytosolic/nuclear receptors work?
Also known as Steroid Hormones
Work by modifying gene transcription
How do cholinergic receptors work?
There are two categories of cholinergic receptors - nicotinic and muscarinic
Agonist = Muscarinic, Nicotine
Antagonistic = Atropine, Curare
Receptors = mAChR, nAChR
Ligand definition
A molecule that binds to another (usually larger) molecule
Antagonist definition
A compound that reduces the effect of an agonist
- full affinity
- ZERO efficacy
Agonist definition
A compound that binds to a receptor and activates it
- full affinity (how well it binds)
- full efficacy (how well the receptor works)
Affinity definition
Describes how well a ligand binds to a receptor
Efficacy definition
Describes how well a ligand activates the receptor
Emax = the maximum response achievable
Describe the difference in agonists and antagonists in terms of affinity and efficacy
Agonists have affinity and efficacy = but antagonists have affinity and ZERO efficacy
What is the two-state model of receptor activation?
Describes how drugs activate receptors by inducing or supporting a conformational change in the receptor from off to on.
Potency definition
The amount of drug that will elicit a 50% response
Full activation definition
Achieves full activation of pathway
Partial agonists defintion
Never achieves full activation of pathway
Intrinsic activity definition
Intrinsic activity (IA) or efficacy refers to the ability of a drug-receptor complex to produce a maximum functional response
Two types of antagonists
Competitive antagonism - binds to same site
- decreases potency but doesn’t affect the efficacy = ligand conc is rate limiting .
Non-competitive antagonism - binds to an allosteric site on the receptor to prevent activation of the receptor
- decreases both potency + efficacy = ligand conc not rate limiting factor.
What is selective agonism?
Potency of a range of agonists
What are selective antagonists?
competitive antagonists
Factors effecting drug action?
Receptor related - affinity, efficacy
Tissue related - receptor number, signal amplification
What is a receptor reserve?
Some antagonists need to activate only a small fraction of the existing receptors to produce the maximal system response.
This holds for a full agonist in a given tissue - reserve can be large or small, depends on tissue
No receptor reserve for a partial agonist - even with 100% occupancy, maximal response not seen.
What is signal transduction?
A basic process involving the conversion of a signal from outside the cell to a functional change within the cell.
What is signal amplification?
To increase the strength of a signal
What is an inverse agonism?
When a drug binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist
Tolerance definition
Reduction in agonist effect over time
Happens when a person is exposed to a drug continuously, repeatedly, and in high concentration
Types of desensitisation
- Uncoupled - receptor can’t interact with G-protein
- Receptor is internalised in vesicle of cell
- Receptor becomes degraded
Desensitisation occurs with many agonist drug infusions, perhaps pulsatile
delivery could avoid this
Difference in tolerance to desensitisation
Tolerance happens slowly over time, desensitisation is fast
Difference between specific and selective
Specific drug = acts on a certain target
Selective = acts on a subtype of target e.g cardio selective Bb inhibit B1 adrenergic receptors not B2
