drug & receptors Flashcards
give 4 targets of drugs
receptors
enzymes
transporters
ion channels
define drug
a medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body
define pharmacology
the branch of medicine concerned with the uses, effects and modes of action of drugs
define receptor
a component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligands observed effects.
what are the 2 categories of ligand
exogenous - drugs
endogenous - hormones, neurotransmitters etc
how do chemicals communicate
via receptors
give examples of chemicals
neurotransmitters - acetylcholine, serotonin
autacoids (local) - cytokines, histamine
hormones - testosterone, hydrocortisone
give 4 types of receptors
- ligand gated ion channels
- g protein coupled receptors
- kinase-linked receptors
- cytosolic/nuclear receptor
example of ligand gated ion channel
nictonic ACh receptor
describe g protein coupled receptors
they are the largest and most diverse group of membrane receptors in eukaryotes
G proteins act as molecular switches (GDO = on. GTP= off)
Targeted by >30% of drugs
Ligands include light energy, peptides, lipids, sugars and proteins
what are ion channels
pore forming membrane proteins that allow ions to pass through the channel pore so that the cell undergoes a shift in electric charge distribution
what can mediate a change in charge
an influx of any kind of cation (+ve) or an influx of any kind of anion (-ve)
what are g proteins also known as
guanine nucleotide binding proteins
a family of proteins (35) involved in transmitting signals from GPCRs
what regulates activity of g proteins
factors that control their ability to bind and hydrolyse gunaosine triphosphate to guanisine diphosphate
what chemical causes allergies
increased histamine
what chemical causes parkinsons
reduced dopamine
what are kinases
enzymes that catalyse the transfer of phosphate groups between proteins - phosphorylation
the substrate gains a phosphate group donated by ‘ATP’
how do kinase linked receptors work
transmembrane receptors become activated when the binding of an extra cellular ligand causes enzymatic activity on the intracellular side
what uses kinase linked receptors
growth factors
which receptors cause myasthenia gravies
loss of Ach receptors
which receptors cause mastocytosis
increased c-kit receptor
how do nuclear receptors work
they are steroid receptors
work by modifying gene transcription
define ligand
a molecule that binds to another (usually larger) molecule
define agonist
a compound that binds to a receptor and activates it
define antagonist
a compound that reduces the effect of an agonist
how does tamoxifen work
Breast Cancer) acts as a selective estrogen receptor modulator (SERM), or as a partial agonist of the estrogen receptors - Used in ER+ cancers.
how to make a therapeutic strategy
- Identify the receptor involved in a pathophysiological response
- Develop drugs that act at that receptor
3,. uantify drug action at that receptor
what is the 2 state model of receptor activation
describes how drugs activate receptors by inducing or supporting a conformational change in the receptor from ‘off’ to ‘on’
what is intrinsic activity
also referred to as efffiacy
refers to the ability of a drug-receptor complex to produce a maximum functional response
what is competitive antagonist
when the antagonist and agonist bin to the same site and compete
what is a non competitive antagonism
antagonist reverses the effect of the agonist
the anatagonist binds to an allostric site on the receptor -different to the agonist
what is selective agonist
potency of a range of agonist
what is selective antagonist
competitive antagonists
what are the 2 categories of choliogernic receptors
nicotinic and muscarinic
what is the antagonist and receptor for muscadine
agonist - muscarine
antagonist - atropine
receptor - mAChR
what is the antagonist and receptor for nicotine
agonist - nicotine
antagonist - curare
receptor - nAChR
what are the factors governing drug action
tissue related
- receptor number
- signal amplification
receptor related
- affinity
- efficacy
define affinity
describes how well a ligand binds to the receptor
define efficacy
describes how well a ligand activates the receptor
what do agonists have
efficacy and affinity
what do antagonists have
have affinity and ZERO efficacy
what happens if b2 adrenoreceptors are inactivated
Isoprenaline is a non-selective β adrenoreceptor agonist an analog of adrenaline).
relaxation of pre-contracted human bronchial rings
what are irreversible antagonists
the receptor itself will never become available for signalling again
will be stuck to it
why are receptor reserves important
Some agonists needs 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
define signal transduction
a basic process involving the conversion of a signal from outside the cell to a functional change within the cell.
define signal amplification
to increase the strength of a signal
what is allosteric modulation
a type of receptor ligand interaction
When an allosteric ligand binds to a different site on the molecule and prevents the signal from being transmitted.
what is tolerance
slow
Reduction in drug effect (agonist) over time
Continuously, repeatedly, high concentrations
occurs in asthma
describe desensitisation
fast
whole system becomes Uncoupled - fail to get a response
could be due to:
- Internalized
- Degradation
what is inverse agonism
when a drug that binds to the same receptor as a agonist but induces a pharmacological response opposite to that of the agonist
is any compound specific
no - no compound is ever truly specific
better to use selective to describe
what is isoprenaline
a non selective B adrenoreveptor agonist
what is isoprenaline used for
bradycardia
heart block
rarely for asthma
what is salbutamol
a selective b2 adrenoreceptor agonist
what does salbutamol do
up the medium and large airways in the lungs, used for COPD/asthma
