Biochemical basis of drug action Flashcards
What are the 4 types of receptor classes
ligand-gated ion channels
G protein-coupled receptors
kinase-linked receptors
nuclear receptors
What is an example of a ligand-gated ion channel
nicotinic ACh receptor (nAChr)
what is an example of a G protein-coupled receptor
Muscarinic ACh receptor (mAChr)
what is an example of a kinase-linked receptor
cytokine receptor
what is an example of nuclear receptors
steroid hormone receptors
What is the relative timescale for ligand gated ion channels mechanism
milliseconds
What is the relative timescale for G protein-coupled receptor mechanisms
seconds
What is the mechanism for ligand-gated ion channels
ligand binds to receptor
ion channel opens
influx on ions
How do agonists stimulate a response
work by binding to specific receptors to elicit a response.
signal molecule
exogenous drug
how do antagonists stimulate a response
bind to receptor
block action of biological molecule
What are nicotinic acetylcholine receptors permeable to
Na+
K+
Ca2+
What are the functions of ligand-gated ion channels
modulate fast synaptic excitation
How are Ca2+ channels activated in neurotransmission
by excitation
What causes vesicles to move down the pre-synaptic neuron
Ca+ ions flow down electrochemical gradient
move down to synaptic cleft
What happens after Acetylcholine diffuses across the cleft and binds to receptors on the post-synaptic membrane
Na+ ions move into cell via receptor conformational change
causes depolarisation
What drug acts as a full agonist at nicotinic acetylcholine receptors
nicotine
what drug acts as a partial agonist at nicotinic acetylcholine receptors
varenicline
How do partial agonists work
inhibits binding of biological molecule
binds to some receptors instead
How can partial agonists be used to reduce drug craving
increases the amount of drug (eg nicotine) required for a maximum response
What is the mechanism of G protein-coupled receptors
single peptide binds
initiates messenger system/cascade
causes cellular response
What are the processes involved in the binding of adrenaline to B2-adrenoreceptors
adrenaline binds
receptor changes conformation
G protein binds
interacts with enzyme adenylyl cyclase
When is the enzyme adenylyl cyclase inactivated
GTP hydrolysed
What is the result of adrenaline binding to B2-adrenoreceptors
bronchodilation
How are signals amplified by G proteins
ATP converted to cAMP
Activates kinase (via phosphorylation?)
sets of signalling pathway
amplification
What part of the autonomous nervous system is adrenaline part of
sympathetic
What response does adrenoreceptor a1 cause
vasoconstriction of blood vessels
what response does adrenoreceptor a2 cause
relaxation of the GI tract
what response does adrenoreceptor B1 cause
increase heart rate
increased cardiac muscle contraction
what response does adrenoreceptor B2 cause
dilation of bronchi
what response does adrenoreceptor B3 cause
thermogenesis in skeletal muscle
Why do specific drugs need to be used instead or adrenaline which activates all adrenoreceptors?
want to activate specific receptors to get desired therapeutic effect
which drug should be given for asthma
salbutamol
only activates B2
only causes bronchodilation
what happens a receptor is continuously activated by drugs
receptors break down
less receptors on cell surface
desensitisation
How can drugs that stimulate receptors be given chronically
via enzymes that stop the amplification of G proteins
What inhibitor can be used to give salbutamol chronically for asthma
theophylline
What are the main properties of kinase linked receptors
hormone binds
triggers multiple parallel responses
relay proteins
what are the mechanisms of nuclear receptors
steroid hormone crosses bilipid layer
binds to receptor
moves to nucleus
causes changes in gene transcription
What are the 4 drug targets
receptors
enzymes
ion channels
carrier proteins
