L 05 Treatment of Asthma (B2 agonist, corticostiroids) Flashcards
(38 cards)
Where are B2 receptors found?
Lungs
Where are B1 receptors found?
heart
Why do adrenergic receptors need to be selective?
So you don’t stimulate tachycardia(increased heart rate) for someone with hypertension while you are trying to treat their asthma.
Stimulation of B2 receptors in the lungs causes?
Bronchodilation, decreased secretions, increased airway diameter (good target for asthma)
Stimulation of B1 receptors in the heart causes?
Increased heart rate & contractility,
Causes atrial arrhythmias,
Increased cardiac output,
Be suppressed by partially blocking impulses being conducted through the AV node
Stimulation of receptors in the bladder (Beta) and sphincter (Beta 2R )?
Relaxation (if B receptors stimulated)
Beta 2R is stimulated causes Contraction of the sphincter (to prevent urination)
What type of receptor is the adrenoreceptor?
a class of GPCR NOTE: adrenergic receptor (AR) and adrenoreceptor (AR) are the same.
Name the 2 AR types and the subtypes of each?
Types: alpha and beta (x and b)
Subtypes: x1, x2, b1, b2, b3
How are the different adrenoreceptor subtypes relevant therapeutically?
As they all have different: - Structure of the ligand binding site - Signalling pathways - Tissue distribution Therefore we can target one receptor subtype over another.
Define allosteric and orthosteric
Allosteric: binding site outside of where the natural substrate binds
Orthosteric: binding to where the natural substrate binds
Define (full) agonist
A drug that binds and activates a receptor and gives its highest pharmacological response
Define partial agonist
A drug that activates a receptor to less than its highest pharmacological response
Define inverse agonist
A drug that binds to a receptor and produces a pharmacological response that is opposite to that of an agonist.
Define antagonist
A drug that binds to a receptor and blocks its pharmacological response.
How does an agonist cause a signal?
Binds to GPCR, causes shape change. Receptor becomes stabilised in the active conformation.
This change in receptor shape at the intra-membrane face causes a signal
When naming chemical compounds, what does “nor-“ mean?
Minus a methyl group “desmethyl”
What are the endogenous AR agonists? (Class + examples)?
Class: catecholamines
Examples: noradrenaline/adrenaline
Why can’t we use adrenaline to treat asthma?
Need to increase selectivity (otherwise will activate B1)
and increase duration of action. Adrenaline is used as a starting point.
What Changes we do to adrenaline to improve its drug functionality:?
Change catechol group (reduces metabolism)
Extend lipophilic chain (binding site selectivity and duration)
De-amination of amine (reduces metabolism)
Short acting B2-AR agonists (SABAs) are selective for… (+exception)?
Selective for B-AR over x-AR and more selective for B2-AR over B1-AR.
Exception: selectivity is dose related.
Features of SABAs (x4) + example?
- Fast onset
- 4-6 hour duration (longer than the endogenous agonist
- Catechol removed (a common building block of organic synthesis)
- Bulky N group reduces metabolism (MAO) and improves B2 selectivity.
Ex of SABA e.g Salbutamol
Can SABAs be marketed as enantiomers?
Yes, most drugs are racemic mixtures of enantiomers
Features of LABAs + example?
- Long lipophilic chain anchors in membrane = longer duration of action
- More lipophilic than SABAs (higher cLogP)
Example of LABA- e.g salmeterol, formoterol
Do SABAs or LABAs have an ionisable amine @ 7.4? + e.g?
LABAs
They are formulated as a salt to increase lipophilicity and therefore membrane retention.
e.g. formoterol as fumarate dihydrate
