RESP - C. SAR AT BETA-ADRENORECEPTORS-COVERED Flashcards
what is an adrenoceptor
- receptor in the body that can bind to adrenaline
- adrenaline binds to all classes
- noradrenaline only binds to alpha
adrenaline (adrenalin/epinephrine)
- R-stereoisomer
- hormone, neurotransmitter (fight or flight)
- agonist
- heart rate, blood vessel diameters, air passage diameter, metabolism
- treatment for anaphylaxis (epipen, Auvi-Q)
- mono-amine, ‘catecholamines’
- alpha- and beta-AR activation
noradrenaline
- neurotransmitter (fight or flight)
- affects heart rate
- alpha-AR activation
alpha1 and alpha2
alpha1:
- smooth muscle contraction via release of Ca2+ etc
- vasoconstriction in blood vessels
alpha2:
- inhibits insulin release
- inhibits NA release in brain and CNS
- contraction of sphincters in GIT
*phenylephrine is selective agonist for alpha-1 receptor
beta1, beta2, beta3
beta1:
- increases heart rate, renin secretion from kidney etc
beta2:
- relaxes bronchi smooth muscles
- stimulates insulin release
- inhibits histamine release from mast cells
beta3:
- enhances lipolysis in adipose tissue
*isoprenaline is non-selective agonist
how to make isoetharine more resistant to metabolism by COMT
- replace meta-OH with -CH2OH
- B2 agonist but short-acting as methylated by COMT to inactive form
isoprenaline
B1 (heart) and B2 (bronchi)
mortality epidemic
- caused cardiac depression as well as relaxation of smooth muscle
salbutamol (SABA)
B2 (bronchi)
R = active form
S = blocks metabolism of R (racemate will be cheaper and metabolism of R won’t occur)
t-butyl group produces selectivity for B2 receptors
salmeterol (LABA)
- bulky N-substituent
- selective for B2 receptors due to bulkiness
- more lipophilic
- acts 2x longer than salbutamol due to bulkiness
- slower onset - prevention/management rather than relief
fenoterol
- short-acting B2 agonist
- also stimulated B1 when used above recommended dose
- withdrawn due to mortality issues
