lecture 23 - beta blockers Flashcards
where are alpha 1 receptors located, what are the physiological effects and what are their agonists and antagonists ?
alpha 1 receptors are located on vascular smooth muscles.
the physiological effects are smooth muscle contractions, gluconeogenesis and vasoconstriction
agonist are norepinephrine, phenylephrine and methoxamine
antagonist sare doxazosin, phentolamine and prazosin.
where are alpha 2 receptors located, what re the physiological effects and they’re agonists and antagonists?
pres synaptic terminal, pancreas, platelets, ciliary epithelium and salivary glands.
it inhibits the release of neurotransmitter
agonist are clonidine, and monoxidine
antagonists are yohimbine, idazoxan and tolazoline
where are beta 1 receptors located, what are their physiological effects and agonist and antagonists?
heart, kidney and some pre-synaptic terminals
increases heart rate and renin secretion
agonist are isoproterenol, norepinephrine and dobutamine
antagonists are propranolol, metoprolol and atenolol
where re beta 2 receptors located, what are their physiological effects and agonists and antagonists ?
visceral smooth muscles, bronchioles, liver and skeletal muscles
physiological effects arevasodialtion, bronchodialtion and inhibits insulin secretion
agonist are isoproterenol, salbutamol, salmeterol, albuterol, formoterol, terbutaline and levalbuterol
antagonists are propranolol, nadolol and butoxamine
what do beta 1 receptors do in the kidney ?
decrease renin release
what do beta 1 receptors do in the heart?
decrease rate, force, automaticity and cardiac output
what’d od beta 1 receptors do in adipose tissue?
decrease lipolysis
how do beta 2 receptors work specifically as targets in the heart?
beta blockers slow sa node which initiates heartbeat
slow heart rate allows left ventricle to fill completely and lowers the heart workload
what do beta adrenoreceptors activate?
beta adrenoreceptors are GPCRs which activate adenylyl cyclase to form cAMP from ATP when stimulated by noradrenaline
increased cAMP causes increased calcium entry into the cell, increasing isotropy contraction.
GPCR activation also increases heart rate.
PK-A can phosphorylate myosin light chain which may contribute to the psotive inotropic effects of beta adrenoreceptors stimulation
what differs in beta 2 receptors activation?
unlike cardiac myoccytes, in vascular smooth muscles an increased cAMP leads to smooth muscle relaxation because cAMP inhibits myosin light chain kinase that is responsible for phosphorylation, producing less contractile force ie promoting relaxation.
therefore, what does increase in cAMP by beta2 arenoreceptors produce?
therefore, increase in intracellular cAMP caused by beta 2 agonists reduced myosin phosphorylation, producing less contractile force ie promoting relaxation
what properties do we need our drugs to have?
Selective for the target to avoid adverse effects
High affinity for the target (potency)
Chronic disease requires oral administration:
Water solubility to allow for oral formulation (chronic disease treatment)
Lipophilicity to allow absorption from the gastro-intestinal tract
Stability within the gastro-intestinal environment
Slow (hepatic) metabolism to allow for sustained activity and reduced dosing frequency
No toxic metabolites
Bodily distribution to facilitate access to the target and reduce elimination rate
