Flashcards in Week 6: Adrenergic Agonists Deck (74):
Where are alpha 1 receptors found?
vascular smooth muscle of skin and splanchnic regions, GI and bladder sphincters
What is the effect of alpha 1 receptor stimulation?
Which G protein is associated with alpha 1 receptors?
How do alpha 1s exert their effects?
Gq protein -> stim of phospholipase C -> increased IP3 -> inc intracellular [Ca]
Where are alpha 2 receptors found?
sympathetic post-gang nerve terminals (autoreceptors), platelets, fat cells, walls of GI tract
What is the effect of alpha 2 receptor stimulation?
Relaxation or dilation. Inhibition of neural NE release.
Which G protein is associated with alpha 2 receptors?
How do alpha 2s exert their effects
Gi protein -> activates Na/H antiporter OR inhibits adenylate cyclase -> dec cAMP
Where are beta 1 receptors found?
Heart: SA node, AV node, ventricular muscle, JG apparatus, adipose tissue
What is the effect of beta 1 stimulation
Increased HR (chronotropic), inc conduction velocity (dromotropic), inc contractility (inotropic)
Which G protein is associated with beta 1 and 2 receptors?
How do beta 1 and 2s exert their effects?
Gαs -> stimulation of adenylate cyclase -> inc cAMP
Where are beta 2 receptors found?
vascular smooth muscle of skeletal muscle, bronchial smooth muscle, walls of the GI tract and bladder
What is the effect of beta 2 stimulation?
Relaxation e.g. dilation of vascular smooth muscle and bronchioles, relaxation of bladder wall.
Compare isoproterenol, epi, and NE sensitivity of beta 1 receptors
isoproterenol > epi = NE
Compare isoproterenol, epi, and NE sensitivity of beta 2 receptors
isoproterenol > epi >> NE
Compare isoproterenol, epi, and NE sensitivity of alpha 1 receptors
epi >/= NE >> isoproterenol
Compare isoproterenol, epi, and NE sensitivity of alpha 2 receptors
epi >/= NE >> isoproterenol
alpha 1 agonists
Alpha 1 antagonists
-zosin e.g. Prazosin
Alpha 2 agonist
Beta 1 agonists
NE, isoproterenol, dobutamine
Beta 1 antagonists
Propranolol (non-selective), Metoprolol
Beta 2 agonists
Beta 2 antagonists
What components of the CV system are innervated by sympathetics?
Atria, ventricles, arterioles, and veins
How are NE and Epi synthesized?
Tyrosine -> DOPA -> Dopamine -> NE -> Epi (in adrenal medulla)
What enzyme is rate limiting in sympathetic neurotransmitter synthesis?
What does Reserpine do?
Irreversibly blocks vesicular monoamine transporter -> no sequestration of free NE -> NE degraded by MAO and COMT
Where does the cholera toxin act?
Irreversibly activates Gsalpha -> secretion from colon -> death by dehydration
What does Dobutamine do?
Selective B1 agonist. Increases HR and contractility.
B2 agonist -> relaxation of smooth muscle of bronchioles and uterine lining. Decreases BP via dec TPR.
Alpha 1 agonist -> inc BP.
Nonselective Beta agonist
How does epinephrine reversal work?
Give epi -> rise in BP. Then give α-antagonist -> no α actions from epi. E.g. vasoconstriction is interrupted, but vasodilation of other vascular beds caused by stimulation of β receptors is not blocked. Therefore alpha antagonist -> dec BP in response to epi
Where are muscarinic receptors?
Postganglionic parasympathetic targets (heart and vessels) + sweat glands and vessels (postganglionic sympathetic cholinergic)
How are adrenergic amines released?
Stim of nicotinic receptors on postganglionic nerve
How does NE inhibit own release?
Via alpha 2 autoreceptor
Action of cocaine
Inhibits axoplasmic pump -> potentiates sympathetic response
What does Guanethidine do?
Induces release of NE from vesicle leading to degradation by MAO -> reduced sympathetic response
What does pargyline do? (IMPORTANT!)
MAO inhibitor (potentiates sympathetic responses), blocks Guanethidine effects
What 2 enzymes degrade adrenergic amines, and where are they located?
COMT (catechole-O-methyl transferase) in cytoplasm, MAO in mitochondria
Effect of dopamine?
Dilation of renal and mesenteric vasculature (dopaminergic) vasoconstrictor (alpha 1) at higher doses. Positive inotrope (B1), release NE from nerves
Dobutamine therapeutic use
CHF, AMI with HF
What adrenergic agonist can raise HR, SV, and TPR respectively?
HR and SV: B1, TPR: alpha 1
What autonomic activity can result in decreased HR, SV, and TPR respectively?
HR: muscarinic, SV: none, TPR: beta 2 and muscarinic
Therapeutic use of dopamine
shock (maintains renal perfusion at low dose via dopaminergic receptor), hypotension (inc BP and CO), chronic refractory HF
What is midodrine? What is it used for?
Alpha 1 agonist for orthostatic hypotension
What is phenylephrine? What is it used for?
Alpha 1 agonist. Treats hypotension, paroxysmal atrial tachycardia, decongestant, topical vasoconstrictor and mydriatic
B2 selective agonists
Metaproterenol, Terbutaline, Albuterol, Ritodrine, Salmeterol
Uses for B2 selective agonists
asthma (except Ritodrine which does not result in bronchodilation
B2 agonists for delaying labor
Major side effects of B2 agonists
Tremor (skel muscle B2 stim), HA (B2 vasodilation), tachycardia, palpitations (b1)
What is isoproterenol?
Synthetic catecholamine that stimulates beta receptors -> vasodilation (b2) and tachy (b1)
Vasoconstriction (alpha 1), Inc HR and force (B1)
NE therapeutic use
vasoconstricts (a1) vasodilates (b2) - vasoconstriction generally wins therapeutically, inc HR, force (can have reflex vagal stim -> dec HR)
Hypersensitivity reaction, low BP, bronchospasm (a1 and B2). With anesthetic -> vasoconstrict, prevent diffusion away
How do indirectly acting sympathomimetics work? What is an example?
Release NE from nerves by reversing catecholamine axoplasmic uptake pump. Phenylethylamines e.g. amphetamine.
Amphetamine therapeutic uses
Narcolepsy, obesity, hyperkinetic syndrome
How does Ephedrine work?
releases NE -> inc BP via a1 and b1, vasodilates via B2
Therapeutic uses of ephedrine
Bronchospasm. For colds: NE -> vasoconstriction -> dec mucosal congestion (a1), bronchodilates (b2)
How does pseudoephedrine work?
Same as ephedrine, just a stereoisomer.
Which drugs block accumulation of NE in nerves, potentiating sympathetic action? (2)
Which drugs reverse the axoplasmic transporter, mimicking symp stim (3)?
Tyramine, amphetamine, ephedrine
Which drug blocks vesicular accumulation of NE leading to its degradation?
Which drugs release NE from vesicles -> depletion? (2)
Epi acts on what adrenergic receptor(s)?
a1, a2, b1, b2
NE acts on what adrenergic receptor(s)?
a1, a2, b1
Phenylephrine acts on what adrenergic receptor(s)?
Dobutamine acts on what adrenergic receptor(s)?
Ritodrine and Terbutaline act on what adrenergic receptor(s)?