Download Pharm Chapter 10 [4-20

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

5-HT3 antagonist wikipedia , lookup

Discovery and development of antiandrogens wikipedia , lookup

NMDA receptor wikipedia , lookup

Discovery and development of angiotensin receptor blockers wikipedia , lookup

Toxicodynamics wikipedia , lookup

5-HT2C receptor agonist wikipedia , lookup

Discovery and development of beta-blockers wikipedia , lookup

NK1 receptor antagonist wikipedia , lookup

Stimulant wikipedia , lookup

Nicotinic agonist wikipedia , lookup

Cannabinoid receptor antagonist wikipedia , lookup

Norepinephrine wikipedia , lookup

Neuropsychopharmacology wikipedia , lookup

Neuropharmacology wikipedia , lookup

Psychopharmacology wikipedia , lookup

Transcript
Pharm Chapter 10: Adrenergic Pharm
Adrenergic pharm focuses on pathways mediated by the catecholamines norepinephrine, epinephrine,
and dopamine
The sympathetic nervous system is the major source of catecholamines, and catecholamines are the
major effectors of symps
Effects of catecholamines:
-
Increasing heart rate and force of contraction
Regulating peripheral resistance of arteries
Inhibiting insulin release
Stimulating liver release of glucose
Increasing adipocyte release of fatty acids
Catecholamine synthesis, storage, and release:
-
-
-
-
Catecholamines are made from tyrosine at the symp nerve endings or in chromaffin cells of the
adrenal medulla
Symps make norepinephrine as their main neurotransmitter
Tyrosine is moved into neurons by an amino acid transporter that uses the sodium gradient
across the neuron membrane
o The transporter also moves phenylalanine, tryptophan, and histidine
The first step of making a catecholamine is tyrosine hydroxylase converting tyrosine into
dihydroxyphenylalanine (DOPA)
o Tyrosine hydroxylase is the rate limiting step in making catecholamines
A decarboxylase then converts DOPA into dopamine
Dopamine-β-hydroxylase converts dopamine into norepinephrine
In tissues that make epinephrine, phenylethanolamine N-methyltransferase (PNMT) adds a
methyl to norepinephrine to make epinephrine
o Expression of PNMT in the adrenal medulla depends on high concentrations of cortisol,
that move into the medulla through veins draining the adrenal cortex
Tyrosinedopamine happens in the cytoplasm, and then dopamine is taken to synaptic vesicles
by vesicular monamine transporter (VMAT)
o Once in the vesicles, dopaminenorepinephrine by dopamine-β-hydroxylase
o VMAT 1 and 2 both carry serotonin (5-HT), histamine, and catecholamines
o VMAT1 is expressed peripherally in the adrenals and symps
o VMAT2 is expressed in the CNS
o The vesicular acetylcholine transporter (VAChT) is expressed in cholinergic neurons like
motor nerves
o All 3 of these use the proton gradient from an H+ATPase in the vesicle membrane to
concentrate dopamine inside the vesicle

-
Norepinephrine made then couples with ATP to stabilize the osmotic pressure
from the concentration gradient made
o In the adrenal medulla, norepinephrine is moved out of vesicles into the cytoplasm,
where PNMT converts it to epinephrine, which then goes back into the vesicle
Activation of symps and therefore catecholamines is started by processing area of the CNS,
especially the limbic system
o These CNS neurons project axons that synapse on symp pregang neurons int eh
intermediolateral columns of the spinal cord
o The pregang axons then project to symp ganglia
 The pregangs use ACh to activate nicotinic receptors, leading to depolarization
and postsynaptic potential in postgang neurons
o Ganglionic blockers like hexamethonium and mecamylamine block the ganglionic
nicotinic ACh receptor, without effecting skeletal muscle
o The symp postgangs then synapse with target organs
o When an action potential gets to postgang symp nerve endings, it opens calcium
channels to cause calcium influx, which leads to exocytosis of vesicles that contain
catecholamine
o Ziconitide is a pain drug that blocks this release
o Norepinephrine then diffuses away from the nerve endings and acts on adrenergic
receptors
 The nerve endings also have adrenergic receptors, which can regulate
neurotransmitter release
Reuptake and metabolism of catecholamines:
-
-
-
Once a catecholamine exerts its effect at a postsynaptic receptor, the response is terminated by
one of three things:
o Reuptake of catecholamine into the presynaptic neuron
o Metabolism of catecholamine into an inactive metabolite
o Diffusion of catecholamine away from the synaptic cleft
o The first two use enzymes, so they can be targeted with drugs
Reuptake of catecholamine into the neuron is done by norepinephrine transporter (NET)
o Most of the released norepinephrine gets recycled like this
o NET uses a sodium gradient to concentrate catecholamines in the cytoplasm of the
symp nerve endings
Inside the nerve ending, catecholamines are further concentrated into synaptic vesicles by
VMAT
So the pool of catecholamines available for release comes from molecules made in the vesicle,
and recycled molecules
MAO-A degrades serotonin, norepinephrine, and dopamine
MAO-B degrades dopamine quicker than norepinephrine and serotonin
MAO inhibitors are used for depression
Catecholamine receptors
-
-
Adrenergic receptors (aka adrenoreceptors) are selective for norepinephrine and epinephrine
o 3 main classes: α1 , α2 , and β
 Each has 3 subtypes
 So α1A, α1B, α1C ; α2A, α2B, α2C; β1, β2, β3
 Each subtype is part of a G protein superfamily
α1 and α2 adrenergic receptors
o α1 adrenergic receptors usually work by a G protein pathway activating phospholipase C,
which cleaves phosphatidylinositol-4,5-bisphosphate into inositol triphosphate (IP3) and
diacylglycerol (DAG)
 IP3 mobilizes intracellular calcium
 DAG activates protein kinase C
 This leads to activation of things downstream, like calcium and potassium
channels, MAP kinases, and other kinases like phosphatidylinositol 3-kinase
 α1 adrenergic receptors are expressed in vascular smooth muscle, GU smooth
muscle, heart, liver, etc.
 in vascular smooth muscle, stimulation of α1 adrenergic receptors increases
intracellular calcium, via release of endogenous calcium stores, and by influx of
calcium from ECF
 leads to activation of calmodulin, which activates myosin light chain
kinase to phosphorylate the myosin light chain, causing myosin to bind
to actin, causing muscle contraction
 So α1 adrenergic receptors are important regulating increases in
peripheral vascular resistance, which can increase blood pressure and
redistribute blood flow
 α1 adrenergic antagonists help treat benign prostatic hyperplasia
o α2 adrenergic receptors activate GI, an inhibitory G protein that inhibits adenylyl cyclase,
which decreases cAMP
 can also activate potassium channels to hyperpolarize the cell, and can also
inhibit calcium channels
 so α2 adrenergic receptors inhibit neurotransmitter release from the target
neuron
 α2 adrenergic receptors are found on both presynaptic neurons, and
postsynaptic cells
 the presynaptic α2 adrenergic receptors, are autoreceptors to mediate
feedback inhibition of symp transmission
 α2 adrenergic receptors are also found on platelets and pancreas β cells
 they mediate platelet aggregation and inhibit insulin release
 α2 adrenergic agonists therefore decrease symp activity, and are used in
hypertension

o
o
works at CNS sites to decrease symp outflow to the periphery,
resulting in decreased norepinephrine release at symp nerve
terminals, causing decreased vascular smooth muscle contraction
β adrenergic receptors activate adenylyl cyclase to increase cAMP, which activates
protein kinases like protein kinase A, which phosphorylate cellular proteins, including
ion channels
 β1 adrenergic receptors – found mainly in the heart and kidney
 in the kidney, they’re found on juxtaglomerular cells, where activation
causes renin release
 Heart β1 adrenergic receptors cause an increase in force of contraction
and heart rate
 Force of contraction is regulated by increased phosphorylation of
calcium channels, including in the sarcolemma and phoshpolamban in
the SR
 Heart rate is controlled by β1 adrenergic receptor controlled SA node
 Both increase cardiac output (HR x SV)
 Activation of β1 adrenergic receptors also increase conduction velocity
in the AV node since it causes calcium entry to increase depolarization
 β2 adrenergic receptors – found in smooth muscle, liver, and skeletal muscle
 β2 adrenergic receptor activation stimulates adenylyl cyclase,
increasing cAMP, and activating protein kinase A
 Protein kinase A can phosphorylate myosin light chain kinase, reducing
it’s affinity for calcium-calmodulin, causing relaxation of muscle
 β2 adrenergic receptors can also relax bronchial smooth muscle by
activating potassium channels, causing hyperpolarization
 In the liver, activation of a β2 adrenergic receptors cause
phosphorylation that leads to activating glycogen phosphorylase,
causing glycogenolysis (glycogen breakdown)
 In skeletal muscle, both glycogenolysis and potassium hyperpolarization
are triggered
 Activating β2 adrenergic receptors in adipose increases lipolysis
So α1 and β1 cause symp actions on cardio, and α2 and β2 cause parasymp actions on
cardio
The ability of the agonists to cause signaling depends on the # of receptors activated
-
So changes in the # of receptors on the cell surface will affect how effective an agonist is
o Includes both short term (desensitization) and long term (down regulation)
When an agonist activates an adrenergic receptor, the dissociation of G proteins leads to downstream
signaling, and negative feedback to limit tissue responses
Accumulation of βγ subunits in the membrane recruits a G protein receptor kinase, which
phosphorylates the receptor at inhibitory residues to inhibit it
Protein kinase A and protein kinase C can phosphorylate G proteins
-
Phosphorylated G proteins can bind to a protein called β-arrestin, which inhibits receptor-G
protein interaction, inhibiting receptor signaling
Down regulation – when the receptor-β-arrestin complex is put into endosomes to be
internalized
o Uses clathrin coated pits
Effects of catecholamines:
-
-
-
Epinephrine and norepinephrine act as agonists of α and β adrenergic receptors
Epinephrine
o At low concentrations, epinephrine has mostly β1 and β2 effects
 At the β1 receptors – epinephrine increases cardiac output and contractility,
increasing systolic blood pressure
 At the β2 receptors, epinephrine causes vasodilation to decrease diastolic blood
pressure by decreasing peripheral resistance
 Stimulating a β2 also increased blood flow to muscle, relaxes lung
smooth muscle, and increases the concentrations of glucose nd free
fatty acids in the blood
o At higher concentrations, epinephrine has more α effects
o Epinephrine is used to treat anaphylaxis
o Locally injected epinephrine causes vasoconstriction and prolongs the action of local
anesthetics
o Epinephrine is ineffective orally due to a big first pass effect
o Epinephrine works quickly and has a short lasting effect when given IV
 Adverse effects to the IV form are arrhythmia and increased blood pressure
Norepinephrine
o Norepinephrine is an agonist at α1 and β1 receptors (so only symp cardio effects)
o So norepinephrine increases both systolic and diastolic blood pressures, and total
peripheral resistance
o Norepinephrine is used to treat hypotension, usually in shock
Dopamine
o Exogenously given dopamine has very little effect cause it can’t cross the blood-brain
barrier
o Dopamine is given by IV
o At low doses, dopamine works on mainly D1 dopaminergic receptors of the kidneys,
stomach, and heart
 D1 dopaminergic receptors activate adenylyl cyclase in vascular smooth muscle,
which increases cAMP and vasodilation
o
o
o
At higher doses, it activates β1 receptors
At even higher doses, dopamine acts on α1 adrenergic receptors to cause
vasoconstriction
Dopamine is used for shock, especially when the kidneys fail
Inhibitors of catecholamine making:
-
Not used often cause they aren’t specific and inhibit all catecholamines
α methyltyrosine- structural analogue of tyrosine that is taken into nerve terminals, where it
inhibits tyrosine hydroxylase, the first enzyme in the making of catecholamines
o Used sometimes to treat hypertension from a pheochromocytoma (tumor of the
chromaffin cells of the adrenal medulla)
o It’s use is limited because it causes orthostatic hypotension and sedation
Inhibitors of catecholamine storage:
-
-
-
Catecholamines that work on a receptor come from either being made or being recycled
Something that inhibits catecholamine storage can have two effects:
o Short term – it increases the release of catecholamines from the synaptic terminal
 This mimics symp stimulation, so it’s called sympathomimetic
o Long term – it inhibits symp activity, called a sympatholytic
Reserpine- binds to VMAT and irreversibly inhibits it
o So the vesicles then can’t store norepinephrine and dopamine
o At low doses, reserpine causes neurotransmitter leak into the cytoplasm, where the
catecholamine gets destroyed by MAO
o At high doses, the rate of catecholamine leak can be high enough to overwhelm the
MAO in the presynaptic neuron
 When this happens, there’s lots of catecholamine in the cytoplasm, that can be
put into the synaptic space by reverse NET, causing a sympathomimetic effect
o Reserpine’s inhibition of VMAT is irreversible, new vesicles have to be made to store
catecholamines
 This can take days to weeks
o Reserpine can cause severe depression
o Reserpine can be used for hypertension, but it’s side effects make it poor choice over
other less riskier treatment
Tyramine- normal dietary amine usually metabolized by MAO in the GI and liver
o When taking an MAO inhibitor, tyramine is taken up by symp neurons and transported
by VMAT to vesicles, where it can displace norepinephrine and cause big release of
norepinephrine through reversal of NET
o Fermented foods like red wine and cheese have lots of tyramine in them
o Tyramine itself is poorly held in synaptic vesicles
 Its metabolite octopamine can be stored at high concentrations in the vesicles
 Made by vesicular dopamine-β-hydroxylase
o
-
-
-
-
When taking MAO inhibitors and decreasing tyramine intake, norepinephrine can be
replaced in the vesicles by octopamine
o Octoopamine has little agonist activity at adrenergic receptors, so you have decreased
symp effects
 So MAO inhibitors can cause hypotension by kicking out catecholamines and
taking their place instead in the vesicles
Guanethidine- works just like tyramine, and is actively transported into vesicles by NET,
displacing norepinephrine, and decreasing symp effect
o Like octopamine, guanethidine isn’t an agonist at adrenergic receptors
o Used to treat hypertension
Both MAO inhibotors and guanethidine can cause hypotension after exercise or when standing
up (postural hypotension)
Guanadrel – another false neurotransmitter similar to guanetidine
o Used to treat hypertension
Ampthetamine
o Jobs:
 Displaces catecholamines from vesicles
 It’s a weak inhibitor of MAO
 Blocks catecholamine reuptake mediated by NET
o So amphetamine basically is a thing to kick out catecholamines to cause temporary
symp effects, followed by a crash when the catecholomines go away
o Although amphetamine binds to postsynaptic adrenergic receptors, it has little agonist
action at adrenergic receptors
o Amphetamine causes increased alertness, decreased fatigue, depressed appetite, and
insomnia
o Amphetamine is used to treat depression, narcolepsy (attacks of drowsiness and sleep
during the daytime), and to suppress appetite
o Has substantial side effects, like fatigue and depression following the stimulation it
caused
Ephedrine, pseudoephedrine, and phenylpropanolamine
o Have some ability to activate adrenergic responses
o Phenylpropanolamine was removed from over the counter markets int eh US due to
concerns of cerebral hemorrhage
o Ephedrine is used to treat hypotension
o An herbal source of ephedrine is ma huang, which the Chinese use to treat asthma
o Pseudoephedrine is used as an over the counter decongestant in cold remedies
Methylphenidate- structural analogue of amphetamine used to treat ADHD
o It enhances attention
Amphetamine can cause psychological and physiologic dependence, and tolerance
o Amphetamine can cause paranoia and hallucinations
o Methamphetamine is a drug that’s often abused
Inhibitors of catecholamine reuptake
-
-
These have an acute and powerful sympathomimetic effect by prolonging how long the
released catecholamine stays in the synaptic cleft
Cocaine- strong inhibitor of NET that eliminates catecholamine transport
o It’s used sometimes as a local anesthetic because it can inhibit action potentials
o Often abused
Tricyclic antidepressants- inhibit NET mediated reuptake of norepinephrine into presynaptic
terminal, allowing norepinephrine to stay in the synaptic cleft
Inihbitors of catecholamine metabolism:
-
Monoamine oxidase inhibitors (MAOI’s) – prevent secondary deamination of catecholamines at
presynaptic terminals or the liver
o In the absence of metabolism, more catecholamine accumulates in presynaptic vesicles
for release during each action potential
o Most MAOIs are oxidized by MAO to intermediates that irreversibly inhibit MAO
o Nonselective agents inhibit both MAO-A and MAO-B
 Includes phenelzine, tranylcypromine, and iproniazid
o Clorgyline is selective for MAO-A
o Selegiline is selective for MAO-B
o Brofaromine, befloxatone, and moclobemide, are reversible inibitors of MAO-A
o MAOIs are used to treat depression
o Selegiline is also used to treat Parkinson’s
o Patients taking MAOIs need to avoid eating fermented foods with tyramine and other
monamines, because MAOIs block any inhibiting of monoamines in the GI and liver,
allowing them to enter the circulation and cause hypertensive crisis
o Don’t mix MAOIs and SSRIs, because it could cause serotonin syndrome
 Shows restlessness, tremors, seizures, coma, or death
o The reversible MAOIs have less adverse effects
Adrenergic receptor agonists - These are used to regulate vascular tone, smooth muscle tone, and
contractily
-
So they’re used for hypertension, asthma, and heart conditions
α adrenergic agonists
o α1 adrenergic agonists- increase peripheral resistance to increase blood pressure
 can cause bradycardia through activating a reflex vagal response through
baroreceptors
 systemically given α1 adrenergic agonists, like methoxamine, don’t have much
clinical use, but are sometimes used for shock

-
topical α1 adrenergic agonists, like phenylephrine, oxymetazoline, and
tetrahydrozoline, are used in nonprescription Afrin and Visine, cause
vasoconstriction for nasal congestion and hyperemia, to relieve symptoms
 Extended use of these can cause damage to the nasal mucosa and
hypersensitivity, along with return of symptoms
 Phenylephrine is used IV to treat shock
o α2 adrenergic agonists
 Clonidine is an α2 adrenergic agonist that lowers blood pressure by acting in
brainstem vasomotor centers to suppress symp flow to the periphery
 Clonidine may decrease heart problems in hypertension, and has a little
ability to help with symptoms from alcohol or opiate withdrawal
 Adverse effects of clonidine are postural hypotension, bradycardia, dry
mouth, and sedation, from increase vagus and decreased symps
 Guanabenz and guanfacine are also α2 adrenergic agonists that similar adverse
effects to clonidine
 Dexmedetomidine- α2 adrenergic agonist that is used to cause sedation in
surgery, since it has no respiratory effects
 Helps to avoid swings in blood pressure during surgery
 α methyldopa- prodrug precursor of the α2 adrenergic agonist αmethylnorepinephrine
 Used in hypertension to decrease symp flow from the CNS
 Rarely used cause it can cause liver toxicity, hemolytic anemia, and CNS
problems
o Exception is hypertension in pregnancy, where it is the drug of
choice
β adrenergic agonists
o β1 adrenergic agonists - Stimulating a β1 adrenergic agonist increases heart rate and
force of contraction to increase cardiac output
o β2 adrenergic agonists - stimulating a β2 adrenergic agonist causes relaxation of vascular,
bronchial, and GI smooth muscle
 β2 adrenergic agonists are used to treat asthma
 They’re good choices because they have less effects at non-target
tissues, like the heart
 Specificity for the lungs only, is further enhanced by delivering the drug
through aerosols inhaled directly into the lungs
 They relax bronchial smooth muscle and decrease airway resistance
 Adverse effects come from not being completely selective, and
therefore skeletal muscle tremor from muscle β2’s, and tachycardia
from β1’s
o Nonselective β adrenergic agonists


Isoproterenol- lowers peripheral resistance and diastolic pressure, while
increasing or leaving unchanged the systolic pressure
 It increases cardiac output by increasing HR and contractility
 Used to relieve bronchoconstriction in asthma
o Use for asthma can cause adverse heart effects, so more
selective β2 adrenergic agonists are usually used
 Isoproterenol can sometimes be used to stimulate heart rate in
emergencies with lots of bradycardia, especially when putting in a
pacemaker
Dobutamine- a β1 agonist
 Dobutamine increase contractility and cardiac output
 Dobutamine can be used IV in severe heart failure
 It’s also used with heart imaging to diagnose ischemic hearts
Receptor antagonists:
-
α-adrenergic antagonists - They cause vasodilation, decreased blood pressure, and decreased
peripheral resistance
o Block binding to α1 and α2
o The baroreceptor reflex usually attempts to compensate for the fall in blood pressure,
causing a reflex increase in heart rate and cardiac output (reflex tachycardia)
o Phenoxybenzamine- irreversibly blocks α1 and α2 receptors, and inhibits catecholamine
uptake into adrenergic nerves and the tissue
 Used to treat hypertension and benign prostatic hyperplasia
 Because it has so many effects on the symps, it’s rarely used clinically
 Can be used before surgery on a pheochromocytoma to decrease risk for
problems during the surgery
o Phentolamine- reversible, nonselective α-adrenergic antagonist
 Used for hypertension and before surgery on a pheochromocytoma
o Prazosin- has a much higher affinity for α1 receptors than α2
 It’s selective block of α1 causes decreased peripheral resistance, and dilation of
veins (called capacitance)
 Capacitance decreases venous return, and therefore cardiac output
 Prazosin is an antihypertensive drug
 A lot of times the first dose of prazosin can cause postural hypotension and
syncope, so you start by giving them a low dose
o Terazosin and doxazosin work similar to prazosin, but have longer half lives
o α1-adrenergic antagonists aren’t often used for hypertension, cause other meds work
better
o Some α1-adrenergic antagonists are used to treat the symptoms of benign prostatic
hyperplasia
 They are more effective and work faster than other drugs


-
The main receptor of GU is α1A
Tamsulosin- selective antagonist for α1A
 May have less risk for orthostatic hypotension
o Drugs like yohimbine are selective antagonists for α2 receptors, and cause release of
norepinephrine, which then stimulates heart β1 receptors and peripheral α1 receptors
 They also cause insulin resistance by blocking α2 receptors in the pancreatic
islets, suppressing insulin secretion
 Yohimbine has been used to treat erectile dysfunction
β-adrenergic antagonists - block catecholamines at β1 receptors, to decrease heart rate and
contractility
o β-adrenergic antagonists decrease blood pressure in hypertensive patients, but don’t
have an effect on people with normal blood pressure
o Long term use decreases peripheral resistance
o So β-adrenergic antagonists are used to treat hypertension
o Nonspecific β-adrenergic antagonists also affect β2’s in the lungs, which can cause life
threatening bronchoconstriction in people with asthma
o β-adrenergic receptor therapy can be divided into:
 Nonselective β-adrenergic antagonists
 Nonselective β and α1 adrenergic antagonists
 β-adrenergic partial agonists
 β1-adrenergic antagonists
 page 141
o Propranolol, nadolol, and timolol are nonselective, and are used to treat hypertension
and angina
 Although nonselective β blockers are usually contraindicated in people with
asthma, these ones are good for COPD
 Nadalol can be used to prevent bleeding from esophageal varices in cirrhosis
 Good cause it has a long half life, and is excreted by the kidneys
o Timolol is a nonselective β blocker used for glaucoma, and can cause adverse effects
o Levobunolol and carteolol are nonselective β blockers used in eye drops for glaucoma
o Labetalol and carvedilol block α1, and β1 and β2 blockers
 Labetalol has 4 stereoisomers that make it hard to predict its effect on the
patient
 The α1 part lowers peripheral resistance, and the β block decreases blood
pressure
 So it’s used for hypertension IV
 Labetalol can cause hepatitis
 Carvedilol is used for hypertension and systolic heart failure
o Pindolol- partial agonist of β1 and β2
 Used for hypertension

o
o
o
o
Since it’s only a partial agonist of β1, it has less of a decrease in heart rate and
blood pressure than pure β antagonists
Acebutolol- partial agonist of β1
 Used for hypertension
Esmolol, metoprolol, atenolol, and betaxolol – β1 selective adrenergic antagonists
 Esmolol has a very short half life of minutes
 Metoprolol and atenolol have intermediate half lives of hours
 Becauase of its shorter half life, esmolol may be safer in unstable patients
 Esmolol gets rapidly metabolized by esterases
 Metoprolol may increase life expectancy in people with mild heart failure, or
who have survived an MI
Nebivolol- selective β1 adrenergic antagonist that causes vasodilation with NO
Adverse effects of β-adrenergic antagonists are related to their jobs they do
 Includes worsened bronchoconstriction in asthma, decreased cardiac output in
decompensated heart failure, difficulty recovering from hypoglycemia of
diabetes
Receptors
-
Alpha 1 – vasoconstriction from phospholipase C
Alpha 2 – vasodilation from inhibiting adenylyl cyclase
Beta 1 – symps at heart and kidney from activating adenylyl cyclase
Beta 2 – muscle relaxation (including vessels and lungs) from protein kinase A inhibiting myosin
light chain, and increase gluconeogenesis