Sympathomimetics & Agonists Flashcards
endogenous catecholamines
- epinephrine
- norepinephrine
- dopamine
synthetic catecholamines
- isoproterenol
- dobutamine
synthetic noncatecholamines
- ephedrine
- amphetamine
- phenylephrine
selective alpha-2 adrenergic agonists
- clonidine
- dexmedetomidine
selective beta-2 adrenergic agonists
- albuterol
- terbutaline
- ritodrine
CV effects of SNS stimulation
- increased HR
- increased BP
- increased contractility
- susceptibility to ectopy
pulm effects of SNS stimulation
bronchodilation
effects of SNS stimulation on vasculature
- vasodilation/improved blood flow to skeletal muscle
- vasoconstriction/decreased flow to skin, GI, renal systems
how does SNS stimulation impact CNS
increased cognition
(except alpha-2 stim, which inhibits)
endocrine effects of SNS stimulation
- lipolysis
- glycogenolysis
- increased blood sugar
how are sympathomimetics used in regional anesthesia
- increase contractility or vascular tone r/t sympathetic blockade
- to prolong regionals
clinical uses of sympathomimetics (5)
- treat sympathetic blockade from regional blocks
- prolong regionals
- increase or maintain BP/prevent tissue ischemia while hypovolemia corrected
- bronchodilation in asthmatic
- to manage anaphylaxis
how does SNS stimulation affect coagulation
increased rate of coagulation
how do alpha agonists vs. alpha blockers affect your pupils
(table 13.2)
- agonist: mydriasis - dilation
- blocker: miosis (slight) - constriction
one of these days i’ll remember what these are
how do beta-agonists vs. blockers impact eyeballs
(table 13.2)
- agonists: no clinical effect
- blockers: decreased IOP
how do alpha agonists vs. blockers impact HR
(table 13.2)
- agonists: reflex bradycardia
- blockers: reflex tachycardia
how do beta-agonists vs. blockers impact HR
(table 13.2)
- agonists: increased HR
- blockers: decreased HR
how do beta agonists vs. blockers impact contractility
(table 13.2)
- agonists: increased
- blockers: decreased
how do beta agonists vs. blockers impact conduction velocity (table 13.2)
- agonists: increased
- blockers: decreased
how do alpha agonists vs. blockers impact blood vessels
(table 13.2)
- agonists: constriction
- blockers: dilation
how do beta agonists vs. blockers impact HR
(table 13.2)
- agonists: increase
- blockers: decrease
how do cholinergics affect:
- eyes
- heart rate, contractility, and conduction velocity
- blood vessels
- lungs
- GI
- uterus
- liver
(table 13.2)
- eyes: miosis and decreased IOP
- dec. HR & conduction velocity
- slightly dec. contractility
- bronchoconstriction
- increased GI motility and secretion
- no effect on blood vessels, uterus, liver
how do beta agonists vs. blockers impact blood vessels
(table 13.2)
- agonists: dilation
- blockers: constriction
how do alpha and beta agonists impact the GI tract vs. alpha and beta blockers?
(table 13.2)
- alpha & beta agonists decrease motility and secretion
- alpha blockers - no effect
- beta blockers - GI relaxation
how do alpha and beta agonists impact the uterus?
(table 13.2)
- alpha agonist = contraction
- beta agonist = relaxation
how does a sympathomimetic have direct effects?
which ones have this MOA?
bind to receptors and activate directly
catecholamines & phenylephrine
(both endogenous and exogenous catecholamines)
epi, NE, DA, isoproterenol, dobutamine + phenylephrine
how does a sympathomimetic have indirect effects?
what drugs fall in these categories?
- cause release of NE from postganglionic sympathetic nerve endings (amphetamine)
or
- block reuptake of NE to keep more in circulation (cocaine, TCAs)
patients who may not respond to indirect-acting sympathomimetics
- denervation (heart transplant)
- depletion (sepsis)
- pt taking MAOIs
what is tachyphylaxis?
the greater the concentration of the sympathomimetic, the lower the number of receptors in tissues or decreased response
(need more drug for desired response)
how can increased concentrations of norepi result in tachyphylaxis?
fewer adrenergic receptors on cell membranes
how can albuterol lead to tachyphylaxis?
chronic treatment causes the number of beta 2 receptors to decrease (down-regulation)
which sympatomimetic given for BP has a big problem with tachyphylaxis?
ephedrine - might give 5mg and then when BP drops 10 min later have to give 10 mg for same resposne as before
what mechanism is the most responsible for termination of catecholamine effect?
uptake back into post-ganglionic sympathetic nerve endings
why are catecholamines short-lived?
metabolism by MAO and COMT
the lungs are responsible for filtering some portion of what 2 catecholamines
norepi & dopamine
metabolism of noncatecholamine sympathomimetics
- inactiated by MAO only
- no reuptake
which tends to last longer - catecholamines or noncatecholamines?
noncatecholamines
which receptors does epi act on
alpha and beta (dose dependent)
α1 = α2
β1 = β2
which sympathomimetic is the most potent alpha stimulant
epi
why is SQ epi absorbed more slowly than IV?
epi-induced vasoconstriction
does epi have cerebral effects?
no - poorly lipid-soluble, doesn’t cross BBB
where is epi synthesized, stored, and released from?
(Flood)
adrenal medulla
what effect of high dose epi can contribute to mortality in anaphylaxis?
alpha stimulation
make sure you give the correct dose and concentration :)
clinical uses of epi (4)
- decrease absorption and prolong duration of LAs
- treat anaphylaxis
- treat cardiac arrest
- increase contractility
what is considered a low-dose epi gtt?
receptors affected & their actions
.01-.03 mcg/kg/min mcg/min
- β1: increase HR, BP, CO, inotropy
- β2: decreased DBP d/t decreased SVR
why might low-dose epi decrease coronary perfusion?
decreased DBP
per Flood, epi enhances coronary blood flow (I guess at higher doses, doesn’t say)
net vascular effect of low-dose epi gtt
- distribution of blood flow to skeletal muscle
- decreased SVR
- decreased RBF
moderate-dose epi gtt
receptors affected & their actions
.03-1.5 mcg/kg/min
or 4 mcg/min according to that stupid PDA sheet
- β1 - increased SBP, HR, CO, inotropy
- I guess some α too
- increased venous return
- increased susceptibility to arrhythmias mixed with α
why does moderate dose epi cause increased venous return?
vasoconstriction r/t high concentration of α receptors in venous vascualture
large dose epi gtt
receptors impacted
10-20 mcg/min
both beta & alpha-1
(was this the answer on the test?)
predominant receptor activated with high dose epi gtts
what are its effects?
alpha
vasoconstriction of skin, mucosa, hepatorenal vessels
decreased RBF
SVT is common with what dose epi gtt
high (>0.15 mcg/kg/min)
what determines epi’s overall effect on blood flow to a specific organ?
(Flood)
the relative balance of alpha1 & beta2 receptors in the vasculature of particular organ
when might epi cause bronchonstriction?
in a pt taking beta-blockers (especially nonselective) d/t unopposed alpha1 effects
how does epi affect bronchial smooth muscle?
this is due to which receptor?
relaxed (beta 2)
how does epi affect blood sugar
increases
metabolic effects of beta 2 activation with epi
Flood says its beta 1 so idk
increased glycogenolysis and lipolysis
metabolic effects of alpha-2 stimulation with epi
again, Flood says alpha 1
inhibits release of insulin (hyperglycemia)
electrolyte abnormality that may be seen with epi
why?
hypokalemia
stress-induced d/t activation of Na-K pump on RBCs (beta 2)
buttt hyperkalemia initially because it follows glucose out of the cell or something like that
ocular effects of epi
which receptor is reponsible
alpha-1
- contraction of radial msucles of iris = pupil dilation
- contraction of orbital muscles = eye bulging
why is BP generally increased with epi?
(Flood)
increase in cardiac index as well as increase in SVR
affects of epi on HR
(Flood)
initial tachycardia may be followed by decrease d/t baroreceptor reflexes
increased HR by accelerating rate of spontaneous 4 depolarization (also inc. dysrhythmias)
which catecholamine has the most significant metabolic effects?
epi
what is the most likely explanation for periop hyperglycemia?
(Flood)
release of endogenous epi resulting in glycogenolysis and inhibition of insulin secretion
what’s the explanation for why beta 2 agonist effects are responsible for hypokalemia?
(Flood)
a nonselective beta blocker (propranolol) can prevent hypokalemia but a selective beta-1 blocker (atenolol) can’t
how does epi affect GI/GU smooth muscle
- relaxation of GI smooth muscle
- beta - relaxation of bladder detrusor muscle
- alpha1- contracts bladder sphincter
- (slowed GI motility and urinary retention)
which receptors does norepi activate?
potent alpha, beta-1
α1= α2; β1>>β2
clinical use of norepi
vasoconstriction to increase SVR and BP
(ex - sepsis, coming off bypass)
why is it important to have a NE infiltration protocol?
(lol we def didnt have this)
infiltration of NE into sub-q tissue can cause necrosis d/t vasoconstriction
which endogenous neurotransmitter is synthesized and stored in postganglionic sympathetic nerve endings and released with sympathetic nerve stimulation?
(Flood)
norepi
alpha 1 effects of norepi
- vasoconstriction of arterial and venous vessels of all vascular beds
- increased SVR, MAP
- increased venous return (at lower doses)
- decreased HR
venous return with higher vs. lower doses of NE
lower doses - increased
higher - decreased d/t constriction proximal to capillary bed (causes fluid trapping, leakage into interstitial space)
what receptor does “low dose” norepi work on?
what are the effects of activation?
beta 1 selective
increased HR, increased inotropy
receptors activated by “high dose” norepi
effects of activation
α1, α2, β1
increased SVR, BP
decreased HR (baroreceptor reflex)
dose range of norepi gtt
0.02 - 0.4 mcg/kg/min
according to Flood, norepi causes potent arterial and venous vasoconstriction in all vascular beds except
coronary arteries
why might you see minimal changes in HR with a norepi gtt?
(Flood)
baroreceptor reflexes triggered by arterial vasoconstriction are counteracted by beta1 mediated increased HR
how does norepi primarily increase MAP?
(Flood)
vasoconstriction
(to lesser degree by increased SV & CO)
what effect do epi and norepi have on coronary arteries?
(Flood)
both dilate
what are the metabolic effects of norepi?
really aren’t any
why are resp effects not really seen with norepi?
no beta 2 effects
what conditions is norepi ideal for?
when should it be used v cautiously?
- ideal for sepsis or post bypass with decreased SVR
- caution/avoid in pts with cardiogenic shock or LV failure due to increased afterload and mycocardial O2 demands
which neurotransmitter is the immediate precursor to norepi
(Flood)
dopamine
which catecholamine is described:
endogenous neurotransmitter in the central and peripheral nervous systems
dopamine
receptors activated by dopamine
D1=D2 >> β >> α
what dose of dopamine has an indirect sympathomimetic effect via NE release?
moderate (2-10 mcg/kg/min)
what is a low dose dopamine gtt?
what receptors are activated?
0.5-3 mcg/kg/min
or 1-2 mcg/kg/min depending on who ya ask
D1 (Flood says D2 also)
moderate dopamine gtt dose
what receptors are activated & where
3-10 mcg/kg/min
beta-1 in the heart
CV effects of low dose dopamine gtt
vasodilation
may have decreased BP
Flood: diuresis, natriuresis; may have reflex increased HR d/t decreased DBP
why does moderate dose dopamine increase CO?
beta-1 activation, increased inotropy
Per Flood, also: increased chronotropy, vasodilation, afterload reduction, increased stroke volume
what is a high-dose dopamine gtt?
what receptor(s) does it act on & where?
10-20 mcg/kg/min
alpha-1 in peripheral vessels
effects of alpha-1 stimulation in vascular smooth muscle with high-dose dopamine gtt?
(Flood)
- arterial and venous vasoconstriction
- increased SVR
- increased BP
why might dopamine be an unreliable mechanism for increasing CO in pts with chronic heart failure?
(Flood)
a portion of dopamine’s effect is d/t stimulation of endogenous NE release - may not work well for pts with depleted catecholamine stores
did giving our kidney transplant patients dopamine for BP and maintaining UOP help with M&M?
nope, apparently not :)
why might you have a hard time weaning a pt off the vent while they’re on a dopamine gtt?
inhibits ventilatory response to arterial hypoxemia
why might a dopamine gtt increase susceptibility to arrhythmias?
NE release
(still less susceptible than with epi)
how does a dopamine gtt affect myocardial O2 supply and demand
may make demand > supply
indications for a dopamine gtt
- increase CO in pts with low BP, inc. atrial filling pressures, and low UOP
- “renal dose dopamine” though studies show this is a waste of time
indications for a dopamine gtt
- increase CO in pts with low BP, inc. atrial filling pressures, and low UOP
- “renal dose dopamine” though studies show this is a waste of time
renal effects of dopamine gtt
increased:
- RBF
- GFR
- UOP
- Na+ excretion (inhibits aldosterone)
3 things that antagonize renal effects of a dopamine gtt
- arterial hypoxemia
- droperidol
- reglan
which 2 catecholamines are useful when combined together?
why?
(Flood but I think she mentioned this)
- dopamine & dobutamine
- both are inotropic but each dilates different vascular beds
- objective is to increase coronary perfusion and CO while decreasing afterload
which catecholamine can depress the immune system?
(Flood)
dopamine
there are a bunch more details in the book but skipping since she didnt mention this
why does dopamine interfere with ventilatory response to hypoxemia & hypercarbia?
(Flood)
inhibitory actions at carotid bodies
which catecholamine is unique in that can simultaneously increase contractility, RBF, Na+ excretion, and UOP?
(Flood)
dopamine
which receptors does dobutamine work on
beta 1 > beta 2 >>>>> alpha
dose used for dobutamine gtt
0.5-15 mcg/kg/min
2-10mcg/kg/min (from PDA)
how does dobutamine cause increase CO?
(Flood)
primarily by increase in SV
how does dobutamine affect SVR and PVR?
both decrease
how does dobutamine impact myocardial O2 demand vs dopamine
dobutamine - minimal increase in O2 demand, less imbalance in myocardial O2 supply/demand
how does dobutamine affect coronaries?
coronary dilation = increased supply (balances increased demand)
how does dobutamine affect renal perfusion?
does not cause renal vasodilation, but can still improve renal perfusion via increased CO
adverse effects of high dose dobutamine
increased HR, dysrhythmias
respiratory affects of dobutamine
(Flood)
pulmonary vasodilation may worsen V/Q mismatch
inhibits HPV
indication for a dobutamine gtt
increase CO in pts with CHF
indication for a dobutamine gtt
increase CO in pts with CHF
when is it beneficial to combine dobutamine with a vasodilator?
significant LV failure - to decrease SVR and improve CO
which catecholamine is the most potent beta-agonist
isoproterenol
beta 1 effects of isoproterenol
- increased HR
- inotropy
- susceptibility to dysrhythmias
beta 2 effects of isoproterenol
- decreased SVR
- vasodilation in skeletal muscle
overall CV effects of isoproterenol
decreased MAP, decreased coronary blood flow, increasd O2 demand
why is isoproterenol no good for pts with CAD
decreased coronary blood flow r/t decreased MAP and increased HR
clinical uses of isoproterenol
- increase HR in pts with heart block
- induce dysrhythmias in cath lab
- chemical pacemaker
- pHTN and RV dysfunction (Flood)
how does ephedrine have both direct and indirect effects?
- direct effect on beta receptors
- indirect effect on alpha receptors from the NE release
duration of ephedrine
prolonged - slow inactivation & excretion
initial vs subsequent IV dose of ephedrine
general dose: 2.5 - 10 mg
increase subsequent doses to obtain same response (tachyphylaxis)
beta 1 effects of ephedrine
- increased SBP and DBP
- increased HR
- increased CO
- increased contractility (principle effect)
alpha 1 effects of ephedrine
- vasoconstriction
- decreased renal & splanchnic flow
beta 2 effects of ephedrine
- vasodilation
- increased coronary artery & skeletal muscle flow
potency of ephedrine vs epi
epi is 250x more potent
effects of epi vs ephedrine on DBP
epi may decrease DBP
ephedrine increases DBP
is SVR affected by ephedrine? why or why not?
may not change much as vasodilation of some vessels will offset vasoconstriciton of others
effects of ephedrine if given to a patient on beta blockers
response may resemble alpha agonist
CNS effects of ephedrine
crosses BBB, increases MAC
respiratory effects of ephedrine
beta 2 stim = bronchodilation
why is ephedrine maybe not the drug of choice for preggos (according to TC and not MBG, who doesn’t know shit)
higher incidence of fetal acidosis vs. phenylephrine
indications for ephedrine
- temporarily increase BP d/t sympathetic blockade from neuraxial
- hypotension d/t inhaled or IV anesthesia
- bronchodilation
- nasal congestion
- antiemetic (0.5 mg/kg IM)
direct and indirect effects of phenylephrine
- mostly direct effects - alpha 1
- very small indirect effects - can evoke NE release
CV effects of alpha 1 stimulation with phenylephrine
- increased BP
- susceptibility to dysrhythmias
- decreased CO d/t increased afterload or reflex bradycardia
- decreased blood flow to kidneys, skin, splanchnic system
how does phenylephrine affect coronaries
increased flow d/t prolonged diastolic time
CNS effect of phenylephrine
decreased cerebral O2 sat
indications for phenylephrine
- increase BP d/t sympathetic blockade or vasodilation (volatiles)
- increase BP in pts with CAD or aortic stenosis
- maintain BP during carotid endarterectomy
- slow HR r/t SVT
- nasal decongestant
- prolong duration of spinal anesthesia
as a rule, what is the preferred agent for treatment of hypotension in CAD?
phenylephrine
(increased coronary perfusion without increased HR)
how does a phenylephrine gtt impact concurrent potassium supplementation?
(Flood)
stimulation of alpha receptors during acute K+ loading interferes with movement of K+ ions across cell membranes
(admin. in absence of acute K+ load doesn’t change plasma K+ concentrations)
MOA of clonidine
centrally acting partial alpha 2 agonist
CNS effects of clonidine
- decreased sympathetic output from CNS
- hyperpolarizes cell membranes in CNS (potential to decrease MAC up to 50%)
CNS effects of clonidine
- decreased sympathetic output from CNS
- hyperpolarizes cell membranes in CNS (potential to decrease MAC up to 50%)
does clonidine cause vasodilation or constriction?
why?
vasodilation via stimulation of alpha2 inhibitory neurons in medullary vasomotor center
how does clonidine affect neuraxial blocks?
inhibits substance P release, blunts perception of noxious stimuli
CV effects of clonidine
dose-dependent decreases in BP, HR, and CO
does clonidine affect renal blood flow?
maintained, but could still have decreased renal perfusion r/t decreased BP/CO
why is clonidine no longer used as a premed?
most common side effect is sedation
also issues with BP, HR, CO changes
why might bradycardia with clonidine require treatment with an anticholinergic?
decreased catecholamine levels
adverse effect of suddenly stopping clonidine
rebound HTN
indications of clonidine
- neuraxial analgesia
- use as a premed
- prolongs effects of regional anesthesia
- to diagnose pheochromocytoma
- treat opioid withdrawal
- treat shivering
benefits of clonidine in neuraxial techniques
analgesia without ventilatory depression, pruritis, N/V, delayed gastric emptying
uses of clonidine as a premed
(which isn’t really done anymore)
- blunts response from DL
- decreased lability of BP/HR ((((this seems opposite of why she said we dont use it)))
- decreases catecholamine concentrations
- decreases MAC and IV induction requirements
- accentuates ephedrine
- decreases incidence of myocardial ischemic episodes in pts with CAD
how is clonidine used to diagnose pheochromocytoma?
if reduced release of catecholamines from nerve endings is seen with clonidine admin (whatever that means), the patient doesn’t have pheo
why is clonidine considered a sympatholitic?
decreased release of NE
which agent can be used to treat shivering? why?
clonidine - inhibits central thermoregulatory control
MOA of dexmedetomidine
(Precedex)
alpha 2 agonst
AE of rapid precedex admin
HTN
recommended loading dose and gtt maintenance rate of precedex
loading: 1 mcg/kg over 10 min
gtt: 0.2-0.7 mcg/kg/hr
how does precedex affect MAC?
decreases > 90%
which has an increased likelihood of hypotension and hypothermia - precedex or clonidine?
precedex
withdrawal symptoms may be seen after precedex is used for how long?
24 hours
a large IV bolus of precedex resembles what catecholamine? why?
(Flood)
0.25-1 mcg/kg over 3-5 min results in paradoxical HTN with decreased HR
resembles phenylephrine - resultant effect of crossover alpha 1 stim.
MOA of albuterol
selective beta 2 agonist
beta 2 >> beta 1 >>>>> alpha
2 uses of albuterol
- prevent/treat bronchoconstriction in asthma or COPD
- stop premature uterine contractions
why might you want to avoid albuterol in hypotensive pts?
vasodilation can offset protective vasoconstriction
side effects of albuterol r/t beta 2 receptors on skeletal muscles
tremors
lab values that might change with acute albuterol admin
- hyperglycemia
- hypokalemia
- hypomagnesemia
