Sympathomimetics and Sympatholytics Flashcards
Which branches of the nervous system have ganglions?
Both the parasympathetic and the sympathetic
BUT NOT the somatic. All motor neurons are one long neuron
The peripheral nervous system employs three neurotransmitters:
Acetylcholine
Norepinephrine
Epinephrine
What are cholinergic receptors?
Regulate responses to Acetylcholine
What are adrenergic receptors?
mediate response to epinephrine and norepinephrine
Where are NM Receptors located?
Where are Muscarinic Receptors located?
Where are NN receptors located?
What are the muscarinic target organs?
Eye (miosis)
Heart (decreased HR)
Lung (Bronchial constriction)
Bladder and Bowels
Sweat Glands
Sex organs (erection)
Blood vessels (vasodilation)
Does parasympathetic stimulation cause vasodilation?
NO! Even though there are muscarinic receptors on blood vessels, there are NO ParaSNS nerves that terminate on blood vessels
These receptors only matter when we’re using drugs
Epinephrine is specific to what receptors?
Alpha 1
Alpha 2
Beta 1
Beta 2
Dopamine is specific to what receptors?
Alpha 1
Beta 1
Dopamine
Norepinephrine is specific to which receptors?
Alpha 1
Alpha 2
Beta 1
Where are alpha 1 receptors found?
Eyes (dilation)
Arterioles (vasoconstriction in the skin, viscera, and mucous membranes)
Sex organs (ejaculation)
Prostate and bladder
Where are alpha 2 receptors found?
Presynaptic nerve terminals
Inhibit transmitter release
Where are Beta 1 receptors located?
Heart (increased rate, contractility, and conduction)
Kidney (release of renin, which increases BP)
Where are beta 2 receptors located?
Arterioles (dilation of arterioles in the heart, lungs, and skeletal muscles)
Bronchodilation
Uterus (relaxation)
Liver (glycogenolysis)
Skeletal muscle (contraction, glycogenolysis)
Where are dopamine receptors located?
Kidney (dilate kidney vasculature)
Which neurotransmitters act on Beta 2 receptors?
ONLY EPINEPHRINE
Where is epinephrine released from?
The adrenal medulla, NOT neurons
What are the naturally occurring catecholamines?
Epinephrine
Norepinephrine
Dopamine
What cerebral effects does epinephrine cause?
NONE
it isn’t lipid soluble, so it doesn’t cross the BBB
Which two adrenergic receptors effect the heart?
Alpha 1
Beta 1
What determines epinephrine’s specificity for alpha or beta receptors?
The dose
beta receptors are more sensitive to lower epinephrine doses (inotropy dose)
Alpha 1 receptors are more sensitive to higher doses (pressor dose)
A patient who takes a beta blocker develops a bronchospasm and you give them epinephrine. What will happen?
It will get worse.
Epinephrine causes bronchodilation via beta 2 receptors BUT it also stimulates bronchial alpha 1 receptors
If they’re on a beta blocker, you’ll get unopposed alpha 1 bronchoconstriction
What electrolyte changes does Epinephrine cause?
Beta 2 stimulation leads to increased transfer of potassium into cells, decreasing serum potassium
This is why a lot of patients with high pre-op anxiety come in with low K
BUT epinephrine also stimulates potassium release from the liver, so offsets most of the effect
Norepinephrine is a derivative of _______
and is the precursor of _______
dopamine
epinephrine
Which endogenous catecholamine exerts the strongest effect on BP and SVR?
Norepinephrine exerts a much stronger effect than epinephrine
What are the metabolic effects of norepinephrine?
Unlike epinephrine, there really aren’t that many
Doesn’t usually cause hyperglycemia
Is norepinephrine an inotrope?
yes and no
it acts on Beta 1 receptors to increase HR, contractility and conduction BUT it’s alpha 1 action is so strong that the increased afterload may decrease CO
Does dopamine cross the BBB?
No. It’s very polar.
What Dopamine dose rate stimulates D1 and D2 receptors?
0.5-3 mcg/kg/min
What happens when D1 and D2 receptors are stimulated?
Decreased BP
vasodilation
increased renal and splanchnic flow
Diuresis
Natriuresis
What dopamine dose rate stimulates Beta 1 receptors and alpha 1 receptors?
3-10 mcg/kg/min
What dopamine dose rate stimulates primarily alpha 1 receptors?
> 10 mcg/kg/min
Which hormones does Dopamine inhibit?
anterior pituitary hormones:
Prolactin (which causes immune problems)
GH (impaired anabolism)
central hypothyroidism
How does dopamine impact ventilation?
low dose dopamine interferes with pulmonary hypoxic vasoconstriction and raises the CO2 threshold
Name the synthetic catecholamines:
Isoproterenol
Dobutamine
ISOPROTERENOL
CLASSIFICATION & MOA
Synthetic catecholamine
Beta 1 and Beta 2 selective agonist
Which causes more reflex tachycardia: dobutamine or isoproterenol?
isoproterenol
both because of direct beta 2 effects and because it causes more vasodilation, causing reflexive increase from decreased vascular tone
DOBUTAMINE
CLASSIFICATION AND MOA
Synthetic Catecholamine
Racemic mixture derived from isoproterenol
Potent Beta 1 effects
Weak Beta 2 effects
Some alpha effects at high dose
What makes dobutamine an inotrope?
It increases cAMP, increasing Ca release from the SR and increasing contractility
Is blood pressure effected by dobutamine?
It usually isn’t, because one enantiomer stimulates alpha 1, but the other antagonizes it
So usually the two equal out
How does dopamine impact pulmonary vasculature?
It does dilate, but not as much as phosphodiesterase inhibitors
Which is more dysrhythmogenic: dobutamine or dopamine?
Dopamine
Why does epinephrine results in increased lactate levels?
Decreased splanchnic flow means decreased lactate metabolism
There are two synthetic noncatecholamine sympathomimetics:
Ephedrine
Phenylephrine
EPHEDRINE
CLASSIFICATION & MOA
synthetic noncatecholamine sympathomimetic
DIRECTLY stimulates alpha and beta receptors
INDIRECTLY stimulates alpha and beta receptors by increased NE release
What are the clinical uses of ephedrine?
Increase BP
Decrease nausea (IM)
What is the PRINCIPAL reason that ephedrine increases BP?
increased contractility from Beta 1 activation
If beta blockers are on board, ephedrine will only cause vasoconstriction
How do the cardiovascular effects of ephedrine differ from those of epinephrine?
they’re less intense and longer lasting
Phenylephrine mimics the effects of ______
norepinephrine
PHENYLEPHRINE
CLASSIFICATION & MOA
Synthetic noncatecholamine sympathomimetic
Mimcs the action of NE mostly at alpha 1 receptors
Which one raises the heart rate: ephedrine or phenylephrine?
Ephedrine
Does phenylephrine cause venoconstriction or vasoconstriction?
mostly venoconstriction
What happens to cardiac output when phenylephrine is given?
It decreases
Maybe from increased afterload, but more likely from reflex bradycardia from baroreceptor response to the sudden increase in BP
Name two beta two agonists
albuterol
terbutaline
What is the primary side effect of using beta 2 agonists?
Muscle tremors because of B2 receptors in skeletal muscle
DIGOXIN
CLASSIFICATION & MOA
Cardia Glycoside
Inhibit the Na-K sodium pump in the sarcolemma
Bind to the alpha subunit on the ATPase enzyme and stop it from transporting sodium ions out
The increased sodium ion concentration blocks the Na-Ca pump, so calcium builds up inside the cell
having more calcium inside the cell = stronger contraction
What electrolyte imbalance may cause dig toxicity?
Hypokalemia
Hypomagnesemia
Hypoxemia
How are potassium and digoxin related?
Potassium interferes with the binding of digitalis on cardiac muscle
Which phosphodiesterase inhibitors impact cardiac cells?
PDE III
In the myocardium, increased intracellular cAMP concentration results in:
stimulation of protein kinases that phosphorylate the sarcoplasmic reticulum → increased inward calcium current → increased intracellular calcium → increased contractility
In vascular smooth muscle, increased cAMP results in:
facilitates uptake of calcium by the sarcoplasmic reticulum → decreased intracellular calcium → vasodilation and smooth mm relaxation
Milrinone improves cardiac output by:
improving contractility (increased ca in myocardium)
Decreasing preload and afterload (reduced ca in vasculature)
What are the three invariable side effects of all alpha blockers?
Orthostatic hypotension (can’t shunt blood)
Baroreceptor mediated reflex tachycardia
Impotence
PHENTOLAMINE
CLASSIFICATION & MOA
Non selective, competitive Alpha blocker
Alpha 1: peripheral vasodilation and decreased BP
Alpha 2: increased release of NE from the brain leads to increased HR and CO
What is the primary use for phentolamine?
acute hypertensive emergencies from pheochromocytoma manipulation or ANS hyperreflexia
PHENOXYBENZAMINE
CLASSIFICATION & MOA
Nonselective, irreversible alpha blocker
Blockade at both receptors, but primarily alpha 2
What is the primary use of phenoxybenzamine?
chronic alpha blockade for patients awaiting pheochromocytoma resection
Any drug ending in “-osin” belongs to what class?
Alpha blockers
Which beta blockers are preferred for patients with asthma and reactive airway disease?
Cardioselective beta blockers (beta 1 selective)
What are the effects of beta 2 blockade?
Bronchospasm
peripheral vascular insufficiency
Which beta blocker has the shortest half-life?
Esmolol
Which beta blocker has the longest half life?
Betaxolol and/or Nebivolol
How does propranolol impact clearance of LAs and opioids?
LAs: decrease clearance of amides because it decreases hepatic blood flow and inhibits metabolism
Opioids: decreases the first pass uptake of fentanyl. 2-4x as much drug enters the systemic circulation after injection
A patient with asthma is receiving metoprolol, but needs increasingly large doses. Eventually they develop wheezing. What should be given?
A Beta 2 agonist (terbutaline)
A patient with severe coronary artery disease should receive which beta blocker?
One that is as beta selective as possible BECAUSE beta 2 blockade will prevent coronary artery dilation
Atenolol is the current favorite for pre-treating cardiac patients undergoing noncardiac surgery
What does it mean if a beta blocker has intrinsic sympathomimetic activity?
It means that in addition to blocking certain beta receptors, it also agonizes others
If a patient cannot tolerate tachycardia due to intubation, which meds should be given?
Interestingly, lidocaine or fentanyl will reduce the BP response, but they will NOT stop the tachycardic response. Esmolol is a great choice for those patients.
How does esmolol interact with propofol?
It significantly decreases the plasma concentration of propofol required to prevent patient movement
How would giving a beta blocker impact blood sugar?
May cause hypoglycemia AND may mask the s/s of hypoglycemia
What’s the difference between membrane stabilization and blockade?
Most beta blockers act by removing SNS innervation to the heart. BUT at high doses they will also hyperpolarize the cardiac resting membrane potential
Name two beta blockers that are partial beta agonists
pindolol
acebutolol
What is the initial drug if a beta blocker overdose is suspected?
Atropine
A beta selective agonist (like isoproterenol)
Glucagon
Why is glucagon given in beta blocker overdoses?
It increases intracellular cAMP independent of Beta adrenergic receptors
How do beta blockers impact metabolism?
Ordinarily when BG is low epinephrine is released. Beta blockers prevent it from binding in the liver and initiating glycogenolysis
How do beta blockers influence potassium levels?
Beta 2 receptors facilitate movement of potassium INTRACELLULARLY
beta blockade inhibits the uptake of potassium into skeletal muscles, increasing plasma levels
How do beta blockers and volatile anesthetics interact with one another?
They generally don’t have much of an additive effect as far as myocardial depression goes
Sevo and Des have the least additive effect. Iso has a little.
How is the cardiovascular response to fentanyl altered by beta blockers?
It isn’t!
Even with high doses, the CV response isn’t altered
What impact do beta blockers have on the CNS?
fatigue and lethargy, but not well documented
Fetuses exposed to beta blockers are likely to be born with three symptoms:
bradycardia
hypotension
hypoglycemia
There are two combined alpha and beta receptor antagonists:
Labetalol
Carvedilol
Which receptors is labetalol selective for?
Selective Alpha 1
Nonselective Beta (1 and 2)
Alpha 2 is spared
Which calcium channel blockers are selective for the AV node?
Verapamil and Diltiazem
Which calcium channel blockers are selective for the arteriolar beds?
All the dihydropyridines:
Clevidipine, Nifedipine, Nicardipine, Nimodipine, Amlodipine
What are common side effects of calcium channel blockers?
hypotension
peripheral edema
flushing
headache
All calcium channel blockers bind to the same subunit of slow calcium channels:
the alpha 1 subunit
Which calcium channel blockers are effective in treating coronary artery spasm?
All of them
Which calcium channel blockers exert negative inotropic effects?
All of them, but verapamil and diltiazem are the most significant
Which patients should not receive verapamil?
Patients in heart failure or who have any kind of heart block
Verapamil may precipitate ventricular dysrhythmias in patients with what disease?
WPW
What is special about nimodipine?
It favors cerebral vessels
Are the dihydropyridines vasodilators or venodilators?
Almost exclusively arterial
What should you be on the lookout for anytime you begin a dihydropyridine?
reflex tachycardia
You’re decreasing BP but not blunting the heart
Why is nifedipine used as a tocolytic?
It prevents calcium from moving into the uterine cells, which decreases contractile strength
What is special about nicardipine?
It can be given IV. All the other dihydropyridines have to be given PO.
How do calcium channel blockers impact NMBAs?
They potentiate the effects of ALL NMBAs
Which calcium channel blockers have a local anesthetic effect?
verapamil and dilt
Do calcium channel blockers have effects at the NMJ?
Not in healthy patients, but in patients with muscular dystrophy they seem to cause pretty profound skeletal muscle weakness that isn’t consistent with just decreased neurotransmitter release
How do calcium channel blockers impact potassium movement across the cell membrane?
the slow the inward movement of potassium, which increases the risk for hyperkalemia
