Discussion: Part I
For answering the questions of the instructions given, the discussion of part I and part II each drug´s
characteristics will be presented chronologically along with the respective specificity and affinity of different
adrenergic receptors. The most important clinical responses will be discussed. Part III will include discussion of
the different effects by different combinations of the drugs in part I and part II.
Propranolol blocks β1 β2 β3
It is a beta antagonist (beta blocker), it is nonselective meaning it blocks beta-1, beta-2 and beta-3 receptors. It
causes bronchoconstriction and vasoconstriction. It lowers the heart rate and might lead to loss of consciousness
(syncope). Important to keep in mind that this drug in particular should be avoided in patients with peripheral
vascular disease because of the vasoconstriction. It might also worsen the symptoms of asthma/COPD patients
because of bronchoconstriction (11) (12) (17). Regarding blood pressure the drug is able to reduce it, something
that is consistent with the results observed in our simulations.
Atenolol blocks β1 (in the heart)
It is a beta antagonist (beta blocker), it is selective for beta-1 receptors mainly found in the heart (we say it is
cardioselective). The drug decreases the contractility, the atrioventricular node conductivity and the heart rate.
It can be used therapeutically to lower high blood pressure in patients (11) (12) (13) (17).
Phentolamine block ⍺1 ⍺2
It is a sympatholytic drug (it is antisympathetic), it is a nonselective antagonist for alpha receptors. The drug is
used to deal with an increase in blood pressure over 180/120 mm Hg (a hypertensive emergency). This can
happen with patients that are on MAO-inhibitors and have consumed tyramine (from fermented food/wine).
Another indication for administering phentolamine is in a patient with a tumor originating from “chromaffin
cells” of the adrenal medulla will have too much catecholamine secreted, this tumor is called
pheochromocytoma. The drug increases heart contractility and rate (18).
Part II
10
, Norepinephrine (noradrenaline) act on ⍺-1 > ⍺-2 > β1
It is a direct sympathomimetic endogenous agonist, it acts on both alpha and beta receptors. It has the highest
affinity for alpha-2, then alpha-2 then lastly beta-1 receptors. The drug lowers blood pressure as a result of
vasoconstriction, lowers the heart rate. It causes no change /or increase of cardiac output.
Epinephrine (adrenaline) act on β > ⍺ (at high doses: ⍺)
It is a direct sympathomimetic endogenous agonist, it acts on beta receptors at higher affinity than alpha
receptors. However at high dose alpha receptor effects dominate. Epinephrine has a stronger beta-2 receptor
effect than that of norepinephrine. While at an increased dose the drug is able to raise the blood pressure.
Increases heart rate and cardiac output (14).
Isoprenaline (Isoproterenol) act on β1 = β2 (minimal effect on ⍺)
It is a direct sympathomimetic drug, a non-specific beta-adrenergic agonist. The drug acts on both beta-1 and
beta-2 receptors. Minimal effect on alpha receptors. The drug raises heart rate and lowers blood pressure as a
result of vasodilatation and raises cardiac output. (11)(12)(13).
Phenylephrine act on ⍺1 > ⍺2
Is a direct sympathomimetic drug, alpha-adrenergic agonist. Acting on alpha-1 and alpha-2 receptors, favoring
alpha-1 receptors. The drug raises blood pressure as a result of vasoconstriction. The drug causes no change or
decrease in cardiac output. But it is able to lower the heart rate through reflex bradycardia, based on the
feedback from the baroreceptors.
The four different adrenoreceptor agonists cause different responses because they have different specificity for
receptors and affinity. Norepinephrine has a lower affinity for beta-1 receptors compared to epinephrine which
has high affinity for beta receptors (beta-1 and beta-2). Epinephrine is specific for both beta and alpha receptors
but higher affinity beta that is why we see a larger response from beta receptors on relaxation of blood vessels
and vasodilatation (baseline ABP 99 mmHG injected with epinephrine 10 mcg/kg 539.33 BPM) but at high
concentration alpha effect with increased contractility of the heart (baseline 363 BPM injected with epinephrine
10 mcg/kg 449 BPM).
Norepinephrine on the other hand has the highest affinity for alpha-1 receptors and characteristic effect of
increased peripheral vasoconstriction, it does not have the “break” that beta-2 would lead to since it does not
have specificity for this receptor at all. Since epinephrine also binds to beta-2 receptors which has the opposite
effect of alpha-1 and 2 this creates a smaller overall effect compared to norepinephrine.
Epinephrine Norepinephrine
beta-1, beta-2, beta-3 > alpha-1, alpha-2 alpha-1 > alpha-2 > beta-1
11
For answering the questions of the instructions given, the discussion of part I and part II each drug´s
characteristics will be presented chronologically along with the respective specificity and affinity of different
adrenergic receptors. The most important clinical responses will be discussed. Part III will include discussion of
the different effects by different combinations of the drugs in part I and part II.
Propranolol blocks β1 β2 β3
It is a beta antagonist (beta blocker), it is nonselective meaning it blocks beta-1, beta-2 and beta-3 receptors. It
causes bronchoconstriction and vasoconstriction. It lowers the heart rate and might lead to loss of consciousness
(syncope). Important to keep in mind that this drug in particular should be avoided in patients with peripheral
vascular disease because of the vasoconstriction. It might also worsen the symptoms of asthma/COPD patients
because of bronchoconstriction (11) (12) (17). Regarding blood pressure the drug is able to reduce it, something
that is consistent with the results observed in our simulations.
Atenolol blocks β1 (in the heart)
It is a beta antagonist (beta blocker), it is selective for beta-1 receptors mainly found in the heart (we say it is
cardioselective). The drug decreases the contractility, the atrioventricular node conductivity and the heart rate.
It can be used therapeutically to lower high blood pressure in patients (11) (12) (13) (17).
Phentolamine block ⍺1 ⍺2
It is a sympatholytic drug (it is antisympathetic), it is a nonselective antagonist for alpha receptors. The drug is
used to deal with an increase in blood pressure over 180/120 mm Hg (a hypertensive emergency). This can
happen with patients that are on MAO-inhibitors and have consumed tyramine (from fermented food/wine).
Another indication for administering phentolamine is in a patient with a tumor originating from “chromaffin
cells” of the adrenal medulla will have too much catecholamine secreted, this tumor is called
pheochromocytoma. The drug increases heart contractility and rate (18).
Part II
10
, Norepinephrine (noradrenaline) act on ⍺-1 > ⍺-2 > β1
It is a direct sympathomimetic endogenous agonist, it acts on both alpha and beta receptors. It has the highest
affinity for alpha-2, then alpha-2 then lastly beta-1 receptors. The drug lowers blood pressure as a result of
vasoconstriction, lowers the heart rate. It causes no change /or increase of cardiac output.
Epinephrine (adrenaline) act on β > ⍺ (at high doses: ⍺)
It is a direct sympathomimetic endogenous agonist, it acts on beta receptors at higher affinity than alpha
receptors. However at high dose alpha receptor effects dominate. Epinephrine has a stronger beta-2 receptor
effect than that of norepinephrine. While at an increased dose the drug is able to raise the blood pressure.
Increases heart rate and cardiac output (14).
Isoprenaline (Isoproterenol) act on β1 = β2 (minimal effect on ⍺)
It is a direct sympathomimetic drug, a non-specific beta-adrenergic agonist. The drug acts on both beta-1 and
beta-2 receptors. Minimal effect on alpha receptors. The drug raises heart rate and lowers blood pressure as a
result of vasodilatation and raises cardiac output. (11)(12)(13).
Phenylephrine act on ⍺1 > ⍺2
Is a direct sympathomimetic drug, alpha-adrenergic agonist. Acting on alpha-1 and alpha-2 receptors, favoring
alpha-1 receptors. The drug raises blood pressure as a result of vasoconstriction. The drug causes no change or
decrease in cardiac output. But it is able to lower the heart rate through reflex bradycardia, based on the
feedback from the baroreceptors.
The four different adrenoreceptor agonists cause different responses because they have different specificity for
receptors and affinity. Norepinephrine has a lower affinity for beta-1 receptors compared to epinephrine which
has high affinity for beta receptors (beta-1 and beta-2). Epinephrine is specific for both beta and alpha receptors
but higher affinity beta that is why we see a larger response from beta receptors on relaxation of blood vessels
and vasodilatation (baseline ABP 99 mmHG injected with epinephrine 10 mcg/kg 539.33 BPM) but at high
concentration alpha effect with increased contractility of the heart (baseline 363 BPM injected with epinephrine
10 mcg/kg 449 BPM).
Norepinephrine on the other hand has the highest affinity for alpha-1 receptors and characteristic effect of
increased peripheral vasoconstriction, it does not have the “break” that beta-2 would lead to since it does not
have specificity for this receptor at all. Since epinephrine also binds to beta-2 receptors which has the opposite
effect of alpha-1 and 2 this creates a smaller overall effect compared to norepinephrine.
Epinephrine Norepinephrine
beta-1, beta-2, beta-3 > alpha-1, alpha-2 alpha-1 > alpha-2 > beta-1
11
