Catecholamines (DA/ NE / E)

T/F: Dopamine, Norepinephrine, and Epinephrine are endogenous substances that can be given exogenously (drug)

• true

what type of drug is dopamine?

a) vasoconstrictor

b) central vasodilator

c) peripheral vasodilator

d) none of the above

c) peripheral vasodilator

T/F: DA can cross the BBB, thus it works centrally and peripherally

• false

  • does NOT cross BBB = peripheral vasodilator

what type of receptor does dopamine bind to/ activate the most (highest affinity) ? 

a) beta 1

b) beta 2

c) D1

d) D2

c) D1

what type of receptors are D1 that dopamine bind to?

a) Gq - coupled 

b) Gs - coupled 

c) Gi - coupled

d) membrane-potential bound

b) Gs - coupled (increases cAMP formation) 

where are D1 receptors found? what happens when they are activated? 

1. vascular smooth muscle

• Gs → dilation of blood vessels → vasodilation

2. cardiac myocytes 

• Gs → increases contractility = positive inotropic effect

what is dopamine used for? (indications)

• HF

  • positive inotropic effect to increase cardiac output

  • renal perfusion (renal artery dilation)

  • oliguria (inability to form urine because of poor renal perfusion)

    • increases urine output

how is dopamine given?

a) orally ER 

b) orally IR 

c) constant infusion 

d) intermittent infusions

c) constant infusion (low dose for D1 receptors only) 

T/F: increasing the concentration of dopamine can also activate beta 1 receptors and D1 receptors together 

• true 

  • increase infusion rate/concentration 

why is dopamine able to activate some of the adrenergic receptors 

• dopamine = structurally similar to NE or E (catecholamines)

  • DA = precursor to formation of NE 

highest dose vs high dose vs low dose DA indications

• low dose = D1 receptor activation only = HF pts 

• high dose = D1 + B1 receptor activation = increase chronotropic rate 

• highest dose = D1 + B1 + A1 receptor activation (blood vessels) = vasoconstriction (“pressor”)

why would I use dopamine (very high infusion rate) when I can simply give phenylephrine or one of those other pressers?

• effects on the heart and on the renal artery = beneficial with dopamine infusion

  • more A1 receptors > D1 receptors in blood vessels = higher infusion rate = pressor effect dominates

T/F: adjusting infusion rate of DA can produce different effects

• true

what receptors does NE activate?

• alpha-1 (innervated)

• alpha-2

• beta-1 (innervated)

• not a lot of affinity for B2 or B3 

why are we not as concerned about alpha-2 receptor activation of NE? 

• alpha-2 receptor activation = decrease NE release

  • BUT 

    • NE is given exogenously = activating receptors

what are the effects of administering NE as a constant infusion?

• a1, a2, and b1 receptor activation 

  • vasoconstriction (can lead to reflex decrease SANS) 

  • decrease NE release 

  • positive chronotropic, inotropic, dromotropic effect 

T/F: alpha-2 activation is decreased/little effect when given exogenous NE compared to endogenous NE 

• true 

what happens during/activating a reflex response from NE

• change in vessel tone → 

  • baroreceptor reflex sends info → CNS 

  • increase PANS firing

    • reflex bradycardia (increase ACh → muscarinic receptors in heart) 

  • decreases sympathetic firing 

    • reflex bradycardia (decrease NE → b1 receptors)

which factor determines what effect of NE activation of receptors predominates? 

• affinity for receptor

which receptor does NE have a higher affinity for?

a) beta-1

b) beta-2 

c) alpha-1 

d) alpha-2

c) alpha-1 

what is the indication for NE? why?

• “pressor” (vasoconstriction because of increased affinity for a1 receptors) 

  • hypotension 

  • shock (ex. septic shock) 

T/F: whatever dose of NE is administered, the positive chronotropic effect is going to predominate 

• false 

  • alpha-1 receptor affinity = vasoconstriction → reflex bradycardia predominates 

does phenylephrine (a1 agonist) or NE have a stronger effect on TPR? compare it to a control.

• equal effect on TPR

  • greater TPR than control 

does phenylephrine (a1 agonist) or NE have a stronger effect on HR? Compare it to a control

• NE = stronger effect (raises HR more) (??)

  • lower HR than a control because of reflex response (bradycardia) 

  • higher HR than a1 agonist because it still activates B1 slightly 

    • alpha-1 agonists = reflex bradycardia only (no effect on B1)

which drug has more reflex bradycardia?

a) phenylephrine 

b) NE

a) phenylephrine 

• NE = still activates B1 receptors slightly = less bradycardia

what is the difference between phenylephrine and NE when they’re both vasoconstrictors/pressors? 

• effect on HR

  • do you want HR to remain low? → phenylephrine 

  • do you want HR to just drop slightly → NE

what receptors can epinephrine activate? how is it given?

• ALL adrenergic receptors

  • alpha1, alpha2, beta1, beta2 (don’t really talk about b3)

• given as constant infusion 

what is the main difference between NE and E in terms of receptor activation ?

• Epinephrine can activate B2 receptors very well while NE = weak activator

what is the effect of administering epinephrine as a constant infusion?

• a1 receptor activation → vasoconstriction (+ reflex bradycardia)

• a2 receptor activation → decrease NE release

• b1 receptor activation → positive chronotropic, inotropic, dromotropic effect 

• b2 receptor activation → vasodilation (increased cAMP)

T/F: there are more b2 receptors in the large blood vessels than alpha-1 receptors

• false

  • more alpha1 receptors > beta2 receptors

when epinephrine is released in small amounts (ex. endogenously from adrenal medulla), it has a higher affinity for 

a) alpha-1 receptors

b) alpha-2 receptors

c) beta-1 receptors

d) beta-2 receptors

d) beta-2 receptors (vasodilation)

When epinephrine is given in large amounts (ex., exogenously from infusions), it has a greater 

a) pressor effect

b) NE release

c) dromotropic effect

d) vasodilation effect

a) pressor effect

why do large amounts of Epinephrine cause a net effect of vasoconstriction rather than vasodilation 

• large amounts 

  • higher affinity = b2 receptors → once all bound (relatively few) → goes to bind to alpha-1 receptors 

  • MORE alpha-1 receptors than beta2 receptors in larger vessels = vasoconstriction effect

T/F: epinephrine’s affinity to the different adrenergic receptors changes based small vs large amounts given 

• false 

  • affinity does NOT change 

  • B2 > a1 affinity but large amounts have the capability to activate alpha-1 receptors = MORE in quantity → vasoconstriction effect dominates

indications for epinephrine 

• vasoconstriction, “pressor” (peripherally)

  • increases TPR → use for shock, hypotension

  • major effect for anaphylactic shock

epinephrine vs norepinephrine ability to constrict blood vessels; which one is true? 

a) epinephrine has a greater effect on vasoconstriction 

b) norepinephrine has a greater effect on vasoconstriction 

c) both are equal in terms of effect on vasoconstriction 

b) norepinephrine has a greater effect on vasoconstriction 

why does NE have a greater vasoconstriction effect than E?

• epinephrine = activates a1 AND b2 (opposing effects) 

• norepinephrine = only a1 (minimal/no b2 activation) 

does epinephrine have higher affinity for a1 receptors or b1 receptors

• beta1 receptors

why does epinephrine have less of a reflex response than NE or phenylephrine? 

• epinephrine = not as strong as a vasoconstrictor as the 2

  • degree of change in vessel = less → reflex response = less

what is the net effect of epinephrine on HR? (in terms of control, NE, and phenylephrine) 

• increases HR higher than the control 

  • less reflex response from vasoconstriction (reflex bradycardia) than NE and phenylephrine

why choose epinephrine instead of NE or phenylephrine when they are all “pressors” ? 

• epinephrine = increased effect on HR

  • what do you want to happen to HR? 

T/F: many local anesthetics are combined with epinephrine to keep the local anesthetic in the area for a longer period of time

true 

• same as adding phenylephrine 

suppose a patient is on propranolol and they were given epinephrine. How is the response going to be different in a patient on propranolol (or any nonselective beta-antagonist) compared to a patient not on propranolol?

• propranolol = nonselective beta blocker (block b1 + b2) 

  • w/ propranolol = LOWER HR (b1 block) + MORE/INTENSE vasoconstriction (b2 block)

How are the effects of epinephrine affected by a patient receiving prazosin?

• prazosin = alpha-1 blocker 

  • w/ prazosin = VASODILATION (b2 activation) 

• NOT DONE CLINICALLY 

epinephrine reversal

• give alpha-1 blocker w/ epinephrine = VASODILATION instead of vasoconstriction = reverse/opposite of usual effect

what happens during anaphylaxis?

• very large release of histamine → activates histamine receptors (ex. H1 receptors in blood, bronchial smooth muscle) → massive vasodilation + bronchoconstriction → shock

what is the hallmark of an anaphylactic reaction?

• huge drop in BP because of histamine (activation of H1 receptors) 

what is the drug of choice for treatment of anaphylactic shock? 

a) dopamine 

b) norepinephrine

c) epinephrine 

c) epinephrine 

what is the preferred route to give epinephrine for an anaphylactic shock treatment? 

• IM injection (ex. epipen ) 

why is epinephrine great for treatment of anaphylactic shock? what is this mechanism called?

• physiological antagonism

  • activation of alpha-1 → vasoconstriction

  • activation of beta-2 → bronchodilation 

  • ( reverses effects of histamine release )

epinephrine during anaphylactic shock

a) physiological antagonism 

b) pharmacological antagonism 

a) physiological antagonism (reverse effects by activating different receptors)

antihistamines blocking histamine receptors

a) physiological antagonism 

b) pharmacological antagonism 

b) pharmacological antagonism