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Cardio Week 2 > Lecture 21: Cardiovascular Effects of Autonomic AGONISTS > Flashcards

Lecture 21: Cardiovascular Effects of Autonomic AGONISTS Flashcards

1
Q

How to understand this lecture’s material?

A
  1. Know the location and actions of cardiovascular muscarinic and adrenergic receptors
  2. Know a particular compound’s activities on these receptors
  3. Understand how the compound’s various actions on the CV system’s components to determine its overall performance
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2
Q

Where are the muscarinic receptors located?

A

In the SA, AV nodes and atrial muscle (not the ventricle)
Long preganglionic fibers
Short Postganglionic fibers
Neurotransmitter at the ganglia and the organs are both acetylcholine
Parasympathetic

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3
Q

Where are the adrenergic receptors located?

A 
Heart, kidney, arterioles
Short preganglionic fibers
Long postganglionic fibers
Ach for ganglia
NE for organs
Sympathetic
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4
Q

What are the two types of receptors in the parasympathetic?

A
  1. muscarinic (1,2)

2. nicotinic (1,2)

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5
Q

What are the two receptors of recepotrs in the sympathetic?

A
  1. alpha (1,2)

2. beta (1,2)

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6
Q

What are the two parasympathetic agonists?

A
  1. Edrophonium

2. Acetylcholine

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7
Q

What are the effects of muscarinic receptors on the heart?

A
  1. Decreases heart rate
    i. decrease SA node conduction
    ii. increased AV node refractoriness
  2. Decreases inotropy
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8
Q

What is the CV response to a generalized parasympathetic discharge?

A

Vagal reaction or faint
Decrease in SA nodal automaticity, decrease in AV nodal conduction (profound bradycardia)
Decrease in systemic arteriolar resistance due to vasodilation

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9
Q

How is the vagal reaction/faint response provoked?

A
  1. may be provoked by fear or pain

2. may be provoked by inappropriate sensitivity of the carotid sinus

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10
Q

Does acetylcholine agonists have any significance?

A

No because they are rapidly degraded by AChE

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11
Q

What is Edrophonium?

A

MoA: AChE inhibitor
Indirectly stimulates parasympathetic activity
Ultra short acetylcholine esterase inhibitor
AKA: Tensilon, Reversol

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12
Q

What are the side effects of edrophonium?

A

Also causes profound abdominal cramping by stimulating contraction of GI smooth muscle

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13
Q

What are the clinical uses of Edrophonium?

A
  1. Used to counter increased HR such as supraventricular tachycardias
    • have been replaced by adenosine due to the side effects
  2. helps diagnose myasthenia gravis
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14
Q

What are examples long acting acetylcholine esterase inhibitors?

A
  1. Sarin
  2. Parathiion and malathion (insecticides)
  3. physostigimine, neostigmine
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15
Q

What are principles for understanding the overall actions of adrenergic agonists?

A
  1. agonists differ in their relative activities at the various adrenergic receptor types
  2. overall action determined by
    i. agonists POTENCY for each receptor type
    ii. organ’s DENSITY of each receptor type
  3. overall action is determined by concentration of agonist (route of administration) as well as interaction of drug induced alterations on each interrelated organ’s function
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16
Q

What are the adrenergic receptor types?

A

A1, A2, B1, B2, B3

Alpha receptors are NOT located in the heart

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17
Q

Where are Alpha1 receptors found?

A

i. vascular smooth muscle (constrictor)

ii. Genitourinary smooth muscle (constrictor)

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18
Q

Where are Alpha2 receptors found

A
  1. vascular smooth muscle (constrictor)

2. platelet aggregation

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19
Q

Where are Beta1 receptors found?

A

i. heart (myocardium-inotropy & specialized tissues-chronotropy)
ii. Kidney (juxtaglomerular cells-renin secretion)

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20
Q

Where are Beta2 receptors found?

A

i. vascular smooth muscle (dilator)

ii. airway smooth muscle (dilator)

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21
Q

Where are Beta 3 receptors found?

A

i. adipose tissue (lipolysis)

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22
Q

What are the CV actions of B1 receptors?

A 
Increase heart rate by
	i. increasing impulse formation
	ii. decreasing refractoriness
	iii. increasing velocity
Increases myocardial inotropy
Increases renin secretion in kidney (which leads to retention of fluid)
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23
Q

What are the CV actions of alpha 1 receptors?

A
  1. Arteriolar vasoconstriction of skin, GI and kidney

2. Large venous constriction

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24
Q

What are CV actions of Beta 2 receptors?

A

Arteriolar vasodilation of heart, skin and skeletal muscle

Airway dilation

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25
Q

What are the types of adrenergic agonists?

A
  1. Endogenous agonists
    i. Epi
    ii. NE
    iii. Dopamine
  2. Synthetic agonists
    i. Phenylephrine
    ii. Dobutamine
    iii. Isoproterenol
26
Q

What receptors does NE bind to?

A

Beta 1 and alpha; NO beta 2 activity

27
Q

What receptors does epinephrine bind to?

A

Beta 1, Beta 2 and alpha

28
Q

What receptors does dopamine bind to?

A

Beta 1, Alpha and delta 1,2; NO beta 2 activity

29
Q

What is Mean Arterial pressure (MAP)?

A

MAP = CO x SVR (systemic vascular resistance)

30
Q

What are the key characteristics of epinephrine?

A

MoA: MIXED alpha, beta1 and beta2 agonist
Increased systemic arterial pressure and thus increased CO and SVR (per MAP equation)
Increased heart rate

31
Q

What are the indications of epinephrine?

A
  1. Cardiac Arrest
  2. Anaphylaxis
  3. hypotension/bradycardia
32
Q

What is epinephrine contraindicated with?

A
  1. arrhythmias

2. narrow angle glaucoma

33
Q

What are the side effects of epinephrine?

A
  1. cardiac arrhythmias
  2. tachycardia excitation
  3. tremulousness
  4. insomnia, nervousness
  5. palpitations
34
Q

What are the key characteristics of norepinephrine?

A

MoA: Mixed alpha, beta 1 agonist with LITTLE beta2 activity
Increase systemic vascular resistance
Eventually, heart rate is decreased because beta1 activity is opposed by strong alpha action to increase SVR
-increase SVR without B2 vasodilation means baroreceptors will tell heart to slow down
Cardiac ouput is UNCHANGED

35
Q

What are the indications for NE treatment?

A
  1. Refractory hypotension especially due to sepsis

Not used to treat anything that requires greater cardiac output

36
Q

What are the side effects of NE?

A
  1. ischemic injury
  2. bradycardia (due to baroreceptor reflex)
  3. substernal pain
37
Q

What are the key characteristics of dopamine?

A

MoA: alpha, beta1, delta1 agonist with LITTLE beta 2 activity
Is does dependent
Has delta1 dopaminergic activity at low doses
i. Low dose = isolated delta1 action = renal VASODILATION (“renal dose dopamine”)
ii. intermediate dose = beta1 action combines with delta 1 action to increase cardiac output with minimal effect of systemic vascular resistance
iii. high dose = alpha action overwhelms the gamma1 actiona nd the effect is similar to norepinephrine

38
Q

What are the effects of dopamine at low doses?

A

Isolated delta 1 reaction
Produces predominately renal vasodilation
“Renal Dose Dopamine” = smallest dose

39
Q

What are the effects of dopamine at intermediate doses?

A

Beta1 action combines with delta 1 to increase cardiac output (since heart rate won’t be decreased due to adequate renal perfusion)
Does NOT effect SVR

40
Q

What are effects of dopamine at high doses?

A
  1. alpha action overwhelms the delta1 action and the effect is similar to norepinephrine (no change in CO and decrease in HR)
41
Q

What is the significance of dopamine for CV therapy?

A

Dopamine is an effective PRESSOR which, in low to intermediate doses, does not reduce renal blood flow

42
Q

What are the indications of dopamine use?

A
  1. Cardiogenic shock
  2. Severe cardiac failure
  3. Hypotension that leads to decreased renal blood flow
  4. Can be used in sepsis
    Use dopamine at low to intermediate doses!
43
Q

What are the contraindications of dopamine?

A

Ventricular arrhythmias, sever AS, pheochromocytoma

44
Q

What is pheochromocytoma?

A

Neuroendocrine tumor that leads to excessive production of catecholamines
Tumor in adrenal medulla

45
Q

What are the alpha-selected adrenergic agonists?

A

Phenylephrine

46
Q

What are the betaadrenergic agonists?

A
  1. isoproterenol

2. dobutamine

47
Q

What are the key characteristics of phenylephrine?

A

MoA: binds predominately to alpha receptors
1. Increase SVR
2. decrease heart rate (due to baroreceptor reflex)
3. decrease CO
Similar to NE effect (minus the CO decrease)

48
Q

What are the indications of phenylephrine?

A

Sepsis

Hypotension

49
Q

What are the side effects of phenylephrine?

A

May lead to cardiac ischemia, vascular ischemia and angina

50
Q

What are the key characteristics of isoproterenol?

A

MoA: binds to beta 1 and beta 2 receptor with little alpha activity

  1. Decrease in SVR
  2. increase in HR
  3. Increase in CO
51
Q

What are the indications for isoproterenol?

A
  1. heart block
  2. stimulate myocardial contraction after heart surgery
  3. treatment of beta-blocker overdose
52
Q

What are the side effects of isoproterenol?

A
  1. tachyarrhythmias
  2. palpitations
  3. nervousness
  4. hyper and hypotension??
53
Q

What are the key characteristics of dobutamine?

A

MoA: binds to B1 receptor

- clinical preparation is a racemic mixture (+ enantiomer = antagonist and – enantiomer is agonist) 1. beta 1 activity is predominantly INOTROPIC with modest chronotropic activity
- modest beeta2 activity, therefore relatively little effect on blood pressure 2. Increase in CO
54
Q

When you need a drug to increase inotropy but only modest increase in chronotropy, what do you use?

A

Dobutamine

55
Q

What are the indications for dobutamine?

A

Circulatory support for congestive heart failure
MI
Something requiring inotropic support

56
Q

What are the side effects of dobutamine?

A

Ventricular arrhythmias

57
Q

What are the clinical uses of adrenergic agonists?

A

Adjunctive treatment of shock

Supports patient until underlying cause can be found

58
Q

What is selection of a drug based upon?

A
  1. heart rate/rhythm
  2. afterload
  3. preload
  4. contractility
59
Q

What adrenergic agonist would you use to treat septic shock?

A

Septic shock = decreased SVR and increased CO
Drug wants to increase SVR and decrease CO (primarily Alpha receptor agonists)
1. Norepinephrine
2. Phenylephrine
Can use dopamine too as suggested in notes

60
Q

What adrenergic agonist would you use for cardiogenic shock?

A

Low CO in this case with high MAP
Thus you want to increase contractility WITHOUT increased blood pressure as well
Drug needs to be pure Beta1 agonist
DOBUTAMINE
Can use dopamine too as suggested in notes

Cardio Week 2 (11 decks)

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