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Pharm 2 > I. Vasopresser & Inotropes > Flashcards

I. Vasopresser & Inotropes Flashcards

1
Q

_____ & ____ were the first vasopressors synthesized.

A

Dopamine & Vaspopressin

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2
Q

Most sympathomimetics are derived from the parent compound ____.

A

Beta-Phenylethylalamine

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3
Q

Catecholamine have a hydroxyl substitution on the ____.

A

Benzene ring

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4
Q

The most basic catecholamine ____, is the precursor for both NE & Epi.

A

Dopamine

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5
Q

A lack of N-substitution indicates a lack of ____. However, bulky side chains indicates the opposite.

A

Beta activity

No N-substitution: Phenylephrine and NE = No Beta

Side-Chains: Isoproterenol & Dobutamine = Beta

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6
Q

End result of inotropes is to:

A

Positively influence the interaction (influx) of Calcium with actin and myosin in the cardiac myocyte

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7
Q

Beta 1 receptor MOA IOT increase INOTROPY:

A
  1. Gs membrane protein activated
  2. Activates Adenylyl Cyclase
  3. Activates cAMP
  4. Activates Protein Kinase A
  5. Increases probability Calcium channels open
  6. Calcium leaves SR & enters mycocardial/muscle cell
  7. Increased force of contraction (inotropy) & speed of contraction (chronotropy)
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8
Q

The vasodilation from PDEI is due to ____ .

A

.cAMP promoting vascular smooth muscle relaxation

reflex VD to accommodate increase in HR - per Weirich

*PDEI inhibit the breakdown of cAMP by PDE3. Increased cAMP enhances Calcium release from the SR and increases the force generated by actin-myosin.

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9
Q

Digoxin increases ____ by inhibiting ____.

A
  • cytosolic Calcium
    -Na/K ATPase on the cell membrane
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10
Q

Most vasopressors exert their effects via ____ receptors.

A

Alpha 1

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11
Q

What is common vasopressor that does not work on alpha 1?

A

Vasopressin (VA receptors)

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12
Q

All vasopressor drugs work by what MOA:

A
  1. Gq cell membrane activated
  2. Activates Phospholipase C
  3. Hydrolyzes PIP2 to IP3 & DAG
  4. IP3 increases Calcium release from SR & DAG activates Protein Kinase C to increase Calcium influx
  5. More calcium influx leads to increase in vascular smooth muscle tone
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13
Q

What does Phospholipase C do?

A

Hydrolyzes PIP2 to IP3 & DAG

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14
Q

What does IP3 do?

A

Increases Calcium release from SR

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15
Q

What does DAG do?

A

Activates protein kinase c to increase Calcium influx

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16
Q

What does protein kinase c do

A

Increases calcium influx

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17
Q

Generally vasopressors & intropes have a short/long half-life.

A

Short

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18
Q

T/F: Generally vasopressors/inotropes are rapidly metabolized.

A

True

usually run as infusions/titrated

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19
Q

Two compounds that metabolize (by methylation) catecholamines:

A
  1. COMT
  2. MOA
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20
Q

Epinephrine is secreted by

A

Adrenal medulla

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21
Q

Epinephrine Clinical uses

A
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22
Q

Epi clinical considerations (causes):

A
  • Cardio: Increase BP, HR, CO, PP, MAP
  • CNS: Increase CBF
  • Resp: Bronchodilation
  • Other: Hyperglycemia, Hyperlipidemia, Arrhythmias, Increase CMRO2
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23
Q

Catecholamines are broken down into:

A

Sugars (hyperglycemia)

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24
Q

Epinephrine concentration & dosing

A

1 mg/cc Epi hydrochloride
100 mcg/cc cardiac Epi
500 mcg auto-injector (Epi Pen)

ACLS: 1 mg IVP
HR/BP IVP: 10 mcg
Anaphylaxis: 0.3-1mg
Infusion: 0.05 - 0.2 mcg/kg/min

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25
Q

Isoproterenol (Isuprel) activates what receptor/s?

A

Beta 1 & Beta 2 non-selective

hint: isoproterenol like a strong ephedrine without alpha 1 vasoconstriction

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26
Q

T/F: Isoproterenol only has chronotropic effects.

A

FALSE

Both chronotropic and inotropic

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27
Q

Beta 2 agonists can cause what S/E (Desirable and Undesirable)

A

Desirable:
- Bronchodilation
- Tx Hyperkalemia by reducing plasma Potassium concentrations

Undesirable
- Smooth Muscle relaxation = peripheral vasodilation
- Reflex Tachycardia
- Tremor

Beta 2 receptors exist in the peripheral vasculature

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28
Q

Beta 2 agonists used to be used after ____ but now have been replaced by pacemakers.

A

Cardiac transplantation

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29
Q

Isuprel concentration

A

0.2 mg/cc

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30
Q

Isuprel infusion dose

A

1-5 mcg/kg/min

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31
Q

Isuprel clinical outcomes:

A
  • increased HR
  • inotropy
  • lusitropy
  • Bronchodilation

*was orginally used to treat asthma but was replaced by Selective Beta 2 Agonists (e.g., Albuterol)

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32
Q

Main indication for Isoproterenol

A

Symptomatic Bradycardia

(Bradycardia so low, BP is also low and unable to compensate)

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33
Q

____ is a profound vasoconstrictor (alpha 1»alpha 2, beta 1)

A

Levophed (NE)

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34
Q

Norepi is secreted by the

A

Adrenal medulla

35
Q

Concentration of Norepi

A

1 mg/cc

36
Q

IVP Norepi

A

~10mcg

37
Q

Infusion dose of Norepi

A

.05-.2 mcg/kg/min

38
Q

T/F: Norepi has anaphylaxis benefits.

A

FALSE

Has no beta-2 activation

39
Q

How to draw up Norepi

A

Double dilute:
1. 10cc syringe, 1cc NE + 9cc Saline, then waste 9cc
2. Add 9cc saline = 10 mcg/cc

OR

  1. Add 1mg to 100cc bag = 10 mcg/cc
40
Q

Vasoconstrictor of choice during shock

A

Norepi

Also used during CPB

41
Q

Levophed causes:

A

BIG increase BP
Increase in MAP
Slight increase HR
Slight Increase CO
Increase CBF

42
Q

The profound vasoconstriction can have negative issues for some patients

A

Decreased perfusion really, hepatically, and to splanchnic (organs of the abdominal cavity)

43
Q

Dopamine unique effects

A
  • Increased contractility
  • Increased RBF
  • Increased GFR
  • Increased Na excretion
  • Increased U/O
44
Q

Dopamine dosing

A

Renal (D1): 0.5-3 mcg/kg/min *(Transient Increase)

Inotropy (B1): 3-10 mcg/kg/min

Vasoconstriction (A1): >10 mcg/kg/min

45
Q

Dopamine activates what receptors:

A

Alpha 1, Beta 1, D1, D2

46
Q

Dobutamine (Dobutrex) has selective beta 1 activation, meaning:

A

Inotropic > chronotropic

47
Q

Stress Test drug

A

Dobutamine

48
Q

T/F: Dobutamine causes renal vasodilation

A

FALSE

49
Q

Dobutamine infusion dose

A

2-10 mcg/kg/min

50
Q

T/F: Dobutamine is a direct-acting synthetic catecholamines.

A

True

51
Q

Dobutamine used for treatment of:

A
  • short-term for CHF
  • Low CO following CPB (like Norepi)
  • non-invasive stress test
52
Q

Milrinone is what type of drug

A

Phosphodiesterase Type III Inhibitor

synthetic non-catecholamine

53
Q

Milrinone is used to increase ____ with reductions in ____.

A
  • cardiac index (relates CO to size of individual)
  • MAP
54
Q

This drug significantly increases success in the first attempt at weaning pts from CPB with less need for catecholamines, but with greater requirement for vasoconstrictors

A

Milrinone

55
Q

Phenylephrine will cause baroreceptor mediated reflex bradycardia; this reflex will be more/less prominent in which demographics?

A

Young population: reflex will be more prominent, b/c vessels are more compliant and reactive.

Older population: reflex will be less prominent, due to increase in atherosclerotic vessels (less compliant/reactive)

56
Q

Nasal Phenylephrine dose

A

0.25-0.5 mg (2-4 drops)

57
Q

Phenylephrine Infusion dose

A

0.2-0.5 mcg/kg/min

58
Q

T/F: Phenylephrine is a synthetic non-catecholamine

A

True

59
Q

Vasopressin is a natural hormone that is synthesized in the ____ and stored in the ____.

A
  • anterior hypothalamus
  • posterior pituitary gland
60
Q

Vasopressin is released naturally in response to:

A

Increase in serum osmolality and dehydration

61
Q

Vasopressin regulates:

A

Total body water & homeostasis

62
Q

Vasopressin works on what receptors:

A

V1 = VC; found in vascular smooth muscle; increases intracellular calcium levels

V2 = Water Regulation/Increase BV; found in collecting ducts

63
Q

Vasopressin concentration

A

20 UNITS/cc

64
Q

IVP & Infusion of Vasopressin

A

IVP: 1 Unit

Infusion: 0.01-0.06 units/min

65
Q

Like Levophed (Norepi), ____ is also useful to manage BP during septic shock.

A

Vasopressin

66
Q

Vasopressin increases:

A

SVR and MAP

67
Q

Ephedrine receptor targets

A

Indirect: Alpha 1, Beta 1 via NE release

Direct: Beta 2 *(may limit increase in BP due to some peripheral VD)

68
Q

Commercial prep of Ephedrine

A

50 mg/cc

69
Q

Ephedrine IVP dose

A

5-10 mg

70
Q

Ephedrine IV dose

A

0.1 -0.2 mg/kg

71
Q

Ephedrine IM dose

A

25-50 mg

72
Q

Tachyphylaxis is a concern with ____.

A

Ephedrine

73
Q

____ is the preferred (FDA) hypotensive treatment drug for parturients.

A

Ephedrine

74
Q

Ephedrine treatment for Bronchial Asthma is administered ____.

A

Orally

uncommon

75
Q

Ephedrine is what kind of drug

A

Non-Selective (alpha & beta) Synthetic non-catecholamine agonist

76
Q

____ is a cardiac glycosides which exerts positive inotropic effects by inhibiting Na/K ATPase in cardiac myocytes.

A

Digoxin

77
Q

Digoxin patients will be a little ____.

A

Tachy (because these patients likely are being treated for A-fib/A-Flutter)

Digoxin itself functions to lower HR by increasing Vagal tone, thereby slowing SA & AV node conduction - this improves filling of the ventricles; also it will increase contractility via increased Ca

Digoxin TOXICITY can manifest as tachycardia as it will stimulate atrial contraction.

78
Q

Digoixin is used for rate control in ____ and treatment of ____, but has been replaced largely by Dobutamine, Isuprel, and Milrinone.

A
  • A-fib
  • Heart Failure
79
Q
A

Drug & receptor Table Picture

80
Q

Digoxin MOA (non-ppt)

A
  • Blocks Na/K ATPase pumps on cardiomyocytes (normally, this allows 2 K to enter & 3 Na to exit - this is blocked) S/E = increased plasma K levels
  • Na builds up inside the cell
  • Na is able to exit the cell via Na/Ca exchanger (1Ca in & 3 Na out)
  • Ca binds to receptors on the SR
  • This releases more Ca into the cell sarcoplasm (Ca-Induced Ca Release) where it can bind Actin & Myosin
  • This improve cardiomyocyte contractility
81
Q

Factors that predispose pts to digoxin toxicity: (non-ppt)

A
  • hypokalemia
  • hypomagnesemia
  • hypercalcemia
82
Q

Dobutamine is highly selective ____.

A

Beta 1 agonist

83
Q

Dobutamine MOA (non-ppt)

A
  1. Beta 1 receptor activates Gs membrane protein
  2. Activates Adenylate Cyclase
  3. Converts ATP to cAMP
  4. Activate PKA
  5. Phosphorylates the Ca channels at the cell membrane
  6. Increase concentration of Calcium
  7. Increase Contractility
84
Q

Cellular Level Beta adrenergic Stimulation of Cardiomyocyte Picture/Schematic

A

Pharm 2 (6 decks)

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