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Anaesthetic FRCA Primary - eLFH Pharmacology > eLFH - Inotropes and Vasopressors > Flashcards

eLFH - Inotropes and Vasopressors Flashcards

1
Q

Inotrope definition

A

Drugs which increase myocardial contractility

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2
Q

Vasopressor definition

A

Drugs which cause peripheral arteriolar vasoconstriction

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3
Q

Mean arterial pressure equation

A

MAP = CO x SVR
= HR x SV x SVR

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4
Q

Systemic vascular resistance definition

A

Resistance to blood flow throughout the systemic peripheral vasculature

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5
Q

Systemic vascular resistance vs Afterload

A

Both often interchanged as SVR is the only part of afterload that can be manipulated

Afterload is a theoretical concept which includes SVR and LV outflow obstruction (e.g. aortic stenosis)

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6
Q

Determinants of Stroke volume

A

Preload

Contractility

Afterload

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7
Q

Preload definition

A

Measure of initial stretch on cardiac myocytes prior to contraction (i.e. end of diastole)

Amount of stretch determines number of myocardial cross bridges available to interact during contraction

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8
Q

Contractility definition

A

Intrinsic ability of cardiac muscle fibres to change the force of contraction independent of preload and afterload

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9
Q

Inotropy definition

A

Change in force of myocardial contraction

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10
Q

Afterload definition

A

Force required by the myocardium to eject the stroke volume during systole

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11
Q

Chronotropy definition

A

A change in the heart rate

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12
Q

Determinants of heart rate

A

Autonomic innervation - sympathetic and parasympathetic

Circulating catecholamines

Hormones (e.g. thyroxine)

Electrolytes

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13
Q

Starling’s law

A

Force of myocardial contraction is proportional to the initial fibre length, up to a certain point

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14
Q

Closest physiological variable that can represent preload

A

LV end diastolic volume

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15
Q

Closest physiological variable that can represent force of contraction

A

Stroke volume

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16
Q

Methods of assessing LVEDV

A

Cannot be routinely measured

Surrogate markers to assess it are:
- Echo
- Central venous pressure
- Pulmonary wedge pressures

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17
Q

Starling’s curve

A

Increasing preload causes increase in SV up to a certain point and then myocardial failure occurs

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18
Q

Effect of inotropes on Starling’s curve

A

Inotropes shift curve up and to left

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19
Q

Effect of increased afterload on Starling’s curve

A
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20
Q

Effect of sympathetic stimulation on cardiac output

A

Acts via beta 1 (and to lesser extent beta 2) adrenergic receptors in the heart

Causes positive inotropy and chronotropy

beta adrenergic receptor stimulation increases available cAMP intracellularly, which results in increased intracellular calcium

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21
Q

Overall common final pathway of all inotropic drugs

A

Increasing intracellular calcium to increase force of myocardial contraction

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22
Q

Mechanisms of action of inotropes

A

Beta 1 and Beta 2 adrenoreceptor stimulation (sympathomimetics)

Phosphodiesterase inhibition

Other mechanisms

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23
Q

Sympathomimetic inotrope examples

A

Adrenaline
Dopamine
Dobutamine
Isoprenaline
Dopexamine

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24
Q

Adrenaline as an inotrope

A

Non selective agonist of all adrenergic receptors

Low dose infusion has inotropic beta effects

Increasing adrenaline dose increases alpha adrenoreceptor agonism

Laeva isomers are 15x more potent than dextro isomers

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25
Q

Side effect of adrenaline as inotrope

A

Diastolic BP can drop due to beta 2 agonism linked to peripheral vasodilatation

26
Q

Isoprenaline as inotrope

A

Potent beta 1 and beta 2 agonist

Increases CO but afterload / SVR can drop due to beta 2 agonism

Commonly used for bradyarrhythmia

27
Q

Methods of administration of isoprenaline

A

Usually IV

can also be inhaled or PO

28
Q

Dopamine as inotrope

A

Low dose infusion mainly beta 1 agonism

Higher doses increase alpha agonism

Does not cross blood brain barrier

Stimulates noradrenaline release

29
Q

Side effect of dopamine as inotrope

A

Nausea and vomiting - acts on chemoreceptor trigger zone via D2 receptors

Inhibits prolactin secretion

Vasodilatation of renal and mesenteric beds by peripheral D1 receptor activation

Increases atrio-ventricular conduction and can cause tachycardia at higher doses

30
Q

Dobutamine as inotrope

A

Structurally similar to isoprenaline

Mainly beta 1 agonism with some beta 2 and alpha 1 action

Half life 2 mins

31
Q

Side effect of dobutamine as inotrope

A

Decreases LV end diastolic pressure via beta 2 agonism

Beta 2 linked vasodilatation reduces venous return and SVR

32
Q

Dopexamine as inotrope

A

Analogue of dopamine

Action on beta 2 and D1 receptors

Minimal beta 1 action and no alpha 1 action

Causes inotropy via cardiac beta 2 agonism

33
Q

Side effect of dopexamine as inotrope

A

Peripheral vasodilatation reduces SVR / afterload via peripheral beta 2

34
Q

Phosphodiesterase inhibitor mechanism of action

A

Phosphodiesterases breakdown cyclic adenosine monophosphate (cAMP)

Inhibition of phosphodiesterase therefore increases intracellular cAMP and thus calcium levels

35
Q

Predominant phosphodiesterase isoenzymes working in the myocardium

A

Phosphodiesterase types III and IV

36
Q

Selective Phosphodiesterase III inhibitor examples

A

Enoximone

Milrinone

37
Q

Non-selective phosphodiesterase inhibitor examples

A

Aminophylline

Therefore also has some positive inotropic effects

38
Q

Administration of enoximone and milrinone

A

IV as infusion +/- loading dose

Cause peripheral vasodilatation - often require co-administration of vasopressor to maintain BP

39
Q

Other mechanism inotrope examples (usually not first line)

A

Levosimendan

Digoxin

Glucagon

Calcium

Thyroxine (T3)

40
Q

Levosimendan as inotrope

A

Increases myocyte sensitivity to calcium by binding to troponin C

Relaxes smooth muscle by opening ATP sensitive potassium channels causing peripheral vasodilatation

Used in severe acute cardiac failure

41
Q

Digoxin as inotrope

A

Inhibits Na+/K+ ATPase pump, increasing myocyte intracellular Na+

Therefore decreases inward movement of sodium via Na+/Ca2+ exchanger pump

Therefore increases intracellular calcium

Used in chronic cardiac failure

42
Q

Glucagon as inotrope

A

Glucagon receptors are Gs protein linked
Activation increases intracellular cAMP

Used in beta blocker OD

43
Q

Calcium as inotrope

A

IV calcium transiently improves cardiac output and BP

Effect is short lived

Used in cardiac arrest secondary to hyperkalaemia or calcium channel antagonist overdose

44
Q

Thyroxine (T3) as inotrope

A

Positively inotropic and chronotropic

Via intracellular Ca2+ ATPase pump (probably)

Not used for its inotropy

45
Q

Use of vasopressors

A

Treat hypotension secondary to reduced SVR

46
Q

Mechanisms of action of vasopressors

A

Alpha 1 adrenergic receptor agonism

Vasopressin receptor activation

47
Q

Structure of adrenoreceptors

A

7 transmembrane G protein couples receptors

48
Q

Site of alpha 1 adrenoreceptors

A

Smooth muscle of peripheral vasculature

49
Q

Alpha 1 agonism vasopressor examples

A

Noradrenaline
Ephedrine
Metaraminol
Phenylephrine

50
Q

Noradrenaline as vasopressor

A

Alpha 1 agonism with some beta 1 agonism

Minor inotropic action which is offset by baroreceptor reflex vagal response to increased BP causing drop in HR

51
Q

Ephedrine as vasopressor

A

Mixed alpha and beta stimulation

Works directly and indirectly by displacing noradrenaline from storage granules

Also inhibits monoamine oxidase (MAO)

Crosses blood brain barrier and placenta

52
Q

Function of Monoamine oxidase

A

Breaks down noradrenaline

Therefore MAO inhibitors (e.g. ephedrine and Parkinson’s medications) reduce noradrenaline break down and therefore lower doses of vasopressor required

53
Q

Side effect of Ephedrine

A

Tachyphylaxis occurs as noradrenaline stores depleted

54
Q

Administration of Ephedrine

A

IV

Can be PO

55
Q

Phenylephrine as vasopressor

A

Potent alpha 1 agonist

No effect on beta receptors

Causes reflex bradycardia due to baroreceptor response

56
Q

Metaraminol as vasopressor

A

Mainly alpha 1 with some beta action

Direct and indirect actions by causing noradrenaline release

57
Q

Side effects of Metaraminol

A

Increases pulmonary vascular resistance

Tachyphylaxis as noradrenaline stores depleted

58
Q

Vasopressin synonyms

A

Anti-diuretic hormone (ADH)

Arginine vasopressin (AVP)

59
Q

Site of vasopressin receptors

A

Throughout body

Including vascular smooth muscle cells

60
Q

Features of vasopressin receptors

A

Gq protein coupled

Stimulation of V1 receptors causes peripheral vasoconstriction

61
Q

Use of vasopressin

A

Second line vasopressor for severe septic shock

Anaesthetic FRCA Primary - eLFH Pharmacology (10 decks)

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