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Y2 Cardiovascular > Cardiovascular pharmacology 2 > Flashcards

Cardiovascular pharmacology 2 Flashcards

1
Q

What are the endogenous mechanisms of positive inotropes?

A
  • increase contractility
  • sympathetic stimulation
  • increase EDVV by increasing preload
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2
Q

How can we create the effect of positive inotropes pharmacologically?

A
  • mimic/enhance sympathetic activity

- increase intracellular calcium

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3
Q

Which 3 drug groups are used to act as positive inotropes?

A
  • PDE III inhibitors
  • Sympathomimetics
  • Cardiac glycosides
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4
Q

What happens when phosphodiesterase is inhibited?

A

Increase in intracellular cAMP (as it usually degrades it)

This leads to increased contractility

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5
Q

What effect will increased intracellular cAMP have in the cardiac myocyte?

A
  • Activated protein kinase A
  • This phosphorylates Ca channels, making them more likely to open
  • Increased flow of Ca into cardiomyocyte + increased Ca induced Ca release
  • Stronger contraction
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6
Q

What are the two other predictable effects of increased intracellular cAMP?

A
  • Vasodilation: because of activated myosin light chain kinase
  • Tachycardia: faster Ca flow into cell = faster depolarisation
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7
Q

Which PDE III inhibitor is used in practice, how is it administered?

A

Pimobendan

  • Positive inotrope and vasodilator
  • Oral or parenteral administration
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8
Q

What is the only cardiac glycoside in use?

A

Digoxin

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9
Q

What is the theory of the supposed positive inotropic effect of Digoxin?

A
  • Inhibits the Na/K pump in cardiac myocytes which increases the intracellular Na
  • Reduced Ca extrusion from the cell because there is a smaller gradient for Na to move into the cell
  • Therefore more Ca moved into SR to be released during an action potential
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10
Q

By inhibiting Na removal from the cell, what other effect do you predict cardiac glycosides to have in the heart?

A

Negative chronotropy - major action of these drugs

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11
Q

What is the target of sympathomimetics?

A

β1 receptors on cardiac myocytes - agonist action will increase contractility

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12
Q

What are the three types of negative inotropes?

A
  • Sympathetic antagonists
  • Cholinergics
  • Calcium channel blockers
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13
Q

A drug affecting perfusion will alter which 3 factors?

A
  • CO
  • Vascular diameter
  • Circulating volume
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14
Q

Drugs affecting arterial pressure will alter which 2 factors?

A
  • CO

- TPR

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15
Q

Why would we want to reduce preload?

A

Reduce congestion
Reduce oedema
Reduce work for the heart

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16
Q

Why would we want to reduce afterload?

A

Forward HF
Vasodilation
Reduce congestion

17
Q

Why would we want to reduce systemic arterial pressure?

A
  • Reduce afterload

- Organ failure will occur if there is chronic hypertension so this needs to be reduced

18
Q

What are the 4 direct vasodilators?

A
  • Nitrates
  • Ca channel blockers
  • PDE III inhibitors
  • Hydralazine
19
Q

Describe the effects of nitrates

A
  • Cause peripheral vasodilation via nitric oxide action

- Leads to vasculature relaxation

20
Q

Which 2 nitrates are used in practice?

A
  • Nitroprusside

- Nitroglycerine

21
Q

Ca channel blockers work as direct vasodilators, but are also in which other drug group?

A

Class IV antidysrhythmics

22
Q

Describe the action of PDE III inhibitors

A

Used for chronic heart failure.

  • Inhibit the breakdown of cGMP
  • This activated protein kinase G
  • This activates myosin light chain phosphatase
  • Dephosphorylates myosin light chain which causes relaxation
23
Q

Hydralazine acts as a …?

A

Arteriodilator

24
Q

What are the 2 indirect vasodilators and through what method do they act?

A
  • Sympathetic NS
  • RAAS
  • Extrinsic mechanism
25
Q

Where do sympathetic antagonists act?

A
  • non-specific

- can act at any point from the brainstem to peripheral receptors

26
Q

What are the 2 sympathetic antagonists used in practice?

A
  • Prazosin

- Phenoxybenzamine

27
Q

What 2 bits of the RAAS cause vasoconstriction?

A
  • Angiotensin II

- Stimulated ADH release

28
Q

What else does the RAAS do that influences blood pressure and preload?

A

At the kidney it retains water and sodium ions

29
Q

Which 3 conditions would benefit from RAAS blockade?

A
  • Chronic heart failure
  • Hypertension
  • Chronic renal failure
30
Q

What is the role of ACE?

A

Converts Angiotensin I to Angiotensin II

31
Q

What do ACE inhibitors cause?

A
  • Vasodilation
  • Reduced circulating volume
  • Thus, improved tissue perfusion
  • Reduced preload
  • Reduced systemic arterial pressure
32
Q

Where are ACE inhibitors activated?

A

Liver

33
Q

What are Aldosterone antagonists used for?

A
  • Reduce retention of sodium and water, which also reduced K loss
  • Reduced cardiac remodelling which is associated with aldosterone
34
Q

What are the 2 aldosterone antagonists used in practice?

A
  • Spironolactone

- Cardalis (Benazepril + spironolactone)

35
Q

What other method can be used to reduce preload?

A

Diuretics

Y2 Cardiovascular (5 decks)

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