Inotropes

Question 1

Inotropy

Answer 1

Contraction; for a given mm fiber length, there’s a given tension

• • inotropic agents incr contractility (with same fiber length, get greater contraction)
• • inotropic agents decr contractility

Question 2

What is the MOA of positive inotropes?

Answer 2

Increase contractility by increasing the amount of Ca available > more binding sites available and increased interaction of actin-myosin

Question 3

What are the costs of positive inotropes?

Answer 3

Myocardial ischemia and myocyte death; generation of malignant arrhythmias

Question 4

What are the 4 classes of inotropes?

Answer 4

1. Cardiac glycosides
2. Beta-adrenergic agonists
3. Phosphodiesterase inhibitors
4. Calcium sensitizing agents

Question 5

Cardiac glycosides- Digoxin

Answer 5

• Agents: Digoxin (found in foxglove)
• MOA: inhibition of Na/K ATPase pump - weak + inotrope; direct stim of vagal nuclei to decr HR, - chronotrope
• Uses: systolic myocardial failure (severe valvular dz/DCM), Afib (to slow V response rate)
• T1/2: (dogs) 24 hrs, variable in cats
• Crosses BBB
• SE: cardiac toxicity, tachy/bradyarrhythmias, CNS signs (CTZ-vomiting), GI signs (PNS effects - vomiting, diarrhea, nausea), azotemia/renal insuffiency predispose, electrolyte disturbances (hypokalemia - same binding sites)

Question 6

Synthetic Catecholamines

Answer 6

MOA: Stimulate B1 adrenoreceptors

Uses: acute inotropic support

T1/2: minutes

Question 7

Dopamine

Answer 7

• Classification: Catecholamine
• MOA: alpha (non-selective), beta1-adrenergic & dopaminergic receptors agonist
• Positive inotrope - increased CO
• Uses: acute inotropic support
• T1/2: minutes
  
  • Low dose - mainly DA = vasodilation (primarily renal)
  • Higher doses - B1 = positive inotropy
  • Very high doses - alpha = vasoconstriction
• Does not cross BBB

Question 8

Dobutamine

Answer 8

• Classification: Synthetic Catecholamine
• MOA: beta-adrenergic agonist (b1>b2) and mild alpha 1
• Positive inotrope - increased CO
• Uses: acute inotropic support
  • Beneficial effect over dopamine in patients with profound pump failure
  • No real change in BP since both beta2 and alpha receptors are stimulated

Question 9

Phosphodiesterase 3 inhibitors

Answer 9

Agents: Amrinone and Milronone

MOA: inhibit the breakdown of cAMP

Positive inotrope - increased CO

Uses: for acute inotropic support as an IV preparation

*Not frequently used

Question 10

Calcium Sensitizing Agents

Answer 10

Agents: Pimobendan

MOA: Increase affinity of troponin C for Ca2+ during systole and diastole; “sensitize” contractile apparatus to enhance contractility

Positive inotrope - increases CO

Question 11

Pimobendan

Answer 11

Calcium sensitizing agent

Phosphodiesterase III activity - positive inotrope as well as systemic and pulmonary vasodilator = inodilator

Uses: either alone or in combo w/ other + inotropic agents and CHF standard therapy

SE: No arrhythmias, great for dogs with DCM and CHF, helpful for MVD, used in cases of myocardial failure and safe in cats

Question 12

The inotropic effects of EPI and NE are primarily mediated by what receptors in cardiac tissues?

Answer 12

Beta1

Question 13

What is the general effect of sympathetic stimulation on the different sites of the heart?

Answer 13

• SA node: incr rate (+ chronotropes)
• Ventricles/Atria (myocytes): incr contractility (+ inotropes)
• AV Nodal Tissue (Atria/Ventricles): incr conduction velocity (+ dromotropes)