G7i / 14B01: Classify commonly used inotropic agents & describe their mechanism of action

14B01: Exam Report

Classify commonly used inotropic agents. (40% of marks) Outline four different mechanisms of action for inotropic agents. (60% of marks)

65% of candidates passed this question.

This question was generally well answered. The poorer answers suffered for want of a useful classification system that enabled them to separate the various drug classes.

G7i / 14B01: Classify commonly used inotropic agents & describe their mechanism of action

  • Inotrope = a drug which ↑/↓ myocardial FoC
  • Inotrope classification:
    • +/-
    • Synthetic/natural
    • MoA

MOA

↑Ca2+

↑Ca2+ binding to TnC

↓

↑FoC

↑Ca2+ Sensitisation

↑Contractility without ↑intrac. Ca2+

  • Stimulate adenyl cyclase
    • Β agonists

ADRENALINE

DOBUTAMINE

ISOPRENALINE

DOPAMINE

    • ↑cAMP

PDE III inhibitor

GLUCAGON

EPHIDRINE

    • ↑Na+/Ca2+ exchanger

DIGOXIN

INSULIN

IV calcium

  • Ca2+ sensitiser

LEVOSIMENDIN

Classified

Stimulates AC

Drug

Adrenaline (β2 > β1)

Noradrenaline (β1 > β2)

Dobutamine (β1)

Isoprenaline (β1 = β2)

Dopamine (β1, β2)

Mechanism

β agonism

Stimulates β1 + β2 receptor on conducting system & myocytes

All β receptor = G5 linked = ↑cAMP = ↑Ca2+ = ↑FoC

Classified

↑cAMP

Drug

MILRINONE

Mechanism

PDE III inhibitor = ↓hydrolysis cAMP = ↑cAMP = ↑Ca2+ = ↑FoC

Classified

Drug

GLUCAGON

Mechanism

Activates cardiac glucagon receptor

G5 = activates AC = ↑cAMP = ↑Ca2+ + ↑FoC

Classified

Drug

EPHIDRINE

Mechanism

Indirect → promotes NA release → stimulates β receptors

Direct → β1 + β2 activation as above

Classified

↑Na/Ca PUMP

Drug

DIGOXIN

Mechanism

Inhibits Na/K/ATPase = ↑intrac. Na+ = ↓activity of Na+/Ca2+ exchanger = ↑Ca2+ → further ↑Ca2+ release from SR → ↑FoC

Classified

Drug

INSULIN

Mechanism

Unclear. Thought to ↑activity of Na+/H+ exchanger → ↑intrac. Na+ → ↓activity Na+/Ca2+ exchanger → ↑intrac. Ca2+ → ↑FoC

Classified

IV CALCIUM

Drug

Mechanism

↑Ca2+ = ↑FoC

Classified

↑Ca2+ SENSITIVITY

Drug

LEVOSIMENDIN

Mechanism

Binds TnC → stabilises Ca2+ induced conformational ∆ of TnC → ↑cross bridge formation without ↑myocardial O2 consumption → ↑FoC