Positive inotropic agents and heart failure Flashcards
Positive inotropic agents
Increase force of contraction and cardiac output.
Heart failure
A state in which the heart fails to maintain an adequate circulation for the needs of the body despite adequate filling pressure.
Causes of acute (sudden onset) heart failure
Acute myocardial infarction.
Valve or septal rupture.
Cardiac dysrhythmia.
Drug induced damage.
Causes of chronic cardiac failure
Incidence increases with age
Haemodynamic overload (increased afterload) - excess pressure, excess volume.
Neural hormone overload (thyrotoxicosis)
Tissue damage (myocardial infarction).
Genetically determined excessive hypertrophic response to pressure (ie human familial hypertrophic cardiomyopathy).
Symptoms of heart failure
Left ventricular failure - fatigue, pulmonary oedema (orthoponea).
Right ventricular failure - venous distention, oedema, cyanosis (blue palor).
Oedema
Sodium concentration raised by aldosterone, capillary pressure raised by por cardiac output.
Frank-starling mechanism
Maintains output in early heart failure by increasing stroke volume as end diastolic volume increases.
Eventually output falls as reserve is used up.
In a patient with HF, for any given end diastolic volume, the stroke volume will be less than that of a normal heart.
Patients with increased sympathetic stimulation have slightly higher stroke volume than those without but still not normal.
Treatment of heart failure
Positive inotropic drugs are never given without other drugs.
Objective is to reduce preload/afterload or make the heart work harder.
Diuretics and ACE inhibitors are commonly used.
Vasodilators,low dose beta-blockers and positive inotropes also used.
Examples of positive inotropes
Autonomic neurotransmitters, cardiac glycosides,phosphodiesterase inhibitors and calcium sensitisers all have direct action on the heart.
NA, Adr and Iso - not used clinically, complex efects on BP, induce arrythmia, only used in emergency, given I.V.
Dopamine and dobutamine - can act on beta receptors, short term inotropic support in advanced HF, for patients who do mot respond to other treatment, may increase mortality.
Contraction of cardiac muscle
Intrinsically controlled by intracellular calcium concentration.
Calcium entry via ion channels
Sodium/calcium exchanger.
Calcium is stored in SR.
Increased calcium causes increased contraction.
Sodium pumped in by sodium calcium exchanger is countered hy sodium/potassium ATPase.
Consequences of inhibiting sodium/potassium ATPase
Intracellular sodium would increase.
This will reduce the driving force of the sodium calcium exchanger.
This in turn will lead to reduced extrusion of calcium
Therefore higher intracellular calcium and increased force of contraction.
Cardiac glycosides
Increase quality of life but not survival rate.
Digoxin -
Only one used clinically in the UK.
Not first line therapy for HF, no evidence for long term benefit.
Used if ACE inhibitors are ineffective
Low therapeutic index.
Tendency of doctors to underdose due to toxicity fear.
Severe side effects including cardiac dysrhythmia.
Elimination of drug reduced in those with decreased renal function.
Interacts with diuretics causing decreased potassium.
Interactions with verapamil and quinidine cause increased digoxin in plasma.
Non-selective Phosphodiesterase (PDE) inhibitors
Inhibits the enzyme that hydrolyses cAMP/cGMP, potentiating cAMP/cGMP action.
This causes vasodilation due to increased cGMP action on vascular smooth muscle
And increased force of contraction of the heart due to increased cAMP action.
Calcium sensitisers
Novel agents for the future.
Stabilise calcium troponin c complex whilst causes relaxation of vascular smooth muscle via selective PDE inhibition.
SERCA agonists - increasd calcium uptake during diastole, improving relaxation and filling, more calcium to be released from SR during diastole, larger force of contraction.
