| Question | Answer |
| Effects of reduced cardiac output | under perfusion of:
Tissues - acidosis
Brain - lethargy, cerebral damage
Kidneys - acute tubular necrosis, renal failure |
| Uses of positive inotropes | Cardiac failure - chronic, ischaemic - reduction in CO to the point that it does not satisfy requirements
Hypovolaemia - actual e.g. haemorrhage or functional e.g. vasodilation |
| Effects of cardiac failure | Hypotension
Tachycardia
Lethargy
Exercise intolerance
Breathlessness
Oedema |
| Acute shock | Hypovolaemic shock - haemorrhage
Septic shock - toxic vasodilation
Cardiogenic shock - myocardial infarction |
| Influences on cardiac output | Cardiac input - venous return and circulating fluid volume
Contractility
Peripheral resistance |
| Effects of ischaemia on frank starling curve | Shifts downwards
Decreased coronary blood supply, decreased oxygen availability
Decreases cardiac output for a given venous return |
| Causes of ischaemia | Increased oxygen demand when this cannot be met - tachycardiac or increased contractility
Reduced oxygen supply - coronary atherosclerosis and small vessel disease |
| Other causes of hypoxia | Reduced oxygen carriage - anaemia
Reduced oxygen exchange - asthma and COPD
Does not cause build up of CO2 so does not disturb H and K gradients |
| Circle of cardiac failure | Fall in cardiac contractility
Fall in cardiac output
Fall in coronary perfusion
Cardiac ischaemia
Circle repeats |
| Consequences of ischaemia | Reduced contractility
Dysrhythmias
Infarction
Death |
| Treatment of ischaemic failure | Positive inotropic agent - with no increase in oxygen demand
Cheat - vasodilate to increase cardiac output and limit work to match cardiac oxygen |
| Treatments for failure | Must increase cardiac output
Must not increase oxygen demand - no increase in ion pumping
Should reduce outflow resistance slightly |
| Treatments for shock | Must increase cardiac output
Oxygen demand less critical - may use ion pumping and increase oxygen supply
Must not vasodilate |
| Positive inotropes | Sympathomimetics
Glycosides
Calcium sensitising agents
Indirect - vasodilators |
| Effects of ischaemia on contractility | Increased calcium all the time - cannot be taken up into SR
Reduced contractility as less Ca to release and stiff walls
Increased diastolic pressure |
| Effects of adrenaline on contractility | Increased Ca in systole as more taken up into SR
Increased contractility as more Ca to be released
Decreased diastolic pressure |
| Alternative approaches | vasodilators - for chronic ischaemic failure
Vasoconstrictors for acute shock |
| Inotropic mechanisms | Sympathetic stimulation - direct or indirect
Altered contractile mechanism - calcium sensitization |
| Phosphodiesterase inhibitors | Phosphodiesterase breaks down the second messenger of adrenaline signalling at beta receptors
Inhibiting this via methyl xanthines e.g. aminophylline and theophylline increase the effects of sympathetic stimulation |
| Adrenaline effects | Tachycardia
Increased cardiac contractility
Splanchnic vasoconstriction
Skeletal muscle vasodilation at low conc and vasoconstriction at high conc - saturates beta due to high affinity then see alpha effects due to higher potency |
| Dopamine effects | Increased cardiac output - beta 1 adrenergic
Generalised vasoconstriction - alpha adrenergic and dopaminergic
Vasodilation of gut and kidney - dopaminergic |
| Dopamine analogues | Dobutamine - act via beta 1 receptors to increase contractility with limited vascular effects
Dopexamine |
| Calcium sensitizers | Levosimendan - binds to TnC
Omecamtiv - myosin activator
These increase contractility with no increase in ion pumping - although do have small effects |
| Glycoside actions | Positive inotropic effect
No increase in oxygen demand
Diuretic effect
Decreased sympathetic tone
No decrease in life expectancy as is seen in other cardiac failure drugs
Delay in onset
Narrow therapeutic ratio - easy to overdose
Highly toxic |
| Mechanism of glycosides | Inhibit Na K pump
Removes Na gradient
Stops removal of Ca via Na Ca exchanger
More Ca remains in cell to be taken up by SR |
| Endogenous glycosides | Progesterone derivatives
Hypertensive
Absent in cardiac failure - may develop when glycosides stop being produced - potential treatment option |
| Endogenous inotropes | Glycosides
Apelin - don't fully know role in cardiac failure but seems to be absent - potential treatment option |
