Positive Ionotropes Notes

Positive ionotropes

Treating reduced cardiac output it treated by positive inotropes- involves increase in force of contraction that is independent of Frank-starling effects. Positive inotropic agents shift Frank-starling curve upwards.-effects of positive inotropes can be seen on the pressure volume loop during excercise

Dangers of reduced cardiac output-underperfusion. In tissues underperfusion causes acidosis, in the brain underperfusion leads to lethargy and cerebral damage and in the kidneys underperfusion leads to tubular necrosis

Reasons for decrease in cardiac output

a) Cardiac failure

i) Ischaemic disease

-atheromatous deposits in the coronary arteries

-angina: oxygen supply to the myocardium is insufficient for its needs- pain in the chest, arm , neck brought on by cold, excitement, exertion- pain is caused by chemicals released by ischaemic hears – K+, H+ that trigger nociceptive receptors

-chronic failure- ischaemia, where the cardiac tissues don’t receive enough oxygen due to blockage in the coronary arteries, this leads to decreased contraction- decreased cardiac output

-hypoxia leads to a viscious cycle: cardiac ischaemia leads to a decrease in cardiac contraction, decrease in cardiac output, fall in coronary perfusion-again leading to increased cardiac ischaemia

-heart can suffer from hypoxia due to an increase in oxygen demand: tachycardia or due to decrease in oxygen supply- due to coronary atheroscelrosis. Other causes of hypoxia include anaemia (reduced o2 carriage, or reduced o2 exchange- asthma, chronic obstructive disease

-common symptoms:

-decrease in cardiac output-hypotension

-tachycardia: this is due to the baroreceptor reflex, decrease in mean arterial pressure is detected by the aortic sinus and the carotid sinus and leads to an increase in heart rate

-lethargy: this is due to the acidosis in the tissues

-there is also peripheral and pulmonary oedema.

Failure in the left ventricle, decreases cardiac output, increase in end diastolic volume and there is a reduction in clearing of the venous return. So the blood in the pulmonary veins becomes conjested increasing the venous hydrostatic pressure. Therefore fluid leaks from the capillaries into the pleural space- decrease in respiration-tiredness.

Failure in the right ventricle, reduces the clearing of the venous blood from the venacava, so there is a back log of venous blood which increases the pressure in the inferior vena cava and jugular veins. This leads to ankle swelling

The input is linked to output by the Frank starling mechanism- during physiological volumes, an increase in end diastolic volume increases the cardiac output but after a certain point the increase leads to a decrease in cardiac output as the ventricles dilate too musch

-stable angina: pain on exercise, drugs are used to reduce cardiac work- organic nitrates, beta adrenoreceptor antagonists, calcium antagonists. Treatment with statin, antiplatelet drug- aspirin

b)hypervolaemia (decreased blood volume)

– this is caused by haemorrhage or by vasodilation

CARDIAC INOTROPES ( increase the force of contraction)

Clinical uses:

1) Heart failure

-failure is often due to ischaemia- so drug must increase cardiac contractility without increasing oxygen demand

-vasodilation is a useful side-effect in chronic heart failure- helps to reduce the cardiac workload- afterload

2) acute hypovolaemic shock

-treated by restoring effective circulating volume

-vasoconstriction- increases systemic arterial pressure-vasodilation is hazard in hypovolaemia- reduces the blood pressure

-ischaemia is still a problem- reduced coronary perfusion

Positive inotropes

Sympathomimetics

-useful in acute shock/ hypotension where myocardial ischaemia is not a prominent feature of the disease

-use is limited as it increases the oxygen requirement.

Phosphodiesterase inhibitors

Methylxanthines- E.g aminophylline/ milrinone

-inhibit phosphodiesterase 3- reduces the break down of cyclic AMP- therefore there is a greater concentration of the 2^nd messenger cyclic AMP on Beta stimulation and amplifies the intracellular cascade

Catecholamines

Noradrenaline, adrenaline, dopamine, doubutamine

-act on cardiac beta-1 receptors

-increase the rate and force of contraction

-increase myocardial oxygen consumption

Adrenaline:

increases vascular tone

Moderate elevation of adrenaline: BENEFICIAL TO THE HEART

-increased cardiac output- (beta-1) -increased stroke volume and increased heart rate

-low to moderate doses: main effect of adrenaline is to cause vasodilation and a fall in diastolic blood pressure and a rise in systolic blood pressure due to increase in heart rate. But...

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