Case 37: Pulmonary Oedema

Author: Dr Danielle Coleman

An 84 year old female presented with an abrupt onset of breathlessness. She had a history of ischaemic heart disease and had coronary stents.

On examination she was clammy, sweaty, in respiratory distress; and had inspiratory crackles. BP 167/75, HR 130, RR 40, Sats 81% on air, and she had a metabolic acidosis on arterial blood gas.

The diagnosis made was pulmonary oedema.

 

1. The standard first-line drug for pulmonary oedema is glyceryl trinitrate (GTN). How does it work?

 

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Nitric oxide (NO) is released by enzymatic action on GTN. NO acts as a local signalling molecule in vessels, being released by the endothelium to cause smooth muscle relaxation and vasodilation. So GTN increases NO levels, increasing vessel dilatation. The main action in pulmonary oedema is to dilate capacitance vessels in the legs, reducing pre-load; there is also an effect on after-load. Although the stroke volume is unchanged, the myocardial workload, and hence oxygen consumption, is reduced.


 

2. What is the problem with GTN as a long-term therapy for heart failure?

 

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GTN, in common with other nitrates, has a gradually declining effect over several weeks. This phenomenon is known as drug tolerance or tachyphylaxis; larger doses are needed to achieve the same effect. The problem is reduced, for example with transdermal patches, if they are removed at night.

 

3. What other medical uses are there for GTN?

 

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The main other use of GTN is to relax the anal sphincter to allow healing of anal fissures. It has also been added to condoms to increase vasodilation and hence improve erectile performance. Its major non-medical use is an explosive. Following it’s discovery in 1847, it was Alfred Nobel (of Nobel prize fame) who developed it’s commercial use. The pure form is highly explosive if shaken. Nobel made it more stable by mixing it with clay to form dynamite. It was the headaches suffered by those who handled GTN which led ultimately to it’s medical exploitation for angina in 1887.