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POTS is characterised by orthostatic intolerance. This means that patients feel significantly worse when they adopt an upright posture compared to when they are lying down. To try and find effective treatments, it is vital that we try and understand the physiology of what happens in the body when normal healthy people stand up.

When we stand up, blood in our vessels tends to get sucked down into our legs because of the effect of gravity. This means that there is less blood getting to our brain and ordinarily we would all pass out and fall because of a shortage of blood to the brain. This does not happen because two reflex mechanisms come into action which serve to maintain the blood flow to our brains. The first is regulated by stretch receptors in our blood vessels in the legs which try and constrict the best they can to prevent blood from pooling in the legs. Secondly the heart rate increases to try and maintain adequate blood flow to the brain. In some patients, the leg vessels don’t constrict as well and therefore they are not able to contribute to increasing the blood flow to the brain and therefore the body has to compensate for this by increasing the heart rate even further. As the heart rate goes up excessively the heart doesn’t have as much time to fill with blood and therefore pumps out less blood than it should which exacerbates the situation.

If we can in some way reduce the stretching of blood vessels especially in the lower limbs when we adopt an upright posture, it means that there is relatively more blood going round and less blood pooling which can improve symptoms.

Midodrine works by increasing the tone of our peripheral blood vessels and therefore reduces the likelihood of pooling of blood. It doesn’t really directly affect the heart as such but if there is more blood getting to the heart then that means that every heart beat is more effective and that can have the effect of improving orthostatic tolerance. Interestingly though this can also have an unwanted effect on the bladder. Because of the effect of the agent on tone, the bladder does not stretch as much and therefore bladder emptying is delayed.