[johnep]

Hydrochlorothiazide content in co-aprovel is 12.5mg. indapamide dose is 2.5mg . Whatever they do to my BP, neither seem to act as diuretics as frequently stay at dispensing bench all morning.

Theory that lower dose might be fewer side efects based on the idea that side effects can be due to therapeutic action or simply to the actual molecule.

Eg the original diuretic Saluric was a 500mg dose and closely related to the sulphonamides with associated side effects, hydrosaluric was 50mg dose and standard dose of bendro was originally 5mg. Along the way the sulphonamide side effects were lost.

That is why I got changed from 50mg atenolol to 5mg bisoprolol.

weight for weight frusemide has fewer side effects than bumetanide but as the dose of bumetanide is 1mg, then side effects due to the actual molecule are very much reduced.

With regard to paracetamol and diclofenac, then different things entirely.

Classic example of a side effect that developed into different area was the observation that pts became euphoric on isoniazide. The tuberculostatic iproniazide 'marsilid' was an early MAOI. Roche developed this into isocarboxazide 'Marplan', but this was superceded by phenelzine 'Nardil' which is only surviving MAOI left.

I have forgotten the details, but the progression from antihistamines to the tricyclics and amitryptyline was a similar process I believe.

All known as 'molecular manipulation' in the old days.

consider the following: nicotinamide (vitamin), nicotinic acid (vasodilator)
isonicotinyl acid hydrazide (isoniazide tuberculostatic), iproniazide (tuberculostatic and maoi), isocarboxazide (maoi), procarbazine (cytotoxic)

all related chemically. I expect the molecular chemists can give other examples.
johnep