Omeprazole: might it increase the risk of statin induced myopathy?
The, "Six cases ..[of].. funduscopically confirmed irreversible
anterior ischaemic optic neuropathy", reported in the BMJ a few years ago
(1) are of additional concern for patients taking statins for it is so
commonly subscribed and the mechanisms of actions appear to be similar:
i.e a fall in pH and decline in Daniel Atkinson energy charge induced by
an energy supply/demand mismatch.
Thus the graded responses to a progressive increase in reductive
stress would seem to be, 1: upregulation of oxidative phoshorylation by
an increase in protonmotive force, 2: preservation of ATP stores by down
regulation of ATP-dependent reactions, and 3: possibly the local increase
in availability of nutrients derived from autophagy, apoptosis and even
necrosis in extremis. These actions would presumably be independent of
any effect upon cytochrome P450 (2). Thus the short term gains from
statins might always come with longer term risks of cellular dysfunction,
apoptosis and even necrosis.
"Proton pump inhibitors seem not to act specifically on potassium-
hydrogen ATPases in gastric mucosa. Omeprazole inhibits the secretion of
cerebrospinal fluid in rats by decreasing ATPase activity [i.e. ATP-
dependent reactions]. Reduction in intracellular pH by omeprazole induced
blockade of potassium-hydrogen ATPase results in decreased renal function,
and renal failure as well as interstitial nephritis have been observed
with omeprazole. Potassium-hydrogen ATPase is present in vascular smooth
muscle cells, and reduction in intracellular pH causes vasoconstriction.
Chest pain or angina and raised blood pressure are mentioned as adverse
reactions in the United States data sheet on omeprazole. Anterior
ischaemic optic neuropathy may, therefore, be caused by proton pump
inhibitors blocking potassium-hydrogen ATPase, possibly inducing
vasoconstriction and ischaemia in end arteries such as the retinal
artery". The same might pathophysiological process might also cause
microscopic colitis (3).
Might, therefore, the risks of anterior ischaemic optic neuropathy,
myopathy and organ dysfunction and even damage be increased by taking
omeprazole in patients taking statins?
1. P S Schönhöfer, B Werner, and U Tröger. Drug points: Ocular damage
associated with proton pump inhibitors. BMJ 1997; 314: 1805.
2. Robert J. Herman. Drug interactions and the statins. CMAJ •
November 16, 1999; 161 (10)
Rapid Response:
Omeprazole: might it increase the risk of statin induced myopathy?
The, "Six cases ..[of].. funduscopically confirmed irreversible
anterior ischaemic optic neuropathy", reported in the BMJ a few years ago
(1) are of additional concern for patients taking statins for it is so
commonly subscribed and the mechanisms of actions appear to be similar:
i.e a fall in pH and decline in Daniel Atkinson energy charge induced by
an energy supply/demand mismatch.
Thus the graded responses to a progressive increase in reductive
stress would seem to be, 1: upregulation of oxidative phoshorylation by
an increase in protonmotive force, 2: preservation of ATP stores by down
regulation of ATP-dependent reactions, and 3: possibly the local increase
in availability of nutrients derived from autophagy, apoptosis and even
necrosis in extremis. These actions would presumably be independent of
any effect upon cytochrome P450 (2). Thus the short term gains from
statins might always come with longer term risks of cellular dysfunction,
apoptosis and even necrosis.
"Proton pump inhibitors seem not to act specifically on potassium-
hydrogen ATPases in gastric mucosa. Omeprazole inhibits the secretion of
cerebrospinal fluid in rats by decreasing ATPase activity [i.e. ATP-
dependent reactions]. Reduction in intracellular pH by omeprazole induced
blockade of potassium-hydrogen ATPase results in decreased renal function,
and renal failure as well as interstitial nephritis have been observed
with omeprazole. Potassium-hydrogen ATPase is present in vascular smooth
muscle cells, and reduction in intracellular pH causes vasoconstriction.
Chest pain or angina and raised blood pressure are mentioned as adverse
reactions in the United States data sheet on omeprazole. Anterior
ischaemic optic neuropathy may, therefore, be caused by proton pump
inhibitors blocking potassium-hydrogen ATPase, possibly inducing
vasoconstriction and ischaemia in end arteries such as the retinal
artery". The same might pathophysiological process might also cause
microscopic colitis (3).
Might, therefore, the risks of anterior ischaemic optic neuropathy,
myopathy and organ dysfunction and even damage be increased by taking
omeprazole in patients taking statins?
1. P S Schönhöfer, B Werner, and U Tröger. Drug points: Ocular damage
associated with proton pump inhibitors. BMJ 1997; 314: 1805.
2. Robert J. Herman. Drug interactions and the statins. CMAJ •
November 16, 1999; 161 (10)
3. Richard G Fiddian-Green. Re: Microscopic colitis: the tip of an
omeprazole iceberg? (26 November 2004)
www.cmaj.ca/cgi/eletters/171/11/1326
Competing interests:
None declared
Competing interests: No competing interests