Background: Proton pump inhibitors (PPIs) are widely used for the treatment of g
ID: 3480519 • Letter: B
Question
Background:
Proton pump inhibitors (PPIs) are widely used for the treatment of gastro-esophageal reflux disease. Long term use of these drugs are notoriously toxic to kidney due their mild inhibition of the kidney H+K+-ATPase and subsequent hyponatremia. PPIs also have been associated with direct and indirect effects on serum cation intestinal absorption or renal reabsorption. Hypomagnesemia is the newest complication ascribed to the use of PPIs.
Magnesium homeostasis is governed by two principle mechanisms- intestinal absorption and renal re-uptake. In both tissues, the transient receptor potential melastatin-6 and -7 (TRPM6/7) is primarily responsible for the majority of magnesium transport, although some evidence for transcellular transport from the lumen to blood exists.
Questions:
a. What is the central role of magnesium in human health? What are the long-term effects of hypomagnesemia?
b. What conclusions would you make from data that suggest that treatment of patients with PPI-induced SIBO show a concomitant increase in serum magnesium levels?
c. Do PPIs interfere with the absorption of magnesium in Intestine, kidney or both? What experiment has been done or could be done to differentiate? Feel free to propose a tractable and feasible experiment or cite one that has been published. Explain the experiment and the outcome and the conclusions that could be made.
d. The target effect of PPIs is the inhibition of the H+ ATPase primarily expressed in gastrointestinal tissue. How could one determine whether the effects of PPIs on serum magnesium levels are due to a direct effect on TRPM6/7 transport or indirect due to pH changes? As above, propose a simple, tractable experiment to determine this or cite an experiment that has been published.
e. Suppose that a patient’s GERD symptoms were too severe to not be treated, what are two simple strategies that could be employed to reduce the risk of hypomagnesemia.
Explanation / Answer
a) The role of magnesium is it is needed for more than 300 biochemical reactions.
the hypo magnesia causes long term effects like
B) The data shows that the proton pump inhibitors are having a major role and the magnesium homeostatisis should be maintained because it leads to cardiac arrest. The proton pump inhibitors that are used to treat the gastro oesophageal reflux disorder inhibit the protan pump in the parietal cells of the gastric mucosa.
C) Proto pump inhibitors inhibit the active magnesium in the body.They inhibit the magnesium absorption in the intestine.
To conduct an experiment the control is given with standard magnesium diet and the test is given the magnesium diet then after four days the proton pump inhibitors are given along with magnesium.
The data of the control and the test reveals the amount of magnesium that is absorbed by calculating the metal concentration in the blood and urine.
D) The proton pump inhibitors acts primarily on the mucosa of the gastro intestinal tract. The protan pump inhibitors inhibit the absorption of the magnesium due to the direct effect on TRPM6/7 transport and due to the PH change.
the above tractable experiment shows the amount of the magnesium that is absorbed when given in PPIs and only given with the magnesium diet.
E) The simple stategies are
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