dihydropyridines and Hyperaldosteronism

Primary aldosteronism, caused by autonomous secretion of aldosterone by the adrenals, is estimated to account for at least 5% of hypertension cases. Hypertension explains the considerable cardiovascular morbidity caused by aldosteronism only partly, calling for specific anti-aldosterone drugs. The pharmacology of aldosterone is complex due to high homology with other steroids, the resemblance of steroid receptors, and the common pathways of steroid synthesis. Classically, pharmacological treatment of aldosteronism relied on the mineralocorticoid receptor (MR) antagonist spironolactone, which is highly effective, but causes considerable, mainly sexual side-effects due to limited selectivity for the MR. New agents have been developed or are being developed that aim at higher selectivity for MR antagonists (eplerenone, dihydropyridine-derived calcium channel blockers (CCB)), or inhibition of aldosterone synthesis. Eplerenone is less potent than spironolactone, but causes fewer adverse effects due to its selectivity for the MR. Non-steroidal MR antagonists have been developed from dihydropyridine CCBs, having lost their CCB activity and being highly selective for the MR. The first clinical studies with these drugs are underway. Aldosterone synthase inhibitors are an attractive alternative, but are prone to interference with cortisol synthesis due to the inhibition of 11-β-hydroxylation, an essential step in both cortisol and aldosterone synthesis, and accumulation of mineralocorticoid precursors. In coming years clinical research will provide the answers as to which drugs and strategies to treat high-aldosterone states are the most effective.

Topics: Aldosterone; Cytochrome P-450 CYP11B2; Dihydropyridines; Drug Interactions; Epithelial Sodium Channel Blockers; Eplerenone; Glucocorticoids; Heart Failure; Hyperaldosteronism; Hypertension; Mineralocorticoid Receptor Antagonists; Spironolactone

We report a 46-year-old man with primary aldosteronism presenting hypokalemia, periodic paralysis and hypokalemic myopathy whose clinical course paralleled with the dosage of benidipine hydrochloride, a dihydropyridine calcium channel blocker (DHP-CCB), administered for the treatment of hypertension. To see relations between DHP-CCB and episodes of motor weakness in patients with primary aldosteronism, we surveyed retrospectively the history of motor weakness and anti-hypertensive drugs in 14 consecutive cases with primary aldosteronism in our institute. Five patients out of 11 cases (45.5%) who had received DHP-CCB experienced muscle weakness, however, the rest of three patients receiving other anti-hypertensive drug had not experienced weakness. Though, less attention has been paid as thiazide diuretics, it is reported that DHP-CCB also induces hypokalemia through several mechanisms. However, the occurrence of motor weakness by DHP-CCB is very rare. Our results show that primary aldosteronism should be taken into account when we encounter patients manifesting episodic motor weakness by the use of DHP-CCB.

Topics: Calcium Channel Blockers; Dihydropyridines; Humans; Hyperaldosteronism; Hypokalemia; Hypokalemic Periodic Paralysis; Male; Middle Aged; Muscular Diseases

Topics: Adult; Aldosterone; Calcium Channel Blockers; Delayed Diagnosis; Dihydropyridines; Drug Resistance; Female; Humans; Hyperaldosteronism; Hypertension; Hypokalemia; Male; Middle Aged; Potassium; Renin

The absence of long-term effect of calcium channel blockers in primary aldosteronism due to adrenal adenoma is described in two patients. Calcium entry channel blockers, which were claimed to be a new medical therapy for primary aldosteronism, neither prevented the increase of plasma aldosterone nor decreased potassium levels over time in these patients. The drugs did not even lower blood pressure in one patient. Whereas calcium channel blockers may be effective in adrenal hyperplasia, they are apparently not effective enough in the long term treatment of patients with primary aldosteronism due to adrenal adenoma.

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Aldosterone; Calcium Channel Blockers; Dihydropyridines; Humans; Hyperaldosteronism; Male; Potassium; Renin