Doxazosin Mesylate

Preoperative medical management is critical to prevent intraoperative cardiovascular complications in patients with pheochromocytomas and paragangliomas (PPGLs). Initial treatment involves α-adrenergic receptor blockers. However, while the routine use of metyrosine alongside these blockers is not strongly recommended due to a lack of evidence supporting its efficacy and associated safety concerns, there are previous studies on combination therapy with phenoxybenzamine and metyrosine. There are few reports on combination therapy with the selective α1-adrenergic receptor blocker doxazosin. Therefore, we investigated this combination treatment, which theoretically can affect perioperative outcomes in patients with PPGLs. To our knowledge, this is the first such study.

This retrospective single-center observational study involved 51 patients who underwent surgical resection of PPGLs at Kobe University Hospital between 2014 and 2022. All patients received doxazosin at maximum doses. Fourteen patients received concomitant metyrosine, while 37 received doxazosin alone. Their perioperative outcomes were compared.

No severe event, such as acute coronary syndrome, was observed in either group. Intraoperatively, the doxazosin + metyrosine group exhibited a lower median minimum systolic blood pressure (56 [54-60] vs. 68 [59-74] mmHg, P = 0.03) and required lower median remifentanil (P = 0.04) and diltiazem (P = 0.02) doses than the doxazosin-alone group.

The combination of metyrosine and doxazosin as a preoperative treatment for PPGLs affects intraoperative circulatory hemodynamics, such as a reduced occurrence of blood pressure elevation during surgery. Further research is necessary to identify patients who will benefit most from this combination treatment.

Resistant hypertension is a condition where blood pressure levels remain elevated above target despite changes in lifestyle and concurrent use of at least three antihypertensive agents, including a long-acting calcium channel blocker (CCB), a blocker of the renin-angiotensin system (ACE inhibitor or angiotensin receptor blocker) and a diuretic. To be diagnosed as resistant hypertension, maintaining adherence to therapy is required along with confirmation of blood pressure levels above target by out-of-office blood pressure measurements and exclusion of secondary causes of hypertension. The key management points of this condition include lifestyle changes such as reduced sodium and alcohol intake, regular physical activity, weight loss and discontinuation of substances that can interfere with blood pressure control. It is also recommended that current treatment be rationalised, including single pill combination treatment where antihypertensive drugs should be provided at the maximum tolerated dose. It is further recommended that current drugs be replaced with a more appropriate and less difficult treatment regimen based on the patient's age, ethnicity, comorbidities and risk of drug-drug interactions. The fourth line of treatment for patients with resistant hypertension should include mineralocorticoid receptor antagonists such as spironolactone, as demonstrated in the PATHWAY-2 trial and meta-analyses. Alternatives to spironolactone include amiloride, doxazosin, eplerenone, clonidine and beta-blockers, as well as any other antihypertensive drugs not already in use. New approaches under research are selective non-steroidal mineralocorticoid receptor antagonists such as finerenone, esaxerenone and ocedurenone, selective aldosterone synthase inhibitors such as baxdrostat, and dual endothelin antagonist aprocitentan.