What are the hypertension (HTN) treatment medications to avoid in patients with neurogenic orthostatic hypotension and which medications are preferred for treating hypertension in this condition?

From the Guidelines

For patients with neurogenic orthostatic hypotension who also require hypertension treatment, it's best to avoid medications that worsen orthostatic symptoms, particularly diuretics, alpha-blockers, and vasodilators, and instead prefer angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), or calcium channel blockers, as recommended by the most recent guidelines 1. When managing hypertension in patients with neurogenic orthostatic hypotension, it's crucial to consider the potential impact of antihypertensive medications on orthostatic blood pressure regulation.

• Medications to avoid include:
  • Diuretics, which can lead to volume depletion and exacerbate orthostatic hypotension 1
  • Alpha-blockers, such as doxazosin, which can cause vasodilation and worsen orthostatic symptoms 1
  • Vasodilators, like hydralazine or minoxidil, which can also exacerbate blood pressure drops upon standing 1
• Preferred medications include:
  • ACE inhibitors, such as lisinopril, which have a minimal impact on orthostatic blood pressure regulation 1
  • ARBs, like losartan, which also have a favorable effect on orthostatic blood pressure control 1
  • Calcium channel blockers, such as amlodipine, which can help control hypertension without worsening orthostatic symptoms 1 It's essential to start with low doses and titrate slowly while monitoring both supine and standing blood pressures to minimize orthostatic symptoms and control hypertension, as suggested by the 2022 guidelines on diabetes care 1. Additionally, consider treating hypertension only when the patient is supine, as many patients with neurogenic orthostatic hypotension have supine hypertension but normal or low blood pressure when upright, and non-pharmacological approaches should be pursued as the first-line treatment of orthostatic hypotension among persons with supine hypertension, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

From the FDA Drug Label

The potential for supine and sitting hypertension should be evaluated at the beginning of midodrine therapy. Midodrine should be used cautiously in patients with urinary retention problems, as desglymidodrine acts on the alpha-adrenergic receptors of the bladder neck Midodrine should be used with caution in orthostatic hypotensive patients who are also diabetic, as well as those with a history of visual problems who are also taking fludrocortisone acetate, which is known to cause an increase in intraocular pressure and glaucoma. Avoid concomitant use of drugs that increase blood pressure. If concomitant use cannot be avoided, monitor blood pressure closely Alpha-adrenergic blocking agents, such as prazosin, terazosin, and doxazosin, can antagonize the effects of midodrine

HTN treatment meds to avoid in neurogenic orthostasis hypotension:

• Alpha-adrenergic blocking agents, such as prazosin, terazosin, and doxazosin
• Drugs that increase blood pressure, such as phenylephrine, pseudoephedrine, ephedrine, dihydroergotamine, thyroid hormones or droxidopa
• MAO inhibitors or linezolid

Preferred med HTN meds to use:

• Midodrine can be used to treat symptomatic orthostatic hypotension, but it should be used with caution in certain patients, such as those with renal impairment, hepatic impairment, or urinary retention problems 2 2

From the Research

HTN Treatment Meds to Avoid in Neurogenic Orthostatic Hypotension

• Vasodilators and β-blockers can exacerbate neurogenic orthostatic hypotension (nOH) and concomitant symptoms 3
• Medications that can worsen supine hypertension, such as certain antihypertensives, should be used with caution in patients with nOH 3

Preferred Meds for HTN in Neurogenic Orthostatic Hypotension

• Midodrine, a specific alpha-1-agonist, has been shown to be effective in treating nOH by producing arteriolar constriction and decreasing venous pooling 4
• Droxidopa may be less likely than midodrine to exacerbate supine hypertension, based on conclusions of a limited meta-analysis 3
• Other medications such as pyridostigmine, atomoxetine, and yohimbine may be effective in patients with relatively preserved "sympathetic reserve" 5
• Fludrocortisone and octreotide may also be used as nonspecific treatments for nOH 5

Considerations for Treatment

• Treatment should be individualized based on the patient's underlying pathophysiology and clinical conditions 5
• The presence of associated clinical conditions, such as supine hypertension, heart failure, postprandial hypotension, PD, MSA, and diabetes, should be considered in the pharmacologic management of nOH 5, 3