Orthostatic Hypotension

Central alpha blockers

Clonidine Guanabenz Guanfacine Methyldopa Reserpine

Orthostatic hypotension symptoms

Common: Dizziness, lightheadedness, blurred vision, weakness, fatigue, nausea, palpitations, headache, falls, slurred speech, and confusion Rare: Syncope, dyspnea, chest pain,, and neck and shoulder pain

Non-pharmacologic Strategies

-Head elevation 10-30° during sleep -Increase salt and fluid intake -Elastic stocking/abdominal binding -Avoidance of contributory medications -Avoid sudden postural changes

Treatment Goals Orthostatic Hypotension

-Treatment of the underlying cause -Improve orthostatic blood pressures without an excessive supine blood pressure increase -Alleviate symptoms -Prevent falls -Improve standing time to perform activities of daily living

Treatment Algorithm

1. Symptoms consistent with OH --> Confirm orthostatic BP lowering of >20/10 mmHG 2. Modify or remove medications that cause/worsen OH 3. Lab and other assessments to determine correctable causes (eg., CBC, BUN/CR, B12, ECG to screen for anemia, dehydration, and cardiac cause) 4. Nonpharmacologic management 5. Pharmacotherapy 6. Consultation -At risk, symptomatic pts: neurologist or movement disorder specialist) -(Severe cases: cardiologist for cardiac abnormalities)

Antidepressants

Antidepressants Amitriptyline Amoxapine Desipramine Doxepin >6mg/d Imipramine Nortriptyline Paroxetine Protriptyline Trimipramine

Medications that may cause Orthostatic Hypotension

Antipsychotics Peripheral alpha-1 blockers Central alpha blockers Non-dihydropyridine calcium channel blocker Antidepressants Diuretics Nitrates Phosphodiestrase Type 5 Inhibitor Antithrombotics

Diagnosis

BP measurement in supine/sitting and upright positions -Decrease of 20/10 mmHg at 3 minutes Heart rate increase within 3 minutes -Neurogenic: Increase <15bpm -Non-neurogenic: Increase >15bpm

Antipsychotics

Chlorpromazine Clozapine Risperidone Thioridazine Olanzapine

Antithrombotics

Dipyridamole

Peripheral alpha-1 blockers

Doxazosin Prazosin Terazosin

Etiology: Neurogenic

Primary neurodegenerative disorders -Pure autonomic failure -Multiple system atrophy -Parkinson's disease Secondary to neurological diatheses -Diabetes -Amyloidosis, or -Advanced renal failure

Diuretics

Furosemide Torsemide Bumetanide Etharcynic acid Hydrochlorothiazide Chlorthalidone

Etiology: Non-neurogenic

Impairment of the autonomic nervous system -treatment with vasodilators, tricyclic antidepressants, diuretics, or chemotherapeutic agents Absolute or relative reduction in circulating blood volume Venous pooling Inotropic and/or chronotropic heart failure

Nitrates

Isosorbide mononitrate Isosorbide dinitrate Nitroglycerine

Midodrine (Proamatine®, Orvaten®)

MOA Activates alpha-adrenergic receptors of the arteriolar and venous vasculature which results in increased vascular tone and elevation of blood pressure Dosing Oral Tablet: 10 mg TID Q4hrs during the day Adverse Events Pruritus, chills, piloerection, and urinary urgency or retention Monitoring Parameters Improvement of OH, renal and hepatic function, BP Drug Interactions TCAs, pseudoephedrine, dihydroergotamine

Pyridostigmine (Mestinon®, Regonol®)

MOA Inhibits acetylcholinesterase, generally used in neurogenic OH to improve acetylcholine concentrations in the efferent limb of the baroreflex Dosing Initial dose 30 mg PO 2 or 3 times daily but may be titrated to 60 mg PO 3 times daily Available in oral tablets, oral syrup, extended release oral tablets and injection solution Adverse Effects Diaphoresis, hypersalivation, diarrhea, muscle cramping, urinary incontinence Monitoring Parameters Heart rate, signs of muscle weakness, gastric irritation (take with food) Drug Interactions Succinylcholine

Fludrocortisone (Florinef®)

MOA Its mineralcorticoid effects produce sodium retention (increasing volume) and urinary potassium excretion Dosing Oral: 0.1 mg/day but may be titrated to 0.2 mg/day if needed AE Edema, hypokalemia, hyperglycemia, hypertension, muscle weakness, headache Monitoring Parameters BP, serum electrolytes, symptomatic improvement Drug Interactions Desmopressin, flouroquinolones

Droxidopa (Northera®)

MOA Synthetic precursor of norepinephrine. After converting to norepinephrine, it increases blood pressure by causing vasoconstriction of peripheral arteries and veins Dosing Oral Capsule: Initial 100 mg TID, may be titrated as needed in 100 mg TID increments, MAX dose is 1800 mg/day Adverse Effects Hypertension, headache, dizziness, and nausea Monitoring Parameters BP, kidney function, hyponatremia, nocturia Drug Interactions Tranylcypromine, midodrine, carbidopa

Desmopressin (DDAVP®)

MOA Analog of naturally occurring antidiuretic hormone (ADH) which affects conservation of water in the kidneys. This causes volume expansion by increasing water reabsorption and reducing nocturia. Dosing Nasal spray: 5-40 mcg/day 30 min before bedtime ODT: 25-100mcg/day 1 hour before bedtime Oral tablets: 100-800 mcg/day at bedtime Also available in IV and SubQ formulations Adverse effects Hypertension, xerostomia, fatigue, hyponatremia Monitoring Parameters BP, kidney function, hyponatremia, nocturia Drug Interactions Corticosteroids, Diuretics

Avoidance of contributory medications

Medications that promote volume depletion (example: diuretics) and peripheral vasodilation (example: nitrates) increase the risk of OH

Avoid sudden postural changes

Moving from supine to sitting to standing position should be done slowly to minimize sudden blood pressure changes.

Head elevation 10-30° during sleep

Reduces nocturia, volume depletion, and supine hypertension

Elastic stocking/abdominal binding

Reduction of peripheral pooling in lower extremities

Pharmacologic Agents used to treat Orthostatic Hypotension

Short acting pressor agents -Droxidopa (Northera®) -Midodrine (Proamatine®, Orvaten®) Volume expanders -Fludrocortisone (Florinef®) -Desmopressin (DDAVP®) Other agents -Pyridostigmine (Mestinon®, Regonol®)

Phosphodiestrase Type 5 Inhibitor

Sildenafil Tadalafil

OH Etiology

Structural (Neurogenic) Functional (Non-neurogenic)

Orthostatic hypotenstion

Sustained reduction in: -systolic blood pressure of 20 mmHG -diastolic blood pressure of 10 mmHg *within 3 minutes of standing from a seated or supine position

Non-dihydropyridine Calcium channel blockers

Verapamil Diltiazem

Increase salt and fluid intake

Volume expansion. Dietary salt intake of up to 10g/day and fluid intake of up to 1.5L per day is recommended if not contraindicated by comorbidities.