eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases
Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes: Treatment & Medication
Updated: Dec 9, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The treatment of autoimmune autonomic neuropathy (AAN) is based on anecdotal evidence. No data from large, controlled trials are available owing to the rarity of the disorder. The treatment of chronic pure autonomic failure syndromes is symptomatic only. Postural orthostatic tachycardia syndrome can be treated by using low doses of beta-blockers as patients are normally sensitive to their adverse effects.
- Nonpharmacologic measures are useful for all patients with autonomic dysfunction.5
- Discontinue antihypertensive medications and other medications known to lower blood pressure, if feasible.
- Increase fluid and salt intake.
- Equipment aids may be helpful. These include tight support stockings, abdominal binders, or antigravity suits for symptomatic hypotension and bladder catheterization for urinary retention.
- Dietary fiber and enemas may help improve bowel motility and decrease straining during defecation.
- Patients with decreased sweating should limit their physical activity, particularly in hot weather. Sponging with water during activity may help prevent overheating.
- Large meals may exacerbate hypotension and should be avoided.
- Perform positional changes, such as standing up, slowly and gradually.
- Elevate the head of the bed and avoid prolonged recumbency.
- Immunomodulatory therapy has been used successfully to shorten the duration of symptoms and improve overall prognosis in acute and chronic pandysautonomia.6
- Cases in which clinical improvement began within a few days of intravenous immunoglobulin (IVIg) administration (2 g/kg body weight over 2-5 d), along with normalization of autonomic test parameters, have been reported.7,8
- Presumably, IVIg has an immunomodulatory action, but the exact mechanism of its effect in this disorder is unclear.
- In 1 series, 2 patients with acute pandysautonomia were treated with prednisone 60 mg/d for several months and reported subjective improvement. No quantitative follow-up data were obtained.
- In a series of 3 patients with autoimmune autonomic ganglionopathy, patients treated with prednisone, mycophenolate mofetil, and plasmapheresis reported improvement when plasmapheresis or IVIg alone was not effective.9
- Other pharmacologic treatment options are directed toward symptomatic relief only (See Medication).5
Activity
Symptoms limit activity. Precautions for falling should be taken in patients who have orthostatic hypotension. In those with decreased sweating, vigorous exercise should be limited, and patients should be advised to have spray bottles of water or wet sponges available during hot weather or during physical activity.
Medication
Several medications are available to help manage symptoms of autonomic dysfunction. The most commonly used are listed below.
Mineralocorticoids
These agents play a role in hemodynamics and can be used to control orthostatic hypotension.
Fludrocortisone (Florinef)
Used to increase standing blood pressure. Acts to increase sodium retention and expand plasma volume.
Adult
0.1-0.2 mg PO qd
Pediatric
Not established
Antagonizes effects of anticholinergics; rifampin, hydantoins, and barbiturates decrease effects; decreases salicylate levels
Documented hypersensitivity; systemic fungal infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Supine hypertension may limit use; may cause adrenal insufficiency if withdrawn too rapidly; increased dose may be required in times of physiologic stress
Alpha-adrenergic agonists
These agents improve the hemodynamic status by increasing myocardial contractility and heart rate, resulting in increased cardiac output. They also increase peripheral resistance by causing vasoconstriction. Increased cardiac output and increased peripheral resistance lead to increased blood pressure.
Midodrine (ProAmatine)
Alpha-adrenergic agonist used in orthostatic hypotension to increase standing blood pressure. Acts at level of resistance vessels and is useful for peripherally mediated hypotension.
Adult
2.5-10 mg PO tid
Pediatric
Not established
Drugs that stimulate alpha-adrenergic agonists may enhance or potentiate pressor effects; cardiac glycosides may enhance or precipitate bradycardia; psychopharmacologic agents or beta-blockers may enhance or precipitate AV block or arrhythmia
Documented hypersensitivity; acute renal disease; severe organic heart disease; pheochromocytoma; urinary retention; persistent and excessive supine hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in diabetes or visual complications; discontinue drug and reevaluate if any signs or symptoms suggesting bradycardia occur
Beta-adrenergic blocking agents
These agents limit heart rate and reduce blood pressure.
Propranolol (Inderal)
Nonselective beta-blocker that is lipophilic (penetrates CNS).
Adult
10-60 mg PO qd
Pediatric
Not established
Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease propranolol effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity of propranolol; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase with propranolol
Documented hypersensitivity; history of bronchospasm; congestive heart failure; bradycardia; cardiogenic shock; AV conduction abnormalities
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockade may hide signs of acute hypoglycemia and hyperthyroidism, Raynaud phenomenon, hypotension, decreased libido, impotence, lethargy, depression, and decreased HDL; caution in Wolff-Parkinson-White syndrome and renal or hepatic dysfunction
Vasopressors
These agents augment both coronary and cerebral blood flow that occurs during the low flow state associated idiopathic hypotension.
Desmopressin (DDAVP, Stimate)
Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys. Helpful for symptoms of nocturia.
Adult
0.1-0.4 mL of 100-mcg/mL solution intranasally qd or divided bid/tid
Pediatric
Not established
Demeclocycline and lithium decrease effects; fludrocortisone and chlorpropamide increase effects
Documented hypersensitivity; platelet-type von Willebrand disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Avoid overhydration; may exacerbate hyponatremia
Erythropoietins
Anemia may occur due to low blood levels of endogenous erythropoietin, which can result from a lack of sympathetic innervation. Erythropoietins may also increase blood pressure through other mechanisms.
Epoetin alfa (Epogen, Procrit)
Stimulates RBC production in bone marrow. Increases sensitivity to pressor effects of angiotensin II, intravascular volume, cytosolic free calcium in vascular smooth muscle, and plasma endothelin level. Enhances renal tubular reabsorption.
Adult
50 U/kg IV/SC, initially once or twice weekly
Pediatric
Not established
None reported
Documented hypersensitivity; uncontrolled hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Sufficient bodily iron stores are needed for EPO to increase hematocrit; may predispose patients to seizures, usually due to uncontrolled hypertension; caution in porphyria, hypertension, or history of seizures
Gastroprokinetic agents
These agents promote motility of the GI tract.
Metoclopramide (Reglan)
Dopamine agonist helpful in relieving GI paresis.
Adult
5-15 mg PO qid given 30 min ac and hs
Pediatric
Not established
May antagonize effects of metoclopramide; opiate analgesics may increase toxicity in CNS; may slow absorption of drugs from stomach but increase rate of absorption of drugs from small bowel
Documented hypersensitivity; pheochromocytoma; GI hemorrhage, obstruction, or perforation; history of seizure disorders
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in history of mental illness, Parkinson disease, or hypertension
Anticholinesterase inhibitors
These agents inhibit acetylcholinesterase (AChE), raising the concentration of ACh at cholinergic synapses and increasing the chance of activating the AChR.
Pyridostigmine bromide (Mestinon)
Stimulates muscarinic AChR, increasing salivation and gastric motility.
Adult
60-960 mg/d PO in divided doses; individualize to patient
Pediatric
7 mg/kg/d PO in divided doses
Increases effects of depolarizing neuromuscular blockers; increases edrophonium toxicity
Documented hypersensitivity, peritonitis, mechanical obstruction of GI or GU tract
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Overdose may cause cholinergic crisis, which may be fatal; use cautiously in patients with bronchial asthma and those receiving a cardiac glycoside; adverse effects stem from dose-related, excessive muscarinic AChR effects
Bulk agents
Chronic treatment of constipation
Psyllium (Metamucil, Fiberall)
Must be taken with water or may cause obstruction. Increase dose gradually. Inform patient that effect not immediate.
Adult
15-60 g/d PO with at least 8 glasses of water
Pediatric
7.5-15 g/d PO with at least 4 glasses water
May reduce bioavailability of medications if taken within 30-60 min of fiber supplements because of adsorption to fiber; may decrease absorption of salicylates, nitrofurantoin, tetracyclines, and diuretics
Documented hypersensitivity; fecal impaction, intestinal obstruction, or undiagnosed abdominal pain
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with poor mobility, intestinal adhesions, ulcers, or bowel stenosis
Antispasmodic agents
These agents may be helpful for urinary symptoms.
Oxybutynin (Ditropan)
Useful for urinary urgency. Inhibits action of ACh on smooth muscle and direct antispasmodic effect on smooth muscle, which increases bladder capacity and decreases uninhibited contractions.
Adult
5 mg PO bid/tid; not to exceed 5 mg qid
Pediatric
<5 years: Not established
>5 years: 5 mg PO bid/tid
CNS effects increase with concurrent CNS depressants
Documented hypersensitivity; untreated angle-closure glaucoma or untreated narrow anterior chamber angles; GI obstruction; paralytic ileus; colitis; myasthenia gravis; unstable cardiovascular status
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in the elderly and in patients with hepatic or renal disease; may exacerbate symptoms of hyperthyroidism, coronary artery disease, tachycardia or other cardiac arrhythmias, hiatal hernia, hypertension, and prostatic hypertrophy; may contribute to decreased GI motility
Cholinergic agents
These agents stimulate cholinergic receptors in the smooth muscle of the urinary bladder for stimulation of bladder emptying.
Bethanechol hydrochloride (Duvoid, Urecholine)
For selective stimulation of the bladder to produce contraction to initiate micturition and empty bladder. Most useful in bladder hypotonia. Rarely used because of GI stimulation and difficulty in timing effect.
Adult
10-50 mg PO tid/qid
Pediatric
Not established
Concurrent ganglion-blocking compounds may critically decrease BP
Documented hypersensitivity; peptic ulcer disease; obstructive pulmonary disease; bradycardia; vasomotor instability; hypotension; AV conduction defects; hyperthyroidism; epilepsy; mechanical GI/GU obstruction.
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Urinary retention secondary to possible urine reflux into kidneys
Phosphodiesterase inhibitors
These oral agents act peripherally to induce smooth muscle relaxation of the corpora cavernosa.
Sildenafil (Viagra)
Selective PDE5 inhibitor that inactivates cGMP, attenuating vasodilatory effect of NO. Effective in mild-to-moderate erectile dysfunction. Patient should take on an empty stomach about 1 h before sexual activity. Sexual stimulation necessary to activate response. Increased sensitivity for erections may last 24 h.
Adult
25-100 mg PO 1 h before sexual activity
Pediatric
Not established
Potentiates vasodilatory effect of NO, resulting in potentially fatal drop in blood pressure; coadministration with ketoconazole, erythromycin, or cimetidine increases plasma sildenafil concentrations; coadministration with rifampin decreases plasma levels of sildenafil
Documented hypersensitivity; concurrent or intermittent use of organic nitrates in any form
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Headaches (16%), flushing (10%), upset stomach (7%), nasal congestion (4%), blue haze at the periphery of vision (3%); AEs more common in men taking 100 mg; serious AEs in severe heart disease and those taking nitrates; rates of MI 1.7 (drug) and 1.4 (placebo) per 100 man-years
Corticosteroids
These agents regulate key factors in the immune system.
Prednisone (Deltasone, Orasone, Meticorten)
Shorten duration of symptoms and improves overall prognosis in acute pandysautonomia.
Adult
Not established; in 1 series, 2 patients given 60 mg/d PO for several months, with subjective improvement but no quantitative follow-up data
Pediatric
Not established
Estrogens may decrease clearance; may increase digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); diuretics may cause hypokalemia
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor for hypokalemia if diuretics taken concurrently; long-term use may predispose patients to various problems including hyperglycemia, manifestation of latent diabetes mellitus, nonketotic hyperosmolar state, osteoporosis, avascular necrosis of hip, peptic ulcer disease, cataracts and glaucoma, steroid myopathy, cushingoid appearance, weight gain, suppression of pituitary-hypothalamic axis, growth suppression (in children); water retention may precipitate congestive heart failure and hypertension; unmasking of latent infections (eg, tuberculosis, herpes zoster) and predisposition to fungal and parasitic infection; because of suppressed pituitary-hypothalamic axis, additional steroid dosing may be necessary at times of stress (eg, systemic infections, surgery)
Immune globulins
These agents are used to improve clinical and immunologic aspects of the disease. May decrease autoantibody production, and increase solubilization and removal of immune complexes.
Immune globulins intravenous (IVIG, Gammagard, Gamimune)
Shortens duration of symptoms and improves overall prognosis in acute pandysautonomia. Clinical improvements have been reported within few days of administration, with normalization of autonomic parameters.
Neutralize circulating myelin antibodies through antiidiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).
Adult
2 g/kg body weight IV divided over 2-5 d
Pediatric
Administer as in adults
None reported
Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies; renal insufficiency or renal artery stenosis (may cause renal failure)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Consider checking serum IgA before IVIG and using IgA-depleted IVIG (G-Gard-SD) if indicated; IVIG may increase serum viscosity and thromboembolic events; adverse effects have included migraines; 10% increased risk of aseptic meningitis; increased risk of urticaria, pruritus, or petechiae 2-5 d after infusion (may last 1 mo); increased risk of renal tubular necrosis in older, diabetic, and volume-depleted patients and in preexisting kidney disease; can change laboratory values: elevated antiviral or antibacterial antibody titers for 1 mo; 6-fold increased ESR for 2-3 wk; apparent hyponatremia
More on Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes |
| Overview: Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes |
| Differential Diagnoses & Workup: Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes |
 Treatment & Medication: Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes |
| Follow-up: Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes |
| References |
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References
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Further Reading
Keywords
acute idiopathic dysautonomia, multiple system atrophy, MSA, olivopontocerebellar atrophy, pure autonomic failure, PAF, Shy-Drager syndrome, striatonigral degeneration, postural tachycardia syndrome, POTS, autoimmune autonomic neuropathy, AAN, autoimmune autonomic ganglionopathy, AAG, acute pandysautonomia, acute panautonomic neuropathy
