Autonomic Neuropathy Medication
- Author: Steven D Arbogast, DO; Chief Editor: Nicholas Lorenzo, MD more...
Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent complications. Many of the medications used to treat dysautonomia are considered off label.
Sympathomimetic agents
Class Summary
These are used in orthostatic hypotension if simple measures yield no improvement.
Midodrine (ProAmatine)
Prodrug metabolized to desglymidodrine, a selective alpha1-adrenoreceptor agonist. Effects via arterioconstriction and venoconstriction.
Mineralocorticoids
Class Summary
These agents can be used to treat orthostatic hypotension.
Fludrocortisone (Florinef)
Promotes increased reabsorption of sodium and loss of potassium at renal distal tubules.
Anticholinergic agents
Class Summary
These agents are useful in cases of difficult bladder emptying.
Oxybutynin (Ditropan)
Commonly used drug in bladder disorder. Known for anticholinergic-antispasmodic effects. Smooth muscle relaxing effect distal to cholinergic receptor site. Long-acting form available for qd dosing.
Tolterodine tartrate (Detrol)
Competitive muscarinic receptor antagonist for overactive bladder, but differs from other anticholinergic types because of selectivity for urinary bladder over salivary glands. High specificity for muscarinic receptors. Minimal activity or affinity for other neurotransmitter receptors and other potential targets (eg, calcium channels).
Beta-adrenergic blocker
Class Summary
This agent can be used to treat orthostatic tachycardia in POTS patients.
Metoprolol (Lopressor, Toprol XL)
For treatment of orthostatic tachycardia. Inhibits beta-adrenergic input.
Vasopressin analogues
Class Summary
Oral or nasal spray agents acting to prevent nocturnal urinary production.
Desmopressin acetate (DDAVP)
Vasopressin analogue without effect on V1 receptors responsible for vasopressin-induced vasoconstriction. Acts on V2 receptors at renal tubuli, increasing cellular permeability of collecting ducts, responsible for antidiuretic effect. Prevents nocturnal diuresis and elevated morning BP, resulting in renal water reabsorption. Nasal spray and tab (more convenient).
Acetylcholinesterase inhibitor
Class Summary
This agent can be used to treat orthostatic hypotension or orthostatic tachycardia.
Pyridostigmine (Mestinon)
Increases acetylcholine neurotransmission at peripheral
autonomic ganglia, which likely increases peripheral vasoconstriction sympathetic nerve fiber transmission. May also increase vagal cardiac input in POTS patients.
Cholinergic agents
Class Summary
These agents stimulate cholinergic receptors in the smooth muscle of the urinary bladder for stimulation of bladder emptying.
Bethanechol hydrochloride (Duvoid, Urecholine)
Used for selective stimulation of the bladder to produce contraction to initiate micturition and empty bladder. Most useful in bladder hypocontractility, if sphincters functional and coordinated. Rarely used because of GI stimulation and difficulty in timing effect.
Phosphodiesterase inhibitors
Class Summary
These oral agents act peripherally to induce smooth muscle relaxation of the corpora cavernosa.
Sildenafil (Viagra)
Selective inhibitor of PDE5 that inactivates cGMP, allowing attenuation of the vasodilatory effect of NO. Effective in men with mild-to-moderate erectile dysfunction. Take on an empty stomach about 1 h before sexual activity. Sexual stimulation is necessary to activate response. The increased sensitivity for erections may last 24 h. Available as 25-, 50-, and 100-mg tabs.
Neuromuscular blocker agent, toxin
Class Summary
Used in patients with hyperhydrosis localized to palmar or axillary region.
Botulinum toxin type A (Botox)
One of several toxins produced by clostridium botulinum. Blocks neuromuscular transmission through a 3-step process: (1) Blockade of neuromuscular transmission; botulinum toxin type A (BTA) binds to the motor nerve terminal. The binding domain of the type A molecule appears to be the heavy chain, which is selective for cholinergic nerve terminals. (2) BTA is internalized via receptor-mediated endocytosis, a process in which the plasma membrane of the nerve cell invaginates around the toxin-receptor complex, forming a toxin-containing vesicle inside the nerve terminal. After internalization, the light chain of the toxin molecule, which has been demonstrated to contain the transmission-blocking domain, is released into the cytoplasm of the nerve terminal. (3) BTA blocks acetylcholine release by cleaving SNAP-25, a cytoplasmic protein that is located on the cell membrane and that is required for the release of this transmitter. The affected terminals are inhibited from stimulating muscle contraction. Toxin does not affect synthesis or storage of acetylcholine or conduction of electrical signals along the nerve fiber. Prevents calcium-dependent release of acetylcholine and produces a state of denervation at the neuromuscular junction and postganglionic sympathetic cholinergic nerves in the sweat glands.
Typically, a 24-72 h delay between administration of toxin and onset of clinical effects exists, which terminate in 2-6 mo.
This purified neurotoxin complex is a vacuum-dried form of purified BTA, which contains 5 ng of neurotoxin complex protein per 100 U.
BTA has to be reconstituted with 2 mL of 0.9% sodium chloride diluent. With this solution, each 0.1 mL results in 5 U dose. Patient should receive 5-10 injections per visit.
Must be reconstituted from vacuum-dried toxin into 0.9% sterile saline without preservative using manufacturer's instructions to provide injection volume of 0.1 mL; must be used within 4 h of storage in refrigerator at 2-8°C.
Preconstituted dry powder must be stored in freezer at < 5°C. Each injection produces an area of anhydrosis approximately 1.2 cm in diameter. Results in anhydrosis lasting 4-12 months.
Injections of botulinum toxin must be repeated at varying intervals to maintain long-term results.
Colony-stimulating Factor
Class Summary
May be used in patients with orthostatic hypotension or POTS.
Epoetin alfa (Epogen, Procrit)
Purified glycoprotein produced from mammalian cells modified with gene coding for human erythropoietin (EPO). Amino acid sequence is identical to that of endogenous EPO. Biological activity mimics human urinary EPO, which stimulates division and differentiation of committed erythroid progenitor cells and induces release of reticulocytes from bone marrow into the blood stream.
Has been shown to increase the functional capacity of patients with MSA, particularly those who have the characteristic mild anemia associated with this disease. Up to 38% of patients with severe autonomic failure are anemic. Lack of sympathetic stimulation may lead to a decrease of erythropoietin production and development of anemia. Sympathetic impairment and low plasma norepinephrine levels have been found to correlate with severity of anemia. Therapy with recombinant erythropoietin, even low doses (25-50 units/kg body weight SC, 3 times a week) has successfully corrected anemia and improved upright BP.
Anticholinergic agent
Class Summary
Used for hyperhidrosis.
Glycopyrrolate (Robinul)
Acts in smooth muscle, CNS, and secretory glands to blocks action of acetylcholine at parasympathetic sites.
Immune globulin
Class Summary
Used for autoimmune causes of autonomic neuropathy.
Immune globulin intravenous (CarimuneGammagard S/D, Gammar-P, Gamunex, Polygam S/D)
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%).
Anti-inflammatory agent
Class Summary
Can be used if an inflammatory cause of the autonomic neuropathy is considered to be autoimmune in nature.
Prednisone (Deltasone, Sterapred, Orasone)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production.
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| HSAN | Mode of Inheritance | Onset | Symptoms | Signs |
| Type I | Autosomal dominant, point mutations in SPT, 9q22.1-9q22.3 | Second decade of life | Distal lower-limb involvement, ulceration of the feet, particularly the soles | Low sensory action potential amplitude |
| Type II, Morvan disease | Autosomal recessive | Congenital onset | Pansensory loss of upper and lower limbs, also trunk and forehead; early ulcers | Loss of myelinated and unmyelinated fibers |
| Type III, Riley-Day syndrome or familial dysautonomia) | Autosomal recessive, 9q31 | Childhood onset, predominantly Ashkenazi Jews | Pallor in infancy, irregularities in temperature and blood pressure; Difficulties in eating and swallowing | Absence of unmyelinated fibers |
| Type IV | Autosomal recessive, 1q21-1q22 | Congenital onset | Widespread anhidrosis, lost sense of pain, mental retardation | Loss of myelinated and small unmyelinated fibers |
| Type V | Autosomal recessive | Congenital onset | Pain insensitivity in extremities | Not applicable |
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