Autonomic Neuropathy Medication
- Author: Steven D Arbogast, DO; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE more...
The goals of pharmacotherapy are to reduce morbidity and prevent complications. Many of the medications used to treat dysautonomia are considered off label.
These are used in orthostatic hypotension if simple measures yield no improvement.
Prodrug metabolized to desglymidodrine, a selective alpha1-adrenoreceptor agonist. Effects via arterioconstriction and venoconstriction.
These agents can be used to treat orthostatic hypotension.
Promotes increased reabsorption of sodium and loss of potassium at renal distal tubules.
These agents are useful in cases of difficult bladder emptying.
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.
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).
This agent can be used to treat orthostatic tachycardia in POTS patients.
For treatment of orthostatic tachycardia. Inhibits beta-adrenergic input.
Oral or nasal spray agents acting to prevent nocturnal urinary production.
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).
This agent can be used to treat orthostatic hypotension or orthostatic tachycardia.
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.
These oral agents act peripherally to induce smooth muscle relaxation of the corpora cavernosa.
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.
Sexual stimulation causes nitric oxide to be released in the corpus cavernosum; nitric oxide activates the enzyme guanylate cyclase, which in turn increases cGMP levels; increase in cGMP levels causes smooth muscle relaxation.
Phosphodiesterase type 5 inhibitors enhance the effects of nitric oxide in smooth muscle relaxation of the corpus cavernosum by inhibiting the degradation of cGMP.
Erectile dysfunction: Inhibits PDE-5, increasing cyclic guanosine monophosphate (cGMP) to allow smooth-muscle relaxation and inflow of blood into corpus cavernosum
Pulmonary arterial hypertension (PAH): Inhibits PDE-5, increasing cGMP to allow relaxation of pulmonary vascular smooth-muscle cells and vasodilation of pulmonary vasculature
Sexual stimulation causes nitric oxide to be released in corpus cavernosum, and nitric oxide activates guanylate cyclase, which in turn increases cyclic guanosine monophosphate (cGMP), thus causing smooth-muscle relaxation; PDE-5 inhibitors enhance smooth muscle-relaxing effects of nitric oxide in corpus cavernosum by inhibiting degradation of cGMP
Neuromuscular blocker agent, toxin
Used in patients with hyperhydrosis localized to palmar or axillary region.
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.
May be used in patients with orthostatic hypotension or POTS.
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.
Used for hyperhidrosis.
Acts in smooth muscle, CNS, and secretory glands to blocks action of acetylcholine at parasympathetic sites.
Used for autoimmune causes of autonomic neuropathy.
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%).
Can be used if an inflammatory cause of the autonomic neuropathy is considered to be autoimmune in nature.
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.
Cholinergic agonist agents
These agents stimulate cholinergic receptors in the smooth muscle of the urinary bladder for stimulation of bladder emptying.
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.
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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|