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Sympatholytic

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Sympatholytic

A sympatholytic (or sympathoplegic) drug is a medication which inhibits the postganglionic functioning of the sympathetic nervous system (SNS).[1] They are indicated for various functions, for example they may be used as antihypertensives. They are also used to treat anxiety, such as Generalized Anxiety Disorder, Panic Disorder and PTSD.

Antiadrenergic

Antiadrenergic agents inhibit the signals of epinephrine and norepinephrine. They are primarily adrenergic antagonists, (Alpha Blockers and Beta Blockers) inhibiting adrenergic receptors, but, there are exceptions: clonidine is an adrenergic agonist on the α2 receptor, since this receptor is located presynaptically to inhibit further release of adrenaline and noradrenaline.

Other ways of inhibiting adrenergic signaling is by catecholamine synthesis blocking, e.g. by methyltyrosine. Reserpine works by inhibiting transport into synaptic vesicles of noradrenaline by inhibiting the VMAT.

In hypertension

Many antiadrenergic agents used as antihypertensives include:

In Anxiety

Beta Blockers

There is clear evidence from many controlled trials in the past 25 years that beta blockers are effective in anxiety disorders, though the mechanism of action is not known (2). Some people have used beta blockers for 'performance anxiety'. In particular, musicians, public speakers, actors, and professional dancers, have been known to use beta blockers to avoid stage fright and tremor during public performance and especially auditions. The physiological symptoms of the fight/flight response associated with performance anxiety and panic (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand. Stutterers also use beta blockers to avoid fight/flight responses, hence reducing the tendency to stutter.

Since they promote a lower heart rate and reduce tremor, beta blockers have been used by some Olympic marksmen to enhance performance, though beta blockers are banned by the International Olympic Committee (IOC). [2] Although they have no recognisable benefit to most sports, it is acknowledged that they are beneficial to sports such as archery and shooting. A recent, high-profile transgression took place in the 2008 Summer Olympics, where 50 metre pistol silver medallist and 10 metre air pistol bronze medallist Kim Jong-su tested positive for propranolol and was stripped of his medal.

Post traumatic stress disorder (PTSD) is theorized to be the result of neurological patterns caused by adrenaline and fear in the brain. By administering beta blockers immediately following a traumatic event, as well as over the next couple weeks, the formation of PTSD has been reduced in clinical studies. [2]

Alpha Blockers

Alpha Blockers can also be used to treat anxiety and panic, such as Generalized Anxiety Disorder, Panic Disorder or PTSD. Alpha2-adrenergic receptor agonists, such as clonidine and guanfacine, act at noradrenergic autoreceptors to inhibit the firing of cells in the locus ceruleus, effectively reducing the release of brain norepinephrine (3). Clonidine has shown promise among patients with Anxiety, Panic and PTSD in clinical trials and was used to treat severely and chronically abused and neglected preschool children. It improved disturbed behavior by reducing aggression, impulsivity, emotional outbursts, and oppositionality (4). Insomnia and nightmares were also reported to be reduced.

Kinzie and Leung (5) prescribed the combination of clonidine and imipramine to severely traumatized Cambodian refugees with Anxiety, Panic and PTSD. Global symptoms of PTSD were reduced among sixty-six percent and nightmares among seventy-seven percent. Guanfacine produces less sedation than clonidine and thus may be better tolerated. Guanfacine reduced the trauma-related nightmares (6). A recently completed randomized double-blind trial among veteran patients with chronic PTSD showed that augmentation with guanfacine was associated with improvement in anxiety and PTSD.

Prazosin is an alpha1-receptor antagonist. Raskin and colleagues (7) studied the efficacy of prazosin for PTSD among Vietnam combat veterans in a 20-week double-blind crossover protocol with a two-week drug washout to allow for return to baseline (7). The CAPS and the Clinical Global Impressions-Change scale (CGI-C) were the primary outcome measures. Patients who were taking prazosin had a robust improvement in overall sleep quality (effect size, 1.6) and recurrent distressing dreams (effect size, 1.9). In each of the PTSD symptom clusters the effect size was medium to large: 0.7 for reexperiencing or intrusion, and 0.6 for avoidance and numbing, and .9 for hyperarousal. The reduction in CGI-C scores (overall PTSD severity and function at endpoint) also reflected a large effect size (1.4). Prazosin appears to have promise as an effective treatment for PTSD-related sleep disturbance, including trauma-related nightmares, as well as overall Anxiety and PTSD symptoms.

References

  1. ^ "Dorlands Medical Dictionary:sympatholytic". 

2. Tryer, Peter. "Anxiolytics not acting at the benzodiazepine receptor: Beta blockers." Progress in Neuro-Psychopharmacology and Biological Psychiatry. Volume 16, Issue 1, January 1992, Pages 17–26.

3 Kaplan HI, Sadock B: Synopsis of Psychiatry, 8th ed. Baltimore, Lippincott Williams & Wilkins, 1998

4 Harmon RJ, Riggs P: Clonidine for posttraumatic stress disorder in preschool children. Journal of the American Academy of Child and Adolescent Psychiatry 35:1247–1249, 1996[CrossRef][Medline]

5 Kinzie JD, Leung P: Clonidine in Cambodian patients with posttraumatic stress disorder. Journal of Nervous and Mental Disease 177:546–550, 1989[Medline]

6 Horrigan JP, Barnhill LJ: The suppression of nightmares with guanfacine. Journal of Clinical Psychiatry 57:371, 1996

7 Raskind MA, Peskind ER, Kanter ED, et al.: Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo controlled study. American Journal of Psychiatry 160:371–373, 2003[Abstract/Free Full Text]

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