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PERSPECTIVE
Year : 2015  |  Volume : 10  |  Issue : 4  |  Page : 557-558

Prazosin: a potential new management tool for iatrogenic autonomic dysreflexia in individuals with spinal cord injury?


1 Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver V5Z 1M9; International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver V5Z 1M9, Canada
2 Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver V5Z 1M9; Centre for Heart, Lung, and Vascular Health, Faculty of Health and Social Development, University of British Columbia, Kelowna V1V 1V7, Canada
3 International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver V5Z 1M9; Department of Psychiatry, University of British Columbia, Vancouver V6T 2A1; Department of and Urologic Sciences, University of British Columbia, Vancouver V5Z 1M9; Vancouver Sperm Retrieval Clinic, Vancouver Coastal Health Authority, Vancouver V5Z 1M9; G.F. Strong Rehabilitation Center, Sexual Health Rehabilitation Service, Vancouver V5Z 2G9, Canada
4 International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver V5Z 1M9; G.F. Strong Rehabilitation Center, Sexual Health Rehabilitation Service, Vancouver V5Z 2G9; Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver V5Z 2G9, Canada

Date of Acceptance03-Mar-2015
Date of Web Publication30-Apr-2015

Correspondence Address:
Aaron A Phillips
Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver V5Z 1M9; Centre for Heart, Lung, and Vascular Health, Faculty of Health and Social Development, University of British Columbia, Kelowna V1V 1V7
Canada
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1673-5374.155422

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How to cite this article:
Zheng MM, Phillips AA, Elliott SL, Krassioukov AV. Prazosin: a potential new management tool for iatrogenic autonomic dysreflexia in individuals with spinal cord injury?. Neural Regen Res 2015;10:557-8

How to cite this URL:
Zheng MM, Phillips AA, Elliott SL, Krassioukov AV. Prazosin: a potential new management tool for iatrogenic autonomic dysreflexia in individuals with spinal cord injury?. Neural Regen Res [serial online] 2015 [cited 2020 Oct 20];10:557-8. Available from: http://www.nrronline.org/text.asp?2015/10/4/557/155422

Spinal cord injury (SCI) is a devastating condition that not only results in a loss of motor functions but also severe autonomic dysfunctions (Krassioukov and Claydon, 2006). Autonomic dysreflexia (AD) is a life threatening episode of transient hypertension that occurs up to 30x/day (11x/day on average) in those with cervical or high thoracic SCI (Hubli et al., 2015). Most common triggers of AD are from stimuli such as a full bowel and/or bladder, or sexual arousal (Teasell et al., 2000). Penile vibrostimulation (PVS) is a clinical procedure for sperm retrieval used for the purpose of family planning or fertility assessment that unfortunately iatrogenically induces episodes of AD (Elliott, 2006). Recently, we published a clinical trial highlighting that prazosin may be a viable option for treating AD secondary to PVS (Phillips et al., 2014).

Currently, the most commonly used medication to mitigate the severity of AD episodes during PVS is nifedipine (Adalat), an immediate-release calcium channel blocker (Krassioukov et al., 2009). However, individuals with SCI experience persistently low resting blood pressure (BP) as well as orthostatic hypotension (Krassioukov and Claydon, 2006). While nifedipine is effective at significantly reducing the severity of BP increases secondary to AD, it unfortunately has the tendency tolower resting BP for up to 5 hours. Also, SCI patients with persistent hypotension may experience dizziness, fatigue, and weakness after being administered nifedipine (Krassioukov et al., 2009). Together, these factors contribute to the need to explore alternative therapies for mitigating AD severity in the SCI population.

Nifedipine lowers BP by blocking both the renin-angiotension (RAS) pathway and the α-adrenergic receptors. Prazosin (Minipress), on the other hand, is a selective α-adrenergic blocker that preserves the vasoactive actions of the RAS pathways (Jaillon, 1980; Krassioukov and Claydon, 2006). Consequently, prazosin exudes a less abrupt suppressive effect on resting BP (Jaillon, 1980). A previous clinical study suggests that prazosin may be a feasible prophylactic treatment of AD, as it has shown a reduced incidence and severity of AD episodes in hospitalized SCI patients due to urogenic complications or other causes (Krum et al., 1992).

We recently conducted a clinical trial to examine the efficacy of prazosin at reducing AD severity in SCI outpatients undergoing PVS who regularly experienced severe iatrogenically-induced episodes of AD. Six patients with complete chronic SCI (> 2 years) were tested in a placebo controlled trial using a 1 mg tablet of prazosin at home the night before testing (loading dose), followed by a second 1 mg tablet 2 hours prior to the PVS procedure. Participants acted as their own controls. Hemodynamic assessments took place for 10 minutes prior to and during the procedure. The resting BP was calculated from minutes 3-8 of the 10 minute recording before the procedure, after both doses of prazosin were administered. All six participants experienced AD episodes following ejaculation from PVS after taking either placebo or prazosin. We noted two major findings: 1) patients experienced a significantly smaller increase in SBP after ejaculation after being administered prazosin compared to placebo (97 ± 34 mmHg vs. 141 ± 46 mmHg, P = 0.02), 2) no difference in resting BP between prazosin and placebo trials ([Figure 1]). The results suggest that like nifedipine, prazosin is effective at reducing the severity of iatrogenically-induced AD due to PVS. However, prazosin did not result in a decrease in resting BP, suggesting it may be a viable alternative for mitigating AD severity, with particular benefit in patients suffering from persistent hypotension.
Figure 1 Comparing systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) at baseline (figure on left) to development of autonomic dysreflexia during ejaculation with penile vibrostimulation (figure on right), after either placebo or prazosin was administered.
The increase in SBP was mitigated during ejaculation when prazosin was administered compared to placebo (*P = 0.02), as shown with two-way repeated measures ANOVA; however, resting blood pressure was not different between the two trials.


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One critical consideration when administering prazosin to manage AD symptoms in SCI is the risk of eliciting what is referred to as a "first-dose phenomenon"; where patients experience a severe drop in BP the first time it is administered (Graham et al., 1976). It is recommended that if administering as prophylactic, the first dose (i.e., "loading dose") should be ingested before night-time sleep (when patient is in supine position) to mitigate the risk of severe orthostatic hypotension. This phenomenon does not occur on subsequent days of administration. Larger clinical trials should be conducted in the future, using more sophisticated BP measurements (i.e., 15 minute interval 24 hour ambulatory BP monitoring), to further establish the use of prazosin as a prophylactic management of AD. This would allow for more powerful and generalizable results.

In conclusion, we have shown for the first time that 1 mg prazosin (administered orally once the night before, and once 2 hours prior to ejaculation) is effective at reducing the severity of iatrogenically-induced AD in those with SCI during PVS. Importantly, low resting BP was not exacerbated by prazosin in SCI patients.[9]

AAP is supported by the Heart and Stroke Foundation of Canada, and the Michael Smith Foundation for Health Research. AVK is supported by the Paralyzed Veterans of America, the Craig Neilson Foundation, the Canadian Institute of Health Research, and the Heart and Stroke Foundation of Canada. We would like to thank the editors of Neural Regeneration Research for their invitation to editorialize our findings.

 
  References Top

1.
Elliott SL (2006) Problems of sexual function after spinal cord injury. Prog Brain Res 152:387-399.  Back to cited text no. 1
    
2.
Graham RM, Thornell IR, Gain JM, Bagnoli C, Oates HF, Stokes GS (1976) Prazosin: the first-dose phenomenon. Br Med J 2:1293-1294.  Back to cited text no. 2
    
3.
Hubli M, Gee CM, Krassioukov AV (2015) Refined assessment of blood pressure instability after spinal cord injury. Am J Hypertens 28:173-181.  Back to cited text no. 3
    
4.
Jaillon P (1980) Clinical pharmacokinetics of prazosin. Clin Pharmacokinet 5:365-376.  Back to cited text no. 4
    
5.
Krassioukov A, Claydon VE (2006) The clinical problems in cardiovascular control following spinal cord injury: an overview. Prog Brain Res 152:223-229.  Back to cited text no. 5
    
6.
Krassioukov A, Warburton DE, Teasell R, Eng JJ (2009) A systematic review of the management of autonomic dysreflexia after spinal cord injury. Arch Phys Med Rehabil 90:682-695.  Back to cited text no. 6
    
7.
Krum H, Louis WJ, Brown DJ, Howes LG (1992) A study of the alpha-1 adrenoceptor blocker prazosin in the prophylactic management of autonomic dysreflexia in high spinal cord injury patients. Clin Auton Res 2:83-88.  Back to cited text no. 7
    
8.
Phillips AA, Elliott SL, Zheng MM, Krassioukov AV (2014) Selective alpha adrenergic antagonist reduces severity of transient hypertension during sexual stimulation after spinal cord injury. J Neurotrauma doi:10.1089/neu.2014.3590..  Back to cited text no. 8
    
9.
Teasell RW, Arnold JM, Krassioukov A, Delaney GA (2000) Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil 81:506-516.  Back to cited text no. 9
    


    Figures

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