Propantheline bromide

Propantheline bromide in the management of hyperhidrosis associated with spinal cord injury

Objective: To report 2 cases in which oral propantheline reduced the discomfort associated with sweating related to spinal cord injury (SCI), and to review the literature on the management of SCI-related sweating. Case summaries: Case 1: A 27-year-old quadriplegic man with an American Spinal Injury Association (ASIA) Frankel class C injury to C5/C6 experienced profuse sweating and requested propantheline. He stated that he had received the medication previously and reported that propantheline 15 mg tid had controlled his sweating. Propantheline bromide was reinstituted, and within 24 hours, the patient's episodes of profuse sweating had decreased markedly in number and frequency. Case 2: A 35-year-old quadriplegic woman had an ASIA class D lesion at C3. Since her injury, she had experienced profuse sweating that worsened when she became cold and at night. She stated that her sweating was under control as long as she took propantheline. Propantheline therapy was continued and no further sweating episodes have occurred. Data source: A MEDLINE search was used to identify pertinent literature including reviews. Standard texts and texts referenced in the pertinent literature also were examined. Study selection: All available sources of information were reviewed. Data synthesis: The earliest case reports of systemic therapy for hyperhidrosis described the use of the anticholinergic methantheline bromide. Methantheline in combination with ergoloid mesylates also was suggested for the treatment of congenital hyperhidrosis. Local topical therapy for hyperhidrosis, such as aluminum chlorohydrate and aluminum chloride, the active ingredients in some antiperspirants, have been tried with some success. Talc, starch, and other powders have been suggested to absorb excessive sweat. Formalin and glutaraldehyde also have been used. Topical propantheline bromide has been used successfully in treating palmar and plantar hidrosis. Clonazepam has been used successfully in a case of unilateral localized hyperhidrosis. Systemic phenoxybenzamine has been used with some success and there have been attempt at other systemic therapy using mecamylamine, atropine, propoxyphenel, and methenamine. Scopolamine patches also have been used successfully in a small number of patients. Other agents that have been used include dibenamine, piperoxan, and phentolamine. Systemic propantheline also has been listed as an agent with potential efficacy in treating the profuse sweating associated with SCI, but was not recommended primarily because of adverse effects and difficulty in titrating to the lowest effective dosage. However, studies or case reports specific to the use of propantheline in patients with SCI appear to be lacking, as are reports of direct comparison between propantheline and other agents. Discussion: Concerning the mechanism of action of propantheline bromide for hyperhidrosis, it seems reasonable to attribute its effects to the drug's well-documented anticholinergic/antimuscarinic actions. At dosages used to effectively treat neurogenic bladder, propantheline bromide also should block the muscarinic receptors responsible for sweat gland stimulation. Central nervous system adverse effects should be minimal at usual clinical dosages, as propantheline does not cross the blood-brain barrier. Conclusions: It would appear that in some patients with SCI who are subject to incidental episodes of profuse sweating, oral propantheline may offer some relief and may, in fact, be well tolerated, as in the cases described. Additionally, propantheline would seem a good therapeutic choice in SCI patients with excessive sweating and neurogenic bladder dysfunction who may derive dual benefit from the agent.

Reproductive toxicology. Propantheline bromide

Propantheline bromide in primary dysmenorrhoea

Clinical efficacy of propantheline bromide in neurocardiogenic syncope: pharmacodynamic implications

The pharmacological response with tilt-table testing predicts long-term efficacy in neurocardiogenic syncope. However, beta-blockers for neurocardiogenic syncope are often not tolerated or are ineffective. Since cholinergic tone is important in the efferent part of the neurocardiogenic reflex, we investigated the pharmacodynamics and efficacy of propantheline bromide in preventing neurocardiogenic syncope. We studied 16 patients (11 males) with a mean age of 48.8 (+/- 15.1) years with presyncope or syncope and who had positive baseline tilt-table studies at a mean of 15.8 (+/- 10.3) minutes into the upright 60 degrees tilt. They were given propantheline bromide orally, an anticholinergic agent, at a dose of 64.3 (+/- 21.8) mg/day for 7 days, and tilt-table testing was repeated 1 hour after readministration of propantheline bromide, 30 mg orally. After propantheline bromide treatment, 13 of 16 patients (81%) had no inducible presyncope or syncope on repeat tilt-table testing. In this group of responders, the mean minimum heart rate during upright tilt-table testing increased from 43.2 (+/- 77.3) beats/min to 77.3 (+/- 17.2) beats/min after propantheline bromide (p < 0.005). More significantly, the minimum mean arterial blood pressure increased from 42.2 (+/- 25) mmHg to 81.3 (+/- 16.7) mmHg (p < 0.0005) during upright tilt. At a follow-up of 15.2 (+/- 7.4) months, in the responder group (12 patients with long-term follow-up), the average dose of propantheline bromide was 32.5 (+/- 23.8) mg/day, which was significantly reduced from the initial dose (p < 0.05). A clinical recurrence of symptoms occurred in only 4 out of 12 patients on propantheline bromide (33%), none of which were directly attributable to drug failure. It was concluded from this study that propantheline bromide is highly effective in preventing neurocardiogenic syncope. In addition, propantheline bromide's effectiveness is more than would be expected by prevention of cardioinhibition in neurocardiogenic syncope and would support a role for direct cholinergic control of vascular tone.

Pharmacokinetics of propantheline bromide in normal man

1 Six normal men were administered propantheline bromide (15 mg) in single doses intravenously, and as an oral solution in a balanced random crossover study.

2 Plasma concentrations and urinary excretion of the drug were measured after each treatment, using a stable isotope dilution assay.

3 Initial plasma concentrations of propantheline bromide ranged from 494 to 1310 ng ml^-1 3 min after the intravenous dose. Plasma levels of the drug decreased rapidly to reach concentrations of 4.5 to 27.2 ng ml^-1 4 h after dosage. A total of 17.3% (range 8.73 to 23.69%) of the intravenous propantheline bromide was eliminated by excretion in urine.

4 Pharmacokinetic analysis of these data indicated mean biological half-lives of 3.2 min (range 1.2 to 4.2 min; distribution phase) 57.9 min (range 12.6 to 106.2 min; fast elimination phase) and 2.93 h (range 2.16 to 3.69 h; slow elimination phase).

5 Total plasma clearance was calculated as 79.2 l h^-1 (range 28.1 to 137.7 l h^-1) and the renal clearance was 11.5 l h^-1 (range 6.7 to 15.7 l h^-1) demonstrating the importance of extra-renal routes in the elimination of propantheline bromide.

6 Following the oral dose of propantheline bromide plasma concentrations of the drug were at or below the precision level of the assay (5 ng ml^-1) at all times after dosage. A total of 1.08% (range 0.33 to 2.05%) of the propantheline bromide administered was excreted in urine.

7 The results of this study show that propantheline bromide was rapidly distributed and eliminated in man, and that extra-renal routes (probably metabolism) were the major pathways of elimination. Comparison of the data obtained following oral and intravenous administration indicate a low systemic availability of orally administered propantheline bromide. This may reflect the importance of the extra-renal routes of elimination in a `first-pass' effect for the drug.