The effectiveness of intravesical oxybutynin, propantheline, and capsaicin in the management of neuropathic bladder following spinal cord injury.

The objective of this study was to compare the therapeutic response of intravesical oxybutynin, propantheline, and capsaicin in the treatment of neurogenic detrusor overactivity. Carried out in the Department of Physical Medicine and Rehabilitation at a university teaching hospital in India, patients acted as their own controls. Oxybutynin 5 mg in solution or propantheline 15 mg in solution and capsaicin were instilled intravesically in each patient. Urodynamic studies were done before and after the intravesical instillation of each drug. The nonparametric tests were used for statistical analysis. The efficacy of intravesical capsaicin in the treatment of neurogenic detrusor overactivity was statistically significant for reflex volume (RV) (p = 0.018), cystometric capacity (CC) (p = 0.0440), leak volume (LV) (p = 0.000), and leak frequency (LF) (p = 0.009). The Kruskal-Wallis test for paired sample comparing pre- and post-LV and LF for intravesical capsaicin was significant at 2nd week (p = 0.002 and 0.054, respectively). There was a significant difference in therapeutic response between intravesical oxybutynin, propantheline, and capsaicin in the treatment of detrusor overactivity for LV and LF at 2nd week (p = 0.017 and 0.003, respectively). When comparing responses of oxybutynin and propantheline, more subjects demonstrated improvement with intravesical propantheline than oxybutynin for RV, detrusor leak point pressure (LPP), clean intermittent catheterization volume (CICV), and LV. This study suggests that intravesical agents may be used as effective adjuvants in the management of incontinence due to neurogenic detrusor overactivity following spinal cord injury.

Sialorrhea as a side effect of lithium: a case report.

A 37-year-old male patient developed sialorrhea while being treated with lithium carbonate. The sialorrhea was associated with salivary gland enlargement and was reversed by discontinuation of lithium. Concomitant treatment with propantheline bromide provided symptomatic relief.

Management of bladder dysfunction in multiple sclerosis.

Sixty-seven consecutive patients participated in a prospective urodynamic study of the diagnosis and treatment of urinary bladder symptoms in multiple sclerosis. The etiology of symptoms was classified as either failure to store urine (30%), failure to empty the bladder (18%), or a combination of the two (50%). Treatment was individualized on the basis of the underlying pathophysiology and consisted of intermittent self-catheterization (21%), none (20%), surgical (12%), drugs (9%), voiding maneuvers (6%), and external condom drainage (6%). In 18 patients (27%), lesser forms of treatment were unsuccessful, and indwelling vesical catheters were required. Symptoms correlated poorly with urodynamic findings, and treatment based on symptoms alone would have been ineffective in over half the patients.

Anticholinesterase drugs in the treatment of chronic pain.

Two patients with severe thalamic pain and one patient with causalgia from the shoulder-hand syndrome are described whose pain was markedly improved or abolished by anticholinesterase drugs. Both short-acting parenteral and oral anticholinesterase preparations were employed. Anticholinesterase drugs are a new and potentially valuable approach to the treatment of chronic pain.

The effect of cimetidine and propantheline on the symptoms of a patient with systemic mastocytosis.

A 24 year old white woman with a lifelong history of systemic mastocytosis and symptoms of diarrhea and flushing was demonstrated to have a normal gastric analysis and inconsistent steatorrhea. She responded well to oral cimetidine therapy for 11 months. A symptomatic recurrence was controlled with the addition of propantheline. Gastric secretory studies demonstrated cimetidine suppression of both basal acid and basal pepsin secretion, as well as maximal pentagastrin-stimulated acid secretion; suppression of stimulated pepsin secretion was minimal. The combination of cimetidine and propantheline markedly suppressed both peak acid and peak pepsin secretion in response to pentagastrin stimulation. These data support a dominant role of cholinergic mechanisms in the control of gastric pepsin secretion; additional data obtained with maintenance of constant intragastric pH are required for further clarification.

Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states.

The H2-histamine receptor antagonists ranitidine and cimetidine were compared for their abilities to control gastric acid hypersecretion on a short- and long-term basis in 22 patients with gastric acid hypersecretory states. Nineteen patients had Zollinger-Ellison syndrome, one patient had systemic mastocytosis, and two patients had idiopathic hypersecretion. The rates of onset of the action of cimetidine and ranitidine were the same. The actions of both drugs were increased by anticholinergic agents, and there was a close correlation between the daily maintenance dose of each drug needed to control acid secretion. However, ranitidine was threefold more potent than cimetidine both in acute inhibition studies and in the median maintenance dose needed (1.2 g per day for ranitidine and 3.6 g per day for cimetidine). Sixty percent of the males developed breast changes or impotence while taking cimetidine and in all cases these changes disappeared when cimetidine was replaced by ranitidine. Treatment with high doses of cimetidine (one to 60 months; median, 11 months) or ranitidine (two to 31 months; median, 14 months) was not associated with hepatic or hematologic toxicity or alterations of serum gastrin concentrations, but ranitidine therapy was associated with a significantly lower serum creatinine level than seen with cimetidine therapy. The results show that both drugs can adequately inhibit acid secretion in patients with gastric hypersecretory states. Both are safe at high doses, but ranitidine is threefold more potent and does not cause the antiandrogen side effects frequently seen with high doses of cimetidine.

Carotid sinus hypersensitivity and syncope.

The patient with a hypersensitive carotid sinus reflex and syncope may pose special challenges in evaluation and treatment. Specifically, although the finding of carotid sinus hypersensitivity may indeed indicate an exaggerated vagal tone that causes syncope, it may also be a chance association in a patient with syncope due to another cause. Careful clinical and electrophysiologic testing may be needed to distinguish these two possibilities. Furthermore, the need for drug therapy or cardiac pacing (or both) must be determined on an individual basis, depending on the relative contributions of cardioinhibitory and vasodepressor components to the patient's symptoms and also on the degree of patient limitation.

Influence of the pharmacological modification of gastric emptying on lactose digestion and gastrointestinal symptoms.

BACKGROUND: In lactose maldigesters the ingestion of food which retards gastric emptying improves tolerance to lactose. AIM: To study the effects of the pharmacological modification of gastric emptying on the speed of development of lactose-induced symptoms. METHODS: After an overnight fast, 18 lactose maldigesters were given, in a randomized double-blind study design at 1-week intervals, either propantheline (as bromide 15 mg), metoclopramide (as hydrochloride 10 mg) or placebo, in identical capsules, 60 min before ingesting 50 g lactose coloured with 1 g carmine dye (to measure gastrointestinal transit time). Gastrointestinal symptoms, urinary galactose excretion, and breath hydrogen and blood glucose concentrations were recorded. RESULTS: The propantheline-induced prolongation of gastric emptying improved tolerance to lactose, as measured by reduced area under the gastrointestinal symptom score curve 0-12 h, compared to placebo (by 26%) (P < 0.05) or metoclopramide (by 30%) (P < 0.05). The total hydrogen excretion AUC (180 min follow-up) increased by 15% after metoclopramide as compared with placebo (P = 0.18). Propantheline decreased this variable by 15% from placebo (P = 0.17). No significant differences in blood glucose, urinary galactose or gastrointestinal transit time were found. CONCLUSIONS: In an oral lactose tolerance test, delaying gastric emptying with propantheline improved tolerance in lactose maldigesters, as measured by diminished gastrointestinal symptoms and reduced breath hydrogen concentration.

Management of life-threatening bradycardia in spinal cord injury.

A 19-year-old man with SCI at C5 suffered recurrent life-threatening bradycardia and asystole. We detail his course, which included continual movement in a motion bed and propantheline-bromide (Pro-Banthine) therapy, over 3 1/2 months. Possible causes of bradycardia and autonomic dysfunction in this setting are discussed.

Propantheline as an adjuvant to weight loss after vertical gastroplasty.

BACKGROUND: Weight loss after gastroplasty surgery is sometimes unsatisfactory despite normal surgical anatomy and no evidence of deliberate dietary indiscretion. METHODS: Two morbidly obese female patients were treated with a modified Long vertical gastroplasty following failed attempts at weight loss using nonsurgical means. One of these (109 kg) complained of a lack of satiety soon after the surgery and her weight loss was unsatisfactory at 11 kg after 90 days. The other patient (128 kg) lost weight as expected but at 3 months leveled off her weight at 93 kg also with an associated loss of satiety. Both patients noted an increased capacity for food and ease of eating solids including red meat. Gastroscopy revealed normal gastric anatomy in both and the patients were prescribed oral propantheline. RESULTS: There was an immediate subjective improvement in satiety, a reduction in capacity for food and an increase in difficulty with eating some solids. There was a resumption of weight loss that has been sustained down to healthy weight range. CONCLUSION: In two patients with unsatisfactory weight loss after gastroplasty but no demonstrable surgical defect, adjuvant propantheline appeared to induce an excellent further weight loss.

Propantheline protects the oral mucosa after high-dose ifosfamide, carboplatin, etoposide and autologous stem cell transplantation.

Oral mucositis is a dose-limiting toxicity of high-dose etoposide regimens. Since etoposide is excreted in saliva, we tested the hypothesis that the induction of xerostomia would reduce the severity of the mucositis. We designed a phase II trial of propantheline in patients receiving high-dose ICE (ifosfamide 20 mg/m2, carboplatin 1.8 g/m2, etoposide 3 g/m2 in divided doses over 6 days) chemotherapy plus autologous hematopoietic stem cell support. We treated 31 consecutive patients and graded the oral mucositis according to WHO criteria. Mild (WHO grade 0, I, II) mucositis occurred in 28 of 31 (90%) (95% CI 74-98%) patients; severe (WHO grade III, IV) mucositis occurred in three of 31 patients (10%) (95% CI 2-25%) patients. In contrast, a published reference group treated with the same doses and schedule of ICE reported mild mucositis in 10 of 46 (22%) (95% CI 11-36%) patients and severe mucositis in 36 of 46 (78%) (95% CI 64-89%). Propantheline therapy had no protective effect on esophagitis and enteritis associated with high-dose ICE. Minor toxicities were constipation and asymptomatic tachycardia; major toxicities were palpitations in one patient and urinary retention in one patient. We conclude that anticholinergic therapy dramatically reduced the oral mucositis associated with high-dose etoposide and should be considered as a supportive care measure for patients receiving etoposide-containing regimens.

Controlled clinical trial of sedative-anticholinergic drugs in patients with the irritable bowel syndrome.

We studied 16 patients with long-standing irritable bowel syndrome of moderate severity using a controlled, double-blind crossover method. Five sedative-anticholinergic drug combinations and a placebo were tested. The subjective response was assessed with four subjective methods to include an increasing number of response variables. The patients preferred 30 mg phenobarbital plus 8 mg belladonna (P & B) to placebo (P = 0.02). Five of ten patients were helped "some" or "a lot" with placebo, while ten of 15 were helped "some" or "a lot" with P & B (P = 0.07). The ten prominent-symptoms method revealed that subjective symptoms such as nervousness, sleep difficulties, and tiredness were experienced as greater problems than diarrhea. The factor analysis method documented a strong placebo response. Simpler evaluation methods such as drug preference and a five-choice method appear more likely to show a positive drug effect, while the inclusion of a larger number of variables appears to emphasize the placebo portion of the response. These observations may help explain some of the apparent discrepancies between the conclusions of some controlled clinical trials and subsequent clinical experience.

Oxybutynin in bladder spasm, neurogenic bladder, and enuresis.

Oxybutynin chloride (Ditropan), a tertiary amine possessing anticholinergic and papaverine-like, direct muscular antispasmodic effects, has been used in controlled clinical studies in patients with neurovesical reflex activity, uninhibited bladders, enuresis, and primary muscle spasm. The cystometrically documented, synergistic, anticholinergic, and muscle relaxant activity of oxybutynin observed in these studies indicates that the drug can be highly effective in the management of reflex neurovesical dysfunction, enuresis, and bladder spasm.

Disorders of micturition: neuropharmacologic basis and results of drug therapy.

The clinical use of various pharmacologic agents in problems of micturition is based on the new concepts of intrinsic urethrovesical innervation, presence and regional predominance of autonomic neuroreceptors, and experimental evidence of the effects of various drugs on the bladder and the urethra. A new concept, relating to the processes that control bladder filling and emptying, is coming into being and replacing the traditional concept based on anatomic grounds alone. On the basis of the published data, and from personal experience both experimental and clinical, pharmacologic agents singly or in combination can be effectively and safely used in various problems of micturition such as incontinence (enuresis, stress incontinence in women, postprostatectomy, urgency incontinence), and functional outflow obstruction caused by neurologic or non-neurologic disease processes.

Long-term cimetidine and anticholinergic therapy in patients with gastrinoma.

Two patients with gastrinomas were treated with cimetidine and an anticholinergic drug for greater than 20 months after exploratory laparotomy disclosed no solitary resectable tumor. Both have done well, and thus this therapy is recommended as a safe and effective alternative to total gastrectomy in reliable patients. Additional therapeutic methods are needed to control tumor growth.

Swallow syncope.

Swallow syncope is an often misdiagnosed rare disorder due to enhanced vagal tone during eating in patients with underlying esophageal and/or cardiac abnormalities. We present three cases of this disorder, one related to digitalis toxicity and the other two with diffuse esophageal spasm. The investigation, differential diagnosis, prognosis and management of swallow syncope are discussed.

Voiding abnormalities in children: methods of evaluation and results of treatment.

Recent advances in technology have fueled interest in the field of urodynamics and have made possible accurate diagnosis of voiding abnormalities in children. A thorough understanding of the underlying physiology and institution of the appropriate pharmacologic agents and/or teaching techniques results in correction of the underlying problems in 90% of the cases. Symptoms, techniques of diagnosis, therapeutic regimens, and results of therapy are presented.

Clinical effects of trithiozine, a newer gastric anti-secretory agent.

Trithiozine is a new product which in animal studies proved to have a marked anti-secretory and anti-ulcer effect, along with a very low acute and chronic toxicity and no ganglioplegic, anticholinergic and anti-H2 activity. Clinical trials with trithiozine have been performed in some European countries. The results of these trials, most of which were conducted on a double-blind basis, and including already several hundreds of patients, have shown that oral trithiozine: exerts a very significant action on both basal and stimulated gastric acid secretion, without a rebound hypersecretion; promotes, in most patients, a complete endoscopic healing of peptic ulcer, in addition to an early symptomatic relief; has a mild sedative action; does not affect the pancreatic secretion; is well tolerated even for long-term (up to 10 months) treatments.

[Cases of enuresis nocturna treated with single reflexotherapy. Clinical and therapeutic evaluation]. / Casi di enuresi notturna idiopatica trattati con la sola riflessoterapia. Valutazioni clinich e terapeutiche

Treatment of children with nocturnal enuresis by means of acupuncture, auriculotherapy, etc. is reported. The aetiopathogenetic background, the results of treatment, and the neurophysiological mechanisms through which the action of reflexotherapy can be explained are discussed.

Combination of anticholinergic agent and H2 receptor antagonist in duodenal ulcer treatment--a randomized, double blind multicenter study.

BACKGROUND: The acid suppressive abilities of H2 receptor antagonists and anticholinergics have been claimed to be additive. METHODS: A multicenter, double-blind, randomized trial comparing ranitidine (150 mg) plus propantheline bromide 15 mg at bedtime to ranitidine 300 mg alone at bedtime was conducted in 161 patients with endoscopically confirmed uncomplicated duodenal ulcer. RESULTS: After six weeks of therapy, ulcer healing rates in the two groups were comparable ie 80% in the combination group (ranitidine + propantheline) and 79.4% in the ranitidine group. Pain relief after one, two and four weeks of treatment was also comparable in the two groups. Side effects to drugs were minor and comparable in both the groups. CONCLUSION: A combination of 150 mg ranitidine and 15 mg propantheline bromide is as efficacious as 300 mg ranitidine in inducing healing of uncomplicated duodenal ulcers, with similar side-effects but at greatly reduced cost.