Incidence Of Dry Mouth Research Articles

Comparison of the efficacy, safety, and tolerability of propiverine and oxybutynin for the treatment of overactive bladder syndrome

To compare the effects of propiverine and oxybutynin on ambulatory urodynamic monitoring (AUM) parameters, safety, and tolerability in patients with overactive bladder. This was a randomized, double-blind, placebo-controlled, multicentre, crossover study. Patients (n = 77) received two of the following treatments during two 2-week periods: propiverine 20 mg once daily, propiverine 15 mg three times daily, oxybutynin 5 mg three times daily, and placebo. AUM parameters, salivary flow, visual near point, and heart rate were assessed. A consistent order in the efficacy between active treatment groups was observed for the reduction in mean involuntary detrusor contractions (IDCs; oxybutynin 15 mg </= propiverine 45 mg </= propiverine 20 mg). Differences between the oxybutynin and propiverine 20 mg groups were statistically significant for several AUM endpoints. Statistically significant differences between the oxybutynin and both propiverine groups were also noted in salivary flow rate and heart rate (oxybutynin 15 mg < both propiverine regimens) and in heart rate variability (both propiverine regimens < oxybutynin 15 mg). All active treatments lengthened visual near point. The incidence of dry mouth was significantly more pronounced in the oxybutynin group than in either propiverine group. Treatment with propiverine 45 mg resulted in the highest rates of constipation, lengthening of the visual near point, and effects on heart rate. Oxybutynin 15 mg was more effective than propiverine 20 mg in reducing symptomatic and asymptomatic IDCs in ambulatory patients. The primary differences between the two drugs were the incidence and type of adverse events, which varied with the antimuscarinic receptor specificity of each agent.

A double‐blind randomized dose‐response study comparing daily doses of 5, 10 and 15 mg controlled‐release oxybutynin: balancing efficacy with severity of dry mouth

To assess the efficacy, incidence of dry mouth and overall satisfaction with initial doses of 5, 10 and 15 mg of a new, once-daily, controlled-release (CR) form of oxybutynin for treating urge urinary incontinence (UUI). Patients who reported urinary incontinence (UI) (one or more episodes/diary) and voiding frequency (eight or more voids/day) or urgency (one or more episodes/diary) during a 2-week baseline were randomized to once-daily 5, 10 or 15 mg CR oxybutynin for 4 weeks. Daily episodes of UI, voids, urgency, adverse events, dry mouth and satisfaction were recorded in a 3-day diary at baseline and after 4 weeks of treatment. In all, 237 patients were randomized and evaluated. Episodes of UI, voids and urgency were significantly reduced over the study period at all doses. Daily UI episodes were significantly lower with 15 mg/day than 5 and 10 mg/day. Dry mouth symptoms were similar in the 10 and 15 mg/day groups, and higher than in the 5 mg/day group. However, significantly greater overall satisfaction was reported with 15 than 5 mg/day. There were significant dose-response relationships with CR oxybutynin for both UI episodes and dry mouth. The greatest satisfaction was with 15 mg/day, and the severity of dry mouth was comparable at 10 mg/day, indicating that greater efficacy at the higher dose did not compromise tolerability.

Is a long-acting inhaled bronchodilator the first agent to use in stable chronic obstructive pulmonary disease?

Purpose of review This article reviews findings from recently published randomized controlled clinical trials to address the question whether a long-acting inhaled bronchodilator should be the initial choice for maintenance therapy in patients with stable, symptomatic chronic obstructive pulmonary disease (COPD). Recent findings Results of recent clinical trials suggest that a long-acting inhaled bronchodilator, either once-daily tiotropium or twice-daily salmeterol or formoterol, has advantages over a regularly-scheduled short-acting anticholinergic inhaled bronchodilator (ipratropium) as initial maintenance therapy in patients with at least moderate, stable, symptomatic COPD (forced expired volume in 1 second ≤ 60-70% predicted; mean, ~37-45% predicted). For tiotropium, these advantages encompass several important outcomes, including lung function, rescue inhaler use, dyspnea, frequency of exacerbations, and hospitalization for COPD, in addition to greater convenience and therefore potentially better adherence to prescribed therapy, whereas side effects are similar except for a greater incidence of dry mouth. Summary Current evidence supports the recommendation of the Global Initiative for Chronic Obstructive Lung Disease guidelines of at least one of the two classes of long-acting inhaled bronchodilators as initial maintenance therapy for symptomatic COPD. In patients who do not respond satisfactorily to tiotropium or a long-acting inhaled β-agonist as the initially prescribed single maintenance agent, the Global Initiative for Chronic Obstructive Lung Disease guidelines recommend the addition of the alternate class of long-acting inhaled bronchodilator as the next step. Further clinical trials are required to investigate whether this recommendation is preferable to that of adding an inhaled corticosteroid, which has been shown to have additive benefits to those of a long-acting β-agonist with respect to bronchodilation and, variably, dyspnea, rescue bronchodilator use, and quality of life. The choice of agents will depend ultimately on how well the patient responds to a trial of the drug in terms of both efficacy and side effects, and patient preference and cost.

Management of Overactive Bladder

Overactive bladder (OAB), a common condition affecting ≈16–17% of adult men and women in Europe and the US, is characterized by symptoms of urinary urgency, with or without urge urinary incontinence (UUI), usually with micturition frequency and nocturia. OAB is thought to result from abnormal, involuntary detrusor contractions during bladder filling. The symptoms of OAB have a considerable adverse effect on quality of life (QOL) in affected patients, and are associated with an increased risk of comorbidities, and increased direct and indirect costs. Management of OAB focuses on symptom improvement, and includes nonpharmacologic and pharmacologic therapy. Extended-release tolterodine (Detrusitol® XL, Detrol LA®, Detrusitol SR®, Detrusitol® Neo, Detrusitol® Retard, Unidet™) is an oral, once-daily, nonselective, competitive antimuscarinic drug. It acts on smooth muscle motor efferent pathways, including bladder detrusor muscle, and is a first-line therapy for OAB. Extended-release tolterodine is at least as effective as immediate-release tolterodine in improving UUI and other symptoms associated with OAB (including urinary frequency, urgency symptoms, voided volume/micturition), and in improving health-related QOL. It has similar efficacy to oral immediate- or extended-release oxybutynin, or transdermal oxybutynin. The likelihood of dry mouth, the most bothersome anticholinergic adverse effect associated with antimuscarinic drugs, is significantly reduced with extended-release tolterodine in patients with OAB compared with immediate-release tolterodine. Dry mouth also occurs significantly less frequently with extended-release tolterodine than with immediate- or extended-release oxybutynin. The incidence of dry mouth with extended-release tolterodine or transdermal oxybutynin is similar. In economic models, extended-release tolterodine is more cost effective in patients with OAB than no treatment, or treatment with immediate-release tolterodine or immediate-release oxybutynin, and is as cost effective as extended-release oxybutynin. In conclusion, clinical and economic data support the use of extended-release tolterodine as a first-line therapy in the management of adult patients with OAB. It is at least as effective as immediate-release tolterodine, but is associated with a lower incidence of dry mouth. Moreover, the convenient once-daily administration regimen offers the potential for good compliance. The favorable efficacy and tolerability profile of extended-release tolterodine has been demonstrated for up to 12 months. Extended-release tolterodine is as effective as oral immediate- or extended-release oxybutynin, but is better tolerated in terms of dry mouth. It has similar efficacy and tolerability (including dry mouth) to transdermal oxybutynin. Extended-release tolterodine is, therefore, a valuable first-line therapy in the treatment of OAB.

Correlations between in vitro affinity of antipsychotics to various central neurotransmitter receptors and clinical incidence of their adverse drug reactions.

This study was performed to determine whether in vitro affinities of currently available antipsychotics toward dopamine or other neuronal receptor systems are associated with their in vivo incidence of central and peripheral adverse drug reactions (ADRs). For 17 antipsychotic drugs available in Japan, the clinical incidences of 7 different types of drug-induced ADRs (i.e., akathisia, dyskinesia, tremor, rigidity, drowsiness, hypotension and dry mouth) were obtained from both post-marketing ADR databases and the investigational clinical trials of eight pharmaceutical companies. Affinity constants (K(i)) of the respective drugs toward dopamine D(1) and D(2) receptors, alpha(1)-adrenoceptors, histamine H(1) receptors, serotonin 5-HT(2) receptors and muscarinic cholinoceptors, determined using rat brain synaptosomes, were obtained from the literature. Relationships between in vitro receptor-binding properties and in vivo incidences of the respective types of antipsychotic-related ADRs were analyzed using Spearman's rank correlation. Significant (P < 0.05) correlations were observed between the K(i) values for dopamine D(2) receptor and the clinical incidences of akathisia and dyskinesia (r(s) = -0.68 and -0. 66, respectively). Significant (P < 0.05) correlations were also observed between the K(i) values for alpha(1)-adrenoceptor and histamine H(1) receptor and the incidence of drowsiness (r(s)=-0.65 and -0.55, respectively), and between the K(i) values for three receptor systems (i.e., dopamine D(1) receptor, alpha(1)-adrenoceptor and histamine H(1) receptor) and the incidence of dry mouth (r(s) = -0.50, -0.81 and -0.62, respectively). Preclinical receptor-binding data of antipsychotic drugs toward central dopamine and other ancillary neurotransmitter systems may be useful for predicting not only in vivo antipsychotic potency but also clinical incidence of akathisia and dyskinesia for this class of agents. Newly developed antipsychotic drugs with more potent and selective antagonistic activity against the dopamine D(2) receptor may not necessarily be associated with a lower incidence of extrapyramidal ADRs.

An extended-release formulation of oxybutynin chloride for the treatment of overactive urinary bladder

Detrusor instability, or urinary incontinence, is common in elderly patients, particularly elderly women. The clinical symptoms of overactive, or unstable, urinary bladder include urge urinary incontinence, urgency, and frequency. Mixed urinary incontinence, which comprises urge urinary incontinence and stress incontinence, is manifested by increased intraabdominal pressure on coughing or sneezing. The detrusor muscle of the bladder is under the control of the parasympathetic, or muscarinic, nervous system. The drug of choice in this condition is oxybutynin chloride, which has the ability to block acetylcholine released from parasympathetic nerves in the urinary bladder, preventing contractions of the muscle and exerting a direct spasmolytic effect on the bladder. A new extended-release oral tablet formulation, OROS ® oxybutynin, uses osmotic pressure to deliver the drug at a controlled rate over approximately 24 hours. It resembles a conventional tablet but has a two-part core consisting of a drug layer and below it, a “push” layer containing osmotically active components, the whole surrounded by a semipermeable membrane with a laser-drilled opening in the drug side. Water in the gastrointestinal tract enters the tablet and mixes with the drug to form a suspension. The “push” layer expands and pushes the suspended drug out of the orifice and into the gastrointestinal tract for eventual absorption. Pharmacokinetic studies have indicated a slow rise in mean plasma concentration of the isomer R-oxybutynin for 4 to 6 hours after a single dose of OROS oxybutynin, followed by maintenance of steady concentrations for up to 24 hours, minimizing the fluctuations between peak and trough associated with TID dosing of 5-mg immediate-release oxybutynin tablets. Efficacy and safety studies comparing the extended-release with the immediate-release formulation of oxybutynin demonstrated equivalent efficacy in patients with overactive urinary bladder. The adverse-event profile of oxybutynin is similar to that of a typical anticholinergic agent such as atropine—dry mouth, constipation, somnolence, blurred vision, headache, and gastrointestinal pain—although in 2 clinical studies, the incidence of dry mouth was less with the extended-release formulation. Once-daily dosing with OROS oxybutynin appears to be well tolerated and effective, as well as convenient, for the treatment of overactive bladder, particularly for elderly patients using multiple medications.

Efficacy and Safety of Two Doses of Tolterodine Versus Placebo in Patients With Detrusor Overactivity and Symptoms of Frequency, Urge Incontinence, and Urgency: Urodynamic Evaluation

Tolterodine is a new competitive muscarinic receptor antagonist developed for the treatment of the unstable bladder. A total of 242 patients were enrolled in a multicenter, multinational, randomized, double-blind, placebo-controlled study conducted over a period of 4 weeks in patients with detrusor overactivity and symptoms of frequency, urgency, and urge incontinence. The objective of the study was to compare the efficacy and safety of tolterodine given at 1 or 2 mg b.i.d. versus placebo. At week 4 a statistically significant increase in the volume at first contraction (p = 0.030) and maximal cystometric capacity (p = 0.034) was only in the tolterodine 2 mg b.i.d. group. Tolterodine was safe and generally well tolerated. The incidence of dry mouth, as the most commonly reported adverse event, was only 9% and of mild to moderate intensity.

Safety and tolerability of moxonidine in the treatment of hypertension.

Classical centrally acting antihypertensive agents lower blood pressure by reducing excessive sympathetic tone; however, their clinical use is limited by an adverse effect profile resulting from alpha2-adrenoceptor agonism. Moxonidine is a new centrally acting agent showing selective agonism of imidazoline I1 receptors, but very little alpha2-adrenoceptor agonism. The safety and tolerability of moxonidine was reviewed over an 8-year period (1989 to 1997), including 74 clinical trials and an estimated 370000 patient-years of exposure. Dry mouth and somnolence were the most frequently reported adverse events, followed by headache and dizziness. In phase II to IV controlled studies in patients with hypertension (n = 1460), the incidence of dry mouth was 8 to 9%, somnolence 5 to 8% and headache 6%, as recorded by spontaneous reporting; the percentage of patients discontinuing treatment because of adverse events did not exceed 4%. Subgroup analyses revealed no differences in adverse events related to age or gender. Moxonidine did not exacerbate concomitant conditions such as diabetes mellitus or chronic obstructive pulmonary disease, or interact pharmacokinetically with concurrent medications such as hydrochlorothiazide, digoxin and glibenclamide (glyburide). Coadministration of moxonidine with lorazepam resulted in small additional impairments in tasks requiring attention. A similar distribution of adverse events was observed in uncontrolled studies (n = 1058). The incidence and severity of dry mouth and somnolence were found to decrease with increasing exposure to moxonidine over a period of up to 2 years. Serious adverse events were rare in all trials and could not be attributed to administration of moxonidine. Post-marketing surveillance of the adverse effect profile of moxonidine detected 2 additional adverse effects: nausea and allergic skin reactions. The safety profile of moxonidine, combined with proven antihypertensive efficacy, suggests that it may have an important role to play in the management of mild-to-moderate hypertension.

A Double-Blind Comparison of Sertraline and Imipramine in Outpatients with Major Depression: Acute (8 Weeks) and Continuation (16 Weeks) Treatment

In a double-blind multicentre trial in patients with major depression, the efficacy and the tolerability of sertraline were compared to those of imipramine, during an 8-week acute treatment phase followed by a 16-week continuation treatment phase in treatment responders. A total of 104 patients who met DSM-III-R criteria for major depression, HAM-D 17-item≥18 and Raskin Depression score>Covi Anxiety score, were randomized to receive either sertraline or imipramine. The initial daily dosage of 50 mg of sertraline or imipramine was rapidly titrated upwards in increments of 50 mg/day at weekly intervals, tolerability permitting, to a maximum of 200 mg/day by the fourth week. Eighty-eight patients completed at least 3 weeks of treatment and were included in the efficacy evaluable population. Both treatment groups demonstrated similar improvements on depression and anxiety rating scales during acute treatment, however, sertraline demonstrated significantly more improvement relative to imipramine on the HAM-D and Covi Anxiety scales after 1 week of treatment. Sertraline was more effective (HAM-D 17-item, CGI-S, SCL-56 Total score, SCL-56 Depression score, Covi Anxiety score) than imipramine in reducing depressive symptoms at the end of 24 weeks of treatment. There were significant improvements in all rating scales at week 24 relative to week 8 in the sertraline group but not in the imipramine group. The SCL-56 Total score, SCL-56 Depression score, Raskin Depression score and Covi Anxiety score at week 24 relative to week 8 showed significantly greater improvement in the sertraline group compared to the imipramine group. Imipramine was associated with a significantly higher incidence of dry mouth, sweating, constipation, palpitations, and a significantly higher heart rate and blood pressure. Sertraline was associated with a significantly higher incidence of diarrhoea/loose stools and insomnia. This study demonstrated a faster onset of therapeutic effect for sertraline relative to imipramine, reflecting the initiation of sertraline in a therapeutic dose of 50 mg/day and the need for gradual titration of imipramine to a therapeutic dose, at the beginning of treatment. Although efficacy was similar in both treatment groups at the end of the 8 weeks of acute therapy, sertraline-treated patients continued to manifest gradual improvements in depressive and anxiety symptoms during the 16 weeks of continuation therapy such that sertraline-treated patients were significantly more improved at the end of 24 weeks of therapy. © 1997 John Wiley & Sons, Ltd.

Tianeptine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression.

Tianeptine is a novel antidepressant agent, both structurally (modified tricyclic) and in terms of its pharmacodynamic profile. Unlike other antidepressant agents, tianeptine stimulates the uptake of serotonin (5-hydroxytryptamine; 5-HT) in rat brain synaptosomes and rat and human platelets, increases 5-hydroxyindoleacetic acid (5-HIAA) levels in cerebral tissue and plasma, and reduces serotonergic-induced behaviour. Tianeptine reduces the hypothalamic-pituitary-adrenal response to stress, antagonises stress-induced behavioural deficits and prevents changes in cerebral morphology. The antidepressant efficacy of tianeptine, as shown in 2 trials of patients with major depression or depressed bipolar disorder with or without melancholia, is greater than that of placebo. In patients with major depression without melancholia or psychotic features, depressed bipolar disorder or dysthymic disorder, the antidepressant efficacy of short term (4 weeks to 3 months) tianeptine therapy appears to be similar to that of amitriptyline, imipramine and fluoxetine and may be superior to that of maprotiline in patients with coexisting depression and anxiety. However, submaximal dosages of amitriptyline and maprotiline were used in these studies. Preliminary evidence suggests that tianeptine may also be effective in patients with endogenous depression. Progressive therapeutic improvements have been observed with up to 1 year of tianeptine treatment, and long term therapy may reduce the rate of relapse or recurrence. Tianeptine is effective in the treatment of depression in elderly and post-alcohol-withdrawal patient subgroups. Tianeptine was more effective in reducing psychic anxiety than placebo in patients with major depression or depressed bipolar disorder with or without melancholia. The overall anxiolytic properties of tianeptine in patients with coexisting depression and anxiety appear to be similar to those of amitriptyline, imipramine and fluoxetine and may be superior to those of maprotiline, although submaximal dosages of amitriptyline and maprotiline were used. Studies of tianeptine in patients with primary anxiety have not been conducted. Tianeptine is well tolerated in the short (3 months) and long (up to 1 year) term. The incidence of dry mouth (38 vs 20%), constipation (19 vs 15%), dizziness/syncope (23 vs 13%), drowsiness (17 vs 10%) and postural hypotension (8 vs 3%) are greater with amitriptyline than with tianeptine. Insomnia and nightmares occur in more tianeptine than amitriptyline recipients (20 vs 7%). The relative lack of sedative, anticholinergic and cardiovascular adverse effects with tianeptine makes it particularly suitable for use in the elderly and in patients following alcohol withdrawal; these patients are known to have increased sensitivity to the adverse effects associated with psychotropic drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Rilmenidine: a novel approach to first-line treatment of hypertension.

Rilmenidine (RIL) is a novel antihypertensive drug selectively acting at the sites of imidazoline receptors. Compared with diuretics, beta-blockers, Ca2+ antagonists and angiotensin converting enzyme inhibitors, the four major groups recommended by the US Joint National Committee as first-line antihypertensive drugs, RIL appears to meet the same criteria of efficacy, safety, and acceptability. Rilmenidine dose-dependently decreases blood pressure (BP), acting as a vasodilator by decreasing vascular resistance through inhibition of the adrenergic nervous system, even while the BP changes due to standing and exercise. In comparison with placebo, RIL significantly decreased BP. In double-blind comparative trials versus first-line diuretics and beta-blockers, RIL normalized BP in approximately 60% patients, showing a similar efficacy to other drugs. In contrast with hydrochlorothiazide, RIL decreased total cholesterol and did not change plasma potassium levels. No tachyphylaxis was observed during long-term treatment. Central side effects, which have contributed to the limitation of the use of alpha 2-agonists as second- or third-line therapy for hypertension, were significantly less frequent with RIL than with clonidine or methyldopa. Indeed, the incidence of dry mouth and drowsiness during double-blind comparative trials versus clonidine and methyldopa was significantly lower with RIL. This absence of central side-effects was confirmed in double-blind comparative trials versus hydrochlorothiazide and atenolol. In contrast with clonidine, no sodium retention or weight gain were observed during chronic treatment with RIL.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive efficacy and well-being during monotherapy and combination therapy with ketanserin

The effects of ketanserin on blood pressure and well-being were investigated in 188 patients, aged 41-82 years, with mild to moderate essential hypertension. At entry, 107 were untreated, 42 were taking the diuretic combination hydrochlorothiazide (50 mg/day) plus amiloride (5 mg/day) and another 39 were taking the beta-blocker atenolol (100 mg/day). A single-blind, 4-week placebo run-in period was followed by 12 weeks' oral ketanserin treatment at 20 or 40 mg twice a day. This regimen significantly reduced systolic and diastolic blood pressures in each group. Response rates were greater in patients aged over 60 years. Compared with placebo, sleep disturbances, daytime fatigue and overall weakness decreased during ketanserin treatment (P less than 0.05 for all), but the incidence of dry mouth and stuffy nose increased. In patients older than 60 years there was a greater reduction of complaints than in younger patients. Ketanserin proved effective and well tolerated, improving peripheral circulatory symptomatology, particularly in older patients and those with a good blood pressure response.