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Long-term persistence of use, lack of co-prescribed anticholinergic antiparkinson drugs and low mortality may indicate effectiveness and safety of antipsychotic drugs. We aimed to assess 3-year prescription persistence, concomitant use of anticholinergics and mortality related to the use of all antipsychotic agents available in Norway.Data were drawn from the Norwegian Prescription Database on the sales of antipsychotic and anticholinergic antiparkinson agents in 2004 to a total of 52,427 patients. The primary study group was a subgroup of 34,494 patients who were prescribed only one antipsychotic agent in 2004. The patients were re-investigated in 2007. For each of the 13 antipsychotic agents studied, assumed prescription persistence was assessed in light of use of anticholinergic antiparkinson agents in 2004, and casualty rates were noted.The highest persistence was demonstrated for zuclopenthixol (69.8%) and clozapine (88.4%). Zuclopenthixol was often co-prescribed with anticholinergics (22.2%), in contrast to clozapine (3.6%). Ziprasidone was associated with a low mortality (OR = 0.08), while chlorprotixene and haloperidol were associated with a high mortality (OR = 1.34 and 3.97, respectively) compared to levomepromazine.Clozapine demonstrated a high degree of continuity of prescription and a low level of concomitant use of anticholinergics. Zuclopenthixol also demonstrated a high degree of continuity of prescription, despite a considerable degree of co-prescribed anticholinergics. We did not find that any antipsychotic other than ziprasidone was associated with a low mortality. The use of haloperidol seemed to confer a mortality risk three times that of any of the other antipsychotic agents included.

Anticholinergic agents have widespread therapeutic indications in clinical medicine. In addition, certain other drug groups-such as neuroleptics, antidepressants and antihistamines-possess distinct anticholinergic properties that reduce tolerance and compliance. Especially in patients with heart disease, attention should be paid to cardiac anticholinergic drug effects. The analysis of short-term heart rate variability (HRV) provides a noninvasive tool to estimate vagal cholinergic outflow. In this review article, we present the basic principles of the most relevant techniques to study rapid HRV: the time domain analysis methods RMSSD and pNN50, and the high-frequency (HF) spectral component of HRV. We provide examples of previously reported effects of anticholinergic agents on these measures and also describe how adrenergic drugs may influence them. We have the following recommendations for a clinical pharmacologist investigating anticholinergic agents. (1) If the breathing rate of the study subject can be controlled during the assessment and the electrocardiogram recordings contain good-quality, stationary segments that are at least a few minutes long, then the HF power of HRV should be the method of choice. (2) During uncontrolled conditions, RMSSD should be included in the analyses, because it is less affected by changes in the respiratory pattern and it can be measured from shorter segments of electrocardiogram data. (3) Reduced short-term HRV suggests an anticholinergic, but not necessarily an antimuscarinic drug effect, since the inhibition of cholinergic vagal efferent activity may also originate from central or peripheral adrenergic influences.

The use of anticholinergic antiparkinson drugs is almost exclusively confined to treating antipsychotic-induced extrapyramidal side effects (EPS). We investigated the prevalence of concomitant prescription of anticholinergics as a proxy for antipsychotic-induced EPS and compared variance in prevalence with differences in the assumed mechanisms of action of antipsychotics on central nervous system (CNS) transmitter systems (i.e., receptor drug-binding profiles). We paid special attention to potential differences between typical and atypical antipsychotics.Data were drawn from the Norwegian Prescription Database on sales of antipsychotic and anticholinergic antiparkinson drugs to a total of 57,130 outpatients in 2004. We assessed concomitant dispensations of antipsychotic and anticholinergic drugs and correlated the prevalence of concomitantly prescribed anticholinergics to previously assessed receptor-binding profiles of antipsychotics.The concurrent use of anticholinergics varied between 0.4% and 26.0% for patients using a single antipsychotic agent. The prevalence of anticholinergic comedication was more than twice as high in patients using two or more antipsychotic drugs. Four typical antipsychotics (fluphenazine, zuclopenthixol, haloperidol, and perphenazine) were associated with higher concomitant use of anticholinergics than the rest. For the remaining 14 antipsychotic agents, the difference between typical and atypical antipsychotics was neither pronounced nor systematic. A high degree of D2-receptor antagonism and a high 5-HT2A/D2-receptor-affinity ratio coincided with the use of anticholinergics.The liability of antipsychotic drugs to cause EPS seemed to vary considerably and largely independently of the distinction between typical and atypical antipsychotics.

To evaluate the influence of the stomach and the cholinergic system on gallbladder contraction induced by physiological stimuli, the reduction in gallbladder volume in 7 healthy volunteers has been studied by real-time ultrasonography after the oral and intraduodenal administration of olive oil, preceded by pretreatment with cimetropium bromide or placebo. After an overnight fast, each subject swallowed 50 ml olive oil or it was administered through a naso-duodenal tube in the proximal duodenum. Cimetropium bromide 5 mg or placebo was given intravenously under double-blind control. After the placebo pretreatment, gallbladder contraction was greater and faster after intraduodenal oil than after oral oil. Cimetropium bromide decreased the extent, velocity and duration of gallbladder contraction induced by intraduodenal olive oil but it only reduced the velocity of the contraction induced by oil given orally. It is concluded that in normal human subjects the stomach modulates the extent and velocity of postprandial gallbladder contraction and that anticholinergic agents antagonize the gastric and duodenal phases of the response of the gallbladder to a meal.

Nasal symptoms in the general population commonly arise from infection, allergy, or exposure to inhaled irritants. There are two mechanism by which the symptoms occur: first, vasodilatation leading to mucosal swelling and plasma exudation into the nose; second, glandular secretion [1, 2]. These effects can follow either direct stimulation of the blood vessel or glands by either inflammatory mediators [1] or irritants, or stimulation of nasal or extranasal sensory nerves leading to reflex activation of the glands and blood vessels [3]. Gustatory rhinorrhoea has been reported after eating spicy food and is a common and sometimes embarrassing symptom. It could occur through direct irritation by vapours arising from the food during swallowing, through local absorption of the spices, or through stimulation of neural reflexes within the nose or the oropharynx. We have investigated the hypothesis that the symptoms of gustatory rhinorrhoea are due to the stimulation of neural reflexes by giving the antimuscarinic agent ipratropium bromide intranasally to healthy volunteers who all ate the same spicy curry. We studied 43 volunteers aged 27 (SEM 1) y (26 m and 15 f). The volunteers marked visual analogue scales from 0-100 mm documenting their current perception of runny nose, sneezing, cough, blocked nose, itchy nose, sweating, flushing, and use of paper tissues. They then tool either ipratropium bromide 400 ~tg per nostril or a matched placebo from a metered dose inhaler in double-blind random order. After 30 rain they then ate the same quantity of mutton nahari (a strong curry) served with plain boiled rice over 10 min. Then 20 rain later they again marked the visual analogue scales and noted the number of tissues that they had used. The number of tissues and the change in distance from zero in mm on the visual analogue scales were analysed by non-parametric analysis of variance and the Mann-Whitney U test. A summary of the results is shown in Table 1. The volunteers who took placebo reported a significant (P < 0.003) increase in the symptoms of runny nose and flushing and in the use of tissues. Those treated with ipratropium bromide had a similar increase in flushing, but had significantly fewer symptoms of runny nose (P < 0.05). They also used fewer tissues, but this was not statistically significantly different from placebo. This study confirms the results of two earlier studies in small numbers of volunteers [5, 6], and shows that gustatory rhinorrhoea is due to stimulation of a neural reflex, probably arising outside the nose. Treatment with the antimuscarinic agent ipratropium bromide significantly reduced the symptoms of runny nose and reduced the use of tissues, although the latter did not reach statistical significance, probably due to the small number of tissues used in the placebo group. However, the symptom of facial flushing was not reduced, suggesting that ipratropium was exerting its effect locally in the nose. Gustatory rhinorrhoea is therefore probably due to a neural reflex rather than to the direct action of the spices on the glands and blood vessels of the nose itself. This study also confirms the effectiveness of anticholinergic agents in reducing rhinorrhoea, as has been reported in patients suffering from rhinorrhoea due to other causes, such as allergy [7] and vasomotor rhinitis [4]. This implies that maj or control of the volume of nasal secretion

Anticholinergic agents have proved to be powerful bronchodilating drugs in various types of chronic obstructive pulmonary disease. Atropine given as an aerosol had a stronger bronchodilating effect, even in low doses not producing side-effects, than after peroral or intramuscular administration. Sch 1000, a new quater-nized atropine derivative had a stronger and more prolonged bronchodilator effect, even in significantly lower doses, and no side effects were observed. Because of its adventageous characteristics, Sch 1000 seems to be the anticholinergic agent to be preferred in clinical practice. It shows a wider therapeutic range than the beta adrenergic agent orciprenaline. A vagus-mediated reflex mechanism may be involved in histamine-induced bronchoconstriction. Experimental results show that a cholinergic mechanism and increased parasympathetic tone are important factors in the pathological mechanism of chronic airways obstruction.