Efficacy of maintenance use of anticholinergic agents. [Postoperative routine use of physostigmine on vigilance, cardiovascular parameters and need of analgesics]. Effect of switching to atypical antipsychotics on memory in patients with chronic schizophrenia. Anticholinergic prophylaxis does not prevent emesis following strabismus surgery in children. Effect of anticholinergic agents upon acquired nystagmus: a double-blind study of trihexyphenidyl and tridihexethyl chloride. Can the pattern of neuropsychological improvement obtained with cholinergic drugs be used to infer a cholinergic mechanism in other nootropic drugs? Effects of anticholinergics on postoperative vomiting, recovery, and hospital stay in children undergoing tonsillectomy with or without adenoidectomy. Clozapine versus placebo in Huntington's disease: a double blind randomised comparative study. Effect of anticholinergic drugs on the efficacy of activated charcoal.
Twenty-seven long-term psychiatric inpatients maintained on neuroleptics with concomitant antiparkinsonian medication were entered into a study in which anticholinergic medication was gradually withdrawn in a randomized double-blind within-subjects design. The extrapyramidal symptoms of each patient were compared when taking their usual anticholinergic medication, when taking placebo and when taking no antiparkinsonian drug. The relapse rate on no medication was 14%, and if patients relapsed on no medication they also relapsed on placebo. The relapse rate was not significantly different on active medication. Nor were there significant differences in ratings of parkinsonism or dyskinesia. The lack of difference between double-blind and overt withdrawal does not mean that studies that find a much higher relapse rate are necessarily unaffected by nonspecific factors, as significant unblinding may occur in clinical trials. A central anticholinergic syndrome (CAS) can be related to the majority of anesthetic agents, but is often not recognized as such. Thus, most anesthesiologists seem to miss the occurrence of an anticholinergic syndrome especially when agitation and/or restlessness are the major symptoms. Therefore, the following study was undertaken to test the hypothesis that routine administration of the anticholinergic agent physostigmin is of benefit for patients in regard to vigilance, the cardiovascular system and the need of analgesics easing the time in the post anesthesia care unit (PACU).
                After approval by the local ethics committee and written informed consent, 100 patients undergoing a cholecystectomy or a struma resection, were given either physostigmin (n = 51) or saline 0.9 % (n = 49) in a randomized fashion. The study was conceived to block a possible isoflurane-N2O/O2 (opioid-based plus relaxant) induced central anticholinergic syndrome and to evaluate the effects on the cardiovascular system on vigilance and on postoperative analgesic demand. Following parameters were measured: systolic and diastolic blood pressure, heart rate, respiratory rate, and arterial blood gases. In addition, vigilance was determined and typical anticholinergic symptoms (disorientation, slurred speech, agitation, nausea, emesis, cardiac arrhythmia and muscle shivering) were determined 10, 20, 40 and 60 minutes following the intravenous injection of physostigmin. Also, the need for the postoperative analgesic pethidine was evaluated among the two groups.
                Except for a significant reduction in the need of analgesics, a reduced diastolic pressure and heart rate and a lower incidence of muscle shivering there was no difference among the two groups. One major side effect following the use of physostigmin was the higher incidence of nausea in the im mediate minutes following injection. This effect may be due to the rapid injection of the anticholinergic compound. Otherwise there were no detrimental effects of physostigmin in patients.
                From the results it can be concluded that routine administration of an anticholinergic agent results in a short term beneficial effect in regard to vigilance, a lesser incidence of muscle shivering and a lesser demand for analgesics. However, because of the low incidence of a classical central anticholinergic syndrome, routine physostigmine is only indicated when agitation is diagnosed. While the usefulness of atypical antipsychotics for improving cognitive function has been proven, the specific effects of these drugs are still unknown. The objective of this study was to investigate changes of the immediate memory and verbal working memory in patients with chronic schizophrenia after switching to one of four atypical antipsychotic agents and cessation of anticholinergic therapy. The subjects included 77 schizophrenic patients who were treated primarily with typical antipsychotics. Treatment was randomly switched to one of four atypical antipsychotics (olanzapine, perospirone, quetiapine, or risperidone) over a 4-week period, and then the drug was continued for another 4 weeks while the patient was taken off anticholinergics. The immediate memory, verbal working memory, and symptoms were evaluated. Significant improvement of immediate memory was only seen with olanzapine and risperidone. Improvement was also seen after switching to perospirone, but immediate memory worsened after treatment with this anticholinergic drug was discontinued. Deterioration was seen after switching to quetiapine, but immediate memory improved and reached the previous level after treatment with anticholinergic drugs was discontinued. Significant improvement of the verbal working memory was only seen during risperidone administration. The findings suggested that switching chronic schizophrenic patients to atypical antipsychotics can improve both the immediate memory and the verbal working memory when risperidone is used, while improvement of immediate memory can be expected with olanzapine. From the viewpoint of improving the memory, quetiapine should not be administered concomitantly with anticholinergic drugs, and caution should be exercised when discontinuing anticholinergic drugs during treatment with perospirone. One hundred and twenty-one children were studied in this prospective, randomized double-blind, placebo-controlled comparison of the effectiveness of anticholinergic prophylaxis for the prevention of emetic symptoms following strabismus surgery. The children were allocated to three groups, to receive placebo (n = 40), glycopyrrolate (n = 40) or atropine (n = 41). The incidence of intraoperative oculocardiac reflex (OCR) and of postoperative emetic symptoms for 24 h was recorded. The incidence of OCR was 55% in the placebo group compared with 5% and 2% in the glycopyrrolate and atropine groups respectively (P < 0.05). Thirty percent (12/40) of patients in the placebo group, 25% (10/40) in the glycopyrrolate group, and 22% (9/41) in the atropine group experienced nausea and/or vomiting (difference not significant). It is concluded that prophylactic administration of anticholinergic agents during strabismus surgery in children despite being effective against the occurrence of the oculocardiac reflex, does not reduce the incidence of emetic symptoms. We conducted a randomized, double-blind, crossover trial of two anticholinergic agents--trihexyphenidyl and tridihexethyl chloride (a quaternary anticholinergic that does not cross the blood-brain barrier)--in patients with acquired nystagmus and measured visual acuity and nystagmus before and at the end of 1 month on each medication. Of the 10 patients admitted to the study, only five completed trials of both drugs due to intolerance of medication or intercurrent illness. Of six patients who completed the trial of trihexyphenidyl, only one showed improvement. Of six patients who completed a trial of tridihexethyl chloride, four showed improvement. We conclude that (1) trihexyphenidyl is not a reliable treatment for acquired nystagmus, although occasional patients may benefit; (2) anticholinergic agents may suppress nystagmus by peripheral rather than central mechanisms; and (3) the side effects of anticholinergic agents limit their effectiveness in the treatment of nystagmus. 1. Enhancement of episodic memory and reduction of intrusion errors are considered as the most characteristic outcome of cholinergic drugs administration in AD patients. 2. Since the nootropic drugs Piracetam and Oxiracetam are deemed to act through a cholinergic mechanism, we checked whether AD patients treated with these drugs would show the same pattern of neuropsychological improvement. 3. Results were negative, since (a) episodic memory showed a similar degree of improvement both in patients treated with these drugs and in patients treated with placebo; (b) the number of intrusions tended to increase, rather than to decrease, after the treatment period. Nausea and vomiting are the most frequent problems after minor ambulatory surgical procedures. The agents used to induce and maintain anesthesia may modify the incidence of emesis. When neuromuscular blockade is antagonized with anticholinesterases, atropine or glycopyrrolate is used commonly to prevent bradycardia and excessive oral secretions. This study was designed to evaluate the effect of atropine and glycopyrrolate on postoperative vomiting in children.
                Ninety-three patients undergoing tonsillectomy with or without adenoidectomy were studied. After inhalation induction of anesthesia with nitrous oxide, oxygen, and halothane, anesthesia was maintained with a nitrous oxide-oxygen mixture, halothane, morphine, and atracurium. Patients were randomized to receive, in a double-blinded manner, either 15 microg/kg atropine or 10 microg/kg glycopyrrolate with 60 microg/kg neostigmine to reverse neuromuscular blockade. Patient recovery, the incidence of postoperative emesis, antiemetic therapy, and the duration of postoperative hospital stay were assessed.
                There were no significant differences in age, gender, weight, or discharge time from the postanesthesia care unit or the hospital between the groups. Twenty-four hours after operation, the incidence of vomiting in the atropine group (56%) was significantly less than in the glycopyrrolate group (81%; P<0.05). There was no significant difference between the atropine and glycopyrrolate groups in the number of patients who required antiemetics or additional analgesics.
                In children undergoing tonsillectomy with or without adenoidectomy, reversal of neuromuscular blockade with atropine and neostigmine is associated with a lesser incidence of postoperative emesis compared with glycopyrrolate and neostigmine. To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease.
                Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately.
                Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties.
                Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group. Although it is a commonly held belief that the ingestion of drugs with an anticholinergic action would prolong the duration of time after drug ingestion for effective gastrointestinal decontamination, data are lacking to support this belief. The purpose of this study is to determine whether activated charcoal is more effective in the presence of concurrent anticholinergic activity.
                A three-limbed randomized crossover study in 10 healthy volunteers was completed to determine the ability of a 50 g dose of activated charcoal to reduce the bioavailability of a simulated overdose of acetaminophen (12 x 325 mg tablets) in the presence and absence of a concurrently present anticholinergic drug, atropine (0.01 mg/kg I. M. administered 15 min prior to the acetaminophen ingestion).
                After the acetaminophen ingestion, median Cmax occurred at 1 h for all three exposures but was lower in the atropine-treated study arm (31+/-19 mg/L) than in the control or charcoal alone intervention arms (49+/-13 and 51+/-16 mg/L, respectively) (P<0.05). Compared to the control area under the serum concentration vs. time curve, a single dose of activated charcoal 1 h after drug ingestion reduced acetaminophen bioavailability by 20% (95% CI 4-36%) and by 47% (95% CI 35-59%) in the presence of atropine (P<0.05 atropine plus charcoal vs. charcoal alone).
                Our data support the belief that activated charcoal is more effective in the presence of anticholinergic activity. Additional study is required to determine whether in patients with anticholinergic drug overdose, activated charcoal is effective at times beyond the recommendation for overdoses of drugs without this pharmacodynamic effect.
From the available evidence we cannot advocate the use of anticholinergics in MS.