What Is Anticholinergic Toxicity?

Anticholinergic drugs have been used for a long time in clinical practice and there are many types. Commonly used drugs include atropine, anisodamine, scopolamine, belladonna, Jiejingling (bupropion scopolamine), and probencin. This kind of medicine can relax bronchial smooth muscle and gastrointestinal smooth muscle spasm to relieve asthma and gastrointestinal colic, and can also reduce colic and biliary colic caused by ureteral stones. Atropine is essential to rescue organophosphorus pesticide poisoning. Atropine or anisodamine is also commonly used to rescue septic shock. Because anticholinergic drugs are widely used, have good curative effects, are cheap, and some consumers have only a little knowledge of medical knowledge, they take it as an analgesic drug, causing adverse consequences.

Chinese name: Anticholinergic drugs

Clinical application: Septic shock, organophosphate poisoning, etc.

Overview of anticholinergic drugs

Anticholinergic drugs have the effect of inhibiting secretion and spasmolysis, and are often used in gastrointestinal diseases. The vagus nerve is related to some uncomfortable symptoms of gastrointestinal diseases, and it is helpful to treat it by chemically blocking it under certain circumstances. Anticholinergics do not completely relieve the symptoms, which may be because the chemical method has not yet completely blocked the vagus nerve impulses. More precisely, in order to achieve more than 100% blockage of the vagus nerve, the required dose of anticholinergic drugs will also cause severe central nervous system toxicity and other side effects. ^[1]

Selection basis for anticholinergic drugs

The autonomic nervous system response follows the "initial value" principle, that is, any response to a stimulating or inhibiting drug depends on the "tension" or activity level when the drug is applied. It can be inferred that when smooth muscle activity is greater than normal basic digestive or digestive phase activity, the administration of anticholinergic drugs can reduce pain or other subjective gastrointestinal symptoms. This concept is the basis for the application of anticholinergics to symptomatic treatment. Also, this may partly explain why it is often observed that the same case has different effects on different anticholinergics or different patients on the same drug. ^[1]

Characteristics of anticholinergic drugs

1. Symptoms of esophageal disease or dysfunction are difficulty swallowing, pain in swallowing, burning sensation and nausea. Anticholinergics are not effective against mechanical obstruction caused by tumors or esophageal strictures. It has been proven that such drugs can inhibit esophageal peristalsis. Although anticholinergic drugs have been observed to reduce the pressure on the lower esophageal sphincter (cardiac), the effect on this part varies.

There is no positive or beneficial effect of anticholinergic drugs on diffuse spasm or achalasia of the esophagus. In the case of achalasia, it has no effect on the inability to relax the sphincter, nor can it reduce or relax the strong contraction during diffuse spasm. For mild esophageal spasm, anticholinergics may improve symptoms.

Stomach burning sensation is a symptom of gastric acid flowing back into the esophagus, often accompanied by some degree of abnormal activity of varying duration, but the persistence of the burning sensation is parallel to the duration of esophageal pH reduction. Anticholinergics are not suitable for this symptom. If used in patients with chronic repetitive burning sensation, it should be remembered that anticholinergics may reduce the strain on the door. Because, although these drugs can alleviate symptoms, long-term use may promote reflux of gastric acid, and make nausea symptoms worse.

In short, anticholinergics can be prescribed as needed (as appropriate) when treating esophageal symptoms believed to be caused by acid reflux or cramps, but only for relatively short periods of time.

2. The important symptoms of stomach and duodenum are chronic peptic ulcer or erosive ulcer caused by ulcer. The application of anticholinergic drugs in peptic ulcer can be considered as symptomatic treatment, affecting healing and preventing recurrence. The main symptom of peptic ulcer is pain, such as infusion of 0.1N hydrochloric acid into the stomach, which can quickly make the pain recur. Acute severe pain can be alleviated by injection of anticholinergic drugs. However, it should be noted that the use of anticholinergics to control pain may mask non-healing or complications (such as localized perforation). It is important that the relief of ulcer symptoms depends on antacids and frequent meals. If this still cannot be resolved, the existence of complications should be suspected.

The effect of anticholinergic drugs on gastric acid secretion is most obvious when hunger, that is, the basal secretion under the influence of vagus nerve, not the digestive secretion after meal or under the influence of gastrin. According to this observation, as an adjuvant therapy, they should be limited to taking at sleep to reduce basal secretion at night. Anticholinergics are contraindicated in duodenal ulcer disease with any signs of obstruction. The symptoms of early partial obstruction can be exacerbated by anticholinergic drugs that prolong gastric emptying. In this way, the clinical problem of gastric retention is complicated by obstruction, which requires a longer period of gastric decompression and intravenous fluid.

4. Treatment of acute pancreatitis is designed to freeze or "clamp" the pancreas. Anticholinergic drugs must have indications for the treatment of acute pancreatitis, and can be tolerated. The other treatment method is to reduce the acidity, thereby inhibiting the release of secretin.

5. Anticholinergic drugs can be used to control the symptoms of irritable bowel syndrome, and in relatively asymptomatic periods, smaller doses can be used. There are also indications for acute diverticulitis, and with the diet after an acute episode, to try to control recurrence. There is no evidence to suggest whether anticholinergics can reduce the incidence of diverticulitis in patients with existing diverticulosis. Many patients with diverticulosis develop symptoms of irritable bowel syndrome and therefore receive anticholinergic therapy.

6. For irritable bowel syndrome and diverticulosis, anticholinergic drugs should use separate drugs and dosages according to each individual's platinum situation, which depends on side effects and patient tolerance. It should be taken 30 to 60 minutes before meals to reduce segmentation or colonic motor activity due to gastrocolonic reflexes. Considering the prevalence of irritable bowel syndrome, diverticulosis, and diverticulitis, anticholinergics are the most widely used in this aspect of clinical gastroenterology. ^[1]

Anticholinergic side effects

1. Dry mouth, dry skin, flushing face;

2. Palpitations and rapid heart rate;

3. Vision blur due to dilated pupils;

4. Due to the inhibition of urinary function of the central nervous system by this class of drugs on urinary retention caused by bladder detrusor muscles;

5. Dizziness, excitement, irritability, and convulsions.

Anticholinergic drugs with caution

1. Coronary arteriosclerotic heart disease, heart failure;

2. Paralytic intestinal obstruction and intestinal stenosis;

3. Esophageal cardia achalasia;

4. Peptic ulcer with gastric fluid retention in pyloric obstruction;

5. Acute pancreatitis with intestinal paralysis and abdominal distension;

6. Prostatic hypertrophy;

7. Glaucoma ophthalmologist

8. High fever patients;

9. Acute phase of cerebral hemorrhage;

10. Acute gastric bleeding;

11. The elderly should be used with caution.

COPD Mechanism of anticholinergic drugs for COPD

When COPD occurs, the number or function of M receptors in the respiratory tract and lung tissue is often abnormal. Yao Wanzhen et al. ^[2] researched that the number of M receptors in lung tissue of patients with COPD decreased, among which the proportion of M2 receptors decreased and the proportion of M1 and M3 receptors increased. This change plays an important role in the pathogenesis of COPD. The main reversible mechanism of airway obstruction in patients with COPD is cholinergic airway contraction, and anticholinergic drugs have played a role in this important reversible factor. Existing anticholinergic drugs include ipratropium bromide, oxtropium bromide, and tobromide, which mainly antagonize the M3 receptor by acting with endotropium bromide, which is in contrast to other anticholinergic drugs Longer than the action time, the effect is significant. Profita et al. ^[3] tested the levels of leukotriene B4 and M1, M2, and M3 receptors in sputum of COPD patients, and found that M3 receptors increased and M2 receptors decreased in COPD patients, suggesting that M receptors are involved in the respiratory tract Inflammatory response process. Inflammatory stimulation can cause increased acetylcholine synthesis in respiratory epithelial cells.At the same time, studies have shown that most inflammatory cells (such as macrophages, lymphocytes, neutrophils, etc.) can express functional M receptors, indicating that acetylcholine can also pass Paracrine and autocrine mechanisms regulate the inflammatory response of COPD ^[4] . T cells can also release acetylcholine and express the M receptor, indicating that anticholinergic drugs can inhibit the effects of inflammatory cells, thereby exerting a therapeutic effect on COPD. Studies by Barnes ^[5] suggest that the release of acetylcholine outside neurons may activate the M receptors of normal cells and inflammatory cells in the small airways, so inhibiting the tension of cholinergic nerves can inhibit the inflammatory response of COPD, thereby achieving treatment of COPD the goal of.

COPD Clinical application of anticholinergic drugs in COPD

Anticholinergic drugs Pulmonary function test is currently the "gold standard" in the diagnosis of COPD and the measure of improvement in COPD. The most commonly used indicator is forced expiratory volume inone second (FEV1). Hasegawa et al. ^[6] used CT scans to observe the changes in lung function before and after inhalation of anticholinergic drugs in 15 patients with stable COPD, and found that the average FEV1 value after treatment was increased from (1.23 ± 0.11) L to (1.47 ± 0.13) L And the size of grade 4-6 bronchiectasis was closely related to the improvement of lung function, especially FEV1 (r = 0.843, P <0.01). Studies have confirmed that the combined use of 2 receptor agonists and anticholinergic drugs can alleviate the clinical symptoms of patients with COPD, increase exercise endurance, and significantly increase the FEV1 level of patients compared with the use of two drugs alone, greatly reducing the duration of patients with acute attacks Significantly improve the quality of life of patients, reduce the number of hospitalizations and days of hospitalization during acute exacerbations, and reduce adverse reactions. ^[7]